Hepatoprotective and antioxidant effects of Hygrophila auriculata (K. Schum) Heine Acanthaceae root extract.

PubMed

Shanmugasundaram, P; Venkataraman, S

2006-03-08

Hygrophila auriculata (K. Schum) Heine (syn. Asteracantha longifolia Nees, Acanthaceae) was widely used in the Indian systems of medicine for the treatment of various liver ailments. The hepatoprotective activity of the aqueous extract of the roots was studied on CCl(4)-induced liver toxicity in rats. The activity was assessed by monitoring the various liver function tests, viz. alanine transaminase, aspartate transaminase (AST), alkaline phosphatase (ALP), total protein and total bilirubin. Furthermore, hepatic tissues were subjected to histopathological studies. The root extract was also studied for its in vitro antioxidant activity using ferric thiocyanate (FTC) and thiobarbituric acid (TBA) methods. The extract exhibited significant hepatoprotective and antioxidant activities.

Antioxidant and Hepatoprotective Potential of Phenol-Rich Fraction of Juniperus communis Linn. Leaves.

PubMed

Ved, Akash; Gupta, Amresh; Rawat, Ajay Kumar Singh

2017-01-01

Juniperus communis Linn. is an important plant in India traditional system of medicine which is widely used by different tribes in many countries. In the present study, the antioxidant, cytotoxic and hepatoprotective activities of Juniperus communis leaves were investigated against various models. ethanolic extract (70% v/v) of J. communis leaves was successively extracted using hexane and ethyl acetate to prepare various fractions. Total phenol content was resolute by the Folin-Ciocalteau's process. The antioxidant properties of the different fractions/extract of leaves of J. communis were examined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and Fe 2+ chelating ability. Cytotoxic activity was examined by cell viability assay on HepG2 cells. Hepatoprotective activity of ethyl acetate fraction (EAF) evaluated against PCM-Paracetamol-induced hepatic damage in Wistar albino rats. Total phenol content was found maximum 315.33 mg/GAE/g in EAF. Significant scavenging activity were found for EAF (IC 50 = 177 μg/ml) as compared to standard BHT (IC 50 = 138 μg/ml), while EAF showed good Fe 2+ chelating ability having an IC 50 value of 261 mg/ML compared to standard ethylenediaminetetraacetic acid (7.7 mg/mL). It was found that EAF treated group shows remarkable decrease in serum Aspartate aminotransferase, serum Alanine aminotransferase, total bilirubin, direct bilirubin, and alkaline phosphatase level in treatment group as compared to the hepatotoxic group. EAF of J. communis leaves is found to be potent antioxidant and hepatoprotective without any cytotoxicity and it can also be included in nutraceuticals with notable benefits for mankind or animal health. Phenol-rich fraction (PRF) and other fractions/extract of Juniperus communis leaves were screened for antioxidant, cytotoxic, and hepatoprotective activity.Significant antioxidant and hepatoprotective activity without any cytotoxicity were found while treating with ethyl acetate fraction (EAF). Abbreviations used: HepG2: Liver hepatocellular carcinoma, BHT: Butylated hydroxytoluene, PCM: Paracetamol, IC50: Half maximal inhibitory concentration, RSA: Radical Scavenging Activity, WST: Water-soluble tetrazolium.

Methanol extract of Melastoma malabathricum leaves exerted antioxidant and liver protective activity in rats

PubMed Central

2013-01-01

Background Melastoma malabathricum L. (Melastomaceae) is a small shrub with various medicinal uses. The present study was carried out to determine the hepatoprotective activity of methanol extract of M. malabathricum leaves (MEMM) against the paracetamol-induced liver toxicity in rats model. Methods The respective chemicals and herbal solutions (10% DMSO, 200 mg/kg silymarin or MEMM (50, 250 and 500 mg/kg)) were administered orally to rats once everyday for 7 days followed by the hepatotoxicity assay. The blood samples and livers were collected and subjected to biochemical and microscopical analysis. Prior to the hepatoprotective study, MEMM was subjected to determination of the total phenolic content (TPC) and the antioxidant properties using several standard assays (e.g. 2, 2-diphenyl-1-picrylhydrazyl- and superoxide anion- radical scavenging assay, and oxygen radical absorbance capacity assay). Results MEMM exerted significant (p < 0.05) and high antioxidant activity in which high TPC was recorded; while in the hepatotoxicity study, the extract exhibited significant hepatoprotective effects against the paracetamol-induced hepatotoxic model. The results observed for serum liver enzymes (ALT, ALP and AST) as well as the microscopic observations and microscopic scoring supported the hepatoprotective potential of MEMM. The phytochemical and HPLC analysis of MEMM demonstrated the presence of flavonoids as its major constituents. Conclusions The MEMM-induced hepatoprotective activity could be allied partly to its antioxidant activity and the presence of flavonoids. PMID:24267313

Comparative phytochemical, hepatoprotective and antioxidant activities of various samples of Swertia Chirayita collected from various cities of Pakistan.

PubMed

Mahmood, Sidra; Hussain, Shahzad; Tabassum, Sobia; Malik, Farnaz; Riaz, Humayun

2014-11-01

Medicinal plants are crucial for about 80% of the world population in developing and developed countries for their primary and basic health care needs owing to better tolerability, superior compatibility with human body and having lesser side effects. The present study was conducted on various solvent extracts of three plant samples of Indian and Nepali origin Swertia Chirayita (Roxb.) Buch-ham (Chiratia) collected from various places to establish their comparative phytochemical analysis, chromatographic profile, hepatoprotective and antioxidant activities. Nepali Swertia Chirayita was found to have finest Chromatographic profile (TLC). Phytochemical analysis revealed Alkaloids, flavonoids, saponins, ascorbic acid, glycosides, steroids and triterpenoids in all samples. Different solvent fractions of the methanolic plant extracts of Swertia chirayita were assessed for hepatoprotective activity by carbon tetrachloride-induced liver damage in rats. The grade of protection was measured by using biochemical parameters such as serum glutamate oxalate transaminase (SGOT/AST), alkaline phosphatase (ALP), serum glutamate pyruvate transaminase (SGPT/ALT) and total bilirubin. The in-vitro antioxidant activity of the extracts was also evaluated by the 1, 1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay. The methanolic and aqueous extracts, at a dose of 200mg/kg and 300mg/kg, produced significant (p<0.05) hepatoprotection by decreasing the activities of the serum enzymes and bilirubin while there were marked scavenging of the DPPH free radicals by the fractions. Decreased observed in the biochemical parameters suggests that the plant extracts possesses hepatoprotective as well as antioxidant activities without any significant variation amongst them. These activities reside mainly in the methanolic extract of whole plant.

Shiitake Culinary-Medicinal Mushroom, Lentinus edodes (Agaricomycetes): A Species with Antioxidant, Immunomodulatory, and Hepatoprotective Activities in Hypercholesterolemic Rats.

PubMed

Nisar, Jaweria; Mustafa, Imtiaz; Anwar, Haseeb; Sohail, Muhammad Umar; Hussain, Ghulam; Ullah, Muhammad Irfan; Faisal, Muhammad Naeem; Bukhari, Shazia Anwer; Basit, Abdul

2017-01-01

Lentinus edodes is a culinary-medicinal mushroom that has an established history of use in Asian therapies. The mushroom offers well-documented beneficial health effects such as antihypercholesterolemic, antitumor, and antibacterial activities. In this study, dried powder of L. edodes fruiting bodies was used to evaluate immunomodulatory, hepatoprotective, and antioxidant effects in hypercholesterolemic rats. Albino rats (n = 24) were divided into 3 groups: the control (CON) group, the hypercholesterolemia-only group (HCG), and the L. edodes group (LEG). Hypercholesterolemia was induced in rats in the HCG and LEG by feeding cholesterol and cholic acid in a chow maintenance diet (CMD) for 24 days. The CON group was fed the CMD throughout the experiment. The HCG continued on the high-cholesterol diet without any L. edodes supplement. The LEG was fed the high-cholesterol diet supplemented with L. edodes for an additional 42 days. Various biological health biomarkers, such as total antioxidant capacity, total oxidant status, arylesterase, paraoxonase activity, and liver enzymes in serum were studied to evaluate antioxidant and hepatoprotective responses. Cell-mediated immunity was evaluated in each group through a delayed type of hypersensitivity reaction. The total oxidant status decreased significantly (P ≤ 0.05) after administration of L. edodes in the diet. The cell-mediated immune response significantly increased (P ≤ 0.05) in the LEG. The significant decrease in liver enzymes supports the hepatoprotective effect of L. edodes. In conclusion, the results show the immunomodulatory, hepatoprotective, and antioxidant activities of L. edodes supplementation in hypercholesterolemic rats.

Hepatoprotective effect of chitosan-caffeic acid conjugate against ethanol-treated mice.

PubMed

Park, Soo Yeon; Ahn, Ginnae; Um, Ju Hyung; Han, Eui Jeong; Ahn, Chang-Bum; Yoon, Na Young; Je, Jae-Young

2017-10-02

The chitosan-caffeic acid (CCA) conjugate shows a hepatoprotective effect against oxidative stress-induced hepatic damage in cultured hepatocytes. The objective of this study is the verification of the hepatoprotective effect of the CCA in vivo against ethanol-induced liver injury in mice. The administration of ethanol resulted in the increase of the serum-aminotransferase activities (AST and ALT), triglycerides, total cholesterol, and lipid peroxidation. The CCA co-administration, however, significantly (p<0.05) ameliorated these serum biomarkers. The antioxidant-enzyme activities in the liver tissue, including those of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), were significantly decreased by a chronic ethanol administration, whereas the hepatic lipid-peroxidation level was increased. Moreover, the chronic ethanol administration elevated the gene expression of pro-inflammatory cytokines such as tumor-necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the liver tissue. The CCA co-administration, however, significantly (p<0.05) increased the activities of the SOD, CAT, and GPx and caused the down-regulation of the TNF-α- and IL-6-gene expressions in the liver tissue. An histopathologic evaluation also supported the hepatoprotective effect of the CCA against ethanol-induced hepatotoxicity in the mice. Copyright © 2017 Elsevier GmbH. All rights reserved.

Hepatoprotective activity of aqueous extract of Portulaca oleracea in combination with lycopene in rats

PubMed Central

Anusha, M.; Venkateswarlu, M.; Prabhakaran, V.; Taj, S. Shareen; Kumari, B. Pushpa; Ranganayakulu, D.

2011-01-01

Objective: To investigate the hepatoprotective activity of the aqueous extract of the aerial parts of Portulaca oleracea (P. oleracea) in combination with lycopene against carbon tetrachloride induced hepatotoxicity in rats. Materials and Methods: Hepatotoxicity was induced in male Wistar rats by intraperitoneal injection of carbon tetrachloride (0.1 ml/kg b.w for 14 days). The aqueous extract of P. oleracea in combination with lycopene (50 mg/kg b.w) was administered to the experimental animals at two selected doses for 14 days. The hepatoprotective activity of the combination was evaluated by the liver function marker enzymes in the serum [aspartate transaminases (AST), alanine transaminases (ALT), alkaline phosphatase (Alk.P), total bilirubin (TB), total protein (TP) and total cholesterol (TC)], pentobarbitone induced sleeping time (PST) and histopathological studies of liver. Results: Both the treatment groups showed hepatoprotective effect against carbon tetrachloride induced hepatotoxicity by significantly restoring the levels of serum enzymes to normal which was comparable to that of silymarin group. Besides, the results obtained from PST and histopathological results also support the study. Conclusions: The oral administration of P. oleracea in combination with lycopene significantly ameliorates CCl4 hepatotoxicity in rats. PMID:22022001

Diallyl Polysulfides from Allium sativum as Immunomodulators, Hepatoprotectors, and Antimycobacterial Agents.

PubMed

Oosthuizen, Carel; Arbach, Miriam; Meyer, Debra; Hamilton, Chris; Lall, Namrita

2017-07-01

Mycobacterium tuberculosis remains one of the world's deadliest killers, with an annual death rate of ∼1.5 million. The medicinal effects of garlic have been well documented, and natural products have been shown to have antimycobacterial activity. The current study evaluated the efficacy of six Allium sativum L. polysulfide mixtures as antimycobacterial agents together with their cytotoxic, immunomodulatory, and hepatoprotective activities. The microtitre PrestoBlue assay was used to determine the minimum inhibitory concentrations (MIC). Cytotoxicity was evaluated by using peripheral blood mononuclear cells (PBMC). Excreted cytokine levels were determined by utilizing an enzyme-linked immunosorbent assay (ELISA), by exposing isolated PBMCs to varying concentrations of polysulfide mixtures. Human C3A liver cells were utilized in the hepatoprotective study, to assess the protective effect against the toxicity induced by acetaminophen. Samples with higher amounts of diallyl trisulfide (Sample G4) showed the highest antimycobacterial activity, exhibiting an MIC of 2.5 μg/mL against M. tuberculosis H37Rv. Five samples showed moderate toxicity in PBMC, with G1 showing no toxicity. The selective index of G4 was the highest, with a selectivity index close to one. Two samples, G3 and G6 containing higher amounts of diallyl tetrasulfide and lower amounts of diallyl trisulfide, showed >50% hepatoprotection. This is comparable to a hepatoprotective agent, Silymarin, which showed a hepatoprotective effect of 30% at the tested concentration. Diallyl tetrasulfide showed significant antimycobacterial activity. A combination of higher diallyl tetrasulfide and lower diallyl trisulfide was indicative of hepatoprotective activity.

Hepatoprotective activity of punarnavashtak kwath, an Ayurvedic formulation, against CCl4-induced hepatotoxicity in rats and on the HepG2 cell line.

PubMed

Shah, Vaishali N; Shah, Mamta B; Bhatt, Parloop A

2011-04-01

Punarnavashtak kwath (PNK) is a classical Ayurvedic formulation, mentioned in Ayurvedic literature Bhaishajya Ratnavali, for hepatic disorders and asthma. This study investigated the hepatoprotective activity of PNK to validate the traditional use of this formulation. PNK was prepared in the laboratory according to the method given in Ayurvedic literature. Phytochemical screening was performed to determine the presence of phytoconstituents. Hepatoprotective activity was evaluated against CCl(4)-induced hepatotoxicity in rats and by its effect on the HepG2 cell line. Preliminary phytochemical screening revealed the presence of alkaloids, tannins, flavonoids, saponins, and a bitter principle in PNK. Administration of PNK produced significant hepatoprotective effect as demonstrated by decreased levels of serum liver marker enzymes such as aspartate transaminase, serum alanine transaminase, serum alkaline phosphatase, and serum bilirubin and an increase in protein level. Thiopentone-induced sleeping time was also decreased in the PNK-treated animals compared with the CCl(4)-treated group. It also showed antioxidant activity by increase in activity of glutathione, superoxide dismutase, and catalase and by a decrease in thiobarbituric acid reactive substance level compared with the CCl(4)-treated group. Results of a histopathological study also support the hepatoprotective activity of PNK. Investigation carried out on the HepG2 cell line depicted significant increase in viability of cells exposed to PNK as compared with CCl(4)-treated cells. It can be concluded that PNK protects hepatocytes from CCl(4)-induced liver damages due to its antioxidant effect on hepatocytes. An in vitro study on HepG2 cell lines also supports its protective effect.

Antioxidant and Hepatoprotective Potential of Phenol-Rich Fraction of Juniperus communis Linn. Leaves

PubMed Central

Ved, Akash; Gupta, Amresh; Rawat, Ajay Kumar Singh

2017-01-01

Background: Juniperus communis Linn. is an important plant in India traditional system of medicine which is widely used by different tribes in many countries. Objective: In the present study, the antioxidant, cytotoxic and hepatoprotective activities of Juniperus communis leaves were investigated against various models. Materials and Methods: ethanolic extract (70% v/v) of J. communis leaves was successively extracted using hexane and ethyl acetate to prepare various fractions. Total phenol content was resolute by the Folin-Ciocalteau's process. The antioxidant properties of the different fractions/extract of leaves of J. communis were examined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity and Fe2+ chelating ability. Cytotoxic activity was examined by cell viability assay on HepG2 cells. Hepatoprotective activity of ethyl acetate fraction (EAF) evaluated against PCM-Paracetamol-induced hepatic damage in Wistar albino rats. Results: Total phenol content was found maximum 315.33 mg/GAE/g in EAF. Significant scavenging activity were found for EAF (IC50 = 177 μg/ml) as compared to standard BHT (IC50 = 138 μg/ml), while EAF showed good Fe2+ chelating ability having an IC50 value of 261 mg/ML compared to standard ethylenediaminetetraacetic acid (7.7 mg/mL). It was found that EAF treated group shows remarkable decrease in serum Aspartate aminotransferase, serum Alanine aminotransferase, total bilirubin, direct bilirubin, and alkaline phosphatase level in treatment group as compared to the hepatotoxic group. Conclusion: EAF of J. communis leaves is found to be potent antioxidant and hepatoprotective without any cytotoxicity and it can also be included in nutraceuticals with notable benefits for mankind or animal health. SUMMARY Phenol-rich fraction (PRF) and other fractions/extract of Juniperus communis leaves were screened for antioxidant, cytotoxic, and hepatoprotective activity.Significant antioxidant and hepatoprotective activity without any cytotoxicity were found while treating with ethyl acetate fraction (EAF). Abbreviations used: HepG2: Liver hepatocellular carcinoma, BHT: Butylated hydroxytoluene, PCM: Paracetamol, IC50: Half maximal inhibitory concentration, RSA: Radical Scavenging Activity, WST: Water-soluble tetrazolium. PMID:28216892

Phytochemical analysis, hepatoprotective and antioxidant activity of Alchornea cordifolia methanol leaf extract on carbon tetrachloride-induced hepatic damage in rats.

PubMed

Osadebe, Patience O; Okoye, Festus B C; Uzor, Philip F; Nnamani, Nneka R; Adiele, Ijeoma E; Obiano, Nkemakonam C

2012-04-01

To investigate the hepatoprotective and antioxidant activities of Alchornea cordifolia (A. cordifolia) leaf extract. Various solvent fractions of the methanol extract of the leaf of the plant A. cordifolia Mull. Arg (Fam: Euphorbiaceae) were evaluated for hepatoprotective activity by carbon tetrachloride-induced liver damage in rats. The degree of protection was measured by using biochemical parameters such as serum glutamate oxalate transaminase (SGOT/AST), serum glutamate pyruvate transaminase (SGPT/ALT), alkaline phosphatase (ALP) and total bilirubin. The in vitro antioxidant activity of the extract was also evaluated by the 1, 1-diphenyl- 2-picrylhydrazyl (DPPH) free radical scavenging assay. The extract was subjected to preliminary phytochemical screening. The ethyl acetate and chloroform fractions, at a dose of 300 mg/kg, produced significant (P<0.05) hepatoprotection by decreasing the activities of the serum enzymes and bilirubin while there were marked scavenging of the DPPH free radicals by the fractions. The effects were comparable to those of the standard drugs used for the respective experiments, silymarin and ascorbic acid. Alkaloids, flavonoids, saponins and tannins were detected in the phytochemical screening. From this study, it was concluded that the plant of A. cordifolia possesses hepatoprotective as well as antioxidant activities and these activities reside mainly in the ethyl acetate and acetone fractions of methanol leaf extract. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Hepatoprotective activity of Leptadenia reticulata stems against carbon tetrachloride-induced hepatotoxicity in rats

PubMed Central

Nema, Amit Kumar; Agarwal, Abhinav; Kashaw, Varsha

2011-01-01

Objective: To evaluate the hepatoprotective activity of ethanolic and aqueous extract of stems of Leptadenia reticulata (Retz.) Wight. and Arn. in carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. Materials and Methods: The toxicant CCl4 was used to induce hepatotoxicity at a dose of 1.25 ml/kg as 1 : 1 mixture with olive oil. Ethanolic and aqueous extracts of L. reticulata stems were administered in the doses of 250 and 500 mg/kg/day orally for 7 days. Silymarin (50 mg/kg) was used as standard drug. The hepatoprotective effect of these extracts was evaluated by the assessment of biochemical parameters such as serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, total bilirubin, serum protein, and histopathological studies of the liver. Results: Treatment of animals with ethanolic and aqueous extracts significantly reduced the liver damage and the symptoms of liver injury by restoration of architecture of liver as indicated by lower levels of serum bilirubin and protein as compared with the normal and silymarin-treated groups. Histology of the liver sections confirmed that the extracts prevented hepatic damage induced by CCl4 showing the presence of normal hepatic cords, absence of necrosis, and fatty infiltration. Conclusion: The ethanolic and aqueous extracts of stems of L. reticulata showed significant hepatoprotective activity. The ethanolic extract is more potent in hepatoprotection in CCl4-indiced liver injury model as compared with aqueous extract. PMID:21713086

NF-κB activation and proinflammatory cytokines mediated protective effect of Indigofera caerulea Roxb. on CCl4 induced liver damage in rats.

PubMed

Ponmari, Guruvaiah; Annamalai, Arunachalam; Gopalakrishnan, Velliyur Kanniappan; Lakshmi, P T V; Guruvayoorappan, C

2014-12-01

Indigofera caerulea Roxb. is a well known shrub among native medical practitioners in folk medicine used for the treatment of jaundice, epilepsy, night blindness and snake bites. It is also reported to have antioxidant and antimicrobial properties. However its actual efficacy and hepatoprotective mechanism in particular is uncertain. Thus the present study investigates the hepatoprotective effect of the methanolic extract of I. caerulea Roxb. leaves (MIL) and elucidation of its mode of action against carbon tetrachloride (CCl4) induced liver injury in rats. HPLC analysis of MIL when carried out showed peaks close to standard ferulic acid and quercetin. Intragastric administration of MIL up to 2000 mg/kg bw, didn't show any toxicity and mortality in acute toxicity studies. During "in-vivo" study, hepatic injury was established by intraperitoneal administration of CCl4 3 ml/kg bw (30% CCl4 in olive oil; v/v) twice a week for 4 weeks in Sprague-Dawley rats. Further, hepatoprotective activity of MIL assessed using two different doses (100 and 200mg/kg bw) showed that intra-gastric administration of MIL (200mg/kg bw) significantly attenuates liver injury. Investigation of the underlying mechanism revealed that MIL treatment was capable of reducing inflammation by an antioxidant defense mechanism that blocks the activation of NF-κB as well as inhibits the release of proinflammatory cytokine TNF-α and IL-1β. The results suggest that MIL has a significant hepatoprotective activity which might be due to the presence of phytochemicals namely analogues of ferulic acid and other phytochemicals which together may suppress the inflammatory signaling pathways and promote hepatoprotective activity against CCl4 intoxicated liver damage. Copyright © 2014. Published by Elsevier B.V.

Hepatoprotective potential of ether insoluble phenolic components of n-butanol fraction (EPC-BF) of flaxseed against CCl(4) -induced liver damage in rats.

PubMed

Kasote, D M; Badhe, Y S; Zanwar, A A; Hegde, M V; Deshmukh, K K

2012-07-01

to investigate the hepatoprotective potential of ether insoluble phenolic components of n-butanol fraction (EPC-BF) of flaxseed against CCl(4) -induced liver damage in rats. Hepatotoxicity was induced to Wistar rats by administration of 0.2% CCl(4) in olive oil (8 mL/kg, i.p.) on the seventh day of treatment. Hepatoprotective potential of EPC-BF at doses, 250 and 500 mg/kg, p.o. was assessed through biochemical and histological parameters. EPC-BF and silymarin pretreated animal groups showed significantly decreased activities of Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and level of total bilirubin, elevated by CCl(4) intoxication. Hepatic lipid peroxidation elevated by CCl(4) intoxication were also found to be alleviated at almost normal level in the EPC-BF and silymarin pretreated groups. Histological studies supported the biochemical findings and treatment of EPC-BF at doses 250 and 500 mg/kg, p.o. was found to be effective in restoring CCl(4) -induced hepatic damage. However, EPC-BF did not show dose-dependent hepatoprotective potential. EPC-BF depicted maximum protection against CCl(4) -induced hepatic damage at lower dose 250 mg/kg than higher dose (500 mg/ kg). EPC-BF possesses the significant hepatoprotective activity against CCl(4) induced liver damage, which could be mediated through increase in antioxidant defenses.

Hepatoprotective effect against CCl4-induced acute liver damage in mice and High-performance liquid chromatography mass spectrometric method for analysis of the constituents of extract of Rubus crataegifolius.

PubMed

Sun, Yongjiao; Jia, Lingyun; Huang, Zhanbo; Wang, Jing; Lu, Jincai; Li, Jing

2017-11-01

This study is an attempt to evaluate the hepatoprotective activity of Rubus Crataegifolius against carbon tetrachloride-induced liver injury in mice. 70% ethanolic, ethyl acetate and n-BuOH extract of R. crataegifolius were administered daily for 14 days in experimental animals before they were treated with CCl 4 . The hepatoprotective activity of the extracts in this study was compared with the reference drug silymarin. A high-performance liquid chromatography mass spectrometric (HPLC-EIS-MS/MS) method was developed for the determination of the constituents of the extracts. According to the data of HPLC-EIS-MS/MS, the chemical structures of the largely 14 constituents of R. crataegifolius were identified online without time-consuming isolation. Ethyl acetate extracts of R. crataegifolius showed strong antioxidant activities and significant protective effect against acute hepatotoxicity induced by CCl 4 . According to the data of HPLC-EIS-MS/MS, Oleanic acid, Phlorizin dehydrate and Quercetin-3-rhamnoside are considered as the main hepatoprotective factor in ethyl acetate extract.

Hepatoprotective effect of Solanum xanthocarpum fruit extract against CCl4 induced acute liver toxicity in experimental animals.

PubMed

Gupta, Ramesh K; Hussain, Talib; Panigrahi, G; Das, Avik; Singh, Gireesh Narayan; Sweety, K; Faiyazuddin, Md; Rao, Chandana Venkateswara

2011-12-01

To investigate the hepatoprotective potential of Solanum xanthocarpum (Solanaceae) (S. xanthocarpum) in experimental rats to validate its traditional claim. 50% ethanolic fruit extract of S. xanthocarpum (SXE, 100, 200 or 400 mg/kg body weight) was administered daily for 14 days in experimental animals. Liver injury was induced chemically, by CCl(4) administration (1 mL/kg i. p.). The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), Serum alkaline phosphatise (SALP) and total bilirubin. Meanwhile, in vivo antioxidant activities as lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were screened along with histopathological studies. Obtained results demonstrated that the treatment with SXE significantly (P<0.05-<0.001) and dose-dependently prevented chemically induced increase in serum levels of hepatic enzymes. Furthermore, SXE significantly (up to P<0.001) reduced the lipid peroxidation in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and catalase towards normal levels. Histopathology of the liver tissue showed that SXE attenuated the hepatocellular necrosis and led to reduction of inflammatory cells inflltration. The results of this study strongly indicate the protective effect of SXE against acute liver injury which may be attributed to its hepatoprotective activity, and there by scientifically support its traditional use. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Hepatoprotective potential of ether insoluble phenolic components of n-butanol fraction (EPC-BF) of flaxseed against CCl4 -induced liver damage in rats

PubMed Central

Kasote, D. M.; Badhe, Y. S.; Zanwar, A. A.; Hegde, M. V.; Deshmukh, K. K.

2012-01-01

Objective: to investigate the hepatoprotective potential of ether insoluble phenolic components of n-butanol fraction (EPC-BF) of flaxseed against CCl4 -induced liver damage in rats. Materials and Methods: Hepatotoxicity was induced to Wistar rats by administration of 0.2% CCl4 in olive oil (8 mL/kg, i.p.) on the seventh day of treatment. Hepatoprotective potential of EPC-BF at doses, 250 and 500 mg/kg, p.o. was assessed through biochemical and histological parameters. Results: EPC-BF and silymarin pretreated animal groups showed significantly decreased activities of Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and level of total bilirubin, elevated by CCl4 intoxication. Hepatic lipid peroxidation elevated by CCl4 intoxication were also found to be alleviated at almost normal level in the EPC-BF and silymarin pretreated groups. Histological studies supported the biochemical findings and treatment of EPC-BF at doses 250 and 500 mg/kg, p.o. was found to be effective in restoring CCl4 -induced hepatic damage. However, EPC-BF did not show dose-dependent hepatoprotective potential. EPC-BF depicted maximum protection against CCl4 -induced hepatic damage at lower dose 250 mg/kg than higher dose (500 mg/ kg). Conclusion: EPC-BF possesses the significant hepatoprotective activity against CCl4 induced liver damage, which could be mediated through increase in antioxidant defenses. PMID:22923966

Ameliorative effect of methanol extract of Rumex vesicarius on CCl4-induced liver damage in Wistar albino rats.

PubMed

Ganaie, Majid Ahmad; Khan, Tajdar Husain; Siddiqui, Nasir Ali; Ansari, Mohd Nazam

2015-08-01

Rumex vesicarius L. (Polygonaceae), an edible plant, is reported to have many bioactive phytochemicals, especially flavonoids and anthraquinones with antioxidant and detoxifying properties. This study evaluated the methanolic extract of R. vasicarius (MERV) for hepatoprotective activity in rats against CCl4-induced liver damage. The whole plant extract was prepared and investigated for its hepatoprotective activity. Rats were pretreated with MERV (100 and 200 mg/kg, p.o.) for 7 d prior to the induction of liver damage by CCl4. Animals were then sacrificed 24 h after CCl4 administration for the biochemical (AST, ALT, and ALP activity in serum; lipid peroxidation (LPO) and glutathione (GSH) levels in liver tissue) and histological analyses. CCl4-induced hepatotoxicity was confirmed by an increase (p < 0.05) in serum AST (4.55-fold), ALT (3.51-fold), and ALP (1.82-fold) activities. CCl4-induced hepatotoxicity was also manifested by an increase (p < 0.05) in LPO (3.88-fold) and depletion of reduced glutathione (3.14-fold) activity in liver tissue. The multiple dose MERV administration at 200 mg/kg showed promising hepatoprotective activity as evident from significant decrease levels of serum AST (230.01 ± 13.21), serum ALT (82.15 ± 5.01), serum ALP (504.75 ± 19.72), hepatic LPO (3.38 ± 0.33), and increased levels of hepatic glutathione (0.34 ± 0.04) towards near normal. Further, biochemical results were confirmed by histopathological changes as compared with CCl4-intoxicated rats. The results obtained from this study indicate hepatoprotective activity of Rumex plant against CCl4-induced liver toxicity; hence, it can be used as a hepatoprotective agent.

Silymarin-Loaded Eudragit Nanoparticles: Formulation, Characterization, and Hepatoprotective and Toxicity Evaluation.

PubMed

El-Nahas, Amira E; Allam, Ahmed N; Abdelmonsif, Doaa A; El-Kamel, Amal H

2017-11-01

The objectives of this study were to formulate, characterize silymarin-loaded Eudragit nanoparticles (SNPs) and evaluate their hepatoprotective and cytotoxic effects after oral administration. SNPs were prepared by nanoprecipitation technique and were evaluated for particle size, entrapment efficiency, TEM, solid-state characterization, and in vitro drug release. The hepatoprotective activity was evaluated after oral administration of selected SNPs in carbon tetrachloride-intoxicated rats. Potential in vivo acute cytotoxicity study was also assessed. The selected SNPs contained 50 mg silymarin and 50 mg Eudragit polymers (1:1 w/w Eudragit RS 100 & Eudragit LS 100). Morphology of the selected SNPs (particle size of 84.70 nm and entrapment efficiency of 83.45% with 100% drug release after 12 h) revealed spherical and uniformly distributed nanoparticles. DSC and FT-IR studies suggested the presence of silymarin in an amorphous state and absence of chemical interaction. The hepatoprotective evaluation of the selected SNPs in CCl 4 -intoxicated rats revealed significant improvement in the activities of different biochemical parameters (P ≤ 0.01) compared to the marketed product. The histopathological studies suggested that the selected SNPs produced better hepatoprotective effect in CCl 4 -intoxicated rats compared with the commercially marketed product. Toxicity study revealed no evident toxic effect for blank or silymarin-loaded nanoparticles at the dose level of 50 mg/kg body weight. The obtained results suggested that the selected SNPs were safe and potentially offered enhancement in the pharmacological hepatoprotective properties of silymarin.

Hepatoprotective activity of Tribulus terrestris extract against acetaminophen-induced toxicity in a freshwater fish (Oreochromis mossambicus).

PubMed

Kavitha, P; Ramesh, R; Bupesh, G; Stalin, A; Subramanian, P

2011-12-01

The potential protective role of Tribulus terrestris in acetaminophen-induced hepatotoxicity in Oreochromis mossambicus was investigated. The effect of oral exposure of acetaminophen (500 mg/kg) in O. mossambicus at 24-h duration was evaluated. The plant extract (250 mg/kg) showed a remarkable hepatoprotective activity against acetaminophen-induced hepatotoxicity. It was judged from the tissue-damaging level and antioxidant levels in liver, gill, muscle and kidney tissues. Further acetaminophen impact induced a significant rise in the tissue-damaging level, and the antioxidant level was discernible from the enzyme activity modulations such as glutamate oxaloacetic transaminase, glutamate pyruvic transaminase, alkaline phosphatase, acid phosphatase, glucose-6-phosphate dehydrogenase, lactate dehydrogenase, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase, lipid peroxidase and reduced glutathione. The levels of all these enzymes have significantly (p < 0.05) increased in acetaminophen-treated fish tissues. The elevated levels of these enzymes were significantly controlled by the treatment of T. terrestris extract (250 kg/mg). Histopathological changes of liver, gill and muscle samples were compared with respective controls. The results of the present study specify the hepatoprotective and antioxidant properties of T. terrestris against acetaminophen-induced toxicity in freshwater fish, O. mossambicus.

Dietary Aloe vera improves plasma lipid profile, antioxidant, and hepatoprotective enzyme activities in GIFT-tilapia (Oreochromis niloticus) after Streptococcus iniae challenge.

PubMed

Gabriel, Ndakalimwe Naftal; Qiang, Jun; Ma, Xin Yu; He, Jie; Xu, Pao; Liu, Kai

2015-10-01

The current study investigated the effects of dietary Aloe vera on plasma lipid profile status, antioxidant, and hepatoprotective enzyme activities of GIFT-tilapia juveniles under Streptococcus iniae challenge. Five dietary groups were designed including a control and 100 % Aloe powder incorporated into a tilapia feed at 0.5, 1, 2, and 4 %/kg feed, which were administered for 8 weeks. Fish fed dietary Aloe at 4 %/kg feed significantly reduced in total cholesterol, while triacylglycerol reduced (P < 0.05) in those fed 0.5, 2, and 4 % Aloe/kg feed compared to unsupplemented ones. High-density lipoprotein was significantly elevated in fish fed 0.5 and 1 % Aloe/kg feed compared to unsupplemented ones, and no significant changes (P > 0.05) were noted in low-density lipoprotein among test groups. Furthermore, high activities of superoxide dismutase, catalase, and glutathione peroxide in liver tissues were observed in Aloe-supplemented fish compared to unsupplemented ones, before and after S. iniae challenge (7.7 × 10(6) CFU cells/mL). Variations were also noted in malondialdehyde activity throughout the trial, but no significant difference (P > 0.05) was observed between groups. Meanwhile, Aloe-supplemented fish reduced serum aspartate and alanine aminotransferase (AST and ALT) activities before and after challenge. Based on the second-order polynomial regression analysis, dietary Aloe inclusion levels less than or equal to 1.88, 1.86, and 2.79 %/kg feed were determined to be suitable in improving plasma lipid profile status, antioxidant, and hepatoprotective enzyme activities in GIFT-tilapia in this study, respectively. Thus, A. vera extracts may be recommended as a tilapia feed supplement to enhance fish antioxidant and hepatoprotective capacities, especially during disease outbreaks.

A New Type of Liquid Silymarin Proliposome Containing Bile Salts: Its Preparation and Improved Hepatoprotective Effects.

PubMed

Wang, Mei; Xie, Tingting; Chang, Zhanying; Wang, Ling; Xie, Xiangyun; Kou, Yaohong; Xu, Hongxia; Gao, Xiaoli

2015-01-01

Silymarin, a known extract, is used in the treatment of liver diseases with various origins, but its current administration form cannot target the liver because of its poor oral bioavailability. A new type of oral silymarin proliposome aimed at improving silymarin's poor bioavailability and hepatoprotective effects, is introduced in this work. Silymarin-loaded liquid proliposome were prepared using a simple dissolving process. The morphology, particle size, zeta potential, and entrapment efficiency of the silymarin liposomes were analysed. The everted gut sac transport model was used to measure the intestinal transport of liposomes. The liposomal hepatoprotective activity was evaluated in three types of experimental hepatitis animal models. After staining with haematoxylin and eosin, the livers were microscopically examined to analyse any pathological changes. The prepared silymarin proliposome formed silymarin liposomes with a multilayer liposome structure and improved intestinal transport. In an injured liver, the silymarin liposomes produced a stronger hepatoprotective effect through a significant decrease in both the aminotransferase and MDA levels and a significant increase in the SOD and GSH-PX levels compared to orally administered silymarin tablets. This effect was also confirmed histopathologically. In a word, incorporation of silymarin into a liposomal carrier system increased intestinal absorption and showed better hepatoprotective effects compared to silymarin tablets.

A New Type of Liquid Silymarin Proliposome Containing Bile Salts: Its Preparation and Improved Hepatoprotective Effects

PubMed Central

Chang, Zhanying; Wang, Ling; Xie, Xiangyun; Kou, Yaohong; Xu, Hongxia; Gao, Xiaoli

2015-01-01

Silymarin, a known extract, is used in the treatment of liver diseases with various origins, but its current administration form cannot target the liver because of its poor oral bioavailability. A new type of oral silymarin proliposome aimed at improving silymarin’s poor bioavailability and hepatoprotective effects, is introduced in this work. Silymarin-loaded liquid proliposome were prepared using a simple dissolving process. The morphology, particle size, zeta potential, and entrapment efficiency of the silymarin liposomes were analysed. The everted gut sac transport model was used to measure the intestinal transport of liposomes. The liposomal hepatoprotective activity was evaluated in three types of experimental hepatitis animal models. After staining with haematoxylin and eosin, the livers were microscopically examined to analyse any pathological changes. The prepared silymarin proliposome formed silymarin liposomes with a multilayer liposome structure and improved intestinal transport. In an injured liver, the silymarin liposomes produced a stronger hepatoprotective effect through a significant decrease in both the aminotransferase and MDA levels and a significant increase in the SOD and GSH-PX levels compared to orally administered silymarin tablets. This effect was also confirmed histopathologically. In a word, incorporation of silymarin into a liposomal carrier system increased intestinal absorption and showed better hepatoprotective effects compared to silymarin tablets. PMID:26674103

Hepatoprotective Effect of Houttuynia cordata Thunb Extract against Carbon Tetrachloride-induced Hepatic Damage in Mice

PubMed Central

Kang, H.; Koppula, S.

2014-01-01

Houttuynia cordata Thunb (Saururaceae) is a traditional medicinal herb used to treat several disease symptoms. The present study was focused on the hepatoprotective effects of H. cordata ethyl acetate extract in experimental mice. Further the antioxidant potential of the extract was also evaluated to substantiate its hepatoprotective properties. Carbon tetrachloride-induced hepatic damage in mice was used to measure the serum biochemical parameters. Morphological changes in hepatocyte architecture were studied by haematoxylin and eosin staining. In vitro alkyl and hydroxyl free radical scavenging assays were performed to evaluate the antioxidant effect. Administration of H. cordata extract significantly reduced the elevated serum levels and regulated the altered levels of serum cholesterol in carbon tetrachloride-treated mice (P<0.05). The morphological changes in hepatocyte architecture were also reversed by H. cordata treatment. Further, the extract showed significant antioxidant actions by scavenging the alkyl and hydroxyl free radicals. The concentration of the extract necessary for 50% scavenging of alkyl and hydroxyl radicals was 15.5 and 410 μg/ml, respectively. H. cordata extract exhibited significant hepatoprotective property in carbon tetrachloride-induced hepatotoxicity in mice. The strong antioxidant activities possessed by the extract might be responsible for such actions. PMID:25284923

Hepatoprotective Effect of Houttuynia cordata Thunb Extract against Carbon Tetrachloride-induced Hepatic Damage in Mice.

PubMed

Kang, H; Koppula, S

2014-07-01

Houttuynia cordata Thunb (Saururaceae) is a traditional medicinal herb used to treat several disease symptoms. The present study was focused on the hepatoprotective effects of H. cordata ethyl acetate extract in experimental mice. Further the antioxidant potential of the extract was also evaluated to substantiate its hepatoprotective properties. Carbon tetrachloride-induced hepatic damage in mice was used to measure the serum biochemical parameters. Morphological changes in hepatocyte architecture were studied by haematoxylin and eosin staining. In vitro alkyl and hydroxyl free radical scavenging assays were performed to evaluate the antioxidant effect. Administration of H. cordata extract significantly reduced the elevated serum levels and regulated the altered levels of serum cholesterol in carbon tetrachloride-treated mice (P<0.05). The morphological changes in hepatocyte architecture were also reversed by H. cordata treatment. Further, the extract showed significant antioxidant actions by scavenging the alkyl and hydroxyl free radicals. The concentration of the extract necessary for 50% scavenging of alkyl and hydroxyl radicals was 15.5 and 410 μg/ml, respectively. H. cordata extract exhibited significant hepatoprotective property in carbon tetrachloride-induced hepatotoxicity in mice. The strong antioxidant activities possessed by the extract might be responsible for such actions.

A comprehensive overview of hepatoprotective natural compounds: mechanism of action and clinical perspectives.

PubMed

Domitrović, Robert; Potočnjak, Iva

2016-01-01

Hepatoprotective effects of natural compounds have been frequently attributed to their antioxidant properties and the ability to mobilize endogenous antioxidant defense system. Because of involvement of oxidative stress in virtually all mechanisms of liver injury, it is a reasonable presumption that antioxidant properties of these compounds may play a key role in the mechanism of their hepatoprotective activity. Nevertheless, growing evidence suggests that other pharmacological activities of natural compounds distinct from antioxidant are responsible for their therapeutic effects. In this review, we discussed currently known molecular mechanisms of the hepatoprotective activity of 27 most intensively studied phytochemicals. These compounds have been shown to possess anti-inflammatory, antisteatotic, antiapoptotic, cell survival and antiviral activity through interference with multiple molecular targets and signaling pathways. Additionally, antifibrotic properties of phytochemicals have been closely associated with apoptosis of hepatic stellate cells and stimulation of extracellular matrix degradation. However, although these compounds exhibit a pronounced hepatoprotective effects in animal and cell culture models, the lack of clinical studies remains a bottleneck for their official acceptance by medical experts and physicians. Therefore, controlled clinical trials have an imperative in confirmation of the therapeutic activity of potentially hepatoprotective compounds. Understanding the principles of the hepatoprotective activity of phytochemicals could guide future drug development and help prevention of clinical trial failure. Also, the use of new delivery systems that enhances bioavailability of poorly water soluble compounds may improve the results already obtained. Most importantly, available data suggest that phytochemicals possess a various degree of modulation of specific signaling pathways, pointing out a need for usage of combinations of several hepatoprotective compounds in both experimental studies and clinical trials.

A New Octadecenoic Acid Derivative from Caesalpinia gilliesii Flowers with Potent Hepatoprotective Activity

PubMed Central

Osman, Samir M.; El-Haddad, Alaadin E.; El-Raey, Mohamed A.; Abd El-Khalik, Soad M.; Koheil, Mahmoud A.; Wink, Michael

2016-01-01

Background: Caesalpinia gilliesii Hook is an ornamental shrub with showy yellow flowers. It was used in folk medicine due to its contents of different classes of secondary metabolites. In our previous study, dichloromethane extract of C. gilliesii flowers showed a good antioxidant activity. Aim of the Study: Isolation and identification of bioactive hepatoprotective compounds from C. gilliesii flowers dichloromethane fraction. Materials and Methods: The hepatoprotective activity of dichloromethane fraction and isolated compounds were studied in CCl4-intoxicated rat liver slices by measuring liver injury markers (alanine aminotransferase, aspartate aminotransferase and glutathione [GSH]). All compounds were structurally elucidated on the basis of electron ionization-mass spectrometry, one- and two-dimensional nuclear magnetic resonance. Results: A new 12,13,16-trihydroxy-14(Z)-octadecenoic acid was identified in addition to the known β-sitosterol-3-O-butyl, daucosterol, isorhamnetin, isorhamnetin-3-O-rhamnoside, luteolin-7,4’-dimethyl ether, genistein-5-methyl ether, luteolin-7-O-rhamnoside, isovanillic acid, and p-methoxybenzoic acid. Dichloromethane fraction and isorhamnetin were able to significantly protect the liver against intoxication. Moreover, the dichloromethane fraction and the isolated phytosterols induced GSH above the normal level. Conclusion: The hepatoprotective activity of C. gilliesii may be attributed to its high content of phytosterols and phenolic compounds. SUMMARY Bioactive Hepatoprotective phytosterols and phenolics from chloroform extract of Caesalpinia gilliesii Abbreviations used: ALT: Alanine Aminotransferase; AST: Aspartate aminotransferase; GSH: Glutathione; SC50: Scavenging Capacity 50 (SC 50); COSY: Correlation spectroscopy; NMR: Nuclear Magnetic Resonance; CC: Column chromatography; EI-MS: Electron-impact mass spectrometry; HSQC: Heteronuclear single-quantum correlation. PMID:27563221

Antioxidant and protective effect of inulin and catechin grafted inulin against CCl4-induced liver injury.

PubMed

Liu, Jun; Lu, Jian-feng; Wen, Xiao-yuan; Kan, Juan; Jin, Chang-hai

2015-01-01

In this study, the antioxidant activity and hepatoprotective effect of inulin and catechin grafted inulin (catechin-g-inulin) against carbon tetrachloride (CCl4)-induced acute liver injury were investigated. Results showed that both inulin and catechin-g-inulin had moderate scavenging activity on superoxide radical, hydroxyl radical and H2O2, as well as lipid peroxidation inhibition effect. The antioxidant activity decreased in the order of Vc > catechin >catechin-g-inulin > inulin. Administration of inulin and catechin-g-inulin could significantly reduce the elevated levels of serum aspartate transaminase, alanine transaminase and alkaline phosphatase as compared to CCl4 treatment group. Moreover, inulin and catechin-g-inulin significantly increased the levels of hepatic superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione and total antioxidant capacity, whereas markedly decreased the malondialdehyde level when compared with CCl4 treatment group. Notably, catechin-g-inulin showed higher hepatoprotective effect than inulin. In addition, the hepatoprotective effect of catechin-g-inulin was comparable to positive standard of silymarin. Our results suggested that catechin-g-inulin had potent antioxidant activity and potential protective effect against CCl4-induced acute liver injury. Copyright © 2014 Elsevier B.V. All rights reserved.

Bioassay-guided fractionation of a hepatoprotective and antioxidant extract of pea by-product.

PubMed

Seida, Ahmed A; El Tanbouly, Nebal D; Islam, Wafaa T; Eid, Hanaa H; El Maraghy, Shohda A; El Senousy, Amira S

2015-01-01

The hepatoprotective and antioxidant activities of the hydroalcoholic extract (PE) of pea (Pisum sativum L.) by-product were evaluated, using CCl4-induced oxidative stress and hepatic damage in rats. These activities were assessed via measuring alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein and albumin, malondialdehyde (MDA), reduced glutathione (GSH), protein thiols (PSH), nitrite/nitrate levels, glutathione-peroxidase (GSH-Px), glutathione-S-transferase (GST) activities, as well as, histopathological evaluation. PE revealed significant hepatoprotective and antioxidant activities mostly found in n-butanol fraction. Chromatographic fractionation of this active fraction led to the isolation of five flavonoid glycosides namely, quercetin-3-O-sophorotrioside (1), quercetin-3-O-rutinoside (2), quercetin-3-O-(6″″-O-E sinapoyl)-sophorotrioside (3), quercetin-3-O-(6″″-O-E feruloyl)-sophorotrioside (4) and quercetin-3-O-β-D-glucopyranoside (5). The isolated compounds were quantified in PE, using a validated HPLC method and the nutritional composition of pea by-product was also investigated. Our results suggest that pea by-product contained biologically active constituents which can be utilised to obtain high value added products for nutraceutical use.

Hepatoprotective and Antioxidant Effect of Bauhinia hookeri Extract against Carbon Tetrachloride-Induced Hepatotoxicity in Mice and Characterization of Its Bioactive Compounds by HPLC-PDA-ESI-MS/MS

PubMed Central

Al-Sayed, Eman; Seif el-Din, Sayed H.; Sabra, Abdel-Nasser A.; Hammam, Olfat A.; El-Lakkany, Naglaa M.; Abdel-Daim, Mohamed M.

2014-01-01

The hepatoprotective and antioxidant activity of Bauhinia hookeri ethanol extract (BHE) against CCl4-induced liver injury was investigated in mice. BHE was administered (500 and 1000 mg/kg/day) along with CCl4 for 6 weeks. The hepatic marker enzymes: alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were determined in the serum. The antioxidant parameters: glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione transferase (GST), and malondialdehyde (MDA) were estimated in the liver homogenate. BHE treatment significantly inhibited the CCl4-induced increase in ALT (44 and 64%), AST (36 and 46%), ALP (28 and 42%), and MDA (39 and 51%) levels at the tested doses, respectively. Moreover, BHE treatment markedly increased the activity of antioxidant parameters GSH, GPx, GR, GST, and SOD. Histological observations confirmed the strong hepatoprotective activity. These results suggest that a dietary supplement of BHE could exert a beneficial effect against oxidative stress and various liver diseases by enhancing the antioxidant defense status, reducing lipid peroxidation, and protecting against the pathological changes of the liver. The hepatoprotective activity of BHE is mediated, at least in part, by the antioxidant effect of its constituents. The active constituents of BHE were identified by HPLC-PDA-ESI/MS/MS. PMID:24955350

Hepatoprotective and antioxidant effect of Bauhinia hookeri extract against carbon tetrachloride-induced hepatotoxicity in mice and characterization of its bioactive compounds by HPLC-PDA-ESI-MS/MS.

PubMed

Al-Sayed, Eman; Martiskainen, Olli; Seif el-Din, Sayed H; Sabra, Abdel-Nasser A; Hammam, Olfat A; El-Lakkany, Naglaa M; Abdel-Daim, Mohamed M

2014-01-01

The hepatoprotective and antioxidant activity of Bauhinia hookeri ethanol extract (BHE) against CCl4-induced liver injury was investigated in mice. BHE was administered (500 and 1000 mg/kg/day) along with CCl4 for 6 weeks. The hepatic marker enzymes: alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were determined in the serum. The antioxidant parameters: glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione transferase (GST), and malondialdehyde (MDA) were estimated in the liver homogenate. BHE treatment significantly inhibited the CCl4-induced increase in ALT (44 and 64%), AST (36 and 46%), ALP (28 and 42%), and MDA (39 and 51%) levels at the tested doses, respectively. Moreover, BHE treatment markedly increased the activity of antioxidant parameters GSH, GPx, GR, GST, and SOD. Histological observations confirmed the strong hepatoprotective activity. These results suggest that a dietary supplement of BHE could exert a beneficial effect against oxidative stress and various liver diseases by enhancing the antioxidant defense status, reducing lipid peroxidation, and protecting against the pathological changes of the liver. The hepatoprotective activity of BHE is mediated, at least in part, by the antioxidant effect of its constituents. The active constituents of BHE were identified by HPLC-PDA-ESI/MS/MS.

Hepatoprotective Effect and Chemical Assessment of a Selected Egyptian Chickpea Cultivar

PubMed Central

Mekky, Reham H.; Fayed, Mostafa R.; El-Gindi, Mohamed R.; Abdel-Monem, Azza R.; Contreras, María del Mar; Segura-Carretero, Antonio; Abdel-Sattar, Essam

2016-01-01

Chickpea (Cicer arietinum) is a legume of the family Fabaceae, subfamily Faboideae. In Egypt, chickpea seeds are usually consumed at raw green and tender stage, or in the form of mature dry seeds. In our previous study, ‘Giza 1’ seeds exhibited stronger antioxidant activity and higher total phenol content than those from other Egyptian cultivars. In order to assess the biological potential of ‘Giza 1’ seeds in vivo, the extraction procedure was reproduced here. The extract was standardized using liquid chromatography coupled to diode array detector and tandem mass spectrometry (MS/MS) to evaluate their hepatoprotective effect on carbon tetrachloride (CCl4)-induced hepatotoxicity in rats and acute toxicity. Administration of the extract to rats in doses up to 2 g/Kg) did not cause any mortalities or observable signs of toxicity. Further, the plant extract showed a strong hepatoprotective activity based on assessing serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase and levels of albumen, globulin, total protein, total cholesterol, high density lipoprotein, triglycerides, and low density lipoprotein. The antioxidative activity was evaluated by assessing hepatic catalase and superoxide dismutase activity as well as reduced glutathione, and malondialdehyde levels. Additionally, anti-inflammatory activity was observed as the extract significantly lowered the hepatic tumor necrosis factor α content. Histopathological examination of liver tissues indicated that the extract-treated animals showed almost normal hepatic architecture with fewer pathological changes. In conclusion, the current results suggest that the chickpea extract possesses an excellent safety profile with very low acute toxicity. Also, it exhibits a significant hepatoprotective effect against CCl4-induced liver injury in rats. This can be attributed, at least partly, to the antioxidant and anti-inflammatory activity of the isoflavones and phenolic acids content of the extract. PMID:27733831

Hepatoprotective Effect and Chemical Assessment of a Selected Egyptian Chickpea Cultivar.

PubMed

Mekky, Reham H; Fayed, Mostafa R; El-Gindi, Mohamed R; Abdel-Monem, Azza R; Contreras, María Del Mar; Segura-Carretero, Antonio; Abdel-Sattar, Essam

2016-01-01

Chickpea ( Cicer arietinum ) is a legume of the family Fabaceae, subfamily Faboideae. In Egypt, chickpea seeds are usually consumed at raw green and tender stage, or in the form of mature dry seeds. In our previous study, 'Giza 1' seeds exhibited stronger antioxidant activity and higher total phenol content than those from other Egyptian cultivars. In order to assess the biological potential of 'Giza 1' seeds in vivo , the extraction procedure was reproduced here. The extract was standardized using liquid chromatography coupled to diode array detector and tandem mass spectrometry (MS/MS) to evaluate their hepatoprotective effect on carbon tetrachloride (CCl 4 )-induced hepatotoxicity in rats and acute toxicity. Administration of the extract to rats in doses up to 2 g/Kg) did not cause any mortalities or observable signs of toxicity. Further, the plant extract showed a strong hepatoprotective activity based on assessing serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase and levels of albumen, globulin, total protein, total cholesterol, high density lipoprotein, triglycerides, and low density lipoprotein. The antioxidative activity was evaluated by assessing hepatic catalase and superoxide dismutase activity as well as reduced glutathione, and malondialdehyde levels. Additionally, anti-inflammatory activity was observed as the extract significantly lowered the hepatic tumor necrosis factor α content. Histopathological examination of liver tissues indicated that the extract-treated animals showed almost normal hepatic architecture with fewer pathological changes. In conclusion, the current results suggest that the chickpea extract possesses an excellent safety profile with very low acute toxicity. Also, it exhibits a significant hepatoprotective effect against CCl 4 -induced liver injury in rats. This can be attributed, at least partly, to the antioxidant and anti-inflammatory activity of the isoflavones and phenolic acids content of the extract.

The antioxidative and hepatoprotective effects comparison of Chinese angelica polysaccharide(CAP)and selenizing CAP (sCAP) in CCl4 induced hepatic injury mice.

PubMed

Gao, Zhenzhen; Zhang, Chao; Tian, Weijun; Liu, Kuanhui; Hou, Ranran; Yue, Chanjuan; Wu, Yi; Wang, Deyun; Liu, Jiaguo; Hu, Yuanliang; Yang, Ying

2017-04-01

Chinese angelica polysaccharides (CAP) and selenizing CAP (sCAP) were prepared and identified through FTIR and SEM observation. Their antioxidant activities in vitro and hepatoprotective effects in vivo were compared by free radical-scavenging tests or with CCl 4 -induced hepatic injury model mice. The results showed that for DPPH radical, superoxide anion and hydroxyl radical, the scavenging capabilities of sCAP were significantly stronger than those of CAP . In hepatic injury model mice, sCAP could significantly reduce ALT, AST and ALP contents and raised TP content in serum, significantly reduce MDA and ROS contents and raised SOD and T-AOC activities in liver homogenate in comparison with CAP; obviously relieve the pathological changes of liver and significantly inhibit the expressions of p-ERK, p-JNK and p-p38 protein as compared with those in model control group. These results indicate that selenylation modification can enhance the antioxidant and hepatoprotective actions of Chinese angelica polysaccharide. A action mechanism of sCAP is suppressing the protein expression of MAPK signaling pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

Hepatoprotective and antioxidant effects of Cuscuta chinensis against acetaminophen-induced hepatotoxicity in rats.

PubMed

Yen, Feng-Lin; Wu, Tzu-Hui; Lin, Liang-Tzung; Lin, Chun-Ching

2007-04-20

Tu-Si-Zi, the seeds of Cuscuta chinensis Lam. (Convolvulaceae), is a traditional Chinese medicine that is commonly used to nourish and improve the liver and kidney conditions in China and other Asian countries. As oxidative stress promotes the development of acetaminophen (APAP)-induced hepatotoxicity, the aim of the present study was to evaluate and compare the hepatoprotective effect and antioxidant activities of the aqueous and ethanolic extracts of C chinensis on APAP-induced hepatotoxicity in rats. The C chinensis ethanolic extract at an oral dose of both 125 and 250mg/kg showed a significant hepatoprotective effect relatively to the same extent (P<0.05) by reducing levels of glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), and alkaline phosphatase (ALP). In addition, the same ethanolic extract prevented the hepatotoxicity induced by APAP-intoxicated treatment as observed when assessing the liver histopathology. Regarding the antioxidant activity, C chinensis ethanolic extract exhibited a significant effect (P<0.05) by increasing levels of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and by reducing malondialdehyde (MDA) levels. In contrast, the same doses of the aqueous extract of C chinensis did not present any hepatoprotective effect as seen in the ethanolic extract, and resulted in further liver deterioration. In conclusion, these data suggest that the ethanolic extract of Cuscuta chinensis can prevent hepatic injuries from APAP-induced hepatotoxicity in rats and this is likely mediated through its antioxidant activities.

Synergistic hepatoprotective potential of ethanolic extract of Solanum xanthocarpum and Juniperus communis against paracetamol and azithromycin induced liver injury in rats.

PubMed

Singh, Hem; Prakash, Atish; Kalia, A N; Majeed, Abu Bakar Abdul

2016-10-01

Previously explored combination therapies mostly involved the use of bioactive molecules. It is believed that herbal compounds containing multiple plant products have synergistic hepatoprotective effects and could enhance the desired actions. To investigate the combination of ethanolic fruits extract of Solanum xanthocarpum (SX) and Juniperus communis (JC) against Paracetamol (PCM) and Azithromycin (AZM) induced liver toxicity in rats. Liver toxicity was induced by combine oral administration of PCM (250 mg/kg) and AZM (200 mg/kg) for 7 days in Wistar rats. Fruit extract of SX (200 and 400 mg/kg) and JC (200 and 400 mg/kg) were administered daily for 14 days. The hepatoprotective activity was assessed using liver functional test, oxidative parameters and histopathological examination. The results demonstrated that combine administration of AZM and PCM significantly produced liver toxicity by increasing the serum level of hepatic enzymes and oxidative parameters in liver of rats. Histopathological examination also indicated that AZM and PCM produced liver damage in rats. Chronic treatment of SX and JC extract significantly and dose-dependently attenuated the liver toxicity by normalizing the biochemical factors and no gross histopathological changes were observed in liver of rats. Furthermore, combine administration of lower dose of SX and JC significantly potentiated their hepatoprotective effect which was significant as compared to their effect per se. The results clearly indicated that SX and JC extract has hepatoprotective potential against AZM and PCM induced liver toxicity due to their synergistic anti-oxidant properties.

Hepatoprotective activity of twelve novel 7'-hydroxy lignan glucosides from Arctii Fructus.

PubMed

Yang, Ya-Nan; Huang, Xiao-Ying; Feng, Zi-Ming; Jiang, Jian-Shuang; Zhang, Pei-Cheng

2014-09-17

Twelve novel 7'-hydroxy lignan glucosides (1-12), including two benzofuran-type neolignans, two 8-O-4' neolignans, two dibenzylbutyrolactone lignans, and six tetrahydrofuranoid lignans, together with six known lignan glucosides (13-18), were isolated from the fruit of Arctium lappa L. (Asteraceae), commonly known as Arctii Fructus. Their structures were elucidated using spectroscopy (1D and 2D NMR, MS, IR, ORD, and UV) and on the basis of chemical evidence. The absolute configurations of compounds 1-12 were confirmed using rotating frame nuclear overhauser effect spectroscopy (ROESY), the circular dichroic (CD) exciton chirality method, and Rh2(OCOCF3)4-induced CD spectrum analysis. All of the isolated compounds were tested for hepatoprotective effects against D-galactosamine-induced cytotoxicity in HL-7702 hepatic cells. Compounds 1, 2, 7-12, and 17 showed significantly stronger hepatoprotective activity than the positive control bicyclol at a concentration of 1 × 10(-5) M.

Hepatoprotective Flavonoids in Opuntia ficus-indica Fruits by Reducing Oxidative Stress in Primary Rat Hepatocytes.

PubMed

Kim, Jung Wha; Kim, Tae Bum; Kim, Hyun Woo; Park, Sang Wook; Kim, Hong Pyo; Sung, Sang Hyun

2017-01-01

Liver disorder was associated with alcohol consumption caused by hepatic cellular damages. Opuntia ficus-indica fruit extracts (OFIEs), which contain betalain pigments and polyphenols including flavonoids, have been introduced as reducing hangover symptoms and liver protective activity. To evaluate hepatoprotective activity of OFIEs and isolated compounds by high-speed countercurrent chromatography (HSCCC). The extract of O. ficus-indica fruits was fractionated into methylene chloride and n -butanol. The n -butanol fraction was isolated by HSCCC separation (methylene chloride-methanol- n -butanol-water, 5:4:3:5, v/v/v/v). The hepatoprotective activity of OFIEs and isolated compounds was evaluated on rat primary hepatocytes against ethanol-induced toxicity. Antioxidative parameters such as glutathione reductase and glutathione peroxidase (GSH-P x ) enzymes and the GSH content were measured. Two flavonoids, quercetin 3- O -methyl ester (1) and (+)-taxifolin, and two flavonoid glycosides, isorhamnetin 3- O -β- d -glucoside (3) and narcissin (4), were isolated from the n -butanol fraction by HSCCC separation. Among them, compound 2 significantly protected rat primary hepatocytes against ethanol exposure by preserving antioxidative properties of GR and GSH-P x . OFIEs and (+)-taxifolin were suggested to reduce hepatic damage by alcoholic oxidative stress. Hepatoprotective Flavonoids were isolated from Opuntia ficus-indica by high -speed countercurrent chromatography (HSCCC).

Hepatoprotective activity of petroleum ether, diethyl ether, and methanol extract of Scoparia dulcis L. against CCl4-induced acute liver injury in mice.

PubMed

Praveen, T K; Dharmaraj, S; Bajaj, Jitendra; Dhanabal, S P; Manimaran, S; Nanjan, M J; Razdan, Rema

2009-06-01

The present study was aimed at assessing the hepatoprotective activity of 1:1:1 petroleum ether, diethyl ether, and methanol (PDM) extract of Scoparia dulcis L. against carbon tetrachloride-induced acute liver injury in mice. The PDM extract (50, 200, and 800 mg/kg, p.o.) and standard, silymarin (100 mg/kg, p.o) were tested for their antihepatotoxic activity against CCl4-induced acute liver injury in mice. The hepatoprotective activity was evaluated by measuring aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total proteins in serum, glycogen, lipid peroxides, superoxide dismutase, and glutathione reductase levels in liver homogenate and by histopathological analysis of the liver tissue. In addition, the extract was also evaluated for its in vitro antioxidant activity using 1, 1-Diphenyl-2-picrylhydrazyl scavenging assay. The extract at the dose of 800 mg/kg, p.o., significantly prevented CCl4-induced changes in the serum and liver biochemistry (P < 0.05) and changes in liver histopathology. The above results are comparable to standard, silymarin (100 mg/kg, p.o.). In the in vitro 1, 1-diphenyl-2-picrylhydrazyl scavenging assay, the extract showed good free radical scavenging potential (IC 50 38.9 +/- 1.0 mug/ml). The results of the study indicate that the PDM extract of Scoparia dulcis L. possesses potential hepatoprotective activity, which may be attributed to its free radical scavenging potential, due to the terpenoid constituents.

Hepatoprotective activity of Annona muricata Linn. and Polyalthia cerasoides bedd.

PubMed Central

Padma, P.; Chansouria, J.P.N.; Khosa, R.L.

1999-01-01

The hepatoprotective effect of Annona muricata and Polyalthia cerasoides (Annonaceae) were monitored by estimating the serum transaminases (SGOT and SGPT), serum alkaline phosphatase (SALP), liver and brain lipid peroxidation (LOP) and their total protein content. Both drugs at a dose of 100 μg/kg significantly prevented the increase in serum transaminases, SALP, liver and brain LOP and decrease in liver and brain total protein content following carbontetrachloride (CCl) induced hepatoxicity in albino rats. PMID:22556909

Genoprotective and hepatoprotective effects of Guarana (Paullinia cupana Mart. var. sorbilis) on CCl4-induced liver damage in rats.

PubMed

Kober, Helena; Tatsch, Etiane; Torbitz, Vanessa Dorneles; Cargnin, Lara Peruzzolo; Sangoi, Manuela Borges; Bochi, Guilherme Vargas; da Silva, Andreia Regina Haas; Barbisan, Fernanda; Ribeiro, Euler Esteves; da Cruz, Ivana Beatrice Mânica; Moresco, Rafael Noal

2016-01-01

Several biological effects of Paullinia cupana (guarana) have been demonstrated, but little information is available on its effects on the liver. The current study was designed to evaluate the hepatoprotective and genoprotective effects of powder seeds from guarana on CCl4-induced liver injury in rats. Male Wistar rats were pretreated with guarana powder (100, 300 and 600 mg/kg) or silymarin 100 mg/kg daily for 14 days before treatment with a single dose of CCl4 (50% CCl4, 1 mL/kg, intraperitoneally). The treatment with CCl4 significantly increased the serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In addition, CCl4 increased the DNA damage index in hepatocytes. Guarana in all concentrations was effective in decreasing the ALT and AST activities when compared with the CCl4-treated group. The treatment with guarana decreased DNA damage index when compared with the CCl4-treated group. In addition, the DNA damage index showed a significant positive correlation with AST and ALT. These results indicate that the guarana has hepatoprotective activity and prevents the DNA strand breakage in the CCl4-induced liver damage in rats.

Hepatoprotective activity of dried- and fermented-processed virgin coconut oil.

PubMed

Zakaria, Z A; Rofiee, M S; Somchit, M N; Zuraini, A; Sulaiman, M R; Teh, L K; Salleh, M Z; Long, K

2011-01-01

The present study aims to determine the hepatoprotective effect of MARDI-produced virgin coconut oils, prepared by dried- or fermented-processed methods, using the paracetamol-induced liver damage in rats. Liver injury induced by 3 g/kg paracetamol increased the liver weight per 100 g bodyweight indicating liver damage. Histological observation also confirms liver damage indicated by the presence of inflammations and necrosis on the respective liver section. Interestingly, pretreatment of the rats with 10, but not 1 and 5, mL/kg of both VCOs significantly (P < .05) reduced the liver damage caused by the administration of paracetamol, which is further confirmed by the histological findings. In conclusion, VCO possessed hepatoprotective effect that requires further in-depth study.

Hepatoprotective Activity of Dried- and Fermented-Processed Virgin Coconut Oil

PubMed Central

Zakaria, Z. A.; Rofiee, M. S.; Somchit, M. N.; Zuraini, A.; Sulaiman, M. R.; Teh, L. K.; Salleh, M. Z.; Long, K.

2011-01-01

The present study aims to determine the hepatoprotective effect of MARDI-produced virgin coconut oils, prepared by dried- or fermented-processed methods, using the paracetamol-induced liver damage in rats. Liver injury induced by 3 g/kg paracetamol increased the liver weight per 100 g bodyweight indicating liver damage. Histological observation also confirms liver damage indicated by the presence of inflammations and necrosis on the respective liver section. Interestingly, pretreatment of the rats with 10, but not 1 and 5, mL/kg of both VCOs significantly (P < .05) reduced the liver damage caused by the administration of paracetamol, which is further confirmed by the histological findings. In conclusion, VCO possessed hepatoprotective effect that requires further in-depth study. PMID:21318140

Radical Scavenging Activities of Lagerstroemia speciosa (L.) Pers. Petal Extracts and its hepato-protection in CCl4-intoxicated mice.

PubMed

Tiwary, Bipransh Kumar; Dutta, Somit; Dey, Priyankar; Hossain, Mossaraf; Kumar, Anoop; Bihani, Sony; Nanda, Ashis Kumar; Chaudhuri, Tapas Kumar; Chakraborty, Ranadhir

2017-01-18

Lagerstroemia speciosa (L.) Pers. has medicinal importance. Bioactive phytochemicals isolated from different parts of L. speciosa, have revealed hypoglycemic, antibacterial, anti-inflammatory, antioxidant and hepato protective properties. Despite one report from Philippines detailing the use of L. speciosa as curative for fever and as well as diuretic, there is no experimental evidence about the hepatoprotective activity of the flower extracts. Several spectroscopic methods, including GC-MS, were used to characterize phytochemicals present in the petal extract of L. speciosa. Ethanol extract of petals was evaluated for anti-oxidant and free radical scavenging properties by using methods related to hydrogen atom transfer, single electron transfer, reducing power, and metal chelation. This study has also revealed the in vitro antioxidant and in vivo hepatoprotective properties of petal extract against carbon tetra chloride (CCl 4 )-induced liver toxicity in Swiss albino mice. Hepatoprotection in CCl 4 -intoxicated mice was studied with the aid of histology and different enzymatic and non-enzymatic markers of liver damage. Cytotoxicity tests were done using murein spleenocytes and cancareous cell lines, MCF7 and HepG2. GCMS of the extract has revealed the presence of several potential antioxidant compounds, of them γ-Sitosterol and 1,2,3-Benzenetriol (Pyrogallol) were the predominant ones. The antioxidants activities of the flower-extract were significantly higher than curcumin (in terms of Nitric oxide scavenging activity; p = 0.0028) or ascorbic acid (in terms of 2,2-Diphenyl-1-Picrylhydrazyl (DPPH) assay; p = 0.0022). The damage control by the flower extract can be attributed to the reduction in lipid peroxidation and restoration of catalase activity. In vitro cytotoxicity tests have shown that the flower extract did not affect growth and survivability of the cell lines. It left beyond doubt that a flower of L. speciosa is a reservoir of antioxidant and hepatoprotective agents capable of reversing the damage inflicted by CCl 4 -intoxication. Results from the present study may be used in developing a potential hepato-protective health drink enriched with antioxidants from Lagerstroemia speciosa (L.) Pers.

Hepatoprotective activity of Rhus oxyacantha root cortex extract against DDT-induced liver injury in rats.

PubMed

Ben Miled, Hanène; Barka, Zaineb Ben; Hallègue, Dorsaf; Lahbib, Karima; Ladjimi, Mohamed; Tlili, Mounira; Sakly, Mohsen; Rhouma, Khémais Ben; Ksouri, Riadh; Tebourbi, Olfa

2017-06-01

The present investigation aimed to study the antioxidant activity and hepatoprotective effects of ethyl acetate extract of R. oxyacantha root cortex (RE) against DDT-induced liver injury in male rats. The RE exhibited high total phenolic, flavonoid and condensed tannins contents. The antioxidant activity in vitro systems showed a significant potent free radical scavenging activity of the extract. The HPLC finger print of R. oxyacantha active extract showed the presence of five phenolic compounds with higher amounts of catechol and gallic acid. The in vivo results showed that a single intraperitoneal administration of DDT enhanced levels of hepatic markers (ALT, AST and LDH) in serum of experimental animals. It also increased the oxidative stress markers resulting in increased levels of the lipid peroxidation with a significant induction of SOD and GPx, metallothioneins (MTs) and a concomitant decrease of non protein thiols (NPSH) in liver. However, pretreatment of rats with RE at a dose of 150 and 300mg/kg body weight significantly lowered serum transaminases and LDH in treated rats. A significant reduction in hepatic thiobarbituric reactive substances and a decrease in antioxidant enzymes activities and hepatic MTs levels by treatment with plant extract against DDT, were observed. These biochemical changes were consistent with histopathological observations, suggesting marked hepatoprotective effect of RE with the two doses used. These results strongly suggest that treatment with ethyl acetate extract normalizes various biochemical parameters and protects the liver against DDT-induced oxidative damage in rats and thus help in evaluation of traditional claim on this plant. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

In vitro antioxidant and in vivo hepatoprotective activity of leave extract of Raphanus sativus in rats using CCL4 model.

PubMed

Syed, Shariq Naeem; Rizvi, Waseem; Kumar, Anil; Khan, Aijaz Ahmad; Moin, Shagufta; Ahsan, Akif

2014-01-01

Raphanus sativus is reported to have a variety of biological activities. This work screened the hepato-protective and antioxidant activity of ethanol (ERS), and aqueous (ARS), extracts of leaves of Raphanus sativus in Carbon tetrachloride (CCl4), model in rats. The extracts were subjected to antioxidant tests (Total reducing power and Total phenolic content), and preliminary phytochemical screening. A pilot study was done on 100 and 300 mg/kg extracts, form which 300 mg was chosen for further experiments. The albino rats (200-250 grams), were divided into 5 groups of 6 animals each (n=6). There were three control groups comprising of normal control (normal saline -1ml/kg), negative control group (CCl4 1ml/kg in olive oil in a ratio of 1:1 v/v), and positive control group (Silymarin 50mg/kg). The Test drugs were given in a dose of 300 mg/kg for both ERS and ARS extract for 7 days. Biochemical parameters (AST, ALT, Alkaline phosphatase, Total Bilirubin), histo-pathological examination of liver and in vivo antioxidant tests [CAT, GSH and MDA] were done. The phytochemical study showed the presence of flavanoids, terpenoids, alkaloids, saponins and sterols. A dose dependent increase in the oxidative potential was observed in both the extracts with total phenolic content 70.1 and 44.4 GAE/g extract for ERS and ARS respectively. ERS 300mg/kg showed a significant (p<0.001) increase in levels of AST, ALT and alkaline phosphatase as compared to negative control (percentage hepatoprotection =45.3%) while ARS 300 mg/kg (p<.01) group showed 30% hepatoprotection. The GSH (p<0.001) and CAT (p<0.05) in ERS and ARS were significantly increased while MDA levels were decreased (P< 0.01), as compared negative control. The findings were confirmed histo-pathological examination. The ethanol and aqueous extract of Raphanus sativus have partial hepatoprotection against CCl4 toxicity.

Chemical composition and hepatoprotective activity of ethanolic root extract of Taraxacum Syriacum Boiss against acetaminophen intoxication in rats.

PubMed

Nazari, A; Fanaei, H; Dehpour, A R; Hassanzadeh, G; Jafari, M; Salehi, M; Mohammadi, M

2015-01-01

In the present study, the role of ethanol extract of root of Taraxacum Syriacum Boiss (TSBE) against hepatotoxicity caused by acetaminophen (APAP) was studied. The chemical composition of roots of Taraxacum Syriacum Boiss was analyzed by SPME-GC/MS method. Hepatocellular injuries induced by acetaminophen (APAP) were assessed by liver histology, serum aminotransferase activities, antioxidant enzymes activity and lipid peroxidation in liver tissue. TSBE was observed to exhibit hepatoprotective effect as demonstrated by significant decrease in serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), and alkaline phosphatase (ALP) concentration, and by preventing liver histopathologic changes in rats with APAP hepatotoxicity. Administration of APAP, significantly increased, lactate dehydrogenase (LDH) and catalase (CAT) activity in liver tissue and pretreatment with TSBE returned these parameters to control group, moreover TSBE reduces APAP-induced hepatic Glutathione (GSH) depletion. Carvacrol (6.7 %) was the main polyphenolic compound of plant sample. Our results demonstrated hepatoprotective activity of TSBE in rat in vivo. We believe that the mechanism by which the extract was able to protect the liver from the oxidative stress generated by APAP is due to its antioxidant activity. These phenolic compounds of the extract act as antioxidants and free radical scavengers and reduce or inhibit the oxidative stress induced by APAP administration (Tab. 3, Fig. 3, Ref. 39).

Ameliorative Influence of Green Tea Extract on Copper Nanoparticle-Induced Hepatotoxicity in Rats

NASA Astrophysics Data System (ADS)

Ibrahim, Marwa A.; Khalaf, A. A.; Galal, Mona K.; Ogaly, Hanan A.; H. M. Hassan, Azza

2015-09-01

The potential toxicity of copper nanoparticles (CNPs) to the human health and environment remains a critical issue. In the present study, we investigated the protective influence of an aqueous extract of green tea leaves (GTE) against CNPs-induced (20-30 nm) hepatotoxicity. Four different groups of rats were used: group I was the control, group II received CNPs (40 mg/kg BW), group III received CNPs plus GTE, and group IV received GTE alone. We highlighted the hepatoprotective effect of GTE against CNPs toxicity through monitoring the alteration of liver enzyme activity, antioxidant defense mechanism, histopathological alterations, and DNA damage evaluation. The rats that were given CNPs only had a highly significant elevation in liver enzymes, alteration in oxidant-antioxidant balance, and severe pathological changes. In addition, we detected a significant elevation of DNA fragmentation percentage, marked DNA laddering, and significance over expression of both caspase-3 and Bax proteins. The findings for group III clarify the efficacy of GTE as a hepatoprotectant on CNPs through improving the liver enzyme activity, antioxidant status, as well as suppressing DNA fragmentation and the expression of the caspase-3 and Bax proteins. In conclusion, GTE was proved to be a potential hepatoprotective additive as it significantly ameliorates the hepatotoxicity and apoptosis induced by CNPs.

Enhancement of absorption and hepatoprotective potential through soya-phosphatidylcholine-andrographolide vesicular system.

PubMed

Jain, Pushpendra Kumar; Khurana, Navneet; Pounikar, Yogesh; Gajbhiye, Asmita; Kharya, Murli Dhar

2013-06-01

Andrographis paniculata is a medicinal herb used extensively for various ailments and contains therapeutically active phytoconstituent, andrographolide (AN). Although hepatoprotective activity of AN is established, but their bioavailability is restricted due to its rapid clearance. The aim of this study, therefore, was to formulate AN herbosomes (ANH) through complexation with naturally occurring soya-phosphatidylcholine (SPC), in order to enhance absorption. Prepared andrographolide-soy phosphatidylcholine (AN-SPC) complex prepared was subjected for characterisation of complex and formation of vesicular system known as ANH using rotary evaporation techniques. This complex was subjected to in vitro study using everted small intestine sac technique which showed significantly increased absorption of AN from the ANH as compared to the plain AN. The hepatoprotective potential of ANH and plain AN was evaluated using carbon tetrachloride inducing hepatotoxicity rat model and compared, in which ANH equivalent to 50 mg/kg of plain AN significantly restore serum glutamate oxalacetate transaminase (112.4 ± 9.67 for AN whereas 90.2 ± 4.23 for ANH) and serum glutamate pyruvate transaminase (109.3 ± 7.89 for AN whereas 90.6 ± 4.34 for ANH) level as compared to control group. The ANH showed significantly better absorption than plain AN and this effect of ANH was also comparable to the standard drug (Silymarin). The findings of present study reveal that ANH has better bioavailability as shown by in vitro absorption study and hence improved hepatoprotection as compared to plain AN at equivalent dose.

Hepatoprotective activity of petroleum ether, diethyl ether, and methanol extract of Scoparia dulcis L. against CCl4-induced acute liver injury in mice

PubMed Central

Praveen, T.K.; Dharmaraj, S.; Bajaj, Jitendra; Dhanabal, S.P.; Manimaran, S.; Nanjan, M.J.; Razdan, Rema

2009-01-01

Objectives: The present study was aimed at assessing the hepatoprotective activity of 1:1:1 petroleum ether, diethyl ether, and methanol (PDM) extract of Scoparia dulcis L. against carbon tetrachloride-induced acute liver injury in mice. Materials and Methods: The PDM extract (50, 200, and 800 mg/kg, p.o.) and standard, silymarin (100 mg/kg, p.o) were tested for their antihepatotoxic activity against CCl4-induced acute liver injury in mice. The hepatoprotective activity was evaluated by measuring aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and total proteins in serum, glycogen, lipid peroxides, superoxide dismutase, and glutathione reductase levels in liver homogenate and by histopathological analysis of the liver tissue. In addition, the extract was also evaluated for its in vitro antioxidant activity using 1, 1-Diphenyl-2-picrylhydrazyl scavenging assay. Results: The extract at the dose of 800 mg/kg, p.o., significantly prevented CCl4-induced changes in the serum and liver biochemistry (P < 0.05) and changes in liver histopathology. The above results are comparable to standard, silymarin (100 mg/kg, p.o.). In the in vitro 1, 1-diphenyl-2-picrylhydrazyl scavenging assay, the extract showed good free radical scavenging potential (IC 50 38.9 ± 1.0 μg/ml). Conclusions: The results of the study indicate that the PDM extract of Scoparia dulcis L. possesses potential hepatoprotective activity, which may be attributed to its free radical scavenging potential, due to the terpenoid constituents. PMID:20442817

Hepatoprotective and Antioxidant Activity of Dunaliella salina in Paracetamol-induced Acute Toxicity in Rats

PubMed Central

Madkour, Fedekar F.; Abdel-Daim, M. M.

2013-01-01

Paracetamol has a reasonable safety profile when taken in therapeutic doses. However, it could induce hepatotoxicity and even more severe fatal acute hepatic damage when taken in an overdose. The green alga, Dunaliella salina was investigated for hepatoprotective and antioxidant activity against paracetamol-induced liver damage in rats. Male albino Wistar rats overdosed with paracetamol showed liver damage and oxidative stress as indicated by significantly (P<0.05) increased serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total and direct bilirubin, malondialdehyde, cholesterol and nitric oxide. At the same time, there were decreased activities of serum superoxide dismutase and total antioxidant capacity compared with the control group. Treatment with D. salina methanol extract at doses of 500 and 1000 mg/kg body weight or silymarin could significantly (P<0.05) decrease the liver damage marker enzymes, total and direct bilirubin, malondialdehyde, cholesterol and nitric oxide levels and increase the activities of superoxide dismutase and total antioxidant capacity in serum when compared with paracetamol intoxicated group. Liver histopathology also showed that D. salina reduced the centrilobular necrosis, congestion and inflammatory cell infiltration evoked by paracetamol overdose. These results suggest that D. salina exhibits a potent hepatoprotective effect on paracetamol-induced liver damage in rats, which may be due to both the increase of antioxidant enzymes activity and inhibition of lipid peroxidation. PMID:24591738

Hepatoprotective Flavonoids in Opuntia ficus-indica Fruits by Reducing Oxidative Stress in Primary Rat Hepatocytes

PubMed Central

Kim, Jung Wha; Kim, Tae Bum; Kim, Hyun Woo; Park, Sang Wook; Kim, Hong Pyo; Sung, Sang Hyun

2017-01-01

Background: Liver disorder was associated with alcohol consumption caused by hepatic cellular damages. Opuntia ficus-indica fruit extracts (OFIEs), which contain betalain pigments and polyphenols including flavonoids, have been introduced as reducing hangover symptoms and liver protective activity. Objective: To evaluate hepatoprotective activity of OFIEs and isolated compounds by high-speed countercurrent chromatography (HSCCC). Materials and Methods: The extract of O. ficus-indica fruits was fractionated into methylene chloride and n-butanol. The n-butanol fraction was isolated by HSCCC separation (methylene chloride-methanol-n-butanol-water, 5:4:3:5, v/v/v/v). The hepatoprotective activity of OFIEs and isolated compounds was evaluated on rat primary hepatocytes against ethanol-induced toxicity. Antioxidative parameters such as glutathione reductase and glutathione peroxidase (GSH-Px) enzymes and the GSH content were measured. Results: Two flavonoids, quercetin 3-O-methyl ester (1) and (+)-taxifolin, and two flavonoid glycosides, isorhamnetin 3-O-β-d-glucoside (3) and narcissin (4), were isolated from the n-butanol fraction by HSCCC separation. Among them, compound 2 significantly protected rat primary hepatocytes against ethanol exposure by preserving antioxidative properties of GR and GSH-Px. Conclusions: OFIEs and (+)-taxifolin were suggested to reduce hepatic damage by alcoholic oxidative stress. SUMMARY Hepatoprotective Flavonoids were isolated from Opuntia ficus-indica by high -speed countercurrent chromatography (HSCCC). PMID:28839374

Hepatoprotective activity of Tridax procumbens against d-galactosamine/lipopolysaccharide-induced hepatitis in rats.

PubMed

Ravikumar, Vilwanathan; Shivashangari, Kanchi Subramanian; Devaki, Thiruvengadam

2005-10-03

The hepatoprotective activity of aerial parts of Tridax procumbens was investigated against d-Galactosamine/Lipopolysaccharide (d-GalN/LPS) induced hepatitis in rats. d-GalN/LPS (300 mg/kg body weight/30 microg/kg body weight)-induced hepatic damage was manifested by a significant increase in the activities of marker enzymes (aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase and gamma glutamyl transferase) and bilirubin level in serum and lipids both in serum and liver. Pretreatment of rats with a chloroform insoluble fraction from ethanolic extract of Tridax procumbens reversed these altered parameters to normal values. The biochemical observations were supplemented by histopathological examination of liver sections. Results of this study revealed that Tridax procumbens could afford a significant protection in the alleviation of d-GalN/LPS-induced hepatocellular injury.

Antioxidant and hepatoprotective activity of vitex honey against paracetamol induced liver damage in mice.

PubMed

Wang, Yuan; Li, Dan; Cheng, Ni; Gao, Hui; Xue, Xiaofeng; Cao, Wei; Sun, Liping

2015-07-01

Fourteen vitex honeys from China were investigated to evaluate its antioxidant and hepatoprotective activity against paracetamol-induced liver damage. All honey samples exhibited high total phenolic content (344-520 mg GAE per kg), total flavonoid content (19-31 mg Rutin per kg), and strong antioxidant activity in DPPH radical scavenging, ferric reducing antioxidant power and Ferrous ion-chelating ability. Nine phenolic acids were detected in vitex honey samples, in which caffeic acid was the main compound. Honey from Heibei Zanhuang (S2) ranked the highest antioxidant activity was orally administered to mice (5 g kg(-1), 20 g kg(-1)) for 70 days. In high-dose (20 g kg(-1)), vitex honey pretreatment resulting in significant increase in serum oxygen radical absorbance capacity (15.07%) and decrease in Cu(2+)-mediate lipoprotein oxidation (80.07%), and suppression in alanine aminotransferase (75.79%) and aspartate aminotransferase (74.52%), enhancement in the superoxide dismutase and glutathione peroxidase activities and reduction in malondialdehyde (36.15%) and 8-hydroxy-2'-deoxyguanosine (19.6%) formation compared with paracetamol-intoxicated group. The results demonstrated the hepatoprotection of vitex honey against paracetamol-induced liver damage might attribute to its antioxidant and/or perhaps pro-oxidative property.

Hepatoprotective and antioxidant activity of aqueous extract of Hybanthus enneaspermus against CCl4-induced liver injury in rats.

PubMed

Vuda, Madhusudanarao; D'Souza, Roshan; Upadhya, Suhas; Kumar, Vijay; Rao, Namita; Kumar, Vasanth; Boillat, Colette; Mungli, Prakash

2012-11-01

The hepatoprotective, curative and anti-oxidant properties of aqueous extract of Hybanthus enneaspermus (Violaceae) used against CCl4-induced liver damage in rats were investigated in the present study. Liver damage was induced by CCl4 (1 ml/kg i.p.), and silymarin was used as a standard drug to compare hepatoprotective, curative and antioxidant effects of the extract. Rats were treated with aqueous extract of H. enneaspermus at a dose of either 200 or 400 mg/kg after division into pre-treatment (once daily for 14 days before CCl4 intoxication) and post-treatment (2, 6, 24 and 48 h after CCl4 intoxication) groups. Pre-treatment and post-treatment with aqueous extract of H. enneaspermus showed significant hepatoprotection by reducing the aspartate transaminase, alanine transaminase, and alkaline phosphatase enzymatic activities and total bilirubin levels which had been raised by CCl4 administration. Pre- and post-treatment with aqueous extract significantly decreased hepatic lipid peroxidation as well as producing a corresponding increase in tissue total thiols. Post-treatment with aqueous extract improved ceruloplasmin levels. The histopathological examination of rat liver sections treated with aqueous extract confirms the serum biochemical observations. The present study results demonstrate the protective, curative and anti-oxidant effects of H. enneaspermus aqueous extract used against CCl4-induced hepatotoxicity in rats, and suggest a potential therapeutic use of H. enneaspermus as an alternative for patients with acute liver diseases. Copyright © 2011 Elsevier GmbH. All rights reserved.

Hepatoprotective studies on Sida acuta Burm. f.

PubMed

Sreedevi, C D; Latha, P G; Ancy, P; Suja, S R; Shyamal, S; Shine, V J; Sini, S; Anuja, G I; Rajasekharan, S

2009-07-15

Sida acuta Burm. f. (Malvaceae) is used in Indian traditional medicine to treat liver disorders and is useful in treating nervous and urinary diseases and also disorders of the blood and bile. Evaluation of the hepatoprotective properties of the methanolic extract of the root of Sida acuta (SA) and the phytochemical analysis of SA. The model of paracetamol-induced hepatotoxicity in Wistar rats, liver histopathological observations, hexobarbitone-induced narcosis and in vitro anti-lipid peroxidation studies were employed to assess the hepatoprotective efficacy of SA. Phytochemical assay of SA was conducted following standard protocols. Significant hepatoprotective effects were obtained against liver damage induced by paracetamol overdose as evident from decreased serum levels of glutamate pyruvate transaminase, glutamate oxaloacetate transaminase, alkaline phosphatase and bilirubin in the SA treated groups (50, 100, 200mg/kg) compared to the intoxicated controls. The hepatoprotective effect was further verified by histopathology of the liver. Pretreatment with Sida acuta extract significantly shortened the duration of hexobarbitone-induced narcosis in mice indicating its hepatoprotective potential. Phytochemical studies confirmed the presence of the phenolic compound, ferulic acid in the root of Sida acuta, which accounts for the significant hepatoprotective effects observed in the present study. The present study thus provides a scientific rationale for the traditional use of this plant in the management of liver disorders.

[Influence of antitumor system rhenium-platinum on biochemical state of the liver].

PubMed

Ivchuk, V V; Polishko, T M; Golichenko, O A; Shtemenko, O V; Shtemenko, N I

2011-01-01

Influence of the antitumour rhenium-platinum system on biochemical liver characteristics in the model of tumor growth (Guerin carcinoma) was studied and possible hepatoprotective activity of rhenium cluster compounds when introducing them in different forms was shown, that was confirmed by decreasing of diagnostic enzymes activity in blood (aminotransferase--AST 6 times and ALT 5.6 times, lactatedehydrogenase 4.9 times, gamma-glutamyltranspeptidase 3.6 times) and normalization of morphological state of the liver cells. The hepatoprotective activity of the cluster rhenium compound with adamanthyl ligands was confirmed in the model of acute toxic hepatitis. Introduction of this compound led to reduction of the concentration of MDA in homogenates of liver tissue (2 times), and in blood plasma (3.8 times); to reduction of levels of diagnostic liver enzymes in blood--AST and ALT 5.8 and 5.5 times respectively in comparison with control group. Some aspects of the mechanism of hepatoprotection were discussed, that included the presence of conjugated systems around the quadrupol rhenium-rhenium bond and alkyl radicals with significant positive inductive effects.

In vitro enzyme-mimic activity and in vivo therapeutic potential of HSJ-0017, a novel Mn porphyrin-based antioxidant enzyme mimic.

PubMed

Li, Bao-qiu; Dong, Xin; Li, Na; Gao, Ji-you; Yuan, Qiang; Fang, Shi-hong; Gong, Xian-chang; Wang, Shu-juan; Wang, Feng-shan

2014-10-01

Manganese (III) 5, 10, 15, 20-tetrakis [3-(2-(2-methoxy)-ethoxy) ethoxy] phenyl porphyrin chloride, designated HSJ-0017, is a novel antioxidant enzyme mimic. The aim of the present study was to investigate the enzyme-mimic activity and the therapeutic potential of HSJ-0017 in free radical-related diseases. Superoxide dismutase (SOD) mimic activity was measured by the nitroblue tetrazolium chloride monohydrate reduction assay. Catalase (CAT) mimic activity was measured based on the decomposition of hydrogen peroxide. The antitumor, radioprotective and chemoprotective effects of HSJ-0017 were evaluated in H22 or S180 tumor-bearing Kunming mice. The anti-inflammatory and hepatoprotective effects were, respectively, evaluated in histamine-induced edema model and CCl4-induced hepatic damage model in Wistar rats. HSJ-0017 over a concentration range of 0.001-10 µmol/L significantly inhibited the generation of superoxide anion. Significant hydrogen peroxide scavenging activity was observed when the concentration of HSJ-0017 was higher than 0.01 µmol/L. HSJ-0017 at a dose of 3.0 mg/kg exhibited significant antitumor effect on S180 tumor xenografts, whereas no significant antitumor effect was observed in H22 tumor xenografts. HSJ-0017 at a dose of 3.0 mg/kg enhanced the antitumor effects of radiotherapy and chemotherapy, and reduced their toxicity. However, HSJ-0017 counteracted the antitumor effects of radiotherapy when administered simultaneously with radiotherapy. HSJ-0017 showed significant anti-inflammatory and hepatoprotective effects. Our results demonstrate that HSJ-0017 exhibits antioxidant, antitumor, anti-inflammatory, radioprotective, chemoprotective, and hepatoprotective effects. It is a potent dual SOD/CAT mimic. © 2014 by the Society for Experimental Biology and Medicine.

Chemical characterisation and hepatoprotective potential of Cosmos sulphureus Cav. and Cosmos bipinnatus Cav.

PubMed

Saleem, Mohammad; Ali, Hafiz Akbar; Akhtar, Muhammad Furqan; Saleem, Uzma; Saleem, Ammara; Irshad, Iram

2017-12-11

This study was conducted to validate the hepatoprotective activity of Cosmos sulphureus and Cosmos bipinnatus. Aqua-methanolic extracts of both plants were evaluated for the presence of various phyto-constituents through HPLC. Different doses of both plant extracts were administered to rats for nine days. Standard control was silymarin 100 mg/kg. Paracetamol 1 gm/kg was administered 3 h post treatment on 9th day for induction of hepatotoxicity. Blood was collected for the evaluation of liver biochemical markers and livers were removed for histopathological evaluation 24 h post-paracetamol treatment. HPLC analysis revealed the presence of quercetin, gallic acid, caffeic acid and chlorogenic acid in both plant extracts. The extracts of both plants decreased the level of alanine aminotransaminase and total bilirubin significantly (p < 0.05), dose dependently and protected hepatocytes from paracetamol-induced hepatotoxicity. It can be concluded that both plants may possess hepatoprotective activity possibly due to the presence of quercetin and phenolic compounds.

Antioxidant and hepatoprotective effects of silymarin phytosomes compared to milk thistle extract in CCl4 induced hepatotoxicity in rats.

PubMed

El-Gazayerly, O N; Makhlouf, A I A; Soelm, A M A; Mohmoud, M A

2014-01-01

Milk thistle extract is a well-known hepatoprotectant with low bioavailability (20-50%). The objective of the present study is to prepare and characterize silymarin phytosomes and to test the hepatoprotective effect of the phytosomes in CCl4 induced liver injury in rats compared to milk thistle extract. Phytosomes were prepared using lecithin from soybeans and from egg yolk. The prepared phytosomes were examined using scanning electron microscopy, transmission electron microscopy, differential scanning calorimetry, Fourier transform infrared spectroscopy and proton nuclear magnetic resonance spectroscopy (H(1)NMR). The loading efficiency was >85% in all phytosomal formulations. Formula P2 (with the molar ratio of soybean lecithin to silybin 1:1) and P4 (with the molar ratio of egg-yolk lecithin to silybin 0.25:1) exhibited significantly (p < 0.05) faster release than milk thistle extract. The in vivo study revealed that phytosomes significantly (p < 0.05) decreased glutamic pyruvic transaminase and super oxide dismutase activities compared to milk thistle extract.

Hepatoprotective triterpenoids and lignans from the stems of Schisandra pubescens.

PubMed

Wang, Guo-Wei; Deng, Li-Qing; Luo, You-Ping; Liao, Zhi-Hua; Chen, Min

2017-08-01

One new triterpenoid (1) and 13 known compounds (2-14) were isolated from Schisandra pubescens stems. The structure of the new compound was established on the basis of 1D/2D NMR and HRESIMS spectroscopic analyses. The isolated compounds were evaluated for their hepatoprotective activities against D-GalN-induced cell injury in QSG7701 cells. Compounds 1, 13 and 14 at 10 μM showed hepatoprotective activities, with survival rates of 60.5, 50.4 and 48.9%, respectively.

Hepatoprotective effect of Ginkgoselect Phytosome in rifampicin induced liver injury in rats: evidence of antioxidant activity.

PubMed

Naik, Suresh R; Panda, Vandana S

2008-09-01

The protective effects of Ginkgoselect Phytosome (GBP) on Rifampicin (RMP) induced hepatotoxicity and the probable mechanism(s) involved in this protection were investigated in rats. Liver damage was induced in Wistar rats by administering rifampicin (500 mg/kg, p.o.) daily for 30 days. Simultaneously, GBP at 25 mg/kg and 50 mg/kg, and the reference drug silymarin (100 mg/kg) were administered orally for 30 days/daily to RMP treated rats. Levels of marker enzymes (SGOT, SGPT and SALP), albaumin (Alb) and total proteins (TP) were assessed in serum. The effects of GBP on lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and glutathione reductase (GR) were assayed in liver homogenates to evaluate antioxidant activity. GBP (25 and 50 mg/kg) and silymarin elicited a significant hepatoprotective activity by lowering the levels of serum marker enzymes and lipid peroxidation and elevated the levels of GSH, SOD, CAT, GPX, GR, Alb and TP in a dose dependant manner. The present findings suggest that the hepatoprotective effect of GBP in RMP induced oxidative damage may be related to its antioxidant and free radical scavenging activity.

Hepatoprotective and antioxidant capacity of Melochia corchorifolia extracts.

PubMed

Rao, B Ganga; Rao, Y Venkateswara; Rao, T Mallikarjuna

2013-07-01

To evaluate hepato protective and antioxidant capacity of Melochia corchorifolia (M. corchorifolia) aerial part extracts. Antioxidant activity was evaluated by using three free radicals (Superoxide, Hydroxyl and DPPH) and hepatoprotective activity was assessed against CCl4 induced liver intoxication in rats. The extracts produced concentration dependent percentage protection in decrease of serum enzymes and percentage inhibition on free radicals. Among all extracts methanol extract showed better activity with percentage protection of SGOT (78.98%), SGPT (79.65%), ALP (82.48%) and total bilirubin (80.0%) levels against CCl4 liver intoxication and also methanolic extract showed better activity with IC50 values on superoxide, hydroxyl and DPPH radicals were 127 μ g, 240 μ g and 179 μ g. From the results obtained during the study it could be concluded that M. corchorifolia aerial part extracts have antioxidant and hepatoprotective components. Further study is necessary for isolation and characterization of bioactive molecules which are responsible for hepatoprotective and antioxidant activity. Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Hepatoprotective effect of Scoparia dulcis on carbon tetrachloride induced acute liver injury in mice.

PubMed

Tsai, Jen-Chieh; Peng, Wen-Huang; Chiu, Tai-Hui; Huang, Shun-Chieh; Huang, Tai-Hung; Lai, Shang-Chih; Lai, Zhen-Rung; Lee, Chao-Ying

2010-01-01

This study aims to investigate the hepatoprotective activity and active constituents of the ethanol extract of Scoparia dulcis (SDE). The hepatoprotective effect of SDE (0.1, 0.5 and 1 g/kg) was evaluated on the carbon tetrachloride (CCl(4))-induced acute liver injury. The active constituents were detected by high performance liquid chromatography (HPLC). Mice pretreated orally with SDE (0.5 and 1.0 g/kg) and silymarin (200 mg/kg) for five consecutive days before the administering of a single dose of 0.2% CCl(4) (10 ml/kg of bw, ip) showed a significant inhibition of the increase of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Histological analyses also showed that SDE (0.5 and 1.0 g/kg) and silymarin reduced the extent of liver lesions induced by CCl(4), including vacuole formation, neutrophil infiltration and necrosis. Moreover, SDE decreased the malondialdehyde (MDA) level and elevated the content of reduced glutathione (GSH) in the liver as compared to those in the CCl(4) group. Furthermore, SDE (0.5 and 1.0 g/kg) enhanced the activities of anti-oxidative enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRd) and glutathione-S-transferase (GST). The quantities of active constituents in SDE were about 3.1 mg luteolin/g extract and 1.1 mg apigenin/g extract. The hepatoprotective mechanisms of SDE were likely associated to the decrease in MDA level and increase in GSH level by increasing the activities of antioxidant enzymes such as SOD, GPx, GRd and GST. These results demonstrated that SDE could alleviate CCl(4)-induced acute liver injury in mice.

Protective Effect of Flavonoids from Ziziphus jujuba cv. Jinsixiaozao against Acetaminophen-Induced Liver Injury by Inhibiting Oxidative Stress and Inflammation in Mice.

PubMed

Huang, Weizhen; Wang, Yongjie; Jiang, Xiaoyan; Sun, Yueyue; Zhao, Zhongxi; Li, Siying

2017-10-20

This study was aimed to investigate the chemical composition, antioxidant activities and hepatoprotective effect of flavonoids from Ziziphus jujub a cv. Jinsixiaozao (ZJF). The composition of ZJF was analyzed by high performance liquid chromatography (HPLC) and Liquid chromatography-mass spectrometry (LC-MS), and antioxidant properties were investigated by biological assays in vitro. The hepatoprotective activity of ZJF was evaluated in acetaminophen (APAP)-treated BALB/c mice. Results indicate that ZJF displayed significant antioxidant capacity. Pretreatment with ZJF significantly decreased APAP-elevated serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and total bilirubin (TB). Activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were enhanced with ZJF administration, while malondialdehyde (MDA) level and glutathione (GSH) depletion were reduced. Meanwhile, ZJF reversed the suppression of nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, and up-regulated the protein expression of NAD(P)H: quinone oxidoreductase 1(NQO1) in liver damage mice. Furthermore, ZJF attenuated APAP-induced inflammatory mediator production, such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β). Expression of p65 showed that ZJF dampened nuclear factor-κB (NF-κB) activation. The results strongly indicate that the hepatoprotective role of ZJF in APAP-induced hepatotoxicity might result from its induction of antioxidant defense via activation of Nrf2 and reduction of inflammation via inhibition of NF-κB.

Glycyrrhizin, silymarin, and ursodeoxycholic acid regulate a common hepatoprotective pathway in HepG2 cells.

PubMed

Hsiang, Chien-Yun; Lin, Li-Jen; Kao, Shung-Te; Lo, Hsin-Yi; Chou, Shun-Ting; Ho, Tin-Yun

2015-07-15

Glycyrrhizin, silymarin, and ursodeoxycholic acid are widely used hepatoprotectants for the treatment of liver disorders, such as hepatitis C virus infection, primary biliary cirrhosis, and hepatocellular carcinoma. The gene expression profiles of HepG2 cells responsive to glycyrrhizin, silymarin, and ursodeoxycholic acid were analyzed in this study. HepG2 cells were treated with 25 µM hepatoprotectants for 24 h. Gene expression profiles of hepatoprotectants-treated cells were analyzed by oligonucleotide microarray in triplicates. Nuclear factor-κB (NF-κB) activities were assessed by luciferase assay. Among a total of 30,968 genes, 252 genes were commonly regulated by glycyrrhizin, silymarin, and ursodeoxycholic acid. These compounds affected the expression of genes relevant various biological pathways, such as neurotransmission, and glucose and lipid metabolism. Genes involved in hepatocarcinogenesis, apoptosis, and anti-oxidative pathways were differentially regulated by all compounds. Moreover, interaction networks showed that NF-κB might play a central role in the regulation of gene expression. Further analysis revealed that these hepatoprotectants inhibited NF-κB activities in a dose-dependent manner. Our data suggested that glycyrrhizin, silymarin, and ursodeoxycholic acid regulated the expression of genes relevant to apoptosis and oxidative stress in HepG2 cells. Moreover, the regulation by these hepatoprotectants might be relevant to the suppression of NF-κB activities. Copyright © 2015 Elsevier GmbH. All rights reserved.

Hepatoprotective effects of Poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase] on alcohol-damaged primary rat hepatocyte culture in vitro.

PubMed

Jiang, Wenhua; Bian, Yuzhu; Wang, Zhenghui; Chang, Thomas Ming Swi

2017-02-01

We have prepared a novel nanobiotherapeutic, Poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase], which not only transports both oxygen and carbon dioxide but also a therapeutic antioxidant. Our previous study in a severe sustained 90 min hemorrhagic shock rat model shows that it has a hepatoprotective effect. We investigate its hepatoprotective effect further in this present report using an alcohol-damaged primary hepatocyte culture model. Results show that it significantly reduced ethanol-induced AST release, lipid peroxidation, and ROS production in rat primary hepatocytes culture. It also significantly enhanced the viability of ethanol-treated hepatocytes. Thus, the result shows that Poly-[hemoglobin-superoxide dismutase-catalase-carbonic anhydrase] also has some hepatoprotective effects against alcohol-induced injury in in vitro rat primary hepatocytes cell culture. This collaborate our previous observation of its hepatoprotective effect in a severe sustained 90-min hemorrhagic shock rat model.

Hepatoprotective role of Ricinus communis leaf extract against d-galactosamine induced acute hepatitis in albino rats.

PubMed

Babu, Pappithi Ramesh; Bhuvaneswar, Cherukupalle; Sandeep, Gandham; Ramaiah, Chintha Venkata; Rajendra, Wudayagiri

2017-04-01

Ricinus communis (RC) is a traditional medicinal plant which has been used by Chenchu and Yerukula tribes for treating their liver ailments. The present work is aimed to explore the hepatoprotective efficacy of Ricinus communis against d-galactosamine (D-GalN) induced hepatitis rat model and its therapeutic potential compared with standard drug, silymarin (100mg/kg.bw). In vitro antioxidant activity of Methanolic extract of Ricinus communis leaves (MERCL) was assayed through DPPH and H 2 O 2 free radical scavenging activity. Qualitative and quantitative analysis of MERCL using HPLC, demonstrated that Rutin was found to be predominant bioactive compound in the extract. Hepatitis was induced by treating the rats with D-GalN at a single intraperitoneal dose of 800mg/kg.bw. Serum markers viz, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP) and Malondialdehyde (MDA) levels were significantly increased and the activity levels of antioxidant enzymes such as Superoxide dismutase (SOD),Catalase (CAT), Glutathione reductase (GR), Glutathione peroxidase (GPx), non-enzymatic antioxidant Glutathione (GSH) levels were decreased in the liver of hepatitis induced rats when compared to controls. Pre and post treatment with MERCL significantly altered the enzyme activities, GSH and MDA to normal levels. Histopathological observations also showed protective and curative effects of MERCL against D-GalN intoxication. These results demonstrated that MERCL significantly protected the liver from d-galactosamine induced hepatitis, improved the curative effect in the liver and hence, MERCL can be used as a potent hepatoprotective drug in future. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Potential protective effect of honey against paracetamol-induced hepatotoxicity.

PubMed

Galal, Reem M; Zaki, Hala F; Seif El-Nasr, Mona M; Agha, Azza M

2012-11-01

Paracetamol overdose causes severe hepatotoxicity that leads to liver failure in both humans and experimental animals. The present study investigates the protective effect of honey against paracetamol-induced hepatotoxicity in Wistar albino rats. We have used silymarin as a standard reference hepatoprotective drug. Hepatoprotective activity was assessed by measuring biochemical parameters such as the liver function enzymes, serum alanine aminotransferase (ALT) and serum aspartate aminotransferase (AST). Equally, comparative effects of honey on oxidative stress biomarkers such as malondialdyhyde (MDA), reduced glutathione (GSH) and glutathione peroxidase (GPx) were also evaluated in the rat liver homogenates.  We estimated the effect of honey on serum levels and hepatic content of interleukin-1beta (IL-1β) because the initial event in paracetamol-induced hepatotoxicity has been shown to be a toxic-metabolic injury that leads to hepatocyte death, activation of the innate immune response and upregulation of inflammatory cytokines. Paracetamol caused marked liver damage as noted by significant increased activities of serum AST and ALT as well as the level of Il-1β. Paracetamol also resulted in a significant decrease in liver GSH content and GPx activity which paralleled an increase in Il-1β and MDA levels. Pretreatment with honey and silymarin prior to the administration of paracetamol significantly prevented the increase in the serum levels of hepatic enzyme markers, and reduced both oxidative stress and inflammatory cytokines. Histopathological evaluation of the livers also revealed that honey reduced the incidence of paracetamol-induced liver lesions. Honey can be used as an effective hepatoprotective agent against paracetamol-induced liver damage.

Hepatoprotective Effect of Wheat-Based Solid-State Fermented Antrodia cinnamomea in Carbon Tetrachloride-Induced Liver Injury in Rat

PubMed Central

Chiu, Huan-Wen; Hua, Kuo-Feng

2016-01-01

Antrodia cinnamomea (A. cinnamomea) is an indigenous medical fungus in Taiwan and has multiple biological functions, including hepatoprotective and immune-modulatory effects. Currently, the commercially available A. cinnamomea are mainly liquid- and solid-state fermented A. cinnamomea. However, the hepatoprotective effect of solid-state fermented A. cinnamomea has never been reported. Here we evaluate the ability of air-dried, ground and non-extracted wheat-based solid-state fermented A. cinnamomea (WFAC) to protect against carbon tetrachloride (CCl4)-induced hepatic injury in vivo. The results showed that oral administration of WFAC dose dependently (180, 540 and 1080 mg/kg) ameliorated the increase in plasma aspartate aminotransferase and alanine aminotransferase levels caused by chronic repeated CCl4 intoxication in rats. WFAC significantly reduced the CCl4-induced increase in hepatic lipid peroxidation levels and hydroxyproline contents, as well as reducing the spleen weight and water content of the liver. WFAC also restored the hepatic soluble protein synthesis and plasma albumin concentration in CCl4-intoxicated rats, but it did not affect the activities of superoxide dismutase, catalase, or glutathione peroxidase. In addition, a hepatic morphological analysis showed that the hepatic fibrosis and necrosis induced by CCl4 were significantly ameliorated by WFAC. Furthermore, the body weights of control rats and WFAC-administered rats were not significantly different, and no adverse effects were observed in WFAC-administered rats. These results indicate that WFAC is a nontoxic hepatoprotective agent against chronic CCl4-induced hepatic injury. PMID:27046059

Hepatoprotective effect of Bacoside-A, a major constituent of Bacopa monniera Linn.

PubMed

Sumathi, T; Nongbri, A

2008-10-01

Bacoside-A (B-A) was evaluated for its hepatoprotective activity against d-GalN induced liver injury in rats. B-A is a major constituent isolated from the plant Bacopa monniera Linn. B-A (10mg/kg of body weight) was administered orally once daily for 21 days and then d-GalN (300 mg/kg of body weight) was injected on 21st day after final administration of B-A. B-A reduces the elevated levels of serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), gamma-glutamyl transferase (gamma-GT), lactate dehydrogenase (LDH), 5'nucleotidase (5'ND). In addition B-A also significantly restored towards normalization of the decreased levels of Vit-C, and Vit-E induced by d-GalN both in liver and plasma. These results suggest that B-A has hepatoprotective effect against d-GalN induced hepatotoxicity in rats.

Improved hepatoprotective activity of silymarin via encapsulation in the novel vesicular nanosystem bilosomes.

PubMed

Mohsen, Amira Mohamed; Asfour, Marwa Hasanein; Salama, Abeer A A

2017-12-01

The main objective of the present work was to formulate, characterize, and evaluate silymarin (SM)-loaded bilosomes, compared to conventional liposomes, aiming at increasing the hepatoprotective activity of the drug. SM-loaded bilosomes were prepared by thin film hydration technique employing soybean phosphatidyl choline (SPC) and different bile salts. After being subjected to different methods of characterization, SM-loaded bilosomes were investigated for their hepatoprotective activity, in CCl 4 hepatointoxicated rat model. The developed SM dispersions exhibited an entrapment efficiency ranging from 21.80 ± 2.01 to 84.54 ± 2.51% and a particle size diameter in the nanometric dimensions (413 ± 96.9 to 686.9 ± 62.38 nm), with a negative zeta potential values (<-45 mV). In vitro release study revealed a lower cumulative amount of drug released from the developed formulae, compared to free drug. Ex vivo intestinal uptake study, performed using confocal laser scanning calorimetry, revealed the superiority of bilosomal uptake compared to that of liposomes. In vivo studies revealed an enhanced hepatoprotective effect of SM-loaded bilosomes/liposomes compared to free drug. These results were in good correlation with histopathological examination. These findings support the potential use of bilosomes for improving the hepatoprotective activity of SM via oral administration.

Comparative Hepatoprotective Effect of Vitamins A and E Against Gasoline Vapor Toxicity in Male and Female Rats

PubMed Central

Uboh, Friday Effiong; Ebong, Patrick E.; Umoh, Ime B.

2009-01-01

Background Plasma alanine transferase(ALT), aspartate transferase(AST), α-glutamyl transferase(GGT), and alkaline phosphatase(ALP) activities are known biomarkers in assessing hepatic functional integrity. A remarkable rise in the activities of these enzymes normally signifies hepatotoxicity of chemical agent(s) in the biological system. Exposure to 17.8 cm3h-1m-3 of PMS blend unleaded gasoline vapors (UGV) for 6 hr/day, 5 days/week for 20 weeks have been reported to cause hepatotoxicity in rats. Methods In this study, the comparative hepatoprotective effect of vitamins A (retinol) and E (α-tocopherol) against UGV-induced toxicity was assessed in male and female rats. Retinol and α-tocopherol at prophylactic dosage (400 and 200 IU/kg/day, respectively) were separately administered orally to the test rats concomitant with exposure to UGV in the last two weeks of the experiment. Results The results of this study indicated that exposure to UGV caused significant increase (P < 0.05) in the activities of serum ALT, AST, ALP, GGT and bilirubin in male and female rats. Oral administration of prophylactic doses of retinol and α-tocopherol produced a significant decrease (P < 0.05) in the activities of these parameters in male and female test rats, compared with the non-treated test rats; but insignificant increase(P ≥ 0.05), compared with the control. However, the hepatoprotective effect of α-tocopherol was observed to be more potent than that of retinol. Conclusions The result of this study demonstrated that the hepatoprotective potency of α-tocopherol against gasoline vapors toxicity was higher than that of retinol in male and female rats, although the female gender of the animal model responded to treatment with both vitamins better than the males. Hence, the work suggested the beneficial effects of both vitamins against hepatotoxicity in individuals frequently exposed to gasoline vapors. PMID:27956974

Gentiana manshurica Kitagawa prevents acetaminophen-induced acute hepatic injury in mice via inhibiting JNK/ERK MAPK pathway

PubMed Central

Wang, Ai-Yan; Lian, Li-Hua; Jiang, Ying-Zi; Wu, Yan-Ling; Nan, Ji-Xing

2010-01-01

AIM: To investigate the in vivo hepatoprotective effects and mechanisms of Gentiana manshurica Kitagawa (GM) in acetaminophen (APAP)-induced liver injury in mice. METHODS: GM (200, 150 or 50 mg/kg body weight) or N-acetyl-L-cysteine (NAC; 300 mg/kg body weight) was administrated orally with a single dose 2 h prior to APAP (300 mg/kg body weight) injection in mice. RESULTS: APAP treatment significantly depleted hepatic glutathione (GSH), increased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and malonyldialdehyde (MDA) and 4-hydroxynonenal levels, and decreased hepatic activity of glutathione peroxidase (GSH-px) and superoxide dismutase (SOD). However, the pretreatment of GM significantly alleviated APAP-induced oxidative stress by increasing GSH content, decreasing serum ALT, AST and MDA, and retaining the activity of GSH-px and SOD in the liver. Furthermore, GM pretreatment can inhibit caspase-3 activation and phosphorylation of c-Jun-NH2-terminal protein kinase 2 (JNK1/2) and extracellular signal-regulated kinase (ERK). GM also remarkably attenuated hepatocyte apoptosis confirmed by the terminal deoxynucleotidyl transferase mediated dUTP nick end-labeling method. CONCLUSION: Hepatoprotective effects of GM against APAP-induced acute toxicity are mediated either by preventing the decline of hepatic antioxidant status or its direct anti-apoptosis capacity. These results support that GM is a potent hepatoprotective agent. PMID:20082487

Studies on toxicity, anti-stress and hepato-protective properties of Kombucha tea.

PubMed

Pauline, T; Dipti, P; Anju, B; Kavimani, S; Sharma, S K; Kain, A K; Sarada, S K; Sairam, M; Ilavazhagan, G; Devendra, K; Selvamurthy, W

2001-09-01

The objective of the study was to evaluate toxicity, anti-stress activity and hepato-protective properties of Kombucha tea. Kombucha tea was fed orally for 15 days using three different doses i.e. normal dose, five and ten times the dose. Rats were then sacrificed and various biochemical, and histological parameters were estimated. Anti-stress activity was evaluated either by 1) by exposing animals to cold and hypoxia and estimating the levels of malondialdehyde and reduced glutathione in plasma/blood or 2) by subjecting the animals to restraint stress and recording faecal output. Hepato-toxicity was induced by challenging the animals to an acute dose of paracetamol (1 gm/kg) orally and determining the plasma levels of SGPT, SGOT and MDA. The effect of oral administration of different doses of K-tea to albino rats was examined and the results indicate that K-tea has no significant toxicity as revealed by various biochemical and histopathological parameters. K-tea has been found to prevent lipid peroxidation and fall in reduced glutathione level when rats were exposed to cold and hypoxia in simulated chamber. Further, K-tea has also been found to decrease the Wrap-restraint faecal pellet output in rats. K-tea has also been found to decrease paracetamol induced hepatotoxicity significantly. The study shows that K-tea has anti-stress and hepato-protective activities.

Protective effect of chitosan from Sepia kobiensis (Hoyle 1885) cuttlebone against CCl4 induced hepatic injury.

PubMed

Ramasamy, Pasiyappazham; Subhapradha, Namasivayam; Shanmugam, Vairamani; Shanmugam, Annaian

2014-04-01

Carbon tetrachloride (CCl4) is a potent hepatotoxic agent causing hepatic necrosis and it is widely used in animal models for induction of acute and chronic liver damage. The antioxidative and hepatoprotective effects of chitosan from Sepia kobiensis against CCl4 induced liver toxicity in Wistar rats was studied by measuring the activity of lipid peroxidation (TBARS, lipid hydroperoxides), non enzymatic antioxidant (GSH), antioxidant enzyme activities (SOD, CAT and GPx), liver marker enzymes (ALT and AST), lipid profile (FFA, TG, cholesterol and HDL cholesterol) and histopathological changes. Rats treated with chitosan against CCl4 toxicity showed significantly decreased levels of ALT and AST activities, total cholesterol, triglyceride and free fatty acid in plasma and tissue. Whereas the treatment with chitosan along with CCl4 showed markedly increased level of hepatic and circulatory in SOD, CAT, GPx and reduced glutathione and decreased the malondialdehyde level. Histopathological observations proved the marked hepatoprotective effect of chitosan. The CCl4 induced alterations in circulatory and hepatic antioxidant defense system were normalized by chitosan and it could be concluded that the hepatoprotective effect of chitosan may be due to its antioxidant and antilipidemic properties. Copyright © 2014 Elsevier B.V. All rights reserved.

Hepatoprotective effect of 2'-O-galloylhyperin against oxidative stress-induced liver damage through induction of Nrf2/ARE-mediated antioxidant pathway.

PubMed

Wang, Peng; Gao, Yi-Meng; Sun, Xing; Guo, Na; Li, Ji; Wang, Wei; Yao, Li-Ping; Fu, Yu-Jie

2017-04-01

2'-O-galloylhyperin (2'-O-GH), an active compound isolated from Pyrola calliantha, possesses remarkable antioxidant activity. The aims of this study were to investigate the hepatoprotective effect of 2'-O-GH against oxidative stress and elucidate the underlying mechanistic signaling pathways in HepG2 cells as well as in an animal model. Results showed that 2'-O-GH significantly inhibited hydrogen peroxide (H 2 O 2 )-induced HepG2 cell death in a dose dependent manner. The mitogen-activated protein kinase activation, ROS production, mitochondrial membrane potential, intracellular calcium level and subsequent apoptotic protein activation in H 2 O 2 -stimulated HepG2 cells were remarkably inhibited by 2'-O-GH. Furthermore, 2'-O-GH stimulation resulted in a fast and dramatic activation of Akt and nuclear translocation of the NF-E2-related factor 2 (Nrf2), along with the increased expression of heme oxygenase-1 (HO-1) and levels of glutathione (GSH). Meanwhile, histopathological evaluation of the liver also revealed that 2'-O-GH effectively ameliorated CCl 4 -induced the hepatic damage by reducing alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Therefore, these results suggested the hepatoprotective effect of 2'-O-GH might be correlated with its antioxidant and free radical scavenger effect. Copyright © 2017. Published by Elsevier Ltd.

The use of marine-derived bioactive compounds as potential hepatoprotective agents

PubMed Central

Nair, Dileep G; Weiskirchen, Ralf; Al-Musharafi, Salma K

2015-01-01

The marine environment may be explored as a rich source for novel drugs. A number of marine-derived compounds have been isolated and identified, and their therapeutic effects and pharmacological profiles are characterized. In the present review, we highlight the recent studies using marine compounds as potential hepatoprotective agents for the treatment of liver fibrotic diseases and discuss the proposed mechanisms of their activities. In addition, we discuss the significance of similar studies in Oman, where the rich marine life provides a potential for the isolation of novel natural, bioactive products that display therapeutic effects on liver diseases. PMID:25500871

Soya phospholipid complex of mangiferin enhances its hepatoprotectivity by improving its bioavailability and pharmacokinetics.

PubMed

Bhattacharyya, Sauvik; Ahmmed, Sk Milan; Saha, Bishnu Pada; Mukherjee, Pulok K

2014-05-01

Mangiferin is a xanthonoid present in Mangifera indica. It has been reported for a variety of pharmacological activities, including hepatoprotection. However, the major disadvantage of mangiferin is its reduced biological activity due to poor absorption, low bioavailability and rapid elimination from the body after administration. The aim of this study was to prepare a phospholipid complex of mangiferin to overcome these limitations and to investigate the impact of the complex on hepatoprotective activity and bioavailability. The results showed that the complex has an enhanced hepatoprotective and in vivo antioxidant activity as compared to pure mangiferin at the same dose level (30 and 60 mg kg⁻¹). The complex restored the levels of serum hepatic marker enzymes and liver antioxidant enzymes with respect to carbon tetrachloride-treated animals. The complex also increased the bioavailability of mangiferin in rat serum by 9.75-fold compared to pure mangiferin at the same dose level and enhanced the elimination half-life (t(1/2 el)) from 1.71 ± 0.12 h⁻¹ to 3.52 ± 0.27 h⁻¹. The results suggested that the complexation of mangiferin with soya phospholipid enhanced the hepatoprotection and in vivo antioxidant activity, which may be due to the improved bioavailability and pharmacokinetics of mangiferin in rat serum. © 2013 Society of Chemical Industry.

6-gingerol, an active ingredient of ginger, protects acetaminophen-induced hepatotoxicity in mice.

PubMed

Sabina, Evan Prince; Pragasam, Samuel Joshua; Kumar, Suresh; Rasool, Mahaboobkhan

2011-11-01

To investigate the hepatoprotective efficacy of 6-gingerol against acetaminophen-induced hepatotoxicity in mice. Mice were injected with a single dose of acetaminophen (900 mg/kg) to induce hepatotoxicity, while 6-gingerol (30 mg/kg) or the standard drug silymarin (25 mg/kg) was given 30 min after the acetaminophen administration. The mice were sacrificed 4 h after acetaminophen injection to determine the activities of liver marker enzymes such as aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP), total bilirubin in serum, and lipid peroxidation and antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione transferase and glutathione) in liver homogenate. The treatment of 6-gingerol and silymarin to acetaminophen-induced hepatotoxicity showed significant hepatoprotective effect by lowering the hepatic marker enzymes (AST, ALT, and ALP) and total bilirubin in serum (P<0.05). In addition, 6-gingerol and silymarin treatment prevented the elevation of hepatic malondialdehyde formation and the depletion of antioxidant status in the liver of acetaminophen-intoxicated mice (P<0.05). The results evidently demonstrate that 6-gingerol has promising hepatoprotective effect which is comparable to the standard drug silymarin.

The hepatoprotective effect of sea buckthorn (Hippophae rhamnoides) berries on induced aflatoxin B1 poisoning in chickens 1.

PubMed

Solcan, Carmen; Gogu, Mihaela; Floristean, Viorel; Oprisan, Bogdan; Solcan, Gheorghe

2013-04-01

The leaves and berries of sea buckthorn (SB; Hippophae rhamnoides; family Elaeagnaceae) are medically claimed as having phytoantioxidant, antiinflammatory, and anticancerous properties in humans. This study evaluated the hepatoprotective activity of oil from SB berries against toxicity induced by aflatoxin B1 (AFB1) in broiler chickens. The toxicity of AFB1 led to lower total serum proteins and specifically reduced albumin (P < 0.001). Serum aspartate aminotransferase increased from 191.14 ± 11.56 to 218.80 ± 13.68 (P < 0.001). When chickens were simultaneously dosed with AFB1 and an extract of SB berries, subsequent histology of the liver showed a significant reduction of necrosis and fatty formation compared with chickens treated with AFB1 alone. Immunohistochemical results indicated that COX2, Bcl-2, and p53 were highly expressed in the liver of AFB1-treated chickens and their expression was significantly reduced by SB oil supplementation. The levels of AFB1 residues in chickens livers were significantly reduced by SB oil from 460.92 ± 6.2 ng/mL in the AFB1 group to 15.59 ± 6.1 ng/mL in the AFB1 and SB oil group. These findings suggest that SB oil has a potent hepatoprotective activity, reducing the concentration of aflatoxins in liver and diminishing their adverse effects.

Protective effect of ethyl acetate fraction of Rhododendron arboreum flowers against carbon tetrachloride-induced hepatotoxicity in experimental models

PubMed Central

Verma, Neeraj; Singh, Anil P.; Amresh, G.; Sahu, P. K.; Rao, Ch. V.

2011-01-01

Objective: To evaluate the hepatoprotective potential of ethyl acetate fraction of Rhododendron arboreum (Family: Ericaceae) in Wistar rats against carbon tetrachloride (CCl4)-induced liver damage in preventive and curative models. Materials and Methods: Fraction at a dose of 100, 200, and 400 mg/kg was administered orally once daily for 14 days in CCl4-treated groups (II, III, IV, V and VI). The serum levels of glutamic oxaloacetic transaminase (SGOT), glutamate pyruvate transaminase (SGPT), alkaline phosphatase (SALP), γ-glutamyltransferase (γ -GT), and bilirubin were estimated along with activities of glutathione S-transferase (GST), glutathione reductase, hepatic malondialdehyde formation, and glutathione content. Result and Discussion: The substantially elevated serum enzymatic activities of SGOT, SGPT, SALP, γ-GT, and bilirubin due to CCl4 treatment were restored toward normal in a dose-dependent manner. Meanwhile, the decreased activities of GST and glutathione reductase were also restored toward normal. In addition, ethyl acetate fraction also significantly prevented the elevation of hepatic malondialdehyde formation and depletion of reduced glutathione content in the liver of CCl4-intoxicated rats in a dose-dependent manner. Silymarin used as standard reference also exhibited significant hepatoprotective activity on post-treatment against CCl4-induced hepatotoxicity in rats. The biochemical observations were supplemented with histopathological examination of rat liver sections. The results of this study strongly indicate that ethyl acetate fraction has a potent hepatoprotective action against CCl4-induced hepatic damage in rats. PMID:21713093

Protective effect of ethyl acetate fraction of Rhododendron arboreum flowers against carbon tetrachloride-induced hepatotoxicity in experimental models.

PubMed

Verma, Neeraj; Singh, Anil P; Amresh, G; Sahu, P K; Rao, Ch V

2011-05-01

To evaluate the hepatoprotective potential of ethyl acetate fraction of Rhododendron arboreum (Family: Ericaceae) in Wistar rats against carbon tetrachloride (CCl(4))-induced liver damage in preventive and curative models. Fraction at a dose of 100, 200, and 400 mg/kg was administered orally once daily for 14 days in CCl(4)-treated groups (II, III, IV, V and VI). The serum levels of glutamic oxaloacetic transaminase (SGOT), glutamate pyruvate transaminase (SGPT), alkaline phosphatase (SALP), γ-glutamyltransferase (γ -GT), and bilirubin were estimated along with activities of glutathione S-transferase (GST), glutathione reductase, hepatic malondialdehyde formation, and glutathione content. The substantially elevated serum enzymatic activities of SGOT, SGPT, SALP, γ-GT, and bilirubin due to CCl(4) treatment were restored toward normal in a dose-dependent manner. Meanwhile, the decreased activities of GST and glutathione reductase were also restored toward normal. In addition, ethyl acetate fraction also significantly prevented the elevation of hepatic malondialdehyde formation and depletion of reduced glutathione content in the liver of CCl(4)-intoxicated rats in a dose-dependent manner. Silymarin used as standard reference also exhibited significant hepatoprotective activity on post-treatment against CCl(4)-induced hepatotoxicity in rats. The biochemical observations were supplemented with histopathological examination of rat liver sections. The results of this study strongly indicate that ethyl acetate fraction has a potent hepatoprotective action against CCl(4)-induced hepatic damage in rats.

Hepatoprotective effect of Leucophyllum frutescens on Wistar albino rats intoxicated with carbon tetrachloride.

PubMed

Balderas-Renteria, Isaías; Camacho-Corona, Maria Del Rayo; Carranza-Rosales, Pilar; Lozano-Garza, Hector G; Castillo-Nava, Dalila; Alvarez-Mendoza, Francisco J; Tamez-Cantú, Elsa M

2007-01-01

Many hepatoprotective herbal preparations have been recommended in alternative systems of medicine for the treatment of hepatic disorders. No systematic study has been done on protective efficacy of Leucophyllum frutescens to treat hepatic diseases. Protective action of L. frutescens methanol extract (obtained by maceration) was evaluated in an animal model of hepatotoxicity induced by carbon tetrachloride (CCl(4)). Wistar albino rats were divided into five groups. Group I was normal control group; Groups II-V received CCl(4). After inducing hepatic damage, Group II served as control CCl(4); Group III was given silymarin as reference hepatoprotective; and Groups IV and V received different doses of plant extract. Liver marker enzymes were assayed in serum. Samples of livers were observed under microscope for the histopathological changes. Levels of marker enzymes such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were increased significantly in CCl(4) treated rats (Group II). Groups IV and V intoxicated with CCl(4) and treated with L. frutescens methanol extract significant decreased the activities of these two enzymes. Also these groups resulted in less pronounced destruction of the liver architecture, there is not fibrosis and have moderate inflammation compared with Group II. The present study scientifically validated the traditional use of L. frutescens for liver disorders. In conclusion the methanol extract of L. frutescens aerial parts could be an important source of hepatoprotective compounds.

Hepatoprotective and inhibiting HBV effects of polysaccharides from roots of Sophora flavescens.

PubMed

Yang, Hua; Zhou, Zhenhua; He, Lifang; Ma, Hao; Qu, Wensheng; Yin, Jiye; Jia, Mengfan; Zhao, Xiunan; Shan, Junjie; Gao, Yueqiu

2018-03-01

Roots of Sophora flavescens is an important herbal medicine for treatment of HBV and hepatic carcinoma in China. Alkaloids in the root were well known for exhibiting good hepato-protective and anti-HBV effects. However, polysaccharides as main components in the root remained unknown. In the studies, we investigated the chemical features and hepatoprotective effects of Sophora flavescens polysaccharides (SFP-100 and its active fractions) with ConA-induced hepatitis mice, human liver LO2 cells and HepG2.2.15 cells. The results showed that SFP-100 was composed of arabinose, glucose, galactose and galacturonic acid, SFP-100-A mainly contained glucose. SFP-100-B and SFP-100-C were acidic polysaccharides. SFP-100 significantly decreased hepatocytes apoptosis, inhibited the infiltration of neutrophils and macrophages into liver, and improved the production of IFN-γ and IL-6 of splenocytes in ConA-induced hepatitis mice. SFP-100 and its two sugar fractions increased LO2 cell proliferation and reduced cell apoptosis induced by ConA. SFP-100, SFP-100-A and SFP-100-C remarkedly inhibited the secretion of HBsAg and HBeAg by HepG2.2.15 cells.These results suggested Sophora flavescens polysaccharides exerts significant hepatoprotective and anti-HBV roles, and further is used for treatment of immune-mediated liver disease in the future. Copyright © 2017. Published by Elsevier B.V.

PASS-Predicted Hepatoprotective Activity of Caesalpinia sappan in Thioacetamide-Induced Liver Fibrosis in Rats

PubMed Central

Kadir, Farkaad A.; Kassim, Normadiah M.; Abdulla, Mahmood Ameen; Ahmadipour, Fatemeh; Yehye, Wageeh A.

2014-01-01

The antifibrotic effects of traditional medicinal herb Caesalpinia sappan (CS) extract on liver fibrosis induced by thioacetamide (TAA) and the expression of transforming growth factor β1 (TGF-β1), α-smooth muscle actin (αSMA), and proliferating cell nuclear antigen (PCNA) in rats were studied. A computer-aided prediction of antioxidant and hepatoprotective activities was primarily performed with the Prediction Activity Spectra of the Substance (PASS) Program. Liver fibrosis was induced in male Sprague Dawley rats by TAA administration (0.03% w/v) in drinking water for a period of 12 weeks. Rats were divided into seven groups: control, TAA, Silymarin (SY), and CS 300 mg/kg body weight and 100 mg/kg groups. The effect of CS on liver fibrogenesis was determined by Masson's trichrome staining, immunohistochemical analysis, and western blotting. In vivo determination of hepatic antioxidant activities, cytochrome P450 2E1 (CYP2E1), and matrix metalloproteinases (MPPS) was employed. CS treatment had significantly increased hepatic antioxidant enzymes activity in the TAA-treated rats. Liver fibrosis was greatly alleviated in rats when treated with CS extract. CS treatment was noted to normalize the expression of TGF-β1, αSMA, PCNA, MMPs, and TIMP1 proteins. PASS-predicted plant activity could efficiently guide in selecting a promising pharmaceutical lead with high accuracy and required antioxidant and hepatoprotective properties. PMID:24701154

Protective Effects of Silymarin, Alone or in Combination with Chlorogenic Acid and/or Melatonin, Against Carbon Tetrachloride-induced Hepatotoxicity

PubMed Central

Al-Rasheed, Nouf; Faddah, Laila; Al-Rasheed, Nawal; Bassiouni, Yieldez A.; Hasan, Iman H.; Mahmoud, Ayman M.; Mohamad, Raeesa A.; Yacoub, Hazar I.

2016-01-01

Objective: The aim of this study was to evaluate the hepatoprotective effects of silymarin (SIL), alone and combined with chlorogenic acid (CA) and/or melatonin (ME), using a rat model of carbon tetrachloride (CCl4)-induced injury. Materials and Methods: Hepatotoxicity was induced by a single dose of CCl4 (1 ml/kg, IP). One day after, rats were received SIL (200 mg/kg) alone or in combination with CA (60 mg/kg) and/or ME (20 mg/kg) for 21 days. Results: SIL significantly decreased serum alanine aminotransferase, inflammatory cytokines, and vascular endothelial growth factor levels. Histological alterations, fibrogenesis, oxidative DNA damage, inflammatory mediators, and caspase-3 activity were significantly attenuated in SIL treated CCl4-intoxicated rats. On the other hand, cytochrome P450 2E1 activity showed a significant decrease in the liver of CCl4-intoxicated rats, an effect that was reversed following treatment with SIL. All beneficial effects of SIL were markedly potentiated when combined with CA and/or ME. Conclusions: These data indicate that SIL, alone and combined with CA and/or ME, protected the liver against CCl4-induced hepatotoxicity via attenuating inflammation, oxidative DNA damage, apoptosis, and fibrotic changes. The significantly intensified hepatoprotective effects of SIL when combined with both CA and ME suggest a possible synergism. These synergistic effects need to be further confirmed using detailed studies. SUMMARY Silymarin, chlorogenic acid and melatonin possess in vivo hepatoprotective activitySilymarin, chlorogenic acid and melatonin attenuate fibrogenesis, oxidative DNA damage, inflammation and apoptosisChlorogenic acid and melatonin enhance the hepatoprotective effect of silymarin. Abbreviations used: SIL: silymarin, CA: chlorogenic acid, ME: melatonin, CCl4: carbon tetrachloride, CYP2E1, cytochrome P450 2E1, ALT: alanine aminotransferase, IL-6: interleukin 6, IFN-γ: interferon gamma, VEGF: vascular endothelial growth factor, TNF-α: tumor necrosis factor alpha, CRP: C-reactive protein, 8-OxodG: 8-Oxo-2’-deoxyguanosine, TGF-B1: transforming growth factor beta 1, HSCs: hepatic stellate cells. PMID:27563222

Amelioration of CCl4 induced liver injury in swiss albino mice by antioxidant rich leaf extract of Croton bonplandianus Baill.

PubMed

Dutta, Somit; Chakraborty, Arnab Kumar; Dey, Priyankar; Kar, Pallab; Guha, Pokhraj; Sen, Subhajit; Kumar, Anoop; Sen, Arnab; Chaudhuri, Tapas Kumar

2018-01-01

The progress in industrialization has blessed mankind with a technologically superior lifestyle but poor management of industrial waste has in turn poisoned nature. One such chemical is carbon tetra chloride (CCl4), which is a potent environmental toxin emitted from chemical industries and its presence in the atmosphere is increasing at an alarming rate. Presence of CCl4 in human body is reported to cause liver damage through free radical mediated inflammatory processes. Kupffer cells present in the liver are potentially more sensitive to oxidative stress than hepatocytes. Kuffer cells produced tumor necrosis factor-α (TNF-α) in response to reactive oxygen species (ROS), that might further cause inflammation or apoptosis. In this study hepatoprotective capacity of antioxidant rich extract of Croton bonplandianus Baill. (CBL) was evaluated on CCl4 induced acute hepatotoxicity in murine model. Hydro-methanolic extract of C. bonplandianus leaf was used for evaluation of free radical scavenging activity. Liver cells of experimental mice were damaged using CCl4 and subsequently hepatoprotective potential of the plant extract was evaluated using series of in-vivo and in-vitro studies. In the hepatoprotective study, silymarin was used as a positive control. Antioxidant enzymes, pro-inflammatory markers, liver enzymatic and biochemical parameters were studied to evaluate hepatoprotective activity of Croton bonplandianus leaf extract. Free radical scavenging activity of CBL extract was also observed in WRL-68 cell line. The phytochemicals identified by GCMS analysis were scrutinized using in-silico molecular docking procedure. The results showed that CBL extract have potent free radical scavenging capacity. The biochemical parameters were over expressed due to CCl4 administration, which were significantly normalized by CBL extract treatment. This finding was also supported by histopathological evidences showing less hepatocellularnecrosis, inflammation and fibrosis in CBL and silymarin treated group, compared to CCl4 group. ROS generated due to H2O2 in WRL-68 cell line were normalize in the highest group (200 μg/ml) when compared with control and negative control (CCl4) group. After molecular docking analysis, it was observed that the compound α-amyrin present in the leaf extract of C. bonplandianus has better potentiality to protect hepatocellular damages than the standard drug Silymarin. The present study provided supportive evidence that CBL extract possesses potent hepatoprotective capacity by ameliorating haloalkane induced liver injury in the murine model. The antioxidant and anti-inflammatory activities also affirm the same. The synergistic effects of the phytochemicals present in CBL are to be credited for all the hepatoprotective activity claimed above.

Amelioration of CCl4 induced liver injury in swiss albino mice by antioxidant rich leaf extract of Croton bonplandianus Baill.

PubMed Central

Dutta, Somit; Chakraborty, Arnab Kumar; Dey, Priyankar; Kar, Pallab; Guha, Pokhraj; Sen, Subhajit; Kumar, Anoop; Sen, Arnab

2018-01-01

The progress in industrialization has blessed mankind with a technologically superior lifestyle but poor management of industrial waste has in turn poisoned nature. One such chemical is carbon tetra chloride (CCl4), which is a potent environmental toxin emitted from chemical industries and its presence in the atmosphere is increasing at an alarming rate. Presence of CCl4 in human body is reported to cause liver damage through free radical mediated inflammatory processes. Kupffer cells present in the liver are potentially more sensitive to oxidative stress than hepatocytes. Kuffer cells produced tumor necrosis factor-α (TNF-α) in response to reactive oxygen species (ROS), that might further cause inflammation or apoptosis. In this study hepatoprotective capacity of antioxidant rich extract of Croton bonplandianus Baill. (CBL) was evaluated on CCl4 induced acute hepatotoxicity in murine model. Hydro-methanolic extract of C. bonplandianus leaf was used for evaluation of free radical scavenging activity. Liver cells of experimental mice were damaged using CCl4 and subsequently hepatoprotective potential of the plant extract was evaluated using series of in-vivo and in-vitro studies. In the hepatoprotective study, silymarin was used as a positive control. Antioxidant enzymes, pro-inflammatory markers, liver enzymatic and biochemical parameters were studied to evaluate hepatoprotective activity of Croton bonplandianus leaf extract. Free radical scavenging activity of CBL extract was also observed in WRL-68 cell line. The phytochemicals identified by GCMS analysis were scrutinized using in-silico molecular docking procedure. The results showed that CBL extract have potent free radical scavenging capacity. The biochemical parameters were over expressed due to CCl4 administration, which were significantly normalized by CBL extract treatment. This finding was also supported by histopathological evidences showing less hepatocellularnecrosis, inflammation and fibrosis in CBL and silymarin treated group, compared to CCl4 group. ROS generated due to H2O2 in WRL-68 cell line were normalize in the highest group (200 μg/ml) when compared with control and negative control (CCl4) group. After molecular docking analysis, it was observed that the compound α-amyrin present in the leaf extract of C. bonplandianus has better potentiality to protect hepatocellular damages than the standard drug Silymarin. The present study provided supportive evidence that CBL extract possesses potent hepatoprotective capacity by ameliorating haloalkane induced liver injury in the murine model. The antioxidant and anti-inflammatory activities also affirm the same. The synergistic effects of the phytochemicals present in CBL are to be credited for all the hepatoprotective activity claimed above. PMID:29709010

Active chemical fractions of stem bark extract of Khaya grandifoliola C.DC and Entada africana Guill. et Perr. synergistically protect primary rat hepatocytes against paracetamol-induced damage.

PubMed

Njayou, Frédéric Nico; Kouam, Arnaud Fondjo; Simo, Brice Fredy Nemg; Tchana, Angèle Nkouatchoua; Moundipa, Paul Fewou

2016-07-07

Khaya grandifoliola (Meliaceae) and Entada africana (Fabaceae) are traditionally used in Bamun (a western tribe of Cameroon) traditional medicine for the treatment of liver related diseases. In this study, the synergistic hepatoprotective effect of respective active fractions of the plants were investigated against paracetamol-induced toxicity in primary cultures of rat hepatocytes. Paracetamol conferred hepatocyte toxicity, as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay, alanine aminotransferase (ALT), superoxide dismutase (SOD), catalase (CAT) activities, malondialdehyde (MDA) and glutathione (GSH) content assays. The crude extracts were fractionated by flash chromatography and fractions were tested for hepato-(protective and curative) activities. The most active fractions of both plants were tested individually, and in combination based on their respective half effective concentration (EC50). The methylene chloride/methanol fractions of K. grandifoliola (75:25 v/v) (KgF25) and E. africana (90:10 v/v) (EaF10) were found to be the most hepato-protective with EC50 values of 10.30 ± 1.66 μg/ml and 13.47 ± 2.06 μg/ml respectively, comparable with that of silymarin (13.71 ± 3.87 μg/ml). These fractions and their combination significantly (P <0.05) improved cell viability, inhibited ALT leakage and MDA formation, and restored cellular CAT, SOD activities and GSH content. The combination was more effective in restoring biochemical parameters with coefficients of drugs interaction (CDI) less than 1. These findings demonstrate that the active fractions have synergistic action in the protection of rat hepatocytes against paracetamol-induced damage and suggest that their hepatoprotective properties may be maximized by using them in combination.

Hepatoprotective effect of electrolyzed reduced water against carbon tetrachloride-induced liver damage in mice.

PubMed

Tsai, Chia-Fang; Hsu, Yu-Wen; Chen, Wen-Kang; Chang, Wen-Huei; Yen, Cheng-Chieh; Ho, Yung-Chyuan; Lu, Fung-Jou

2009-08-01

The study investigated the protective effect of electrolyzed reduced water (ERW) against carbon tetrachloride (CCl(4))-induced liver damage. Male ICR mice were randomly divided into control, CCl(4), CCl(4)+silymarin, and CCl(4)+ERW groups. CCl(4)-induced liver lesions include leukocytes infiltration, hepatocyte necrosis, ballooning degeneration, mitosis, calcification, fibrosis and an increase of serum alanine aminotransferase (ALT), and aminotransferase (AST) activity. In addition, CCl(4) also significantly decreased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). By contrast, ERW or silymarin supplement significantly ameliorated the CCl(4)-induced liver lesions, lowered the serum levels of hepatic enzyme markers (ALT and AST) and increased the activities of SOD, catalase, and GSH-Px in liver. Therefore, the results of this study show that ERW can be proposed to protect the liver against CCl(4)-induced oxidative damage in mice, and the hepatoprotective effect might be correlated with its antioxidant and free radical scavenging effect.

Hepatoprotective Effect of Citral on Acetaminophen-Induced Liver Toxicity in Mice

PubMed Central

Silva-Filho, Saulo Euclides; Cardia, Gabriel Fernando Esteves; Cremer, Edivaldo; Bersani-Amado, Ciomar Aparecida

2017-01-01

High doses of acetaminophen (APAP) lead to acute liver damage. In this study, we evaluated the effects of citral in a murine model of hepatotoxicity induced by APAP. The liver function markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (γGT) were determined to evaluate the hepatoprotective effects of citral. The livers were used to determine myeloperoxidase (MPO) activity and nitric oxide (NO) production and in histological analysis. The effect of citral on leukocyte migration and antioxidant activity was evaluated in vitro. Citral pretreatment decreased significantly the levels of ALT, AST, ALP, and γGT, MPO activity, and NO production. The histopathological analysis showed an improvement of hepatic lesions in mice after citral pretreatment. Citral inhibited neutrophil migration and exhibited antioxidant activity. Our results suggest that citral protects the liver against liver toxicity induced by APAP. PMID:28717379

Hepatoprotective Effect of Citral on Acetaminophen-Induced Liver Toxicity in Mice.

PubMed

Uchida, Nancy Sayuri; Silva-Filho, Saulo Euclides; Cardia, Gabriel Fernando Esteves; Cremer, Edivaldo; Silva-Comar, Francielli Maria de Souza; Silva, Expedito Leite; Bersani-Amado, Ciomar Aparecida; Cuman, Roberto Kenji Nakamura

2017-01-01

High doses of acetaminophen (APAP) lead to acute liver damage. In this study, we evaluated the effects of citral in a murine model of hepatotoxicity induced by APAP. The liver function markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase ( γ GT) were determined to evaluate the hepatoprotective effects of citral. The livers were used to determine myeloperoxidase (MPO) activity and nitric oxide (NO) production and in histological analysis. The effect of citral on leukocyte migration and antioxidant activity was evaluated in vitro. Citral pretreatment decreased significantly the levels of ALT, AST, ALP, and γ GT, MPO activity, and NO production. The histopathological analysis showed an improvement of hepatic lesions in mice after citral pretreatment. Citral inhibited neutrophil migration and exhibited antioxidant activity. Our results suggest that citral protects the liver against liver toxicity induced by APAP.

Pharmacological evaluation of mangiferin herbosomes for antioxidant and hepatoprotection potential against ethanol induced hepatic damage.

PubMed

Jain, Pushpendra Kumar; Kharya, Murlidhar; Gajbhiye, Asmita

2013-11-01

Fatty liver is the first stage of alcoholic damage which is reversible with abstinence from alcohol. Mangiferin (MF) showed potent scavenging activity on diphenyl-1-picrylhydrazyl radicals which stimulate liver regeneration in various liver injuries. Although, MF shows hepatoprotection against various liver disorders but due to rapid clearance and limited solubility in lipoid environment, there is problem of its poor absorption from intestine hence poor bioavailability. Owing to which there is a need to develop MF herbosomes to resolve the problem of poor bioavailability to enhance the therapeutic potential. Successfully prepared MF herbosomes through complexation with phospholipids were characterized by physicochemical, chromatography, spectroscopy (differential scanning calorimetry (DSC), infrared (IR), and nuclear magnetic resonance (NMR)), ex vivo absorption using everted small intestine sac technique and in vivo studies using ethanol inducing hepatotoxicity in albino rats and comparing the results against plain MF. Ex vivo study showed significant increased absorption of MF from prepared MF herbosomes as compared to plain MF. The hepatoprotective potential of MF herbosomes evaluated by in vivo study revealed significantly decreased levels of serum glutamate oxaloacetate transminase (SGOT), serum glutamate pyruvate transminase (SGPT), total bilirubin, and alkaline phosphatase (ALP) in MF herbosomes as compared to plain MF. MF herbosomes also showed significantly decreased level of malonyl dehydrogenase along with increased levels of reduced glutathione, superoxide dismutase (SOD) and catalase as compared to plain MF which was also comparable to the standard drug, silymarin (SL). The above mentioned results showed that hepatoprotective and antioxidant potency of MF enhanced due to the preparation of its herbosomes.

Hepatoprotective activities of Antrodia camphorata and its triterpenoid compounds against CCl4-induced liver injury in mice.

PubMed

Li, Zi-Wei; Kuang, Yi; Tang, Shu-Nan; Li, Kai; Huang, Yun; Qiao, Xue; Yu, Si-Wang; Tzeng, Yew-Min; Lo, Jen-Yu; Ye, Min

2017-07-12

Antrodia camphorata (AC) is a rare and precious fungus indigenous to Taiwan used as a traditional medicine for the treatment of liver injury. Triterpenoids are the major bioactive constituents of A. camphorata and have been reported to possess hepatoprotective activities. To meet the increasing demand, artificial cultivation techniques have been developed. This study aims to evaluate the hepatoprotective activities of AC samples derived from different cultivation techniques and to dissect the main active triterpenoid compounds. The ethanol extracts of five batches of AC samples, including wild growing fruiting bodies, cutting wood culture fruiting bodies, dish cultures, cutting wood culture mycelia, and submerged fermentation mycelia were orally administered (50mg/kg or 200mg/kg) to ICR mice for 7 days. On the last day, CCl 4 (0.2%, 7mL/kg, i.p.) was used to induce liver injury, and the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined 24h after the injection. Moreover, a HepG2 cell model treated with CCl 4 (0.35%) was used to screen the protective activities of 29 AC triterpenoids. After incubation for 6h, viabilities of the cells were tested using MTS assay. The in vivo hepatoprotective activities of antcin B and antcin K were further studied on the mice model by ALT and AST tests and histopathologic examinations. To elucidate the mechanisms, the mRNA levels of iNOS, COX2, TNF-α and IL-1β, and the protein levels of NF-κB (p65/p-p65), iNOS and COX2 in liver tissues were determined. The wild growing or cutting wood culture fruiting bodies, and the dish cultures of AC showed more potent activities than the mycelia (P<0.001). At 20μM, 16 of 29 triterpenoids showed significant protective activities, increasing HepG2 cell viability from 46% of the CCl 4 group to >90%. Antcin B and antcin K could dose-dependently (10 or 50mg/kg, 7 days, i.g.) decrease the serum levels of ALT and AST, and decrease the incidence of liver necrosis. The effects of 50mg/kg of antcin K or antcin B were almost identical to those of 100mg/kg silymarin. Furthermore, qRT-PCR and Western blotting analyses revealed they could down-regulate IL-1β, TNF-α, iNOS, COX-2 and NF-κB in liver tissues at both transcriptional and translational levels. The results indicate that cultivation techniques remarkably affect the hepatoprotective activities of AC. Antcin K and antcin B are the major hepatoprotective compounds of A. camphorata, and the mechanism is related with anti-inflammation. Given its high natural abundance and good oral absorption, antcin K could be a promising drug candidate for liver injury. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Hepatoprotective effect of ethanolic extract of Curcuma longa on thioacetamide induced liver cirrhosis in rats

PubMed Central

2013-01-01

Background Hepatology research has focused on developing traditional therapies as pharmacological medicines to treat liver cirrhosis. Thus, this study evaluated mechanisms of the hepatoprotective activity of Curcuma longa rhizome ethanolic extract (CLRE) on thioacetamide-induced liver cirrhosis in rats. Methods The hepatoprotective effect of CLRE was measured in a rat model of thioacetamide-induced liver cirrhosis over 8 weeks. Hepatic cytochrome P450 2E1 and serum levels of TGF-β1 and TNF-α were evaluated. Oxidative stress was measured by malondialdehyde, urinary 8-hydroxyguanosine and nitrotyrosine levels. The protective activity of CLRE free-radical scavenging mechanisms were evaluated through antioxidant enzymes. Protein expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins in animal blood sera was studied and confirmed by immunohistochemistry of Bax, Bcl2 proteins and proliferating cell nuclear antigen. Results Histopathology, immunohistochemistry and liver biochemistry were significantly lower in the Curcuma longa-treated groups compared with controls. CLRE induced apoptosis, inhibited hepatocytes proliferation but had no effect on hepatic CYP2E1 levels. Conclusion The progression of liver cirrhosis could be inhibited by the antioxidant and anti-inflammatory activities of CLRE and the normal status of the liver could be preserved. PMID:23496995

Hypoglycemic and Hepatoprotective Activity of Fermented Fruit Juice of Morinda citrifolia (Noni) in Diabetic Rats

PubMed Central

Nayak, B. Shivananda; Marshall, Julien R.; Isitor, Godwin; Adogwa, Andrew

2011-01-01

Morinda citrifolia is a medicinal plant used to treat diabetes and liver diseases. The fermented fruit juice of the M. Citrifolia (optical density = 1.25) was used to study the hypoglycemic and hepatoprotective properties in diabetes-induced rats. The rats were randomly distributed into 4 groups (control, diabetic experimental, diabetic standard, and diabetic untreated) of 6 each. Diabetes was induced by administering Streptozotocin (50 mg/kg body weight). Fasting blood glucose, body mass, liver tissue glycogen content, and the extent of liver degeneration were assessed. Diabetic experimental animals were treated with M. citrifolia juice (2 ml/kg, twice a day) and diabetic standard with reference hypoglycemic drug, glibenclamide orally for 20 days. Both the groups exhibited a significant reduction in blood glucose level of 150 mg/dl ±15.88 and 125 mg/dl ±3.89, respectively, as compared to diabetic untreated with FBS = 360.0 mg/dl ±15.81, (P < .003). On 10th day of experiment, diabetic experimental animals exhibited a decrease in body mass (10.2 g, 5.11%) which increased significantly by the 20th day (6 g, 3.0%, P < .022). Histological study of liver tissue obtained from untreated diabetic animals revealed significant fatty degeneration as compared to other three groups. The data of this study proved the hypoglycemic and hepatoprotective activity of M. citrifolia. PMID:20981320

Quercetin protects liver injury induced by bile duct ligation via attenuation of Rac1 and NADPH oxidase1 expression in rats.

PubMed

Kabirifar, Razieh; Ghoreshi, Zohreh-Al-Sadat; Safari, Fatemeh; Karimollah, Alireza; Moradi, Ali; Eskandari-Nasab, Ebrahim

2017-02-01

Bile duct ligation (BDL) and subsequent cholestasis are correlated with oxidative stress, hepatocellular injury and fibrosis. Quercetin is a flavonoid with antifibrotic, and hepatoprotective properties. However, the molecular mechanism underlying quercetin-mediated hepatoprotection is not fully understood. The current study was to evaluate mechanisms of hepatoprotective effect of quercetin in BDL rat model. We divided male Wistar rats into 4 groups (n=8 for each): sham, sham+quercetin (30 mg/kg per day), BDL, and BDL+quercetin (30 mg/kg per day). Four weeks later, the rats were sacrificed, the blood was collected for liver enzyme measurements and liver for the measurement of Rac1, Rac1-GTP and NOX1 mRNA and protein levels by quantitative PCR and Western blotting, respectively. Quercetin significantly alleviated liver injury in BDL rats as evidenced by histology and reduced liver enzymes. Furthermore, the mRNA and protein expression of Rac1, Rac1-GTP and NOX1 were significantly increased in BDL rats compared with those in the sham group (P<0.05); quercetin treatment reversed these variables back toward normal (P<0.05). Another interesting finding was that the antioxidant markers e.g. superoxide dismutase and catalase were elevated in quercetin-treated BDL rats compared to BDL rats (P<0.05). Quercetin demonstrated hepatoprotective activity against BDL-induced liver injury through increasing antioxidant capacity of the liver tissue, while preventing the production of Rac1, Rac1-GTP and NOX1 proteins.

Hepatoprotective and toxicological studies of Salvia bucharica methanolic extract in rabbits.

PubMed

Ahmad, Mansoor; Muhammed, Shafi; Mehjabeen, -; Jahan, Noor

2014-11-01

Most of the species of genus Salvia are famous for having medicinal properties due to their chemical constituents. Salvia bucharica (Lamiacea) is found in Balochistan near Quetta in Hannaurak and Kalat. It is used in traditional system of medicine and claims to cure liver ailments. In current study crude methanolic extract (CME) of Salvia bucharica was obtained from the leaves and tested for hepatoprotective activity and possible toxicity in rabbits. Liver toxicity was induced in rabbits by administration of carbon tetra chloride (CCl4) and evaluated by biochemical tests and histopathology of tissues. In this study rabbits were divided in to 3 groups (5 rabbit in each group). Rabbits of group I (control) were administered only vehicle (0.9% sodium chloride) orally. Rabbits of group II were given CCl4 and group III were treated with CCl4 and S. bucharica CME orally. For hepatoprotective effect serum enzyme level and total protein level were calculated. Histopathology of liver sections of rabbits was also carried out to observe protective effect. Biochemical, hematological and histoptahological parameters were studied on rabbits for toxicological studies. S. bucharica CME showed significant liver protection with reduction in total bilirubin, direct bilirubin, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), gamma glutamyl transpeptidase (γ-GT). And decrease in Albumin and globulin. In toxicological studies, biochemical and histoptahological parameters showed no significant toxicity in liver, heart and kidneys. It is concluded that S. bucharica CME showed hepatoprotective effects with nontoxic profile.

New Apigenin Glycoside, Polyphenolic Constituents, Anti-inflammatory and Hepatoprotective Activities of Gaillardia grandiflora and Gaillardia pulchella Aerial Parts.

PubMed

Moharram, Fatma A; El Dib, Rabab Abd El Moneim; Marzouk, Mohamed S; El-Shenawy, Siham M; Ibrahim, Haitham A

2017-07-01

Gaillardia grandiflora Hort. ex Van Houte and Gaillardia pulchella Foug are flowering plants widely cultivated in Egypt for their ornamental value. Previous reports demonstrated that sesquiterpene derivatives represent the major compounds in both species. Moreover, only few flavones were identified from genus Gaillardia and few studies on the cytotoxicity of G. pulchella were found. Investigation of the phenolic constituents of the aerial parts of both species and evaluation of their anti-inflammatory and hepatoprotective activities. The 80% aqueous methanol extracts (AME) were prepared for both plants and evaluated for their biological activities. Phytochemical investigation of both extracts resulted in isolation of twelve compounds, which have been identified on the basis of ultraviolet, 1D and 2D nuclear magnetic resonance spectroscopy and negative ESI-MS. The new 8-hydroxyapigenin 6- O -β-D-apiofuranosyl-(1'''→6'')- C -β-D- 4 C 1 -glucopyranoside was isolated from G. grandiflora for the first time in nature, along with schaftoside, luteolin 6-C-β-D- 4 C 1 -glucopyranoside 8-methyl ether, apigenin 6- C -β-D- 4 C 1 -glucopyranoside 8-methyl ether, isoorientin, isovitexin, 6-methoxyluteolin and hispidulin, as well as vicenin-2, vitexin, luteolin and apigenin, which were isolated from G. pulchella together with 6-methoxyluteolin. Furthermore, the AME of both species were found to be nontoxic to mice and exhibited significant anti-inflammatory and hepatoprotective activities in dose dependent manner. Current results shed light on the phenolic constituents of G. grandiflora and G. pulchella aerial parts and the safety of the AME of both species, in addition to their significant anti-inflammatory and hepatoprotective activities. Both plant species may be promising candidates for natural anti-inflammatory and hepatoprotective drugs. Phytochemical investigation of Gaillardia grandiflora and Gaillardia pulchella 80% aqueous methanol extracts of the aerial parts led to the isolation of twelve compoundsThe new compound 8-hydroxyapigenin 6- O -β-D-apiofuranosyl-(1''''→6'')- C -β-D-4C1-glucopyranoside was isolated from G. grandiflora for the first time in natureSchaftoside, luteolin 6- C -β-D-4C1-glucopyranoside 8-methyl ether, apigenin 6- C -β-D-4C1-glucopyranoside 8-methyl ether, isoorientin, isovitexin, 6-methoxyluteolin and hispidulin were isolated from G. grandiflora Vicenin-2, vitexin, luteolin, apigenin and 6-methoxyluteolin were isolated from G. pulchella The extracts of both species were nontoxic to mice up to 5 g/kg body weightBoth extracts exhibited significant anti-inflammatory and hepatoprotective activities in dose dependent manner Abbreviations used: ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AME: The 80% aqueous methanol extract of G. grandiflora or G. pulchella aerial parts; AST: Aspartate aminotransferase; br d: Broad doublet; Comp-PC: Comparative paper chromatography; d: Doublet; 2D-PC: Two-dimensional paper chromatography; DMSO-d6: Deuterated dimethyl sulfoxide; G.: Gaillardia ; GPx: Glutathione peroxidase; GRd: Glutathione reductase; GSH: glutathione; GST: Glutathione-S-transferase; J : Nuclear spin-spin coupling constant; m: Multiplet; [M-H]-: Molecular ion peak; MDA: Malondialdehyde; m / z : Mass/charge ratio; NO: Nitric oxide; p: Probability; PC: Paper chromatography; Rf: Retention flow; rpm: Rotation per minute; s: Singlet; SDE: The ethanol extract of Scoparia dulcis ; SE: Standard error; SOD: Superoxide dismutase; TMS: Tetramethylsilane; λmax: Maximum fluorescence emission wavelength.

New Apigenin Glycoside, Polyphenolic Constituents, Anti-inflammatory and Hepatoprotective Activities of Gaillardia grandiflora and Gaillardia pulchella Aerial Parts

PubMed Central

Moharram, Fatma A.; El Dib, Rabab Abd El Moneim; Marzouk, Mohamed S.; El-Shenawy, Siham M.; Ibrahim, Haitham A.

2017-01-01

Background: Gaillardia grandiflora Hort. ex Van Houte and Gaillardia pulchella Foug are flowering plants widely cultivated in Egypt for their ornamental value. Previous reports demonstrated that sesquiterpene derivatives represent the major compounds in both species. Moreover, only few flavones were identified from genus Gaillardia and few studies on the cytotoxicity of G. pulchella were found. Aim of the Study: Investigation of the phenolic constituents of the aerial parts of both species and evaluation of their anti-inflammatory and hepatoprotective activities. Materials and Methods: The 80% aqueous methanol extracts (AME) were prepared for both plants and evaluated for their biological activities. Phytochemical investigation of both extracts resulted in isolation of twelve compounds, which have been identified on the basis of ultraviolet, 1D and 2D nuclear magnetic resonance spectroscopy and negative ESI-MS. Results: The new 8-hydroxyapigenin 6-O-β-D-apiofuranosyl-(1’’’→6’’)-C-β-D-4C1-glucopyranoside was isolated from G. grandiflora for the first time in nature, along with schaftoside, luteolin 6-C-β-D-4C1-glucopyranoside 8-methyl ether, apigenin 6-C-β-D-4C1-glucopyranoside 8-methyl ether, isoorientin, isovitexin, 6-methoxyluteolin and hispidulin, as well as vicenin-2, vitexin, luteolin and apigenin, which were isolated from G. pulchella together with 6-methoxyluteolin. Furthermore, the AME of both species were found to be nontoxic to mice and exhibited significant anti-inflammatory and hepatoprotective activities in dose dependent manner. Conclusion: Current results shed light on the phenolic constituents of G. grandiflora and G. pulchella aerial parts and the safety of the AME of both species, in addition to their significant anti-inflammatory and hepatoprotective activities. Both plant species may be promising candidates for natural anti-inflammatory and hepatoprotective drugs. SUMMARY Phytochemical investigation of Gaillardia grandiflora and Gaillardia pulchella 80% aqueous methanol extracts of the aerial parts led to the isolation of twelve compoundsThe new compound 8-hydroxyapigenin 6-O-β-D-apiofuranosyl-(1’’’’→6’’)-C-β-D-4C1-glucopyranoside was isolated from G. grandiflora for the first time in natureSchaftoside, luteolin 6-C-β-D-4C1-glucopyranoside 8-methyl ether, apigenin 6-C-β-D-4C1-glucopyranoside 8-methyl ether, isoorientin, isovitexin, 6-methoxyluteolin and hispidulin were isolated from G. grandifloraVicenin-2, vitexin, luteolin, apigenin and 6-methoxyluteolin were isolated from G. pulchellaThe extracts of both species were nontoxic to mice up to 5 g/kg body weightBoth extracts exhibited significant anti-inflammatory and hepatoprotective activities in dose dependent manner Abbreviations used: ALP: Alkaline phosphatase; ALT: Alanine aminotransferase; AME: The 80% aqueous methanol extract of G. grandiflora or G. pulchella aerial parts; AST: Aspartate aminotransferase; br d: Broad doublet; Comp-PC: Comparative paper chromatography; d: Doublet; 2D-PC: Two-dimensional paper chromatography; DMSO-d6: Deuterated dimethyl sulfoxide; G.: Gaillardia; GPx: Glutathione peroxidase; GRd: Glutathione reductase; GSH: glutathione; GST: Glutathione-S-transferase; J: Nuclear spin-spin coupling constant; m: Multiplet; [M-H]−: Molecular ion peak; MDA: Malondialdehyde; m/z: Mass/charge ratio; NO: Nitric oxide; p: Probability; PC: Paper chromatography; Rf: Retention flow; rpm: Rotation per minute; s: Singlet; SDE: The ethanol extract of Scoparia dulcis; SE: Standard error; SOD: Superoxide dismutase; TMS: Tetramethylsilane; λmax: Maximum fluorescence emission wavelength. PMID:28808387

Antioxidant and Hepatoprotective Activities of Crude Polysaccharide Extracts from Lingzhi or Reishi Medicinal Mushroom, Ganoderma lucidum (Agaricomycetes), by Ultrasonic-Circulating Extraction.

PubMed

Chen, Ti Qiang; Wu, Jian-Guo; Kan, Yong-Jun; Yang, Chi; Wu, Yan-Bin; Wu, Jin-Zhong

2018-01-01

We recently proposed, and successfully applied, a novel and efficient technique-ultrasonic-circulating extraction (UCE) integrating superfine pulverization-to extract and prepare antioxidant crude polysaccharides other natural active substances from Ganoderma lucidum. The aim of this study was to evaluate the antioxidant and hepatoprotective activities and active ingredients in the powder from UCE (UCEP) through comparison with powder from hot water extraction (HWEP). The DPPH radical, ABTS radical, superoxide anion, total antioxidant activity, and ferric-reducing antioxidant power assay results showed that the UCEP exhibited stronger (P < 0.01) in vitro antioxidant activity than the HWEP. The hepatoprotective activity of the extracts was evaluated against CCl4-induced oxidative damage in the liver. Measurements of reduced glutathione, superoxide dismutase, and malondialdehyde in rat liver; measurements of alanine transaminase, aspartate transaminase, and lactate dehydrogenase in rat blood; and Western blotting for antioxidant proteins of transforming growth factor-β1, heme-oxygenase 1, and glutathione per-oxidase showed that the UCEP had antioxidant activity in vivo either similar to or slightly stronger than (P < 0.1) the HWEP. Further analysis of the active ingredients revealed that the UCEP and HWEP have similar mean yield and total triterpenoid content, but the former has significantly higher (P < 0.05) mean yield and total polysaccharide content than the latter. Our results suggest that the UCEP displays stronger antioxidant activities because of the larger amount of total polysaccharides; the UCEP may be able to be used as an antioxidant and liver protectant.

Hepatoprotective role of Nicotiana plumbaginifolia Linn. against carbon tetrachloride-induced injuries.

PubMed

Shah, Abdus Saboor; Khan, Rahmat Ali; Ahmed, Mushtaq; Muhammad, Nawshad

2016-02-01

Nicotiana plumbignifolia (Linn) is used as folk medicine in the treatment of liver dysfunction in Pakistan. The present study was designed to investigate the hepatoprotective role of N. plumbignifolia methanolice extract (NPME) against carbon tetrachloride (CCl4)-induced oxidative damage in liver of chicks. Methanolic extract of N. plumbignifolia was obtained and was further evaluated as a hepatoprotective agent against CCl4-induced oxidative damage in liver of chicks. For this study, 60-day-old 50 male chicks were divided into five groups. Chicks of group 1 (control) had free access to food and water. Group II received 1 mL/kg of CCl4 (30% in olive oil v/v) via the intraperitoneal route thrice a week for 4 weeks. Group III received 100 mg/kg body weight (b.w.) of silymarin via gavage after 48 h of CCl4 treatment, whereas group IV were given 200 mg/kg b.w. NPME after 48 h of CCl4 treatment. Hepatoprotective activity was assessed by measuring the activities of the antioxidant enzymes: catalase, peroxidase, superoxide dismutase, glutathione peroxidase, glutathione reductase, and lipid peroxidation (thiobarbituric acid reactive substances (TBARS)). Serum was analyzed for various biochemical parameters. The results revealed that CCl4 induced oxidative stress as evidenced by the significant decrease in the activity levels of antioxidant enzymes, while an increase in the levels of TBARS in liver samples is compared with the control group. Serum levels lactate dehydrogenase, triglycerides, total cholesterol, and low-density lipoprotein was elevated while reducing high-density lipoprotein compared to controls. Cotreatment of NPME treatment reversed these alterations, which seems likely that NPME can protect the liver tissues against CCl4-mediated oxidative damage. © The Author(s) 2013.

Hepatoprotective Effect of Opuntia robusta and Opuntia streptacantha Fruits against Acetaminophen-Induced Acute Liver Damage

PubMed Central

González-Ponce, Herson Antonio; Martínez-Saldaña, María Consolación; Rincón-Sánchez, Ana Rosa; Sumaya-Martínez, María Teresa; Buist-Homan, Manon; Faber, Klaas Nico; Moshage, Han; Jaramillo-Juárez, Fernando

2016-01-01

Acetaminophen (APAP)-induced acute liver failure (ALF) is a serious health problem in developed countries. N-acetyl-l-cysteine (NAC), the current therapy for APAP-induced ALF, is not always effective, and liver transplantation is often needed. Opuntia spp. fruits are an important source of nutrients and contain high levels of bioactive compounds, including antioxidants. The aim of this study was to evaluate the hepatoprotective effect of Opuntia robusta and Opuntia streptacantha extracts against APAP-induced ALF. In addition, we analyzed the antioxidant activities of these extracts. Fruit extracts (800 mg/kg/day, orally) were given prophylactically to male Wistar rats before intoxication with APAP (500 mg/kg, intraperitoneally). Rat hepatocyte cultures were exposed to 20 mmol/L APAP, and necrosis was assessed by LDH leakage. Opuntia robusta had significantly higher levels of antioxidants than Opuntia streptacantha. Both extracts significantly attenuated APAP-induced injury markers AST, ALT and ALP and improved liver histology. The Opuntia extracts reversed APAP-induced depletion of liver GSH and glycogen stores. In cultured hepatocytes, Opuntia extracts significantly reduced leakage of LDH and cell necrosis, both prophylactically and therapeutically. Both extracts appeared to be superior to NAC when used therapeutically. We conclude that Opuntia extracts are hepatoprotective and can be used as a nutraceutical to prevent ALF. PMID:27782042

Antioxidant and Hepatoprotective Efficiency of Selenium Nanoparticles Against Acetaminophen-Induced Hepatic Damage.

PubMed

Amin, Kamal Adel; Hashem, Khalid Shaban; Alshehri, Fawziah Saleh; Awad, Said T; Hassan, Mohammed S

2017-01-01

Overdoses of acetaminophen (APAP), a famous and widely used drug, may have hepatotoxic effects. Nanoscience is a novel scientific discipline that provides specific tools for medical science problems including using nano trace elements in hepatic diseases. Our study aimed to assess the hepatoprotective role of selenium nanoparticles (Nano-Se) against APAP-induced hepatic injury. Twenty-four male rats were classified into three equal groups: a control group that received 0.9 % NaCl, an APAP-treated group (oral administration), and a group treated with Nano-Se (10-20 nm, intraperitoneal (i.p.) injection) and APAP (oral administration). APAP overdose induced significant elevations in liver function biomarkers, hepatic lipid peroxidation, hepatic catalase, and superoxide dismutase (SOD), decreased the reduced glutathione (GSH) content and glutathione reductase (GR) activity, and stimulated significant DNA damage in hepatocytes, compared to control rats. Nano-Se administration improved the hepatic antioxidant protection mechanism and decreased cellular sensitivity to DNA fragmentation. Nano-Se exhibits a protective effect against APAP-induced hepatotoxicity through improved liver function and oxidative stress mediated by catalase, SOD, and GSH and decreases hepatic DNA fragmentation, a hepatic biomarker of cell death. Nano-Se could be a novel hepatoprotective strategy to inhibit oxidative stress.

Walnut polyphenols prevent liver damage induced by carbon tetrachloride and d-galactosamine: hepatoprotective hydrolyzable tannins in the kernel pellicles of walnut.

PubMed

Shimoda, Hiroshi; Tanaka, Junji; Kikuchi, Mitsunori; Fukuda, Toshiyuji; Ito, Hideyuki; Hatano, Tsutomu; Yoshida, Takashi

2008-06-25

The polyphenol-rich fraction (WP, 45% polyphenol) prepared from the kernel pellicles of walnuts was assessed for its hepatoprotective effect in mice. A single oral administration of WP (200 mg/kg) significantly suppressed serum glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) elevation in liver injury induced by carbon tetrachloride (CCl 4), while it did not suppress d-galactosamine (GalN)-induced liver injury. In order to identify the active principles in WP, we examined individual constituents for the protective effect on cell damage induced by CCl 4 and d-GalN in primary cultured rat hepatocytes. WP was effective against both CCl 4- and d-GalN-induced hepatocyte damages. Among the constituents, only ellagitannins with a galloylated glucopyranose core, such as tellimagrandins I, II, and rugosin C, suppressed CCl 4-induced hepatocyte damage significantly. Most of the ellagitannins including tellimagrandin I and 2,3- O-hexahydroxydiphenoylglucose exhibited remarkable inhibitory effect against d-GalN-induced damage. Telliamgrandin I especially completely suppressed both CCl 4- and d-GalN-induced cell damage, and thus is likely the principal constituent for the hepatoprotective effect of WP.

Hepatoprotective effect of Cirsium arisanense Kitamura in tacrine-treated hepatoma Hep 3B cells and C57BL mice.

PubMed

Ku, Kuo-Lung; Tsai, Chu-Tsai; Chang, Wei-Min; Shen, Mei-Lin; Wu, Chia-Tien; Liao, Hui-Fen

2008-01-01

Cirsium arisanense Kitamura (Compositae) has been used for hundreds of years in Taiwan as a folk medicine for hepatoprotection. However, no scientific research has demonstrated this effect. In the present study, we extracted the phenol-containing aqueous components of C. arisanense roots (CaR) and leaves/stem (CaL), and then assessed their hepatoprotective activities in both human hepatocellular carcinoma Hep 3B cells and C57BL/6 mice strain. High performance liquid chromatography (HPLC) analysis revealed that the components of CaR and CaL differed from those of the positive control silymarin. CaR exhibited a higher phenolic content and antioxidant capacity than CaL. Hep 3B cells treated with silymarin (0-200 microg/ml) demonstrated a concentration-dependent decrease in viability; however, both CaR and CaL did not exhibit any apparent cytotoxicity. Silymarin at 100 microg/ml, as well as CaR and CaL, not only protect Hep 3B cells from tacrine-induced hepatotoxicity but also decrease the expression of hepatitis B surface antigen (HBsAg). Moreover, an animal experiment demonstrated that CaR, CaL, and silymarin have hepatoprotective effects in C57BL/6 mice injected with tacrine, and they significantly decrease the levels of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST). These effects of CaR and silymarin, but not of CaL, may occur via an increase in the hepatic glutathione level and the elimination of the nitric oxide production. In conclusion, the phenol-containing aqueous components from C. arisanense have potential in hepatoprotection.

Hibiscus vitifolius (Linn.) root extracts shows potent protective action against anti-tubercular drug induced hepatotoxicity.

PubMed

Samuel, Anbu Jeba Sunilson John; Mohan, Syam; Chellappan, Dinesh Kumar; Kalusalingam, Anandarajagopal; Ariamuthu, Saraswathi

2012-05-07

The roots of Hibiscus vitifolius Linn. (Malvaceae) is used for the treatment of jaundice in the folklore system of medicine in India. This study is an attempt to evaluate the hepatoprotective activity of the roots of Hibiscus vitifolius against anti-tubercular drug induced hepatotoxicity. Hepatotoxicity was induced in albino rats of either sex by oral administration of a combination of three anti-tubercular drugs. Petroleum ether, chloroform, methanol and aqueous extracts of roots of Hibiscus vitifolius (400mg/kg/day) were evaluated for their possible hepatoprotective potential. All the extracts were found to be safe up to a dose of 2000mg/kg. Among the four extracts studied, oral administration of methanol extract of Hibiscus vitifolius at 400mg/kg showed significant difference in all the parameters when compared to control. There was a significant (P<0.001) reduction in the levels of serum aspartate amino transaminase, alanine amino transferase, alkaline phosphatase, lactate dehydrogenase, total and direct bilirubin, where as an increase was found in the levels of total cholesterol, total protein and albumin. Liver homogenate studies showed a significant increase in the levels of total protein, phospholipids and glycogen, and a reduction in the levels of total lipids, triglycerides, and cholesterol against control animals. In the tissue anti-oxidant studies, we found a significant increase in the levels of catalase and superoxide dismutase, whereas there was marked reduction in the levels of thiobarbituric acid reactive substances, as compared to control. Histology of liver sections of the animals treated with the extracts showed significant reduction of necrosis and fatty formation when compared with control specimens. These findings suggest that the root extracts of Hibiscus vitifolius have potent hepatoprotective activity, thereby justifying its ethnopharmacological claim. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Hepatoprotective Effect of Polyphenol-Enriched Fraction from Folium Microcos on Oxidative Stress and Apoptosis in Acetaminophen-Induced Liver Injury in Mice.

PubMed

Wu, Hongtan; Zhang, Gang; Huang, Lisen; Pang, Haiyue; Zhang, Na; Chen, Yupei; Wang, Gueyhorng

2017-01-01

Folium Microcos (FM), the leaves of Microcos paniculata L., shows various biological functions including antioxidant activity and α -glucosidase inhibitory effect. However, its therapeutic potential in acute liver injury is still unknown. This study investigated the hepatoprotective effect and underlying mechanisms of the polyphenol-enriched fraction (FMF) from Folium Microcos . FMF exhibited strong free radical scavenging activities and prevented HepG2/Hepa1-6 cells from hydrogen peroxide- (H 2 O 2 -) induced ROS production and apoptosis in vitro. Antioxidant activity and cytoprotective effects were further verified by alleviating APAP-induced hepatotoxicity in mice. Western blot analysis revealed that FMF pretreatment significantly abrogated APAP-mediated phosphorylation of MAPKs, activation of proapoptotic protein caspase-3/9 and Bax, and restored expression of antiapoptotic protein Bcl2. APAP-intoxicated mice pretreated with FMF showed increased nuclear accumulation of nuclear factor erythroid 2-related factor (Nrf2) and elevated hepatic expression of its target genes, NAD(P)H:quinine oxidoreductase 1 (NQO1) and hemeoxygenase-1(HO-1). HPLC analysis revealed the four predominantly phenolic compounds present in FMF: narcissin, isorhamnetin-3-O- β -D-glucoside, isovitexin, and vitexin. Consequently, these findings indicate that FMF possesses a hepatoprotective effect against APAP-induced hepatotoxicity mainly through dual modification of ROS/MAPKs/apoptosis axis and Nrf2-mediated antioxidant response, which may be attributed to the strong antioxidant activity of phenolic components.

Hydroalcoholic extract of Stevia rebaudiana bert. leaves and stevioside ameliorates lipopolysaccharide induced acute liver injury in rats.

PubMed

S, Latha; Chaudhary, Sheetal; R S, Ray

2017-11-01

Oxidative stress and hepatic inflammatory response is primarily implicated in the pathogenesis of LPS induced acute liver injury. Stevioside, a diterpenoidal glycoside isolated from the Stevia rebaudiana leaves, exerts potent anti-oxidant, anti-inflammatory and immunomodulatory activities. The present study was aimed to investigate the hepatoprotective effect of hydroalcoholic extract of Stevia rebaudiana leaves (STE EXT) and its major phytochemical constituent, stevioside (STE) in LPS induced acute liver injury. The hepatoprotective activity of STE EXT (500mg/kg p.o) and STE (250mg/kg p.o) was investigated in lipopolysaccharide (LPS 5mg/kg i.p.) induced acute liver injury in male wistar rats. Our results revealed that both STE EXT and STE treatment ameliorated LPS induced hepatic oxidative stress, evident from altered levels of reduced SOD, Catalase, GSH, MDA, NO. Histopathological observations revealed that both STE EXT and STE attenuated LPS induced structural changes and hepatocellular apoptosis providing additional evidence for its hepatoprotective effect. Further, STE EXT and STE significantly restored the elevated serum and tissue levels of AST and ALT in LPS treated rats. Furthermore, both STE EXT and STE rescued hepatocellular dysfunctions to normal by altering the level of proinflammatory cytokines such as TNF-α, IL-1β and IL-6 exhibiting its anti-inflammatory potential. In conclusion, both STE EXT and STE demonstrated excellent hepatoprotective effects against endotoxemia induced acute liver injury possibly through suppression of hepatic inflammatory response and oxidative stress, attributing to its medicinal importance in treating various liver ailments. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

In vitro and in vivo antioxidative and hepatoprotective activity of aqueous extract of Cortex Dictamni

PubMed Central

Li, Lin; Zhou, Yun-Feng; Li, Yan-Lin; Wang, Li-Li; Arai, Hiderori; Xu, Yang

2017-01-01

AIM To investigate the antioxidant and hepatoprotective effects of Cortex Dictamni aqueous extract (CDAE) in carbon tetrachloride (CCl4)-induced liver damage in rats. METHODS The in vitro antioxidant effect of CDAE was investigated using α,α-diphenyl-β-picrylhydrazyl (DPPH), 2,2’-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), β-carotene bleaching, reducing power, and thiobarbituric acid reactive substance assays. A linoleic acid system, including ferric thiocyanate (FTC) and thiobarbituric acid (TBA) assays, was used to evaluate the inhibition of lipid peroxidation. The in vivo hepatoprotective and antioxidant effects of CDAE against CCl4-induced liver damage were evaluated in Sprague-Dawley rats. Silymarin was used as a positive control. Liver damage was assessed by determining hepatic histopathology and liver marker enzymes in serum. Enzyme and non-enzyme antioxidant levels and lipid peroxide content were measured in the liver. Cytochrome P450 2E1 (CYP2E1) protein expression was measured via immunohistochemical staining. Nuclear factor E2-related factor (Nrf2), heme oxygenase-1 (HO-1), NAD(P)H quinine oxidoreductase 1 (NQO1), and γ-glutamylcysteine synthetase catalytic subunit (γ-GCSc) protein expression was measured by Western blot. RESULTS Our results showed that CDAE exhibited a strong antioxidant activity in vitro. CDAE scavenged DPPH and ABTS radicals in a dose-dependent manner. CDAE inhibited lipid peroxidation with a lipid peroxide inhibition rate of 40.6% ± 5.2%. In the FTC and TBA assays, CDAE significantly inhibited lipid peroxidation (P < 0.01). In vivo histopathological studies indicated that CCl4-induced liver injury was alleviated following CDAE treatment in rats of both sexes. CDAE (160 and 320 mg/kg) significantly prevented CCl4-induced elevations of alkaline phosphatase, glutamate pyruvate transaminase, aspartate aminotransferase, and total bilirubin levels in rats of both sexes (P < 0.05, 0.01, or 0.001). Moreover, CDAE restored the decreased activities of hepatic antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase, as well as non-enzyme antioxidant glutathione, which were induced by CCl4 treatment. CDAE significantly suppressed the up-regulation of CYP2E1 and promoted Nrf2, HO-1, NQO1, and γ-GCSc protein expression. CONCLUSION CDAE exhibits good antioxidant performance in vitro, with marked radical-scavenging and anti-lipid peroxidation activities. CDAE is effective in preventing CCl4-induced hepatic damage in rats of both sexes. The hepatoprotective activity of CDAE may be attributable to its antioxidant activity, which may involve Keap1-Nrf2-mediated antioxidant regulation. PMID:28522909

Hepatoprotective effects of setarud against carbon tetrachloride-induced liver injury in rats.

PubMed

Khorshid, Hamid Reza Khorram; Azonov, Jahan A; Novitsky, Yury A; Farzamfar, Bardia; Shahhosseiny, Mohammad Hassan

2008-01-01

To assess the hepatoprotective activity of a new herbal drug "setarud" in experimental liver fibrosis, 48 male Wistar rats were divided into four groups: controls, carbon tetrachloride (CCl4) group, and two treatment groups that received CCl4 and setarud at doses of 0.02 or 0.04 g/Kg/day for 30 days. Body weight gain, biochemical liver tests, bile flow rate and composition, and changes in liver morphology in the four groups were studied. CCl4 administration led to morphological and biochemical evidence of liver injury as compared to untreated controls. Setarud administration led to significant protection against CCl4-induced changes in body weight gain, liver morphology, bile flow and concentration. It was also associated with significantly lower serum liver enzyme levels (p<0.01), higher serum albumin level, and reduced increase in narcotic-induced sleeping time. Thus, setarud showed protective activity against CCl4-induced hepatotoxicity in rats. Further studies of its efficacy in liver disease are warranted.

Supplementation of Citrus maxima Peel Powder Prevented Oxidative Stress, Fibrosis, and Hepatic Damage in Carbon Tetrachloride (CCl4) Treated Rats

PubMed Central

Chowdhury, Mohammed Riaz Hasan; Sagor, Md Abu Taher; Tabassum, Nabila; Potol, Md Abdullah

2015-01-01

Citrus maxima peel is rich in natural phenolic compounds and has a long use in the traditional medicine. HPLC-DAD analysis on Citrus maxima peel powder exhibited the presence of various phenolic compounds such as caffeic acid and (−)-epicatechin. To determine the plausible hepatoprotective activity of Citrus maxima peel powder, we used carbon tetrachloride (CCl4) treated rat model. Liver damage in rats was confirmed by measuring the AST, ALT, and ALP enzyme activities. In addition, lipid peroxidation products (MDA), nitric oxide, advanced protein oxidation products level (APOP), and catalase activities were also analyzed along with the histological profiling for the inflammatory cell infiltration, collagen, and iron deposition in liver. Dietary supplementation of Citrus maxima peel powder exhibited significant reduction of serum AST, ALT, and ALP activities in carbon tetrachloride treated rats. Moreover, Citrus maxima peel powder also showed a significant reduction of the oxidative stress markers (MDA, NO, and APOP level) and restored the catalase activity in CCl4 treated rats. Histological examination of the liver section revealed reduced inflammatory cells infiltration, collagen, and iron deposition in CCl4 treated rats. The results from this study demonstrated that Citrus maxima peel powder produced significant hepatoprotective action in CCl4 administered rats. PMID:26106435

Supplementation of Citrus maxima Peel Powder Prevented Oxidative Stress, Fibrosis, and Hepatic Damage in Carbon Tetrachloride (CCl4) Treated Rats.

PubMed

Chowdhury, Mohammed Riaz Hasan; Sagor, Md Abu Taher; Tabassum, Nabila; Potol, Md Abdullah; Hossain, Hemayet; Alam, Md Ashraful

2015-01-01

Citrus maxima peel is rich in natural phenolic compounds and has a long use in the traditional medicine. HPLC-DAD analysis on Citrus maxima peel powder exhibited the presence of various phenolic compounds such as caffeic acid and (-)-epicatechin. To determine the plausible hepatoprotective activity of Citrus maxima peel powder, we used carbon tetrachloride (CCl4) treated rat model. Liver damage in rats was confirmed by measuring the AST, ALT, and ALP enzyme activities. In addition, lipid peroxidation products (MDA), nitric oxide, advanced protein oxidation products level (APOP), and catalase activities were also analyzed along with the histological profiling for the inflammatory cell infiltration, collagen, and iron deposition in liver. Dietary supplementation of Citrus maxima peel powder exhibited significant reduction of serum AST, ALT, and ALP activities in carbon tetrachloride treated rats. Moreover, Citrus maxima peel powder also showed a significant reduction of the oxidative stress markers (MDA, NO, and APOP level) and restored the catalase activity in CCl4 treated rats. Histological examination of the liver section revealed reduced inflammatory cells infiltration, collagen, and iron deposition in CCl4 treated rats. The results from this study demonstrated that Citrus maxima peel powder produced significant hepatoprotective action in CCl4 administered rats.

Chemical composition and hepatoprotective effects of polyphenol-rich extract from Houttuynia cordata tea.

PubMed

Tian, Lingmin; Shi, Xiaolong; Yu, Linhong; Zhu, Jiao; Ma, Rui; Yang, Xingbin

2012-05-09

This study was designed to investigate the antioxidant activity, hepatoprotective effect, and phenolic composition of the ethyl acetate fraction (EAF) extracted from Houttuynia cordata tea. EAF was shown to exhibit strong ferric-reducing antioxidant power (FRAP) and scavenging activity against DPPH radical in vitro, and the antioxidant effects were further verified by suppressing CCl₄-induced oxidative stress in mouse liver at three tested doses of EAF (250, 500, and 1000 mg/kg bw). Pretreatment with EAF (1000 mg/kg bw) prior to CCl₄ administration significantly (p < 0.001) decreased the CCl₄-elevated levels of serum AST, ALT, alkaline phosphatase, total bilirubin, and hepatic MDA in mice and prevented the increases in GSH, SOD, and CAT caused by CCl₄. HPLC analysis revealed that three predominantly polyphenolic compounds present in EAF were quercitrin (111.7 μg/mg), quercetin (43.8 μg/mg), and hyperoside (29.1 μg/mg). These results combined with liver histopathology indicate that EAF possesses a significant protective effect against acute hepatotoxicity induced by CCl₄, which may be due to the strong antioxidant activity of phenolic components.

Silymarin for hepatitis C virus infection

PubMed Central

Polyak, Stephen J; Oberlies, Nicholas H; Pécheur, Eve-Isabelle; Dahari, Harel; Ferenci, Peter; Pawlotsky, Jean-Michel

2014-01-01

Silymarin, an extract of milk thistle seeds, and silymarin-derived compounds have been considered hepatoprotective since the plant was first described in ancient times. Hepatoprotection is defined as several non-mutually exclusive biological activities including antiviral, antioxidant, anti-inflammatory and immunomodulatory functions. Despite clear evidence for silymarin-induced hepatoprotection in cell culture and animal models, evidence for beneficial effects in humans has been equivocal. This review will summarize the current state of knowledge on silymarin in the context of hepatitis C virus infection. The information was collated from a recent workshop on silibinin in Germany. PMID:23011959

Metabolic profile and hepatoprotective activity of the anthocyanin-rich extract of Hibiscus sabdariffa calyces.

PubMed

Ezzat, Shahira M; Salama, Maha M; Seif El-Din, Sayed H; Saleh, Samira; El-Lakkany, Naglaa M; Hammam, Olfat A; Salem, Maha B; Botros, Sanaa S

2016-12-01

Hibiscus sabdariffa L. (Malvaceae) is a common traditional tea that has many biological activities. To evaluate the hepatoprotective effect and study the metabolic profile of the anthocyanin-rich extract of H. sabdariffa calyces (HSARE). The hepatoprotective activity of HSARE was assessed (100 mg/kg/d for 4 weeks) by examining the hepatic, inflammatory, oxidative stress markers and performing a histopathological examination in rats with thioacetamide (TAA)-induced hepatotoxicity. HSARE was analyzed using ultra-performance liquid chromatography-quadrupole-time-of-flight-photodiode array-mass spectrometry (UPLC-qTOF-PDA-MS). The UPLC-qTOF-PDA-MS analysis of HSARE enabled the identification of 25 compounds represented by delphinidin and its derivatives, cyanidin, kaempferol, quercetin, myricetin aglycones and glycosides, together with hibiscus lactone, hibiscus acid and caffeoylquinic acids. Compared to the TAA-intoxicated group, HSARE significantly reduced the serum levels of alanine aminotransferase, aspartate aminotransferase and hepatic malondialdehyde by 37.96, 42.74 and 45.31%, respectively. It also decreased hepatic inflammatory markers, including tumour necrosis factor alpha, interleukin-6 and interferon gamma (INF-γ), by 85.39, 14.96 and 70.87%, respectively. Moreover, it decreased the immunopositivity of nuclear factor kappa-B and CYP2E1 in liver tissue, with an increase in the effector apoptotic marker (caspase-3 positive cells), restoration of the altered hepatic architecture and increases in the activities of superoxide dismutase (SOD) and glutathione by 150.08 and 89.23%, respectively. HSARE revealed pronounced antioxidant and anti-inflammatory potential where SOD and INF-γ were significantly improved. HSARE possesses the added value of being more water-soluble and of natural origin with fewer side effects expected compared to silymarin.

Phytoextract of Indian mustard seeds acts by suppressing the generation of ROS against acetaminophen-induced hepatotoxicity in HepG2 cells.

PubMed

Parikh, Harita; Pandita, Nancy; Khanna, Aparna

2015-07-01

Indian mustard [Brassica juncea (L.) Czern. & Coss. (Brassicaceae)] is reported to possess diverse pharmacological properties. However, limited information is available concerning its hepatoprotective activity and mechanism of action. To study the protective mechanism of mustard seed extract against acetaminophen (APAP) toxicity in a hepatocellular carcinoma (HepG2) cell line. Hepatotoxicity models were established using APAP (2.5-22.5 mM) based on the cytotoxicity profile. An antioxidant-rich fraction from mustard seeds was extracted and evaluated for its hepatoprotective potential. The mechanism of action was elucidated using various in vitro antioxidant assays, the detection of intracellular generation of reactive oxygen species (ROS), and cell cycle analysis. The phytoconstituents isolated via HPLC-DAD were also evaluated for hepatoprotective activity. Hydromethanolic seed extract exhibited hepatoprotective activity in post- and pre-treatment models of 20 mM APAP toxicity and restored the elevated levels of liver indices to normal values (p < 0.05). Post-treatment suppressed the generation of ROS by 58.37% and pre-treatment effectively prevented the generation of ROS by 90.5%. The mechanism of ROS suppression was further supported by antioxidant activity (IC50) data from DPPH (103.37 ± 4.2 µg AAE/mg), FRAP (83.26 ± 1.1 µg AAE/mg), ORAC (1115 µM GAE/ml), ABTS (83.05 µg GAE/ml), and superoxide (345.22 ± 5.15 µg AAE/mg) scavenging assays and by the restoration of cell cycle alterations. HPLC-DAD analysis revealed the presence quercetin, vitamin E, and catechin, which exhibited hepatoprotective activity. A phytoextract of mustard seeds acts by suppressing the generation of ROS in response to APAP toxicity.

Hepatoprotective property of ethanolic and aqueous extracts of fluted pumpkin (Telfairia occidentalis) leaves against garlic-induced oxidative stress.

PubMed

Oboh, Ganiyu

2005-01-01

Fluted pumpkin (Telfairia occidentalis) leaf is a darkish-green leafy vegetable popularly used in soup and in herbal preparations for the management of many diseases in Nigeria. In this study, the hepatoprotective property of ethanolic and aqueous extracts of T. occidentalis leaf (earlier confirmed to have a high level of antioxidant activity) against garlic induced-oxidative stress in rat hepatocytes was investigated. Oxidative stress was induced in Wistar strain albino rats by overdosing them with raw garlic (4%) for 14 days, and this caused a significant increase (P < .05) in serum alkaline phosphatase (ALP), glutamate oxaloacetate transaminase (GOT), and glutamate pyruvate transaminase (GPT), while there was no significant change (P > .05) in serum bilirubin, albumin, globulin, and total proteins. However, intubation of some of the rats fed raw garlic with 5 mg or 10 mg/0.5 mL of T. occidentalis leaf extract (ethanolic or aqueous) caused a significant decrease (P < .05) in serum ALP, GOT, and GPT when compared with rats fed raw garlic without intubation with the T. occidentalis leaf extract. Moreover, 10 mg/0.5 mL of extract was more effective than 5 mg/0.5 mL of extract, while the aqueous extracts appeared to be more effective than the ethanolic extracts in protecting hepatocytes. It could be inferred that both aqueous and ethanolic extracts of T. occidentalis leaf have hepatoprotective properties, although the aqueous extract is more effective than the ethanolic extract, which could be attributed to the higher antioxidant activity of the aqueous extract than the ethanolic extracts of T. occidentalis leaves.

Corn peptides protect against thioacetamide-induced hepatic fibrosis in rats.

PubMed

Lv, Jie; Nie, Zhi-Kui; Zhang, Jiu-Liang; Liu, Feng-Yan; Wang, Zhen-Zhen; Ma, Zhi-Li; He, Hui

2013-10-01

Certain bioactive peptides are reported to be able to alleviate hepatic fibrosis. Our previous work has confirmed the hepatoprotective effect of corn peptides (CPs) that are prepared from a high protein by-product, corn gluten meal, on acute liver injury in an animal model. However, the antifibrotic activity of CPs remained to be elucidated. In this study, the hepatoprotective effect of CPs on thioacetamide (TAA)-induced liver fibrosis was tested. Results showed that CPs (100 mg/kg body weight) significantly decreased the levels of alanine transaminase/aspartate transaminase, laminin, type IV collagen, and type III collagen in serum and increased the serum albumin levels and total antioxidant capacity. Additionally, with CP treatment (100 mg/kg body weight), a significant decrease was observed in the levels of malondialdehyde, nitric oxide, hydroxyproline, transforming growth factor β1, and lactate dehydrogenase activity as well as the liver index, while the activity of superoxidedismutase was significantly increased in livers. The histological and morphological analysis showed that the hepatocyte structure in CP-treated rats was superior to that of TAA-injured rats, and inflammation and fibrosis were also ameliorated. Therefore, CPs can be used as an option for prevention and adjuvant therapy of liver fibrosis.

Oral bioavailability enhancement and hepatoprotective effects of thymoquinone by self-nanoemulsifying drug delivery system.

PubMed

Kalam, Mohd Abul; Raish, Mohammad; Ahmed, Ajaz; Alkharfy, Khalid M; Mohsin, Kazi; Alshamsan, Aws; Al-Jenoobi, Fahad I; Al-Mohizea, Abdullah M; Shakeel, Faiyaz

2017-07-01

Thymoquinone (TQ) is a poorly water soluble bioactive compound which shows poor oral bioavailability upon oral administration. Due to poor aqueous solubility and bioavailability of TQ, various self-nanoemulsifying drug delivery systems (SNEDDS) of TQ were developed and evaluated for enhancement of its hepatoprotective effects and oral bioavailability. Hepatoprotective and pharmacokinetic studies of TQ suspension and TQ-SNEDDS were carried out in rat models. Different SNEDDS formulations of TQ were developed and thermodynamically stable TQ-SNEDDS were characterized for physicochemical parameters and evaluated for drug release studies via dialysis membrane. Optimized SNEDDS formulation of TQ was selected for further evaluation of in vivo evaluation. In vivo hepatoprotective investigations showed significant hepatoprotective effects for optimized TQ-SNEDDS in comparison with TQ suspension. The oral administration of optimized SNEDDS showed significant improvement in in vivo absorption of TQ in comparison with TQ suspension. The relatively bioavailability of TQ was enhanced 3.87-fold by optimized SNEDDS in comparison with TQ suspension. The results of this research work indicated the potential of SNEDDS in enhancing relative bioavailability and therapeutic effects of natural bioactive compounds such as TQ. Copyright © 2017 Elsevier B.V. All rights reserved.

Pharmacological screening of Coriandrum sativum Linn. for hepatoprotective activity

PubMed Central

Pandey, A.; Bigoniya, P.; Raj, V.; Patel, K. K.

2011-01-01

Objective: Coriandrum sativum (Linn.), a glabrous, aromatic, herbaceous annual plant, is well known for its use in jaundice. Essential oil, flavonoids, fatty acids, and sterols have been isolated from different parts of C. sativum. The plant has a very effective antioxidant profile showing 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, lipoxygenase inhibition, phospholipid peroxidation inhibition, iron chelating activity, hydroxyl radical scavenging activity, superoxide dismutation, glutathione reduction and antilipid peroxidation due to its high total phenolic content with the presence of constituents like pyrogallol, caffeic acid, glycitin, etc. Materials and Methods: This study was aimed at investigating the hepatoprotective activity of C. sativum against carbon tetrachloride (CCl4), with estimation of serum serum glutamyl oxaloacetic acid transaminase (SGOT), serum glutamyl pyruvate transaminase (SGPT), alkaine phosphatase (ALP) and bilirubin, and with liver histopathology. Results: Ethanolic extract was found to be rich in alkaloids, phenolic compounds and flavonoids, and high performance liquid chromatography (HPLC) fingerprinting showed the presence of iso-quercetin and quercetin. C. sativum signifies hepatoprotection by reducing the liver weight, activities of SGOT, SGPT, and ALP, and direct bilirubin of CCl4 intoxicated animals. Administration of C. sativum extract at 300 mg/kg dose resulted in disappearance of fatty deposit, ballooning degeneration and necrosis, indicating antihepatotoxic activity. Conclusion: The results of this study have led to the conclusion that ethanolic extract of C. sativum possesses hepatoprotective activity which may be due to the antioxidant potential of phenolic compounds. PMID:21966166

Hepatoprotective effect of withanolide-rich fraction in acetaminophen-intoxicated rat: decisive role of TNF-α, IL-1β, COX-II and iNOS.

PubMed

Devkar, Santosh T; Kandhare, Amit D; Zanwar, Anand A; Jagtap, Suresh D; Katyare, Surendra S; Bodhankar, Subhash L; Hegde, Mahabaleshwar V

2016-11-01

Overdose of acetaminophen (APAP) is common in humans and is often associated with hepatic damage. Withania somnifera (L.) Dunal (Solanaceae) shows multiple pharmacological activities including antioxidant and anti-inflammatory potential. To evaluate the possible mechanism of hepatoprotective activity of withanolide-rich fraction (WRF) isolated from a methanolic extract of Withania somnifera roots. Hepatotoxicity was induced by oral administration of APAP (750 mg/kg, p.o.) for 14 d. The control group received the vehicle. APAP-treated animals were given either silymarin (25 mg/kg) or graded doses of WRF (50, 100 and 200mg/kg) 2 h prior to APAP administration. Animals were killed on 15th day and blood and liver tissue samples were collected for the further analysis. In WRF-treated group, there was significant and dose-dependent (p < 0.01 and p < 0.001) decrease in serum bilirubin, ALP, AST and ALT levels with significant and dose-dependent (p < 0.01 and p < 0.001) increase in hepatic SOD, GSH and total antioxidant capacity. The level of MDA and NO decreased significantly (p < 0.01) by WRF treatment. Up-regulated mRNA expression of TNF-α, IL-1β, COX-II and iNOS was significantly down-regulated (p < 0.001) by WRF. Histological alternations induced by APAP in liver were restored to near normality by WRF pretreatment. WRF may exert its hepatoprotective action by alleviating inflammatory and oxido-nitrosative stress via inhibition of TNF-α, IL-1β, COX-II and iNOS.

Hepatoprotective standardized EtOH-water extract from the seeds of Fraxinus rhynchophylla Hance.

PubMed

Guo, Sen; Guo, Tiantian; Cheng, Ni; Liu, Qingchao; Zhang, Yunting; Bai, Lu; Zhang, Li; Cao, Wei; Ho, Chi-Tang; Bai, Naisheng

2017-04-01

Fraxinus rhynchophylla Hance (Oleaceae), its stem barks are known as Cortex fraxini ( qín pí) listed in Chinese Pharmacopoeia. Phytochemical study has indicated that methanol extracts from Qinpi has protective effect on acute liver injury. The present study investigates the hepatoprotective activity of EtOH-water extract from the seeds of F. rhynchophylla Hance against carbon tetrachloride-induced liver injury in mice. The EtOH-water extract significantly alleviated liver damage as indicated by the decreased levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the malondialdehyde (MDA) content, and increased the levels of superoxide dismutase (SOD), glutathione (GSH) and glutathione peroxidase (GSH-Px), and reduced the pathological tissue injury induced by CCl 4 . Quantitative analysis of seven major constituents ( 1-7 ) in EtOH-water extract (EWE) was developed by high performance liquid chromatography-diode-array detector (HPLC-DAD). The current research indicates that the EWE from the seeds of F. rhynchophylla Hance decreased liver index, inhibited the increase of serum aminotransferase induced by CCl 4 , and decreased hepatic MDA content, SOD and GSH-Px activities. These results suggested that the pretreatment with EWE protected mice against CCl 4 -induced liver injuries. Based on the results, the EtOH-water extract from the seeds of F. rhynchophylla Hance is efficacious for prevention and treatment of CCl 4 -induced hepatic injury in mice. Secoiridoid and tyrosol glucosides might be the active ingredients responsible for the biological and pharmacological activities of hepatoprotection.

Liver metabolomics study reveals protective function of Phyllanthus urinaria against CCl4-induced liver injury.

PubMed

Guo, Qing; Zhang, Qian-Qian; Chen, Jia-Qing; Zhang, Wei; Qiu, Hong-Cong; Zhang, Zun-Jian; Liu, Bu-Ming; Xu, Feng-Guo

2017-07-01

Phyllanthus Urinaria L. (PUL) is a traditional Chinese medicine used to treat hepatic and renal disorders. However, the mechanism of its hepatoprotective action is not fully understood. In the present study, blood biochemical indexes and liver histopathological changes were used to estimate the extent of hepatic injury. GC/MS and LC/MS-based untargeted metabolomics were used in combination to characterize the potential biomarkers associated with the protective activity of PUL against CCl 4 -induced liver injury in rats. PUL treatment could reverse the increase in ALT, AST and ALP induced by CCl 4 and attenuate the pathological changes in rat liver. Significant changes in liver metabolic profiling were observed in PUL-treated group compared with liver injury model group. Seventeen biomarkers related to the hepatoprotective effects of PUL against CCl 4 -induced liver injury were screened out using nonparametric test and Pearson's correlation analysis (OPLS-DA). The results suggested that the potential hepatoprotective effects of PUL in attenuating CCl 4 -induced hepatotoxicity could be partially attributed to regulating L-carnitine, taurocholic acid, and amino acids metabolism, which may become promising targets for treatment of liver toxicity. In conclusion, this study provides new insights into the mechanism of the hepatoprotection of Phyllanthus Urinaria. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Maltol, a Food Flavoring Agent, Attenuates Acute Alcohol-Induced Oxidative Damage in Mice

PubMed Central

Han, Ye; Xu, Qi; Hu, Jiang-ning; Han, Xin-yue; Li, Wei; Zhao, Li-chun

2015-01-01

The purpose of this study was to evaluate the hepatoprotective effect of maltol, a food-flavoring agent, on alcohol-induced acute oxidative damage in mice. Maltol used in this study was isolated from red ginseng (Panax ginseng C.A Meyer) and analyzed by high performance liquid chromatography (HPLC) and mass spectrometry. For hepatoprotective activity in vivo, pretreatment with maltol (12.5, 25 and 50 mg/kg; 15 days) drastically prevented the elevated activities of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP) and triglyceride (TG) in serum and the levels of malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) in liver tissue (p < 0.05). Meanwhile, the levels of hepatic antioxidant, such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) were elevated by maltol pretreatment, compared to the alcohol group (p < 0.05). Histopathological examination revealed that maltol pretreatment significantly inhibited alcohol-induced hepatocyte apoptosis and fatty degeneration. Interestingly, pretreatment of maltol effectively relieved alcohol-induced oxidative damage in a dose-dependent manner. Maltol appeared to possess promising anti-oxidative and anti-inflammatory capacities. It was suggested that the hepatoprotective effect exhibited by maltol on alcohol-induced liver oxidative injury may be due to its potent antioxidant properties. PMID:25608939

Assessment of the hepatoprotective activity of the seeds of Hunteria umbellata (Hallier F.) on carbon tetrachloride (CCl4) induced liver damage in Wistar albino rats

NASA Astrophysics Data System (ADS)

Ogunlana, Olubanke Olujoke; Ogunlana, Oluseyi Ebenezer; Adelani, Isaacson Bababode; Adebayo, Angie Osariem Igbinoba; David, Opetoritse Laju; Adeleye, Oluwaseye Joseph; Udeogu, Stephanie Adaora; Adeyemi, Alaba Oladipupo; Akinyele, Julie Oluranti

2018-04-01

This study was designed to evaluate the hepatoprotective activity of the seeds of Hunteria umbellata (HU) on carbon tetrachloride (CCl4) induced rats. Rats of groups 1 (normal control), 3 and 5 were not treated with CCl4 while rats of groups 2 (negative control), 4 and 6 rats were treated with single dose of CCl4 (2 ml/kg) by intraperitoneal administration. Normal control group 1 rats were given distilled water, groups 3 and 4 rats were given 50 mg/kg of silymarin while groups 5 and 6 rats were given 500 mg/kg of HU. Treatment was administered orally for 28 days and sacrificed on the 29th day after an overnight fast. The weights of the rats were taken before and after the treatment. Blood samples were collected in heparinized tubes and biochemical analysis of liver functions and lipid profile tests were carried out on plasma. There was a significant change (p<0.05) in the levels of alanine aminotransferase, alkaline phosphatase, high density lipoprotein and triglycerides of the CCl4 induced group treated with HU compared to the CCl4 untreated group 2 animals. The results obtained showed that the ethanolic extract of HU has hepatoprotective property.

Antioxidant and Protective Effect of Ethyl Acetate Extract of Podophyllum Hexandrum Rhizome on Carbon Tetrachloride Induced Rat Liver Injury

PubMed Central

Ganie, Showkat Ahmad; Haq, Ehtishamul; Masood, Akbar; Hamid, Abid; Zargar, Mohmmad Afzal

2011-01-01

The antioxidant and hepatoprotective activities of ethyl acetate extract was carefully investigated by the methods of DPPH radical scavenging activity, Hydroxyl radical scavenging activity, Superoxide radical scavenging activity, Hydrogen peroxide radical scavenging activity and its Reducing power ability. All these in vitro antioxidant activities were concentration dependent which were compared with standard antioxidants such as BHT, α-tocopherol. The hepatoprotective potential of Podophyllum hexandrum extract was also evaluated in male Wistar rats against carbon tetrachloride (CCl4)-induced liver damage. Pre-treated rats were given ethyl acetate extract at 20, 30 and 50 mg/kg dose prior to CCl4 administration (1 ml/kg, 1:1 in olive oil). Rats pre-treated with Podophyllum hexandrum extract remarkably prevented the elevation of serum AST, ALT, LDH and liver lipid peroxides in CCl4-treated rats. Hepatic glutathione levels were significantly increased by the treatment with the extract in all the experimental groups. The extract at the tested doses also restored the levels of liver homogenate enzymes (glutathione peroxidase, glutathione reductase, superoxide dismutase and glutathione-S- transferase) significantly. This study suggests that ethyl acetate extract of P. hexandrum has a liver protective effect against CCl4-induced hepatotoxicity and possess in vitro antioxidant activities. PMID:21394192

Hepatoprotective activity of the neem-based constituent azadirachtin-A in carbon tetrachloride intoxicated Wistar rats.

PubMed

Baligar, N S; Aladakatti, R H; Ahmed, Mukhtar; Hiremath, M B

2014-04-01

The aim of this study was to investigate the hepatoprotective role of azadirachtin-A in carbon tetrachloride (CCl4) induced hepatotoxicity in rats. The group allotment for the animals used in the hepatoprotective study included a vehicle treatment group, CCl4 (1 mL · (kg body mass)(-1)) treatment group, silymarin (100 μg · (kg body mass)(-1) · day(-1)) + CCl4 treatment group, and groups treated with different doses of azadirachtin-A (100 or 200 μg · (kg body mass)(-1) · day(-1)) + CCl4. On the 9th day, blood was obtained for measuring the biochemical parameters, and liver tissue was obtained for pathological examination. The acute toxicity test with azadirachtin-A (500, 1000, or 2000 μg · (kg body mass)(-1)) indicated no mortality after 14 days of treatment; further, there was no change in behavior, food consumption, or organ mass. However with the higher dose, some hematological parameters showed changes. Hepatoprotective studies revealed that the CCl4 treatment group exhibited a decrease in total protein and albumin levels, whereas a significant increase in BUN, AST, ALT, and ALP levels were noticed compared with the vehicle-treated control, indicating that there was liver damage caused by CCl4. Histology and ultrastructure study confirmed that pretreatment with azadirachtin-A dose-dependently reduced hepatocellular necrosis and, therefore, protected the liver against toxicity caused by CCl4. The results from this study indicate that pretreatment with azadirachtin-A at the higher dose levels, moderately restores the rat liver to normal. This study confirms that azadirachtin-A possesses greater hepatoprotective action; however, the effective concentration needs to be determined.

Hepatoprotective effect of manganese chloride against CCl4-induced liver injury in rats.

PubMed

Eidi, Akram; Mortazavi, Pejman; Behzadi, Khodabakhsh; Rohani, Ali Haeri; Safi, Shahabeddin

2013-11-01

The aim of the present study is to evaluate the protective effect of manganese chloride against carbon tetrachloride (CCl4)-induced liver injury in rats. Manganese chloride (0.001, 0.01, 0.05 and 0.1 g/kg bw) was administered intragastrically for 28 consecutive days to male CCl4-treated rats. The hepatoprotective activity was assessed using various biochemical parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyltransferase (GGT) and superoxide dismutase (SOD). Histopathological changes in the liver of different groups were also studied. Administration of CCl4 increased the serum ALT, AST, ALP and GGT but decreased SOD levels in rats. Treatment with manganese chloride significantly attenuated these changes to nearly normal levels. The animals treated with manganese chloride have shown decreased necrotic zones and hepatocellular degeneration when compared to the liver exposed to CCl4 intoxication alone. Thus, the histopathological studies also supported the protective effect of manganese chloride. Therefore, the results of this study suggest that manganese chloride exerts hepatoprotection via promoting antioxidative properties against CCl4-induced oxidative liver damage.

Cuscuta arvensis Beyr "Dodder": In Vivo Hepatoprotective Effects Against Acetaminophen-Induced Hepatotoxicity in Rats.

PubMed

Koca-Caliskan, Ufuk; Yilmaz, Ismet; Taslidere, Asli; Yalcin, Funda N; Aka, Ceylan; Sekeroglu, Nazim

2018-05-02

Cuscuta arvensis Beyr. is a parasitic plant, and commonly known as "dodder" in Europe, in the United States, and "tu si zi shu" in China. It is one of the preferred spices used in sweet and savory dishes. Also, it is used as a folk medicine for the treatment particularly of liver problems, knee pains, and physiological hepatitis, which occur notably in newborns and their mothers in the southeastern part of Turkey. The purpose of this study was to investigate the hepatoprotective effects and antioxidant activities of aqueous and methanolic extracts of C. arvensis Beyr. on acetaminophen (APAP)-induced acute hepatotoxicity in rats. The results were supported by subsequent histopathological studies. The hepatoprotective activity of both the aqueous and methanolic extracts at an oral dose of 125 and 250 mg/kg was investigated by observing the reduction levels or the activity of alkaline phosphatase, alkaline transaminase, aspartate aminotransferase, blood urine nitrogen, and total bilirubin content. In vivo antioxidant activity was determined by analyzing the serum superoxide dismutase, malondialdehyde, glutathione, and catalase levels. Chromatographic methods were used to isolate biologically active compounds from the extract, and spectroscopic methods were used for structure elucidation. Both the methanolic and aqueous extracts exerted noticable hepatoprotective and antioxidant effects supporting the folkloric usage of dodder. One of the bioactive compounds was kaempferol-3-O-rhamnoside, isolated and identified from the methanolic extract.

Antioxidant activity of rosemary (Rosmarinus officinalis L.) essential oil and its hepatoprotective potential

PubMed Central

2014-01-01

Background Natural antioxidant products are increasingly being used to treat various pathological liver conditions considering the role of oxidative stress in their pathogenesis. Rosemary essential oil has already being used as a preservative in food industry due to its antioxidant and antimicrobial activities, but it was shown to possess additional health benefits. The aim of our study was to evaluate the protective effect of rosemary essential oil on carbon tetrachloride - induced liver injury in rats and to explore whether its mechanism of action is associated with modulation of hepatic oxidative status. Methods Chemical composition of isolated rosemary essential oil was determined by gas chromatography and mass spectrometry. Antioxidant activity was determined in vitro using DPPH assay. Activities of enzyme markers of hepatocellular damage in serum and antioxidant enzymes in the liver homogenates were measured using the kinetic spectrophotometric methods. Results In this research, we identified 29 chemical compounds of the studied rosemary essential oil, and the main constituents were 1,8-cineole (43.77%), camphor (12.53%), and α-pinene (11.51%). Investigated essential oil was found to exert hepatoprotective effects in the doses of 5 mg/kg and 10 mg/kg by diminishing AST and ALT activities up to 2-fold in serum of rats with carbon tetrachloride - induced acute liver damage. Rosemary essential oil prevented carbon tetrachloride - induced increase of lipid peroxidation in liver homogenates. Furthermore, pre-treatment with studied essential oil during 7 days significantly reversed the activities of antioxidant enzymes catalase, peroxidase, glutathione peroxidase and glutathione reductase in liver homogenates, especially in the dose of 10 mg/kg. Conclusions Our results demonstrate that rosemary essential oil, beside exhibiting free radical scavenging activity determined by DPPH assay, mediates its hepatoprotective effects also through activation of physiological defense mechanisms. PMID:25002023

Antioxidant activity of rosemary (Rosmarinus officinalis L.) essential oil and its hepatoprotective potential.

PubMed

Rašković, Aleksandar; Milanović, Isidora; Pavlović, Nebojša; Ćebović, Tatjana; Vukmirović, Saša; Mikov, Momir

2014-07-07

Natural antioxidant products are increasingly being used to treat various pathological liver conditions considering the role of oxidative stress in their pathogenesis. Rosemary essential oil has already being used as a preservative in food industry due to its antioxidant and antimicrobial activities, but it was shown to possess additional health benefits. The aim of our study was to evaluate the protective effect of rosemary essential oil on carbon tetrachloride - induced liver injury in rats and to explore whether its mechanism of action is associated with modulation of hepatic oxidative status. Chemical composition of isolated rosemary essential oil was determined by gas chromatography and mass spectrometry. Antioxidant activity was determined in vitro using DPPH assay. Activities of enzyme markers of hepatocellular damage in serum and antioxidant enzymes in the liver homogenates were measured using the kinetic spectrophotometric methods. In this research, we identified 29 chemical compounds of the studied rosemary essential oil, and the main constituents were 1,8-cineole (43.77%), camphor (12.53%), and α-pinene (11.51%). Investigated essential oil was found to exert hepatoprotective effects in the doses of 5 mg/kg and 10 mg/kg by diminishing AST and ALT activities up to 2-fold in serum of rats with carbon tetrachloride-induced acute liver damage. Rosemary essential oil prevented carbon tetrachloride-induced increase of lipid peroxidation in liver homogenates. Furthermore, pre-treatment with studied essential oil during 7 days significantly reversed the activities of antioxidant enzymes catalase, peroxidase, glutathione peroxidase and glutathione reductase in liver homogenates, especially in the dose of 10 mg/kg. Our results demonstrate that rosemary essential oil, beside exhibiting free radical scavenging activity determined by DPPH assay, mediates its hepatoprotective effects also through activation of physiological defense mechanisms.

Hypolipidemic and hepatoprotective seeds mixture diet rich in omega-3 and omega-6 fatty acids.

PubMed

Makni, Mohamed; Fetoui, Hamadi; Garoui, El Mouldi; Gargouri, Nabil K; Jaber, Hazem; Makni, Jamel; Boudawara, Tahia; Zeghal, Najiba

2010-01-01

In vitro physicochemical and antioxidant properties of mixture of Flax/Sesame (LS) and Flax/Peanut (LA) and in vivo hypolipidemic, antioxidant and hepatoprotective activities were carried out to ascertain the claim of its utilisation against diseases. The seeds mixture rich in unsaturated fatty acids were prepared with 5/1 ratio of omega-6/omega-3 fatty acids and were orally administered ad libitum to rats by standard diet for 30 days. High cholesterol fed diet rats (CD-chol) exhibited a significant increase in total plasma and liver lipid parameters and atherogenicity and a significant decrease in high-density lipoproteins (HDL) and HDL/TC ratio (HTR). Administration of (LS) or (LA) seeds mixture to hypercholesterolemic rats (MS-LSchol and MS-LAchol groups respectively) significantly ameliorated lipid parameters and showed an increase of PUFAs (ALA and LA) and MUFAs and a decrease of SFAs in plasma and liver of MS-LSchol and MS-LAchol groups. Furthermore, malondialdehyde levels decreased and the efficiency of antioxidant defense system was improved compared to CD-chol group. Liver histological sections showed lipid storage in hepatocytes of CD-chol group and an improvement was noted in both supplemented groups. Our results suggested that seeds mixtures of Flax/Sesame and Flax/Peanut have anti-atherogenic and hepatoprotective effects. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

UPLC/QTOF/MS profiling of two Psidium species and the in-vivo hepatoprotective activity of their nano-formulated liposomes.

PubMed

Saber, Fatema R; Abdelbary, Ghada A; Salama, Maha M; Saleh, Dalia O; Fathy, Magda M; Soliman, Fathy M

2018-03-01

Liver diseases are major health problem in Egypt influencing lifestyle and economy. The demand for nutraceutical hepatoprotective agents is crucial to ameliorate the side effects of synthetic drugs. The present study aims to evaluate antioxidant and hepatoprotective activities of extracts of Psidium guajava L. and Psidium cattleianum Sabine leaves and their nano-formulated liposomes against paracetamol-induced liver damage in rats. Secondary metabolites profile of P. guajava and P. cattleianum leaves was investigated using UPLC-PDA-ESI-qTOF-MSn. The nano-liposomes containing Psidium extracts were prepared using thin film hydration method. Biochemical analysis was based on monitoring serum levels of AST, ALT, ALP and total bilirubin. The liver homogenate was used for determination of GSH and MDA. Histopathological alterations were also studied. Metabolic profiling revealed qualitative differences between the two investigated species providing a comprehensive map for the metabolites present in P. guajava and P. cattleianum leaves cultivated in Egypt. The identified metabolites belong to different phytochemical classes; polyphenolics, flavonoids, triterpenes and meroterpenoids. Significant hepatoprotective effects were observed as evident from the decreased levels of AST, ALT, ALP, MDA and total bilirubin as well as restoration of decreased GSH level in the two studied Psidium extracts (250, 500mg/kg b. wt) and their respective nano-liposomes (500mg/kg b. wt), when compared to the diseased group. Nano-liposomes of Psidium guajava leaves (500mg/kg b. wt) greatly restored the normal architecture of the liver in the histopathological study, as regards to standard silymarin. The present study verified the effectiveness of Psidium guajava and Psidium cattleianum leaves extracts and their nano-liposomes in ameliorating the paracetamol-induced hepatotoxicity in rats. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hepatoprotective activity of Sonchus asper against carbon tetrachloride-induced injuries in male rats: a randomized controlled trial

PubMed Central

2012-01-01

Abstract Background Sonchus asper (SAME) is used as a folk medicine in hepatic disorders. In this study, the hepatoprotective effects of the methanol extract of SAME was evaluated against carbon tetrachloride (CCl4)-induced liver injuries in rats. Methods To evaluate the hepatoprotective effects of SAME, 36 male Sprague–Dawley rats were equally divided into 6 groups. Rats of Group I (control) were given free access to approved feed and water. Rats of Group II were injected intraperitoneally with CCl4 (3 ml/kg) as a 30% solution in olive oil (v/v) twice a week for 4 weeks. Animals of Groups III (100 mg/kg) and IV (200 mg/kg) received SAME, whereas those of Group V were given silymarin via gavage (100 mg/kg) after 48 h of CCl4 treatment. Group VI received SAME (200 mg/kg) twice a week for 4 weeks without CCl4 treatment. Various parameters, such as the serum enzyme levels, serum biochemical marker levels, antioxidant enzyme activities, and liver histopathology were used to estimate the hepatoprotective efficacy of SAME. Results The administration of SAME and silymarin significantly lowered the CCl4-induced serum levels of hepatic marker enzymes (aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase), cholesterol, low-density lipoprotein, and triglycerides while elevating high-density lipoprotein levels. The hepatic contents of glutathione and activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione S-transferase, and glutathione reductase were reduced. The levels of thiobarbituric acid-reactive substances that were increased by CCl4 were brought back to control levels by the administration of SAME and silymarin. Liver histopathology showed that SAME reduced the incidence of hepatic lesions induced by CCl4 in rats. Conclusion SAME may protect the liver against CCl4-induced oxidative damage in rats. PMID:22776436

Antioxidant Activity and Hepatoprotective Potential of Quercetin 7-Rhamnoside In Vitro and In Vivo.

PubMed

Huang, Zhi-Qiang; Chen, Pan; Su, Wei-Wei; Wang, Yong-Gang; Wu, Hao; Peng, Wei; Li, Pei-Bo

2018-05-16

Hypericum japonicum is traditionally used as a folk medicine to treat cholestasis and hepatitis. Quercetin 7-rhamnoside (Q7R) is one of the main flavonoid components of Hypericum japonicum and has been rarely studied. The aim of the present study was to evaluate the antioxidant activity and hepatoprotective potential of Q7R. In the in vitro experiments, DPPH, ABTS and ferric reducing antioxidant power (FRAP) assays were first performed to assess the antioxidant properties of Q7R, and then a H₂O₂-induced oxidative damage cellular model was used to determine the cytoprotective and antioxidant properties of Q7R in human liver L-02 cells. In the in vivo experiment, the hepatoprotective activity of Q7R was evaluated by carbon tetrachloride (CCl₄)-induced liver damage model in mice. The results of the three in vitro assays (DPPH, ABTS and FRAP) demonstrated that Q7R significantly exhibited antioxidant activity. The cell experiment results showed that Q7R possessed cytoprotective and antioxidant effects on H₂O₂-treated L-02 cells. In the in vivo experiments, Q7R suppressed the up-regulation of serum activities of ALT, AST, LDH and triglyceride (TG) levels with dose-dependency. Q7R down-regulated the production of MDA and increased the hepatic GSH content and antioxidant enzymes CAT activities. Hepatic morphological analysis was also performed to confirm the biochemical changes. In summary, these results suggested that Q7R could be considered as a potential source of natural antioxidants, and may become a promising candidate for the treatment of liver injury in the future.

Hepatoprotective effects of kombucha tea: identification of functional strains and quantification of functional components.

PubMed

Wang, Yong; Ji, Baoping; Wu, Wei; Wang, Ruojun; Yang, Zhiwei; Zhang, Di; Tian, Wenli

2014-01-30

Kombucha tea (KT), a traditional health beverage containing potential hepatoprotective agents, is fermented from sugared tea by a symbiotic culture of yeast and bacteria for 8 days. However, the functional strains that produce components for the hepatoprotective property of KT remain unclear. Multiple strains are involved in traditional KT production. Therefore, KT has not been standardized or produced commercially. This study aimed to identify the functional strains and quantify the functional components with hepatoprotective effects in kombucha tea. Gluconacetobacter sp. A4 was one of the microorganisms in KT in which the D-saccharic acid-1,4-lactone (DSL) produced by G. sp. A4 was significantly higher than that produced by original tea fungus at 8 days of fermentation. Traditional KT (TKT, tea broth fermented by mixed tea fungus), modified KT (MKT, fermented by single G. sp. A4), and DSL significantly inhibited the acetaminophen-induced increase of alanine aminotransferase, alkaline phosphatase, triglyceride and malondialdehyde, as well as facilitating the reduction of total antioxidant capacity in mice. Furthermore, MKT and TKT are both similar to DSL in terms of protection against acetaminophen-induced liver injury in mice. These results suggested a positive relationship between DSL content and the hepatoprotective effect of TKT, MKT and DSL groups. G. sp. A4 was concluded to be a potential functional strain and DSL might be the key functional component for the hepatoprotective property in KT. The stronger capability of G. sp. A4 in producing DSL makes it a better choice for the commercial production of KT. © 2013 Society of Chemical Industry.

Protective effect of Anoectochilus roxburghii polysaccharide against CCl4-induced oxidative liver damage in mice.

PubMed

Yang, Zhenguo; Zhang, Xiaohui; Yang, Lawei; Pan, Qunwen; Li, Juan; Wu, Yongfu; Chen, Meizhen; Cui, Shichao; Yu, Jie

2017-03-01

This study investigated the isolation and characterization of Anoectochilus roxburghii polysaccharides (ARP), and further evaluated whether ARP possessed hepatoprotective activities against CCl 4 -induced oxidative liver damage in mice. ARP is comprised of glucose and galactose in a 1.9:1 molar ratio, and the molecular weight is 19.5kDa. ARP displayed significant scavenging effects against hydroxyl radical, superoxide anion radical, DPPH radical and a strong reducing power. In vivo experiment demonstrated ARP (150mg/kg) administrated to mice for 7days prior to carbon tetrachloride treatment, attenuated the elevated expression levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG) in serum and inhibited the formation of hepatic malondialdehyde (MDA). ARP pretreatment also increased antioxidant enzyme activities such as glutathione (GSH), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC) in the liver of CCl 4 -induced mice. Furthermore, hepatic histopathological changes induced by CCl 4 were significantly normalized by ARP pretreatment. These findings demonstrated that ARP possessed hepatoprotective effect against acute CCl 4 -induced liver damage by reducing lipid oxidation. Copyright © 2016 Elsevier B.V. All rights reserved.

Antioxidant and hepatoprotective effect of Garcinia indica fruit rind in ethanol-induced hepatic damage in rodents

PubMed Central

Ashar, Hardik; Srinath, Sudhamani

2012-01-01

The protective effects of aqueous extracts of the fruit rind of Garcinia indica (GIE) on ethanol-induced hepatotoxicity and the probable mechanisms involved in this protection were investigated in rats. Liver damage was induced in rats by administering ethanol (5 g/kg, 20% w/v p.o.) once daily for 21 days. GIE at 400 mg/kg and 800 mg/kg and the reference drug silymarin (200 mg/kg) were administered orally for 28 days to ethanol treated rats, this treatment beginning 7 days prior to the commencement of ethanol administration. Levels of marker enzymes (aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP)), triglyceride (sTG), albumin (Alb) and total protein (TP) were evaluated in serum. Antioxidant parameters (reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR)), hepatic triglycerides (hTG) and the lipid peroxidation marker malondialdehyde (MDA) were determined in liver. GIE and silymarin elicited significant hepatoprotective activity by attenuating the ethanol–elevated levels of AST, ALT, ALP, sTG, hTG and MDA and restored the ethanol-depleted levels of GSH, SOD, CAT, GPx, GR, Alb and TP. GIE 800 mg/kg demonstrated greater hepatoprotection than GIE 400 mg/kg. The present findings indicate that hepatoprotective effects of GIE in ethanol-induced oxidative damage may be due to an augmentation of the endogenous antioxidants and inhibition of lipid peroxidation in liver. PMID:23554565

Baicalin Attenuates IL-17-Mediated Acetaminophen-Induced Liver Injury in a Mouse Model

PubMed Central

Liao, Chia-Chih; Day, Yuan-Ji; Lee, Hung-Chen; Liou, Jiin-Tarng; Chou, An-Hsun; Liu, Fu-Chao

2016-01-01

Background IL-17 has been shown to be involved in liver inflammatory disorders in both mice and humans. Baicalin (BA), a major compound extracted from traditional herb medicine (Scutellariae radix), has potent hepatoprotective properties. Previous study showed that BA inhibits IL-17-mediated lymphocyte adhesion and downregulates joint inflammation. The aim of this study is to investigate the role of IL-17 in the hepatoprotective effects of BA in an acetaminophen (APAP)-induced liver injury mouse model. Methods Eight weeks male C57BL/6 (B6) mice were used for this study. Mice received intraperitoneal hepatotoxic injection of APAP (300 mg/kg) and after 30 min of injection, the mice were treated with BA at a concentration of 30 mg/kg. After 16 h of treatment, mice were killed. Blood samples and liver tissues were harvested for analysis of liver injury parameters. Results APAP overdose significantly increased the serum alanine transferase (ALT) levels, hepatic activities of myeloperoxidase (MPO), expression of cytokines (TNF-α, IL-6, and IL-17), and malondialdehyde (MDA) activity when compared with the control animals. BA treatment after APAP administration significantly attenuated the elevation of these parameters in APAP-induced liver injury mice. Furthermore, BA treatment could also decrease hepatic IL-17-producing γδT cells recruitment, which was induced after APAP overdose. Conclusion Our data suggested that baicalin treatment could effectively decrease APAP-induced liver injury in part through attenuation of hepatic IL-17 expression. These results indicate that baicalin is a potential hepatoprotective agent. PMID:27855209

A Chinese herbal medicine, jia-wei-xiao-yao-san, prevents dimethylnitrosamine-induced hepatic fibrosis in rats.

PubMed

Chien, Shu-Chen; Chang, Wei-Chiao; Lin, Pu-Hua; Chang, Wei-Pin; Hsu, Shih-Chung; Chang, Jung-Chen; Wu, Ya-Chieh; Pei, Jin-Kuo; Lin, Chia-Hsien

2014-01-01

Jia-wei-xiao-yao-san (JWXYS) is a traditional Chinese herbal medicine that is widely used to treat neuropsychological disorders. Only a few of the hepatoprotective effects of JWXYS have been studied. The aim of this study was to investigate the hepatoprotective effects of JWXYS on dimethylnitrosamine- (DMN-) induced chronic hepatitis and hepatic fibrosis in rats and to clarify the mechanism through which JWXYS exerts these effects. After the rats were treated with DMN for 3 weeks, serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) levels were significantly elevated, whereas the albumin level decreased. Although DMN was continually administered, after the 3 doses of JWXYS were orally administered, the SGOT and SGPT levels significantly decreased and the albumin level was significantly elevated. In addition, JWXYS treatment prevented liver fibrosis induced by DMN. JWXYS exhibited superoxide-dismutase-like activity and dose-dependently inhibited DMN-induced lipid peroxidation and xanthine oxidase activity in the liver of rats. Our findings suggest that JWXYS exerts antifibrotic effects against DMN-induced chronic hepatic injury. The possible mechanism is at least partially attributable to the ability of JWXYS to inhibit reactive-oxygen-species-induced membrane lipid peroxidation.

The protective effect of total phenolics from Oenanthe Javanica on acute liver failure induced by D-galactosamine.

PubMed

Ai, Guo; Huang, Zheng-Ming; Liu, Qing-Chuan; Han, Yan-Quan; Chen, Xi

2016-06-20

Water dropwort [Oenanthe javanica (O. javanica)] is an aquatic perennial herb cultivated in East Asian countries. It has been popularly used in traditional Chinese medicine which is beneficial for the treatment of many diseases, including jaundice and various types of chronic and acute hepatitis. In the present study, we investigated the hepatoprotective effect of total phenolics from O. javanica (TPOJ) against D-galactosamine (D-GalN) induced liver injury in mice. The hepatoprotective activity of TPOJ (125, 250 and 500mg/kg) was investigated on D-GalN (800mg/kg)-induced liver damages in mice. Blood and liver were collected for biochemical and microscopic analysis. RT-PCR was used to determine the changes in hepatic nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. Protein levels of iNOS, COX-2, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were determined by western blotting. In the animal studies, TPOJ could improve the survival of acute liver failure model significantly and prevente the D-GalN-induced elevation of the serum enzymatic markers and nonenzymatic markers levels significantly. Meanwhile, TPOJ-treatment decreased the malondialdehyde (MDA) level and elevated the content of glutathione (GSH) in the liver as compared to those in the D-GalN group. Hepatic activities and protein expressions of antioxidative enzymes, including SOD, GPx, and CAT were enhanced dose dependently with TPOJ. At the same time, application of TPOJ effectively suppressed the D-GalN-induced proinflammatory mRNA and protein expression of iNOS and COX-2. Subsequently, the serum levels of proinflammatory mediators, nitric oxide (NO) and prostaglandin E2 (PGE2) were reduced. Additionally, histological analyses also showed that TPOJ reduced the extent of liver lesions induced by D-GalN. Our investigation demonstrated the hepatoprotective activity of TPOJ and revealed that TPOJ attributed its significance in the traditional use for treating liver diseases. Copyright © 2016. Published by Elsevier Ireland Ltd.

The comparison of antioxidative and hepatoprotective activities of Codonopsis pilosula polysaccharide (CP) and sulfated CP.

PubMed

Liu, Cui; Chen, Jin; Li, Entao; Fan, Qiang; Wang, Deyun; Li, Peng; Li, Xiuping; Chen, Xingying; Qiu, Shulei; Gao, Zhenzhen; Li, Hongquan; Hu, Yuanliang

2015-02-01

Codonopsis pilosula polysaccharide (CP) was extracted, purified and modified by chlorosulfonic acid-pyridine method to obtain a sulfated CP (sCP). Their antioxidative activities in vitro were compared through the free radical-scavenging test. The results demonstrated that the scavenging capabilities of sCP were significantly stronger than those of CP. In vivo test, the mice hepatic injury model was prepared by BCG/LPS method, then administrated respectively with sCP and CP at three dosages, the biochemical indexes in serum, antioxidative indexes in liver homogenate and histopathological change in liver of the mice were compared. The results showed that in high (200mg/kg) and middle (150mg/kg) dosages of sCP groups, the contents of ALT, AST and TNF-α in serum and MDA in liver homogenate were significantly lower than those in the model group and numerically lower than those in the CP groups, the activities of SOD and GSH-Px in liver homogenate were significantly higher than those in the model group and numerically higher than those in the CP groups. In the model group there were obvious pathological changes in the liver, while in the sCP groups were near normal. These results indicate that sCP and CP possess antioxidative activity in vitro and in vivo, the activity of sCP is stronger than that of CP and sulfation modification can enhance the antioxidative and hepatoprotective activities of Codonopsis pilosula polysaccharide. Copyright © 2014 Elsevier B.V. All rights reserved.

Nanoparticles formulation of Cuscuta chinensis prevents acetaminophen-induced hepatotoxicity in rats.

PubMed

Yen, Feng-Lin; Wu, Tzu-Hui; Lin, Liang-Tzung; Cham, Thau-Ming; Lin, Chun-Ching

2008-05-01

Cuscuta chinensis is a commonly used traditional Chinese medicine to nourish the liver and kidney. Due to the poor water solubility of its major constituents such as flavonoids and lignans, its absorption upon oral administration could be limited. The purpose of the present study was to use the nanosuspension method to prepare C. chinensis nanoparticles (CN), and to compare the hepatoprotective and antioxidant effects of C. chinensis ethanolic extract (CE) and CN on acetaminophen-induced hepatotoxicity in rats. An oral dose of CE at 125 and 250 mg/kg and CN at 25 and 50mg/kg showed a significant hepatoprotective effect relatively to the same extent (P<0.05) by reducing levels of aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase. These biochemical assessments were supported by rat hepatic biopsy examinations. In addition, the antioxidant activities of CE and CN both significantly increased superoxide dismutase, catalase, glutathione peroxidase, and reduced malondialdehyde (P<0.05). Moreover, the results also indicated that the hepatoprotective and antioxidant effects of 50 mg/kg CN was effectively better than 125 mg/kg CE (P<0.05), and an oral dose of CN that is five times as less as CE could exhibit similar levels of outcomes. In conclusion, we suggest that the nanoparticles system can be applied to overcome other water poorly soluble herbal medicines and furthermore to decrease the treatment dosage.

Hepatoprotective and in vivo antioxidant activities of the hydroethanolic leaf extract of Mucuna pruriens (Fabaceae) in antitubercular drugs and alcohol models.

PubMed

Obogwu, Mercy B; Akindele, Abidemi J; Adeyemi, Olufunmilayo O

2014-04-01

Hepatotoxicity is a significantly increasing health problem worldwide, and the extent of the problem has stimulated interest in the search for hepatotherapeutic agents from plants. This study investigated the hepatoprotective and in vivo antioxidant activities of the hydroethanolic extract of Mucuna pruriens leaves in antitubercular and alcohol-induced hepatotoxicity assays in rats. In each of the models used, seven groups were allotted. The different groups received normal saline (10 mL·kg(-1), p.o.); hepatotoxicant (isoniazid-rifampicin, INH-RIF, 100 mg·kg(-1), i.p. or 20% ethanol 5 g·kg(-1), p.o.) and normal saline (10 mL·kg(-1), p.o.); hepatotoxicant and extract at doses of 100, 200, and 400 mg·kg(-1) p.o.; hepatotoxicant and silymarin 50 mg·kg(-1) p.o.; and extract at 400 mg·kg(-1) p.o. On the 21(st) day of treatment, blood was collected for assessment of serum biochemical parameters and harvested liver samples were assessed for antioxidants. The hepatotoxicants significantly (P < 0.05-0.001) increased the levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), bilirubin, and malondialdehyde (MDA); and reduced the levels of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and reduced glutathione GSH compared to control. M. pruriens significantly reversed (P < 0.05-0.001) the elevation in the level of ALT, AST, ALP, and bilirubin caused by the hepatotoxicants. The extract (200 and 400 mg·kg(-1)) significantly reversed (P < 0.05) the diminution in the level of in vivo antioxidants and increased the level of MDA produced by INH-RIF. M. pruriens (100-400 mg·kg(-1)) elicited significant reduction (P < 0.001) in the level of MDA compared to the alcohol group. Silymarin also reversed the deleterious effects of the hepatotoxicants. The hydroethanolic extract of Mucuna pruriens leaves possesses hepatoprotective activity with enhancement of in vivo antioxidants as a possible mechanism of action. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Virgin coconut oil supplementation attenuates acute chemotherapy hepatotoxicity induced by anticancer drug methotrexate via inhibition of oxidative stress in rats.

PubMed

Famurewa, Ademola C; Ufebe, Odomero G; Egedigwe, Chima A; Nwankwo, Onyebuchi E; Obaje, Godwin S

2017-03-01

The emerging health benefit of virgin coconut oil (VCO) has been associated with its potent natural antioxidants; however, the antioxidant and hepatoprotective effect of VCO against methotrexate-induced liver damage and oxidative stress remains unexplored. The study explored the antioxidant and hepatoprotective effects of VCO against oxidative stress and liver damage induced by anticancer drug methotrexate (MTX) in rats. Liver damage was induced in Wistar rats pretreated with dietary supplementation of VCO (5% and 15%) by intraperitoneal administration of MTX (20mg/kg bw) on day 10 only. After 12days of treatment, assays for serum liver biomarkers (aminotransferases), alkaline phosphatase, albumin and total protein as well as hepatic content of malondialdehyde, reduced glutathione and antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) were carried out. Liver was used to examine histopathological changes. MTX administration induced significant increase in serum liver enzymes along with marked decrease in albumin and total protein compared to control group. Hepatic activities of antioxidant enzymes were significantly decreased, while malondialdehyde increased significantly. Treatment with VCO supplemented diet prior to MTX administration attenuated MTX-induced liver injury and oxidative stress evidenced by significant improvements in serum liver markers, hepatic antioxidant enzymes and malondialdehyde comparable to control group. Histopathological alterations were prevented and correlated well with the biochemical indices. The study suggests antioxidant and hepatoprotective effects of VCO supplementation against hepatotoxicity and oxidative damage via improving antioxidant defense system in rats. Our findings may have beneficial application in the management of hepatotoxicity associated with MTX cancer chemotherapy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Zingiber officinale Roscoe prevents acetaminophen-induced acute hepatotoxicity by enhancing hepatic antioxidant status.

PubMed

Ajith, T A; Hema, U; Aswathy, M S

2007-11-01

A large number of xenobiotics are reported to be potentially hepatotoxic. Free radicals generated from the xenobiotic metabolism can induce lesions of the liver and react with the basic cellular constituents - proteins, lipids, RNA and DNA. Hepatoprotective activity of aqueous ethanol extract of Zingiber officinale was evaluated against single dose of acetaminophen-induced (3g/kg, p.o.) acute hepatotoxicity in rat. Aqueous extract of Z. officinale significantly protected the hepatotoxicity as evident from the activities of serum transaminase and alkaline phosphatase (ALP). Serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT) and ALP activities were significantly (p<0.01) elevated in the acetaminophen alone treated animals. Antioxidant status in liver such as activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase and glutathione-S-transferase (GST), a phase II enzyme, and levels of reduced glutathione (GSH) were declined significantly (p<0.01) in the acetaminophen alone treated animals (control group). Hepatic lipid peroxidation was enhanced significantly (p<0.01) in the control group. Administration of single dose of aqueous extract of Z. officinale (200 and 400mg/kg, p.o.) prior to acetaminophen significantly declines the activities of serum transaminases and ALP. Further the hepatic antioxidant status was enhanced in the Z. officinale plus acetaminophen treated group than the control group. The results of the present study concluded that the hepatoprotective effect of aqueous ethanol extract of Z. officinale against acetaminophen-induced acute toxicity is mediated either by preventing the decline of hepatic antioxidant status or due to its direct radical scavenging capacity.

Hepatoprotective amide constituents from the fruit of Piper chaba: Structural requirements, mode of action, and new amides.

PubMed

Matsuda, Hisashi; Ninomiya, Kiyofumi; Morikawa, Toshio; Yasuda, Daisuke; Yamaguchi, Itadaki; Yoshikawa, Masayuki

2009-10-15

The 80% aqueous acetone extract from the fruit of Piper chaba (Piperaceae) was found to have hepatoprotective effects on D-galactosamine (D-GalN)/lipopolysaccharide-induced liver injury in mice. From the ethyl acetate-soluble fraction, three new amides, piperchabamides E, G, and H, 33 amides, and four aromatic constituents were isolated. Among the isolates, several amide constituents inhibited D-GalN/tumor necrosis factor-alpha (TNF-alpha)-induced death of hepatocytes, and the following structural requirements were suggested: (i) the amide moiety is essential for potent activity; and (ii) the 1,9-decadiene structure between the benzene ring and the amide moiety tended to enhance the activity. Moreover, a principal constituent, piperine, exhibited strong in vivo hepatoprotective effects at doses of 5 and 10 mg/kg, po and its mode of action was suggested to depend on the reduced sensitivity of hepatocytes to TNF-alpha.

New aspects on the hepatoprotective potential associated with the antioxidant, hypocholesterolemic and anti-inflammatory activities of Vernonia condensata Baker.

PubMed

Silva, Jucélia Barbosa da; Mendes, Renata de Freitas; Tomasco, Vívian; Pinto, Nícolas de Castro Campos; de Oliveira, Luiz Gustavo; Rodrigues, Matheus Nehrer; Aragão, Danielle Maria de Oliveira; Aguiar, Jair Adriano Kopke de; Alves, Maria Silvana; Castañon, Maria Christina Nogueira Marques; Ribeiro, Antônia; Scio, Elita

2017-02-23

Vernonia condensata Baker (Asteraceae) is traditionally used in South American Countries as an anti-inflammatory, analgesic and hepatoprotective. This study aimed to investigate the in vivo hepatoprotective and antioxidant, and the in vitro anti-inflammatory activities of the ethyl acetate partition (EAP) from the ethanolic extract of this medicinal plant leaves. For the in vivo hepatoprotective activity, rats were pretreated orally for seven days with vehicle, silymarin 100mg/kg or EAP 50, 100 and 200mg/kg. Then, acetaminophen 3g/kg was also orally administrated. Animals were euthanatized 24h after the damage inducement. The levels of the serum enzymes ALT, AST and ALP were determined, as well as the triglycerides, total cholesterol and fractions. The antioxidant activity was evaluated by TBARS assay and by the measurement of glutathione reductase, superoxide dismutase and catalase activities in the rats liver tissue. The in vitro anti-inflammatory assay using Raw 264.7 cell line induced by lipopolysaccharide was conducted to verify EAP ability to inhibit pro-inflammatory cytokines. EAP was able to inhibit all the acute biochemical alterations caused by acetaminophen overdose. EAP inhibited malondialdehyde formation, maintained the catalase and increased the glutathione reductase activities. Also, EAP decreased NO, IL-6 and TNF-α levels at concentrations from 10 to 20µg/mL. 1,5-dicaffeoylquinic acid was isolated and identified as the major compound in EAP. Apigenin, luteolin, chlorogenic acid were also identified. EAP anti-inflammatory action may be due to its antioxidant activity or its capacity to inhibit the pro-inflammatory cytokines. These results strongly suggested that V. condensata may be useful as a possible therapy against liver damage. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Hepatoprotective potential of ethanolic extract of Ziziphus oenoplia (L.) Mill roots against antitubercular drugs induced hepatotoxicity in experimental models.

PubMed

Rao, Ch V; Rawat, A K S; Singh, Anil P; Singh, Arpita; Verma, Neeraj

2012-04-01

To evaluate the hepatoprotective potential of ethanolic (50%) extract of Ziziphus oenoplia (L.) Mill (Z. oenoplia) root against isoniazid (INH) and rifampicin (RIF) induced liver damage in animal models. Five groups of six rats each were selected for the study. Ethanolic extract at a dose of 150 and 300 mg/kg as well as silymarin (100 mg/kg) were administered orally once daily for 21 d in INH + RIF treated groups. The serum levels of glutamic oxaloacetic transaminase (SGOT), glutamate pyruvate transaminase (SGPT), alkaline phosphatase (SALP), and bilirubin were estimated along with activities of superoxide dismutase, catalase, glutathione S-transferase, glutathione peroxidase, and hepatic melondialdehyde formation. Histopathological analysis was carried out to assess injury to the liver. The considerably elevated serum enzymatic activities of glutamic oxaloacetic transaminase, glutamate pyruvate transaminase, alkaline phosphatase and bilirubin due to INH + RIF treatment were restored towards normal in a dose dependent manner after the treatment with ethanolic extract of Z. oenoplia roots. Meanwhile, the decreased activities of superoxide dismutase, catalase, glutathione S-transferase and glutathione peroxidase were also restored towards normal dose dependently. In addition, ethanolic extract also significantly prevented the elevation of hepatic melondialdehyde formation in the liver of INH + RIF intoxicated rats in a dose dependent manner. The biochemical observations were supplemented with histopathological examination of rat liver sections. The results of this study strongly indicate that ethanolic extract of Z. oenoplia has a potent hepatoprotective action against INH + RIF induced hepatic damage in rats. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Identification of a hepatoprotective peptide in wheat gluten hydrolysate against D-galactosamine-induced acute hepatitis in rats.

PubMed

Sato, Kenji; Egashira, Yukari; Ono, Shin; Mochizuki, Satoshi; Shimmura, Yuki; Suzuki, Yoshio; Nagata, Megumi; Hashimoto, Kaori; Kiyono, Tamami; Park, Eun Young; Nakamura, Yasushi; Itabashi, Mariko; Sakata, Yuka; Furuta, Seigo; Sanada, Hiroo

2013-07-03

A hepatoprotective peptide, pyroglutamyl leucine (pyroGlu-Leu), was identified in wheat gluten hydrolysate through an in vivo activity-guided fractionation approach based on D-galactosamine-induced acute hepatitis in rats and fractionation of peptides with large-scale preparative ampholine-free isoelectric focusing. The active acidic fraction predominantly consisted of pyroglutamyl peptides and free pyroglutamic acid. Pyroglutamyl peptides were derivatized with phenyl isothiocyanate after removal of a pyroglutamyl residue by pyroglutamate aminopeptidase. The derivatives were purified by reversed-phase HPLC and subjected to sequence analysis. The active fraction contained pyroGlu-Ile, pyroGlu-Leu, pyroGlu-Gln, pyroGlu-Gln-Gln, and free pyroGlu. Ingestion of pyroGlu-Leu at 20 mg/kg body weight significantly decreased serum aspartate and alanine aminotransferases to approximately 30% and 20% of those values of the vehicle group, respectively, which were near the normal levels. Thirty minutes after ingestion of pyroGlu-Leu at 20 mg/kg, the concentration of pyroGlu-Leu in portal blood plasma increased to approximately 2 μM.

Vitamin C acts as a hepatoprotectant in carbofuran treated rat liver slices in vitro.

PubMed

Jaiswal, Sunil Kumar; Gupta, Vivek Kumar; Ansari, Md Dilshad; Siddiqi, Nikhat J; Sharma, Bechan

2017-01-01

Carbamates, most commonly used pesticides in agricultural practices, have been reported to produce free radicals causing deleterious effects in animals. The present study was designed to assess the carbofuran induced oxidative stress in rat liver slices in vitro and also to evaluate protective role of vitamin C by incubating them in Krebs-Ringer HEPES Buffer (KRHB) containing incubation media (Williams medium E (WME) supplemented with glucose and antibiotics) with different concentrations of carbofuran. The results demonstrated that carbofuran caused significant increase in lipid peroxidation and inhibition in the activity of hepatic superoxide dismutase (SOD) in concentration dependent manner. The data with incubation medium reflected that carbofuran at lowest concentration caused an increase in SOD activity followed by its inhibition at higher concentration. Carbofuran treatment caused inhibition in the activity of catalase in liver slices and WME incubation medium. Pre-incubation of liver slices and the WME media with vitamin C restored the values of biochemical indices tested. The results indicated that carbofuran might induce oxidative stress in hepatocytes. The pretreatment with vitamin C may offer hepatoprotection from toxicity of pesticide at low concentration only.

Hepatoprotective effect of methyl ferulic acid against carbon tetrachloride-induced acute liver injury in rats

PubMed Central

Yang, Chengfang; Li, Li; Ma, Zuheng; Zhong, Yujuan; Pang, Wenxiao; Xiong, Meili; Fang, Shuping; Li, Yongwen

2018-01-01

The present study aimed to investigate the hepatoprotective effects of methyl ferulic acid (MFA) against oxidative stress and apoptosis in acute liver injury induced by carbon tetrachloride (CCl4) in rats, as well as the underlying mechanisms. Sprague Dawley rats were treated with CCl4 after oral administration of MFA (25, 50, and 100 mg/kg) or dimethyl diphenyl bicarboxylate (200 mg/kg) for 7 days. The hepatoprotective effects of MFA were determined by analyzing serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities as well as changes of oxidant parameters. Histopathological analysis was performed to determine the degree of hepatic injury. The mechanisms were investigated by detecting the levels of NADPH oxidase (NOX) trans-membrane subunit NOX4, its ligand p22phox, as well as caspase3, cleaved caspase3, B-cell lymphoma (Bcl)-2, Bcl-2-associated X protein (Bax), tumor necrosis factor (TNF)-α, interleukin (IL)-1, reactive oxygen species (ROS), thiobarbituric acid-reactive substances (TBARS), total anti-oxidant capacity (TAC), phosphorylated J-Jun N-terminal kinase (p-JNK) and p-p38 mitogen-activated protein kinase (MAPK) using semi-quantitative polymerase chain reaction, western blot analysis and colorimetric assays. MFA treatment significantly decreased serum enzymatic activities of ALT and AST. MFA markedly increased activities of liver superoxide dismutase, catalase and glutathione peroxidase, and reduced the malondialdehyde concentration. Histopathological examination demonstrated that MFA reduced lipid degeneration, cytoplasmic vacuolization, necrosis and inflammatory cell infiltration in the liversof CCl4-treated rats. MFA treatment markedly inhibited the expression of inflammatory factors TNF-α and IL-1β. Mechanistic study revealed that MFA decreased the TAC and the levels of ROS and TBARS. Furthermore, MFA treatment led to a reduction of the mRNA and protein expression of NOX4 and p22phox, as well as the protein levels of caspase3, cleaved caspase-3 and Bax, and an upregulation of p-JNK, p-p38 MAPK and Bcl-2 proteins in the liver. The present study demonstrated that MFA has hepatoprotective effects against CCl4-induced acute liver damage. MFA has anti-oxidant, anti-inflammatory and anti-apoptotic activities and was able to modulate the NOX4/p22phox/ROS-JNK/p38 MAPK signaling pathway. PMID:29467841

Antioxidant and Hepatoprotective Effect of Aqueous Extract of Germinated and Fermented Mung Bean on Ethanol-Mediated Liver Damage

PubMed Central

Mohd Ali, Norlaily; Mohd Yusof, Hamidah; Long, Kamariah; Yeap, Swee Keong; Ho, Wan Yong; Beh, Boon Kee; Koh, Soo Peng; Abdullah, Mohd Puad; Alitheen, Noorjahan Banu

2013-01-01

Mung bean is a hepatoprotective agent in dietary supplements. Fermentation and germination processes are well recognized to enhance the nutritional values especially the concentration of active compounds such as amino acids and GABA of various foods. In this study, antioxidant and hepatoprotective effects of freeze-dried mung bean and amino-acid- and GABA-enriched germinated and fermented mung bean aqueous extracts were compared. Liver superoxide dismutase (SOD), malondialdehyde (MDA), ferric reducing antioxidant power (FRAP), nitric oxide (NO) levels, and serum biochemical profile such as aspartate transaminase (AST), alanine transaminase (ALT), triglycerides (TG), and cholesterol and histopathological changes were examined for the antioxidant and hepatoprotective effects of these treatments. Germinated and fermented mung bean have recorded an increase of 27.9 and 7.3 times of GABA and 8.7 and 13.2 times of amino acid improvement, respectively, as compared to normal mung bean. Besides, improvement of antioxidant levels, serum markers, and NO level associated with better histopathological evaluation indicated that these extracts could promote effective recovery from hepatocyte damage. These results suggested that freeze-dried, germinated, and fermented mung bean aqueous extracts enriched with amino acids and GABA possessed better hepatoprotective effect as compared to normal mung bean. PMID:23484140

Hepatoprotective activity of Trichilia roka on carbon tetrachloride-induced liver damage in rats.

PubMed

Germanò, M P; D'Angelo, V; Sanogo, R; Morabito, A; Pergolizzi, S; De Pasquale, R

2001-11-01

Trichilia roka Chiov. (Meliaceae) is a tree widely distributed in tropical Africa. It has been used in Mali folk medicine for the treatment of various illnesses. A decoction of the roots is taken as a remedy for colds and pneumonia, and it is used as a diuretic and in hepatic disorders. We have evaluated the hepatoprotective effects of a decoction of Trichilia roka root on CCl4-induced acute liver damage in rats. Treatment with the decoction showed a significant protective action made evident by its effect on the levels of glutamate oxalacetate transaminase and glutamate pyruvate transaminase in the serum, on the protein content and lipid peroxidation levels in the liver homogenate. Histopathological changes produced by CCl4, such as necrosis, fatty change, ballooning degeneration and inflammatory infiltration of lymphocytes around the central veins, were clearly recovered by the treatment with Trichilia root decoction. On fractionating this extract into diethyl ether-soluble and water-soluble fractions, the activity was retained in the diethyl ether-soluble fraction. Moreover, the administration of decoction prevented a preferential deposition of collagen around the sinusoidal cell layer, which is responsible for the perisinusoidal fibrosis in the early stage of CCl4 damage. This study showed that treatment with Trichilia roka extracts or silymarin (as reference) appeared to enhance the recovery from CCl4-induced hepatotoxicity. The hepatoprotective properties of Trichilia roka may be correlated to polyphenol content of the decoction and its diethyl ether-soluble fraction.

Hepatoprotective activity of ethanolic extract of Salix subserrata against CCl4-induced chronic hepatotoxicity in rats.

PubMed

Wahid, Ahmed; Hamed, Ashraf N; Eltahir, Heba M; Abouzied, Mekky M

2016-07-29

The liver performs diverse functions that are essential for life. In the absence of reliable liver protective drugs, a large number of natural medicinal preparations are used for the treatment of liver diseases. Therefore the present study aims to investigate the hepatoprotective effects of Salix subserrata Willd flower ethanolic extract (SFEE) against carbon tetrachloride (CCl4)-induced liver damage. Rats were divided into 4 groups of 10 animals each. Group I served as the normal healthy control, groups II rats were intoxicated with CCl4 i.p. (0.8 ml/kg body weight CCl4/olive oil, twice weekly for 9 weeks), group III rats received CCl4 i.p. and SFEE orally (150 mg/kg daily) and group IV rats received CCl4 i.p. and Silymarin orally (100 mg/kg, daily). The hepatoprotective potential of SFEE in rats was evaluated by measuring the protein levels of two inflammatory biomarkers; tumor necrosis factor-alpha (TNF-α) and nuclear factor kappa-B (NF-kB) in addition to other liver biomarkers. Histopathological changes in the liver were assessed using hematoxylin and eosin staining (HE). The administration of SFEE showed hepatic protection at an oral dose of 150 mg/kg. SFEE significantly reduced the elevated serum levels of intracellular liver enzymes as well as liver biomarkers in comparison to CCl4- intoxicated group. Notably, SFEE significantly reduced the expression levels of TNF-α and NFkB proteins compared to their levels in CCl4 intoxicated group. These findings were confirmed with the histopathological observations, where SFEE was capable of reversing the toxic effects of CCl4 on liver cells compared to that observed in CCl4-intoxicated animals. Our results show that SFEE has potential hepatoprotective effects at 150 mg/kg. These effects can be regarded to the antioxidant and anti-inflammatory properties of the extract.

Anti-HCV effect of Lentinula edodes mycelia solid culture extracts and low-molecular-weight lignin.

PubMed

Matsuhisa, Koji; Yamane, Seiji; Okamoto, Toru; Watari, Akihiro; Kondoh, Masuo; Matsuura, Yoshiharu; Yagi, Kiyohito

2015-06-19

Lentinula edodes mycelia solid culture extract (MSCE) contains several bioactive molecules, including some polyphenolic compounds, which exert immunomodulatory, antitumor, and hepatoprotective effects. In this study, we examined the anti-hepatitis C virus (HCV) activity of MSCE and low-molecular-weight lignin (LM-lignin), which is the active component responsible for the hepatoprotective effect of MSCE. Both MSCE and LM-lignin inhibited the entry of two HCV pseudovirus (HCVpv) types into Huh7.5.1 cells. LM-lignin inhibited HCVpv entry at a lower concentration than MSCE and inhibited the entry of HCV particles in cell culture (HCVcc). MSCE also inhibited HCV subgenome replication. LM-lignin had no effect on HCV replication, suggesting that MSCE contains additional active substances. We demonstrate here for the first time the anti-HCV effects of plant-derived LM-lignin and MSCE. The hepatoprotective effect of LM-lignin suggests that lignin derivatives, which can be produced in abundance from existing plant resources, may be effective in the treatment of HCV-related diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

Review on liver inflammation and antiinflammatory activity of Andrographis paniculata for hepatoprotection.

PubMed

Chua, Lee Suan

2014-11-01

Till to date, the advancement of medical science and technology is still unable to provide inclusive treatment to liver inflammation caused by neither microbial invasion nor antibiotics nor environmental toxins. Therefore, this article provides the basic knowledge of liver inflammation up to the cellular level and its current medical treatment for inflammatory symptom suppression. Because of the adverse effects of drug treatment, people start looking for comprehensive alternative nowadays. Herbal medicine is believed to be the best of choice because it is being practiced until now for centuries. Although numerous herbal plants have been reported for their efficacies in liver protection, Andrographis paniculata is the most widely used herb for hepatoprotection, particularly in Ayurveda and traditional Chinese medicine. This review covers the significant observation on the biochemical responses due to the experimental induction of liver damage in vitro and in vivo using the marker compound of the herb, namely andrographolide and its derivatives. The standardized extract of A. paniculata with the right phytochemical composition of diterpenic labdanes is likely to have tremendous potential for the development of hepatoprotective medicine. This standardized herbal medicine may not provide immediate remedy, but it can be considered as a comprehensive therapy for liver inflammation. Copyright © 2014 John Wiley & Sons, Ltd.

In Vitro Antioxidant Activities of Enzymatic Hydrolysate from Schizochytrium sp. and Its Hepatoprotective Effects on Acute Alcohol-Induced Liver Injury In Vivo.

PubMed

Cai, Xixi; Yan, Ana; Fu, Nanyan; Wang, Shaoyun

2017-04-10

Schizochytrium protein hydrolysate (SPH) was prepared through stepwise enzymatic hydrolysis by alcalase and flavourzyme sequentially. The proportion of hydrophobic amino acids of SPH was 34.71%. The molecular weight (MW) of SPH was principally concentrated at 180-3000 Da (52.29%). SPH was divided into two fractions by ultrafiltration: SPH-I (MW < 3 kDa) and SPH-II (MW > 3 kDa). Besides showing lipid peroxidation inhibitory activity in vitro, SPH-I exhibited high DPPH and ABTS radicals scavenging activities with IC 50 of 350 μg/mL and 17.5 μg/mL, respectively. In addition, the antioxidant activity of SPH-I was estimated in vivo using the model of acute alcohol-induced liver injury in mice. For the hepatoprotective effects, oral administration of SPH-I at different concentrations (100, 300 mg/kg BW) to the mice subjected to alcohol significantly decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and hepatic malondialdehyde (MDA) level compared to the untreated mice. Besides, SPH-I could effectively restore the hepatic superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities and glutathione (GSH) level. Results suggested that SPH was rich in biopeptides that could be exploited as antioxidant molecules against oxidative stress in human body.

Triterpenoids of Ganoderma theaecolum and their hepatoprotective activities.

PubMed

Liu, Li-Ying; Chen, Hui; Liu, Chao; Wang, Hong-Qing; Kang, Jie; Li, Yan; Chen, Ruo-Yun

2014-10-01

Five new lanostane triterpenoids, ganoderic acid XL1 (1), ganoderic acid XL2 (2), 20-hydroxy-ganoderic acid AM1 (3), ganoderenic acid AM1 (4) and ganoderesin C (5), together with five known triterpenoids (6-10) were isolated from the fruiting bodies of Ganoderma theaecolum. Chemical structures were elucidated on the basis of spectroscopic evidence, including 1D, 2D NMR, mass spectrometric data and circular dichroism spectra. Compounds 1, 4, 5, 8, 9 and 10 (10 μM) exhibited hepatoprotective activities against DL-galactosamine-induced cell damage in HL-7702 cells. Copyright © 2014 Elsevier B.V. All rights reserved.

Hepatoprotective action of various partitions of methanol extract of Bauhinia purpurea leaves against paracetamol-induced liver toxicity: involvement of the antioxidant mechanisms.

PubMed

Zakaria, Zainul Amiruddin; Yahya, Farhana; Mamat, Siti Syariah; Mahmood, Nur Diyana; Mohtarrudin, Nurhafizah; Taher, Muhammad; Hamid, Siti Selina Abdul; Teh, Lay Kek; Salleh, Mohd Zaki

2016-06-11

Methanol extract of Bauhinia purpurea L. (family Fabaceae) (MEBP) possesses high antioxidant and anti-inflammatory activities and recently reported to exert hepatoprotection against paracetamol (PCM)-induced liver injury in rats. In an attempt to identify the hepatoprotective bioactive compounds in MEBP, the extract was prepared in different partitions and subjected to the PCM-induced liver injury model in rats. Dried MEBP was partitioned successively to obtain petroleum ether (PEBP), ethylacetate (EABP) and aqueous (AQBP) partitions, respectively. All partitions were subjected to in vitro antioxidant (i.e. total phenolic content (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH)- and superoxide-radicals scavenging assay, and oxygen radical absorbance capacity (ORAC) assay) and anti-inflammatory (i.e. lipooxygenase (LOX) and xanthine oxidase (XO) assay) analysis. The partitions, prepared in the dose range of 50, 250 and 500 mg/kg, together with a vehicle (10 % DMSO) and standard drug (200 mg/kg silymarin) were administered orally for 7 consecutive days prior to subjection to the 3 mg/kg PCM-induced liver injury model in rats. Following the hepatic injury induction, blood samples and liver were collected for the respective biochemical parameter and histopathological studies. Body weight changes and liver weight were also recorded. The partitions were also subjected to the phytochemical screening and HPLC analysis. Of all partitions, EABP possessed high TPC value and demonstrated remarkable antioxidant activity when assessed using the DPPH- and superoxide-radical scavenging assay, as well as ORAC assay, which was followed by AQBP and PEBP. All partitions also showed low anti-inflammatory activity via the LOX and XO pathways. In the hepatoprotective study, the effectiveness of the partitions is in the order of EABP>AQBP>PEBP, which is supported by the microscopic analysis and histopathological scoring. In the biochemical analysis, EABP also exerted the most effective effect by reducing the serum level of alanine transaminase (ALT) and aspartate transaminase (AST) at all doses tested in comparison to the other partitions. Phytochemical screening and HPLC analysis suggested the presence of: flavonoids, condensed tannins and triterpenes in EABP; flavonoids, condensed tannins and saponins in PEBP and; only saponins in AQBP. EABP demonstrates the most effective hepatoprotection against PCM-induced liver injury in rats. This observation could be attributed to its remarkable antioxidant activity and the presence of flavonoids that might probably act synergistically with other biocompounds to cause the hepatoprotection.

Hepatoprotective Effect of Low Doses of Caffeine on CCl4-Induced Liver Damage in Rats.

PubMed

Cachón, Andrés Uc; Quintal-Novelo, Carlos; Medina-Escobedo, Gilberto; Castro-Aguilar, Gaspar; Moo-Puc, Rosa E

2017-03-04

Several studies have shown the hepatoprotective effect of the consumption of coffee and tea, which is mainly attributed to caffeine. Many experimental studies have demonstrated this effect; however, these studies used high caffeine doses that are not related to human consumption. The aim of this study was to evaluate the hepatoprotective effect of low doses of caffeine on carbon tetrachloride (CCl 4 )-treated rats. Low doses of caffeine (CAFF) 5 and 10 mg/kg (CAFF5 and CAFF10) were evaluated in chronic liver damage induced by CCl 4 (0.75 mL/kg) in rats. CAFF treatment was administered once a day and CCl 4 administration was twice weekly for 10 weeks. Liver function tests (biochemical markers) and functional (sleeping time) and histological (hematoxylin-eosin and Masson trichrome stains) parameters were carried out at the end of damage treatment. Daily treatments of CAFF5 and CAFF10 exhibited a hepatoprotective effect supported by a decrease of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (AP) serum activities and bilirubin serum levels compared with control and also restored serum albumin levels and liver glutathione (GSH). Moreover, CAFF prevented CCl 4 -induced prolongation in pentobarbital sleeping time and a decrease of liver fibrosis and cell death. Our results demonstrated that low doses of CAFF exert a hepatoprotective effect against CCl 4 -induced liver damage in rats.

Hepatoprotective and hypoglycemic effects of a tannin rich extract from Ximenia americana var. caffra root.

PubMed

Sobeh, Mansour; Mahmoud, Mona F; Abdelfattah, Mohamed A O; El-Beshbishy, Hesham A; El-Shazly, Assem M; Wink, Michael

2017-09-15

Liver diseases and diabetes are serious health disorders associated with oxidative stress and ageing. Some plant polyphenols can lower the risk of these diseases. We investigated the phytochemical profiling of a root extract from Ximenia americana var. caffra using HPLC-PDA-ESI-MS/MS. The antioxidant activities in vitro were investigated. The hepatoprotective activities were studied in rat models with d-galactosamine (d-GaIN)-induced hepatotoxicity and the antidiabetic activities in STZ-diabetic rats were also investigated. HPLC-PDA-ESI-MS/MS was used to identify plant phenolics. The antioxidant activities in vitro were determined using DPPH and FRAP assays. The in vivo hepatoprotective activities were determined for d-GaIN-induced hepatotoxicity in rats. We determined the liver markers alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT), liver peroxidation product malondialdehyde (MDA), glutathione content (GSH), albumin and total bilirubin concentration. The histopathological changes in rat liver were also studied. The antidiabetic activities were also investigated in STZ-diabetic rats and serum glucose, serum insulin hormone, and lipid peroxides were determined. The root extract is rich in tannins with 20 compounds including a series of stereoisomers of (epi)catechin, (epi)catechin-(epi)catechin, (epi)catechin-(epi)catechin-(epi)catechin, and their galloyl esters. Promising antioxidant potential was observed in vitro in DPPH assay with EC 50 of 6.5 µg extract / 26 µg raw material and in FRAP assay with 19.54 mM FeSO 4 compared with ascorbic acid (EC 50 of 2.92 µg/ml) and quercetin (FeSO 4 24.04 mM/mg), respectively. Significant reduction of serologic enzymatic markers and hepatic oxidative stress markers such as ALT, AST, MDA, GGT, and total bilirubin, as well as elevation of GSH and albumin were observed in rats with d-galactosamine-induced liver damage treated with the extract. These findings agree with a histopathological examination suggesting a hepatoprotective potential for the root extract. The root extract can mediate an antidiabetic effect by reducing elevated blood glucose and serum lipid peroxides levels and by increasing insulin in STZ-diabetic rats by -107, -31.1, +11.3%, respectively. The results of this study suggest that the tannin-rich extract from Ximenia americana var. caffra could be an interesting candidate for the treatment of several health disorders associated with oxidative stress such as hepatocellular injury and diabetes. Copyright © 2017. Published by Elsevier GmbH.

Protective Effect of Cymbopogon citratus Essential Oil in Experimental Model of Acetaminophen-Induced Liver Injury.

PubMed

Uchida, Nancy Sayuri; Silva-Filho, Saulo Euclides; Aguiar, Rafael Pazinatto; Wiirzler, Luiz Alexandre Marques; Cardia, Gabriel Fernando Esteves; Cavalcante, Heitor Augusto Otaviano; Silva-Comar, Francielli Maria de Souza; Becker, Tânia Cristina Alexandrino; Silva, Expedito Leite; Bersani-Amado, Ciomar Aparecida; Cuman, Roberto Kenji Nakamura

2017-01-01

To investigate the hepatoprotective effect of Cymbopogon citratus or lemongrass essential oil (LGO), it was used in an animal model of acute liver injury induced by acetaminophen (APAP). Swiss mice were pretreated with LGO (125, 250 and 500[Formula: see text]mg/kg) and SLM (standard drug, 200[Formula: see text]mg/kg) for a duration of seven days, followed by the induction of hepatotoxicity of APAP (single dose, 250[Formula: see text]mg/kg). The liver function markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transferase were determined to evaluate the hepatoprotective effects of the LGO. The livers were used to determine myeloperoxidase (MPO) activity, nitric oxide (NO) production and histological analysis. The effect of LGO on leukocyte migration was evaluated in vitro. Anti-oxidant activity was performed by assessing the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) in vitro. LGO pretreatment decreased significantly the levels of ALT, AST and ALP compared with APAP group. MPO activity and NO production were decreased. The histopathological analysis showed an improved of hepatic lesions in mice after LGO pretreatment. LGO inhibited neutrophil migration and exhibited anti-oxidant activity. Our results suggest that LGO has protective activity against liver toxicity induced by paracetamol.

Influence of olive and rosemary leaves extracts on chemically induced liver cirrhosis in male rats

PubMed Central

Al-Attar, Atef M.; Shawush, Nessreen A.

2014-01-01

The current study was undertaken to evaluate the protective activity of olive and rosemary leaves extracts on experimental liver cirrhosis induced by thioacetamide (TAA) in Wistar male rats. Highly significant decline in the values of body weight gain and highly statistically increase of liver/body weight ratio were noted in rats treated with TAA. Furthermore, the levels of serum alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transferase, alkaline phosphatase and total bilirubin were statistically increased. Additionally, light microscopic examination of liver sections from rats treated with TAA showed a marked increase in the extracellular matrix collagen content and bridging fibrosis was prominent. There were bundles of collagen surrounding the lobules that resulted in large fibrous septa and distorted tissue architecture. Interestingly, the findings of this experimental study indicated that the extracts of olive and rosemary leaves and their combination possess hepatoprotective properties against TAA-induced hepatic cirrhosis by inhibiting the physiological and histopathological alterations. Moreover, these results suggest that the hepatoprotective effects of these extracts may be attributed to their antioxidant activities. PMID:25737646

Hepatoprotective effects of fermented Curcuma longa L. on carbon tetrachloride-induced oxidative stress in rats.

PubMed

Kim, Yongjae; You, Yanghee; Yoon, Ho-Geun; Lee, Yoo-Hyun; Kim, Kyungmi; Lee, Jeongmin; Kim, Min Soo; Kim, Jong-Choon; Jun, Woojin

2014-05-15

The hepatoprotective effect of fermented Curcuma longa L. (FC) was investigated in rats under CCl4-induced oxidative stress. FC at a dose of 30 or 300 mg/kg body weight (b.w.) was orally administered for 14 days followed by a single dose of CCl4 (1.25 mL/kg b.w. in 20% corn oil) on day 14. Pretreatment with FC drastically prevented the elevated activities of serum AST, ALT, LDH, and ALP caused by CCl4-induced hepatotoxicity. Histopathologically evident hepatic necrosis was significantly ameliorated by FC pretreatment. When compared to the CCl4-alone treated group, rats pretreated with FC displayed the reduced level of malondialdehyde. Furthermore, FC enhanced antioxidant capacities with higher activities of catalase, glutathione-S-transferase, glutathione reductase, and glutathione peroxidase, and level of reduced glutathione. These results suggest that FC could be a candidate used for the prevention against various liver diseases induced by oxidative stress via elevating antioxidative potentials and decreasing lipid peroxidation. Copyright © 2013 Elsevier Ltd. All rights reserved.

Protection from liver fibrosis by a peroxisome proliferator-activated receptor δ agonist.

PubMed

Iwaisako, Keiko; Haimerl, Michael; Paik, Yong-Han; Taura, Kojiro; Kodama, Yuzo; Sirlin, Claude; Yu, Elizabeth; Yu, Ruth T; Downes, Michael; Evans, Ronald M; Brenner, David A; Schnabl, Bernd

2012-05-22

Peroxisome proliferator-activated receptor delta (PPARδ), a member of the nuclear receptor family, is emerging as a key metabolic regulator with pleiotropic actions on various tissues including fat, skeletal muscle, and liver. Here we show that the PPARδ agonist KD3010, but not the well-validated GW501516, dramatically ameliorates liver injury induced by carbon tetrachloride (CCl(4)) injections. Deposition of extracellular matrix proteins was lower in the KD3010-treated group than in the vehicle- or GW501516-treated group. Interestingly, profibrogenic connective tissue growth factor was induced significantly by GW501516, but not by KD3010, following CCl(4) treatment. The hepatoprotective and antifibrotic effect of KD3010 was confirmed in a model of cholestasis-induced liver injury and fibrosis using bile duct ligation for 3 wk. Primary hepatocytes treated with KD3010 but not GW501516 were protected from starvation or CCl(4)-induced cell death, in part because of reduced reactive oxygen species production. In conclusion, our data demonstrate that an orally active PPARδ agonist has hepatoprotective and antifibrotic effects in animal models of liver fibrosis, suggesting a possible mechanistic and therapeutic approach in treating patients with chronic liver diseases.

Characterizations and hepatoprotective effect of polysaccharides from Mori Fructus in rats with alcoholic-induced liver injury.

PubMed

Zhou, Xin; Deng, Qingfang; Chen, Huaguo; Hu, Enming; Zhao, Chao; Gong, Xiaojian

2017-09-01

Crude polysaccharides of Mori Fructus (MFPs) were found to have anti-inflammatory antioxidant, and immuno-enhancing activities. However, the structure of the polysaccharides was ambiguous and its holistic hepatic protection evaluation was defective. This study was conducted to illustrate the characterization of MFPs, and evaluate its hepatoprotective activities. The results found that MFPs contained 67.93±1.18% carbohydrates, 31.03±0.54% uronic acid, and little protein and sulfate. The average molecular weight was ranging from 112.2kDa to 181.9kDa. Monosaccharide component analysis indicated that MFPs was mainly composed of glucose, galacturonic acid, rhamnose and galactose. Both the acute and subacute alcoholic-induced liver injury animal models were adopted to evaluate the MFPs's hepatoprotective activity. After administration of MFPs, both serological indexes (aspartate aminotransferase and alanine aminotransferase) and hepatic indicators (glutathione, superoxide dismutase, glutathione peroxidase and malondialdehyde) were improved by comparing with the non-MFPs group. The hepatic histopathology results also showed a prominent lipid degeneration and microvesicular steatosis attenuation in the MFPs groups. These outstanding hepatic protecting activities of MFPs might be related to its activation of ethanol dehydrogenase, elimination of free radicals and/or inhibition of lipid peroxidation capacities. MFPs could be important active substances for preventing and remedying liver injury. Copyright © 2017. Published by Elsevier B.V.

Hepatoprotective glycosides from the rhizomes of Imperata cylindrical.

PubMed

Ma, Jie; Sun, Hua; Liu, Hui; Shi, Gao-Na; Zang, Ying-Da; Li, Chuang-Jun; Yang, Jing-Zhi; Chen, Fang-You; Huang, Ji-Wu; Zhang, Dan; Zhang, Dong-Ming

2018-05-01

Three new C-methylated phenylpropanoid glycosides (1, 2), a new 8-4'-oxyneolignan (3), together with two known analogs (4, 5), were isolated from the rhizomes of Imperata cylindrical Beauv. var. major (Nees) C. E. Hubb. Their structures were determined by spectroscopic and chemical methods. Compounds 1, 2, and 5 (10 μM) exhibited pronounced hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced HepG2 cell damage in vitro assays. Furthermore, their antioxidant activities against Fe 2+ -cysteine-induced rat liver microsomal lipid peroxidation and the effects on the secretion of TNF-α in murine peritoneal macrophages (RAW264.7) induced by lipopolysaccharides were evaluated.

Protective effect of crude Curcuma longa and its methanolic extract in alloxanized rabbits.

PubMed

Ahmad, Mobasher; Kamran, Sairah Hafeez; Mobasher, Afroze

2014-01-01

Curcuma longa (C. longa) is commonly found in different areas of Pakistan. It has been locally utilized as a traditional medicine. The aim of this study was to evaluate the antidiabetic, hepatoprotective and total antioxidant effect of the crude drug and its methanolic extract in rabbits. Diabetes was induced with alloxan (180mg/kg). Two major groups were designed, curative and protective groups. In curative group the crude drug and its methanolic extract was orally administered to the diabetic animals and acute study was performed. On the other hand in protective group the crude drug and its methanolic extract were administered for eight days prior to the diabetes induction. Results indicated that in Curative group the crude and methanolic extract of C. longa significantly improved the levels of serum glucose, serum transaminases and antioxidant activity (AOA). In protective group, serum glucose, serum transaminases were not significantly increased by alloxan, in both crude as well as methanolic extract group. This study shows that C. longa acts as antidiabetic, hepatoprotective and antioxidant in diabetes especially type 1 diabetes.

The Hepatoprotective Effect of Vitamin A against Gasoline Vapor Toxicity in Rats

PubMed Central

Uboh, Friday E.; Ekaidem, Itemobong S.; Ebong, Patrick E.; Umoh, Ime B.

2009-01-01

Background Changes in the activities of plasma alanine amino transferase (ALT), aspartate amino transferase (AST), gamma glutamyl transferase (GGT), and alkaline phosphatase (ALP) are used to assess the functional state of the liver. Significant increase in the activities of these enzymes commonly indicates the hepatotoxicity of chemical agent(s) in the body. Exposure of male and female rats to 17.8 cm3h-1m-3 of Premium Motor Spirit (PMS) blend unleaded gasoline (UG) vapors for 6 hr/day, 5 days/week for 20 weeks have been observed to cause hepatotoxicity. In this study, the potential hepatoprotective effect of vitamin A (retinol) against gasoline vapours-induced toxicity was investigated in male and female rats. Methods Retinol (400 IU/kg/day) was orally administered to the test rats concomitant with the gasoline vapor exposure in the last two weeks of the experiment. Results The results obtained from this study showed that exposure to gasoline vapors caused significant increase (P < 0.05) in the activities of serum ALT, AST, ALP, GGT and bilirubin in both male and female rats. The treatment of the male and female test rats with vitamin A produced a significant decrease (P < 0.05) in the activities of these parameters, compared with the test rats without treatment; but insignificant increase(P ≥ 0.05), compared with the control. Conclusions The result of this study demonstrates the beneficial effects of retinol, at prophylactic dosage, against gasoline vapours hepatotoxicity in male and female rats, thereby suggesting that retinol may be used to prevent hepatotoxicity in individuals frequently exposed to gasoline vapours. PMID:27933127

Protective effects of phenolics rich extract of ginger against Aflatoxin B1-induced oxidative stress and hepatotoxicity.

PubMed

A V, Vipin; K, Raksha Rao; Kurrey, Nawneet Kumar; K A, Anu Appaiah; G, Venkateswaran

2017-07-01

Aflatoxin B 1 (AFB 1 ) is one of the predominant mycotoxin contaminant in food and feed, causing oxidative stress and hepatotoxicity. Ginger phenolics have been reported for its antioxidant potential and hepatoprotective activity. The present study investigated the protective effects of phenolics rich ginger extract (GE) against AFB 1 induced oxidative stress and hepatotoxicity, in vitro and in vivo. The phenolic acid profiles of GE showed 6-gingerol and 6-shogaol as predominant components. Pretreatment of HepG2 cells with GE significantly inhibited the production of intracellular reactive oxygen species (ROS), DNA strand break, and cytotoxicity induced by AFB 1 . A comparable effect was observed in in vivo. Male Wistar rats were orally treated with GE (100 and 250mg/kg) daily, with the administration of AFB 1 (200μg/kg) every alternative day for 28days. Treatment with GE significantly reduced AFB 1 induced toxicity on the serum markers of liver damage. In addition, GE also showed significant hepatoprotective effect by reducing the lipid peroxidation and by enhancing the antioxidant enzymes activities. These results combined with liver histopathological observations indicated that GE has potential protective effect against AFB 1 induced hepatotoxicity. Additionally, administration of GE up-regulated Nrf2/HO-1 pathway, which further proved the efficiency of GE to inhibit AFB 1 induced hepatotoxicity. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Potential hepatoprotective effects of new Cuban natural products in rat hepatocytes culture.

PubMed

Rodeiro, I; Donato, M T; Martínez, I; Hernández, I; Garrido, G; González-Lavaut, J A; Menéndez, R; Laguna, A; Castell, J V; Gómez-Lechón, M J

2008-08-01

The protective effects of five Cuban natural products (Mangifera indica L. (MSBE), Erythroxylum minutifolium, Erythroxylum confusum, Thalassia testudinum and Dictyota pinnatifida extracts and mangiferin) on the oxidative damage induced by model toxicants in rat hepatocyte cultures were studied. Cells were pre-incubated with the natural products (5-200 microg/mL) for 24 h. Then hepatotoxins (tert-butyl hydroperoxide, ethanol, carbon tetrachloride and lipopolysaccharide) were individually added and post-incubated for another 24 h. After treatments, cell viability was determined using the MTT assay. Mangiferin and MSBE exhibited the highest cytoprotective potential (EC50 between 50 and 125 microg/mL), followed by T. testudinum and Erythroxylum extracts, whereas no significant protective effects was produced by Dictyota extract treatment. Antioxidant properties of the natural products against lipid peroxidation and GSH depletion induced by tert-butyl hydroperoxide were then investigated. The results show that at 36 h pre-treatment of cells with mangiferin or MSBE, concentrations of T. testudinum and Erythroxylum extracts ranging from 25 to 100 microg/mL significantly inhibited lipid peroxidation induced by tert-butyl hydroperoxide (100 and 250 microM) and increased the GSH levels reduced by the toxicant. D. pinnatifida inhibited lipid peroxidation, but did not preserve GSH levels. In conclusion, MSBE, E. minutifolium, E. confusum and T. testudinum extracts and mangiferin showed hepatoprotective activity against induced damage in all the experimental series, where mangiferin and the extracts of MSBE and T. testudinum were the best candidates to inhibit "in vitro" damage to rat hepatocytes. This hepatoprotective effect found could be associated with the antioxidant properties observed for the products.

UPLC-ESI-MS/MS and HPTLC Method for Quantitative Estimation of Cytotoxic Glycosides and Aglycone in Bioactivity Guided Fractions of Solanum nigrum L.

PubMed Central

Chester, Karishma; Paliwal, Sarvesh; Khan, Washim; Ahmad, Sayeed

2017-01-01

Solanum nigrum L., is traditionally used for the management of the various liver disorders. Investigating the effect of polarity based fractionation of S. nigrum for its hepatoprotective effect on Hep G2 cells in vitro to provide base of its activity by quantifying in steroidal glycosides responsible for hepatoprotective potential. A new UPLC-ESI-MS/MS method following a high performance thin layer chromatography (HPTLC) has been developed and validated for quantification of steroidal glycosides and aglycone (solasonine, solamargine, and solasodine, respectively). The in vitro antioxidant potential, total phenolics, and flavonoid content were also determined in different fractions. The newly developed UPLC-ESI-MS/MS and HPTLC methods were linear (r2 ≥ 0.99), precise, accurate, and showing recovery more than 97%. The n-butanol enriched fraction of S. nigrum berries was found to be the most potent hepatoprotective fraction against all other fractions as it showed significantly (p < 0.01) better in vitro anti-oxidant potential than other fractions. Quantification by both methods revealed that, content of steroidal glycosides and aglycones are more than 20% in n-butanol fraction as compared to other fractions. The screened steroidal glycoside n-butanol enriched fraction underwent bioefficacy studies against D-galactosamine and H2O2 induced toxicity in HepG2 cell line showing significant (p < 0.05) liver protection. However, developed method can be used for the quality control analysis with respect to targeted metabolites and it can be explored for the pharmacokinetic and pharmacodynamic analysis in future. PMID:28729835

Hepatoprotective potential of Lavandula coronopifolia extracts against ethanol induced oxidative stress-mediated cytotoxicity in HepG2 cells.

PubMed

Farshori, Nida Nayyar; Al-Sheddi, Ebtsam S; Al-Oqail, Mai M; Hassan, Wafaa H B; Al-Khedhairy, Abdulaziz A; Musarrat, Javed; Siddiqui, Maqsood A

2015-08-01

The present investigations were carried out to study the protective potential of four extracts (namely petroleum ether extract (LCR), chloroform extract (LCM), ethyl acetate extract (LCE), and alcoholic extract (LCL)) of Lavandula coronopifolia on oxidative stress-mediated cell death induced by ethanol, a known hepatotoxin in human hapatocellular carcinoma (HepG2) cells. Cells were pretreated with LCR, LCM, LCE, and LCL extracts (10-50 μg/ml) of L. coronopifolia for 24 h and then ethanol was added and incubated further for 24 h. After the exposure, cell viability using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and neutral red uptake assays and morphological changes in HepG2 cells were studied. Pretreatment with various extracts of L. coronpifolia was found to be significantly effective in countering the cytotoxic responses of ethanol. Antioxidant properties of these L. coronopifolia extracts against reactive oxygen species (ROS) generation, lipid peroxidation (LPO), and glutathione (GSH) levels induced by ethanol were investigated. Results show that pretreatment with these extracts for 24 h significantly inhibited ROS generation and LPO induced and increased the GSH levels reduced by ethanol. The data from the study suggests that LCR, LCM, LCE, and LCL extracts of L. coronopifolia showed hepatoprotective activity against ethanol-induced damage in HepG2 cells. However, a comparative study revealed that the LCE extract was found to be the most effective and LCL the least effective. The hepatoprotective effects observed in the study could be associated with the antioxidant properties of these extracts of L. coronopifolia. © The Author(s) 2013.

Hepatoprotective and antioxidant activity of quercetin loaded chitosan/alginate particles in vitro and in vivo in a model of paracetamol-induced toxicity.

PubMed

Tzankova, Virginia; Aluani, Denitsa; Kondeva-Burdina, Magdalena; Yordanov, Yordan; Odzhakov, Feodor; Apostolov, Alexandar; Yoncheva, Krassimira

2017-08-01

The toxic liver impairment caused by free radical injury or excessive reactive oxigen species (ROS) formation could be effectivelly attenuated by natural antioxidants. The present study aimed to explore and compare the hepatoprotective and antioxidant effects of free and encapsulated quercetin in in vitro and in vivo models of hepatotoxicity. Thus, quercetin was encapsulated in chitosan/alginate nanoparticles by gelation method. Both empty and quercetin-loaded nanoparticles revealed good safety profile in vitro, determined by the lack of cytotoxicity in human hepatoma HepG2 cells. The pretreatment of HepG2 cells with encapsulated quercetin (10μg/ml) significantly attenuated the decrease in cell viability in H 2 О 2 -induced oxidative stress (0.1mM H 2 О 2 ) , thus showing an effective in vitro protection. In vivo evaluation of the antioxidant and hepatoprotective potential of free and encapsulated quercetin was performed in a model of paracetamol - induced liver injury in male Wistar rats. The oral pretreatment with encapsulated quercetin (0.18mg/kg b.w., 7days) significantly diminished the increased levels of serum transaminases ALT and AST, attenuated the lipid peroxidation and restored the levels of gluthation (a marker of cell antioxidant defence system). The protective effects of quercetin encapsulated in chitosan-based nanoformulation were superior to those of free quercetin. The results of the study suggest that the encapsulation of quercetin in chitosan/alginate nanoformulations might represent an effective therapeutic approach against oxidative stress induced liver injury. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Methotrexate hepatotoxicity is associated with oxidative stress, and down-regulation of PPARγ and Nrf2: Protective effect of 18β-Glycyrrhetinic acid.

PubMed

Mahmoud, Ayman M; Hussein, Omnia E; Hozayen, Walaa G; Abd El-Twab, Sanaa M

2017-05-25

18β-glycyrrhetinic acid (18β-GA) is a bioactive component of licorice with promising hepatoprotective activity. However, its protective mechanism on methotrexate (MTX) hepatotoxicity in not well defined. We investigated the hepatoprotective effect of 18β-GA, pointing to the role of peroxisome proliferator activated receptor gamma (PPARγ) and the redox-sensitive nuclear factor erythroid 2-related factor 2 (Nrf2). Wistar rats were orally administered 18β-GA (50 and 100 mg/kg) 7 days either before or after MTX injection. MTX induced significant increase in circulating liver function marker enzymes and bilirubin with concomitant declined albumin levels. Serum pro-inflammatory cytokines, and liver malondialdehyde and nitric oxide were significantly increased in MTX-induced rats. Treatment with 18β-GA significantly reduced serum enzymes of liver function, bilirubin and pro-inflammatory cytokines. 18β-GA attenuated MTX-induced oxidative stress and restored the antioxidant defenses. In addition, 18β-GA improved liver histological structure and decreased the expression of Bax whereas increased Bcl-2 expression. MTX-induced rats showed significant down-regulation of Nrf2, hemoxygenase-1 and PPARγ, an effect that was markedly reversed by 18β-GA supplemented either before or after MTX. In conclusion, 18β-GA protected against MTX-induced liver injury, possibly by activating Nrf2 and PPARγ, and subsequent attenuation of inflammation, oxidative stress and apoptosis. Therefore, 18β-GA can provide protection against MTX-induced hepatotoxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

Protective effects of calycosin against CCl4-induced liver injury with activation of FXR and STAT3 in mice.

PubMed

Chen, Xinli; Meng, Qiang; Wang, Changyuan; Liu, Qi; Sun, Huijun; Huo, Xiaokui; Sun, Pengyuan; Yang, Xiaobo; Peng, Jinyong; Liu, Kexin

2015-02-01

Investigating the hepatoprotective effect of calycosin against acute liver injury in association with FXR activation and STAT3 phosphorylation. The acute liver injury model was established by intraperitoneal injection of CCl4 in C57BL/6 mice. Serum alanine aminotransferase, aspartate aminotransferase, HE staining and TUNEL assay were used to identify the amelioration of the liver histopathological changes and hepatocytes apoptosis after calycosin treatment. ELISA kit and 5-bromo-2-deoxyuridine immunohistochemistry were used to measure the liver bile acid concentration and hepatocyte mitotic rate in vivo. The relation between calycosin and activation of FXR and STAT3 was comfirmed using the Luciferase assay, Molecular docking, Real-time PCR and Western Blot in vitro. The liver histopathological changes, hepatocytes apoptosis, liver bile acid overload and hepatocyte mitosis showed significant changes after calycosin treatment. Calycosin promoted the expression of FXR target genes such as FoxM1B and SHP but the effect was reversed by FXR suppressor guggulsterone. Molecular docking results indicated that calycosin could be embedded into the binding pocket of FXR, thereby increasing the expressions of STAT3 tyrosine phosphorylation and its target genes, Bcl-xl and SOCS3. Calycosin plays a critical role in hepatoprotection against liver injury in association with FXR activation and STAT3 phosphorylation.

Hepatoprotective effects of Auricularia cornea var. Li. polysaccharides against the alcoholic liver diseases through different metabolic pathways.

PubMed

Wang, Xiuxiu; Lan, Yufei; Zhu, Yongfa; Li, Shangshang; Liu, Min; Song, Xinling; Zhao, Huajie; Liu, Weiru; Zhang, Jianjun; Wang, Shouxian; Jia, Le

2018-05-15

The present work was designed to evaluate the antioxidation and hepatoprotective effects of Auricularia cornea var. Li. polysaccharides (APS) and enzymatic-extractable APS (EAPS) on the acute alcohol-induced alcoholic liver diseases (ALD). The in vitro antioxidant activities demonstrated that both APS and EAPS had strong reducing power and potential effects on scavenging reactive oxygen species. The in vivo mice experiments showed that the pretreatment with APS or EAPS showed potential hepatoprotective effects on the ALD possibly by increasing the antioxidant activities, reducing the lipid peroxidation, improving the alcohol metabolism, inhibiting the expression levels of inflammatory mediators and preventing the alcohol-induced histopathological alterations. In addition, the fourier-transform infrared (FT-IR), 1 H and 13 C nuclear magnetic resonance spectroscopy (NMR) and gas chromatography (GC) had been analyzed to obtained the primarily characteristics. The results indicated that abundant xylose and glucose contents probably had potential effects on possessing the bioactivities. The findings suggested that the A. cornea var. Li. might be considered as promising natural resource on exploring clinical drugs for the prevention and treatment with ALD and its complications.

In Vitro Antioxidant Activities of Enzymatic Hydrolysate from Schizochytrium sp. and Its Hepatoprotective Effects on Acute Alcohol-Induced Liver Injury In Vivo

PubMed Central

Cai, Xixi; Yan, Ana; Fu, Nanyan; Wang, Shaoyun

2017-01-01

Schizochytrium protein hydrolysate (SPH) was prepared through stepwise enzymatic hydrolysis by alcalase and flavourzyme sequentially. The proportion of hydrophobic amino acids of SPH was 34.71%. The molecular weight (MW) of SPH was principally concentrated at 180–3000 Da (52.29%). SPH was divided into two fractions by ultrafiltration: SPH-I (MW < 3 kDa) and SPH-II (MW > 3 kDa). Besides showing lipid peroxidation inhibitory activity in vitro, SPH-I exhibited high DPPH and ABTS radicals scavenging activities with IC50 of 350 μg/mL and 17.5 μg/mL, respectively. In addition, the antioxidant activity of SPH-I was estimated in vivo using the model of acute alcohol-induced liver injury in mice. For the hepatoprotective effects, oral administration of SPH-I at different concentrations (100, 300 mg/kg BW) to the mice subjected to alcohol significantly decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and hepatic malondialdehyde (MDA) level compared to the untreated mice. Besides, SPH-I could effectively restore the hepatic superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities and glutathione (GSH) level. Results suggested that SPH was rich in biopeptides that could be exploited as antioxidant molecules against oxidative stress in human body. PMID:28394291

Hepatoprotective Activity of Easter Lily (Lilium longiflorum Thunb.) Bulb Extracts.

PubMed

Tang, Wenping; Munafo, John P; Palatini, Kimberly; Esposito, Debora; Huang, Mou-Tuan; Komarnytsky, Slavko; Ho, Chi-Tang; Gianfagna, Thomas J

2015-11-11

The hepatoprotective activities of two different extracts, a hydroethanolic crude bulb extract (CB) and a steroidal glycoside-rich 1-butanol extract (BuOH), prepared from the bulbs of Easter lily (Lilium longiflorum Thunb.), were evaluated in a 24 week study in the female KK.Cg-A(y)/J Type 2 diabetic mouse model. Animals were divided into six groups (n = 16): control mice received Easter lily bulb extract-free drinking water together with a low- or high-fat diet (diabetic control); drinking water for the remaining groups was supplemented with CB extract (1%), BuOH extract (0.1 or 0.2%), and reference drug Metformin (0.001%), together with a high-fat diet. Both CB and BuOH extract treatment groups exhibited significantly improved liver function based on comparisons of triglycerides [diabetic 219 ± 34 mg/dL, CB 131 ± 27 mg/dL, BuOH(0.2%) 114 ± 35 mg/dL], CB total cholesterol (TC) (diabetic 196 ± 12 mg/dL, CB 159 ± 5 mg/dL), average liver mass [diabetic 2.96 ± 0.13 g, CB 2.58 ± 0.08 g, BuOH(0.1%) 2.48 ± 0.13 g], alanine transferase [diabetic 74 ± 5 units/L, CB 25 ± 1 units/L, BuOH(0.1%) 45 ± 1 units/L], and histological examinations. Glucose metabolism was improved only in CB, which was confirmed by oral glucose tolerance tests (OGTT) in diet-induced obese C57BL/6J mice exposed to CB extract. These data suggest that steroidal glycosides 1-5 might play a role in the hepatoprotective activity of the BuOH extracts, while the results of the TC measurements and OGTT study indicate that other constituents present in the CB extract are responsible for its hypocholesterolemic and hypoglycemic activity.

Extract of Citrus maxima (pummelo) leaves improve hepatoprotective activity in Wistar rats submitted to the induction of non-alcoholic hepatic steatosis.

PubMed

Feksa, Denise Lima; Coelho, Ritiéle Pinto; Aparecida da Costa Güllich, Angélica; Dal Ponte, Emanuelle S; da Costa Escobar Piccoli, Jacqueline; Manfredini, Vanusa

2018-02-01

Non-alcoholic fatty liver disease is a spectrum of liver changes, ranging from hepatic steatosis to hepatocellular carcinoma. The Citrus maxima (CM) has been shown to be beneficial to the organism, and these activities are attributed to the presence of phytochemical compounds. The objective of this study was to evaluate the n vitro antioxidant potential of the CM leaves extract and on Wistar rats submitted to hepatic steatosis induction by fructose-associated hyperlipid diet (FHD). For the evaluation of in vivo effects, the animals were distributed in G1 (normal diet - ND), G2 (FHD), G3 (ND + extract 50mg/kg) and G4 (FHD + extract 50 mg/kg). All the parameters were determined through classical methodologies. The extract showed a significant antioxidant potential in vitro. In the in vivo analysis, the diet used was able to induce the development of metabolic abnormalities that favored the formation of hepatic steatosis (G2). Changes in inflammatory markers, increase in markers of oxidative damage, and reduction of antioxidant defenses were also observed. In addition, the extract did not cause changes in the animals' weight gain and acted as an anti-inflammatory, since G4 animals exhibited significantly reduced levels of the inflammatory markers. In the liver, the extract significantly decreased the content of fat, cholesterol and triglycerides compared to G2. The extract also showed antioxidant activity (G4) when compared to G2. The results suggest that the extract of CM leaf showed hepatoprotective, hypolipidemic, anti-inflammatory and antioxidant activities and the presence of phenolic compounds is a probable cause for such activities. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Effect of Vernonia amygdalina Del. Leaf Ethanolic Extract on Intoxicated Male Wistar Rats Liver

PubMed Central

Iwo, Maria Immaculata; Sjahlim, Sergia Louisa; Rahmawati, Siti Farah

2017-01-01

Vernonia amygdalina has been shown to have antioxidant activity, and is also expected to have hepatoprotective activity. This study was conducted to study the effect of V. amygdalina ethanol extracts on intoxicated rat livers. Fresh leaves were extracted in ethanol, and the hepatoprotective activity was tested on male Wistar rats induced with a combination of isoniazid (INH) and rifampicin. Parameters observed were the activity of the enzyme alanine transferase (ALT), serum albumin levels, liver index, and histopathological of the rat liver. The results showed that 50 and 100 mg/kg rat body weight of V. amygdalina ethanol extracts could prevent liver intoxication, starting on day 14. Based on serum albumin concentrations and ALT activity, the high dose extract (100 mg/kg) was more potent as a hepatoprotective agent compared to the extract at a low dose (50 mg/kg). The group of rats treated with a high dose extract showed normal liver index compared to the positive control. Through histology examination, the liver of rats treated with a high dose extract (100 mg/kg) showed minimal liver cell structure damage, and showed similar patterns to the normal rat. Based on these results, it can be concluded that V. amygdalina ethanol extracts can be used to protect the liver in a combination of INH and rifampicin as antituberculosis treatment. PMID:28333116

Effect of Vernonia amygdalina Del. Leaf Ethanolic Extract on Intoxicated Male Wistar Rats Liver.

PubMed

Iwo, Maria Immaculata; Sjahlim, Sergia Louisa; Rahmawati, Siti Farah

2017-03-23

Vernonia amygdalina has been shown to have antioxidant activity, and is also expected to have hepatoprotective activity. This study was conducted to study the effect of V. amygdalina ethanol extracts on intoxicated rat livers. Fresh leaves were extracted in ethanol, and the hepatoprotective activity was tested on male Wistar rats induced with a combination of isoniazid (INH) and rifampicin. Parameters observed were the activity of the enzyme alanine transferase (ALT), serum albumin levels, liver index, and histopathological of the rat liver. The results showed that 50 and 100 mg/kg rat body weight of V. amygdalina ethanol extracts could prevent liver intoxication, starting on day 14. Based on serum albumin concentrations and ALT activity, the high dose extract (100 mg/kg) was more potent as a hepatoprotective agent compared to the extract at a low dose (50 mg/kg). The group of rats treated with a high dose extract showed normal liver index compared to the positive control. Through histology examination, the liver of rats treated with a high dose extract (100 mg/kg) showed minimal liver cell structure damage, and showed similar patterns to the normal rat. Based on these results, it can be concluded that V. amygdalina ethanol extracts can be used to protect the liver in a combination of INH and rifampicin as antituberculosis treatment.

Hepatoprotective effects and antioxidant, antityrosinase activities of phloretin and phloretin isonicotinyl hydrazone.

PubMed

Zuo, Ai-Ren; Yu, Yan-Ying; Shu, Qing-Long; Zheng, Li-Xiang; Wang, Xiao-Min; Peng, Shu-Hong; Xie, Yan-Fei; Cao, Shu-Wen

2014-06-01

Acute liver damage is primarily induced by one of several causes, among them viral exposure, alcohol consumption, and drug and immune system issues. Agents with the ability to inhibit tyrosinase and protect against DNA damage caused by reactive oxygen species (ROS) may be therapeutically useful for the prevention or treatment of ROS-related diseases. This investigation examined the hepatoprotective effects of phloretin and phloretin isonicotinyl hydrazone (PIH) on d-galactosamine (D-GalN)-induced acute liver damage in Kunming mice, as well as the possible mechanisms. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transferase (γ-GT), alkaline phosphatase (ALP), and total bilirubin (TB) as well as the histopathological changes in mouse liver sections were determined. The antioxidant effects of phloretin, quercetin, and PIH on lipid peroxidation in rat liver mitochondria in vitro, 1,1-diphenyl-2-picrylhydrazyl (DPPH) or 2,2-azino-bis-(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) free radical scavenging activity in vitro, and supercoiled pBR322 plasmid DNA were confirmed. The experiment also examined the antityrosinase activity, inhibition type, and inhibition constant of phloretin and PIH. Phloretin, quercetin, or PIH significantly prevented the increase in serum ALT, AST, γ-GT, ALP, and TB in acute liver damage induced by D-GalN, and produced a marked reduction in the histopathological hepatic lesions. Phloretin, quercetin, or PIH also exhibited antioxidant effects on lipid peroxidation in rat liver mitochondria in vitro, DPPH or ABTS free radical scavenging activity in vitro, and supercoiled pBR322 plasmid DNA. Phloretin, quercetin, or PIH also exhibited good antityrosinase activity. To the best of our knowledge, this was the first study of the hepatoprotective effects of phloretin and PIH on D-GalN-induced acute liver damage in Kunming mice as well as the possible mechanisms. This was also the first study of the lipid peroxidation inhibition activity of phloretin and PIH in liver mitochondria induced by the Fe(2+)/vitamin C (Vc) system in vitro, the protective effects on supercoiled pBR322 plasmid DNA, and the antityrosinase activity of phloretin and PIH. Copyright © 2014. Published by Elsevier B.V.

Hepatoprotective effects of Arctium lappa Linne on liver injuries induced by chronic ethanol consumption and potentiated by carbon tetrachloride.

PubMed

Lin, Song-Chow; Lin, Chia-Hsien; Lin, Chun-Ching; Lin, Yun-Ho; Chen, Chin-Fa; Chen, I-Cheng; Wang, Li-Ya

2002-01-01

Arctium lappa Linne (burdock) is a perennial herb which is popularly cultivated as a vegetable. In order to evaluate its hepatoprotective effects, a group of rats (n = 10) was fed a liquid ethanol diet (4 g of absolute ethanol/ 80 ml of liquid basal diet) for 28 days and another group (n = 10) received a single intraperitoneal injection of 0.5 ml/kg carbon tetrachloride (CCl(4)) in order to potentiate the liver damage on the 21st day (1 day before the beginning of A. lappa treatment). Control group rats were given a liquid basal diet which did not contain absolute ethanol. When 300 mg/kg A. lappa was administered orally 3 times per day in both the 1-day and 7-day treatment groups, some biochemical and histopathological parameters were significantly altered, both in the ethanol group and the groups receiving ethanol supplemented with CCl(4). A. lappa significantly improved various pathological and biochemical parameters which were worsened by ethanol plus CCl(4)-induced liver damage, such as the ethanol plus CCl(4)-induced decreases in total cytochrome P-450 content and NADPH-cytochrome c reductase activity, increases in serum triglyceride levels and lipid peroxidation (the deleterious peroxidative and toxic malondialdehyde metabolite may be produced in quantity) and elevation of serum transaminase levels. It could even restore the glutathione content and affect the histopathological lesions. These results tended to imply that the hepatotoxicity induced by ethanol and potentiated by CCl(4) could be alleviated with 1 and 7 days of A. lappa treatment. The hepatoprotective mechanism of A. lappa could be attributed, at least in part, to its antioxidative activity, which decreases the oxidative stress of hepatocytes, or to other unknown protective mechanism(s). Copyright 2002 National Science Council, ROC and S. Karger AG, Basel

Hawthorn ethanolic extracts with triterpenoids and flavonoids exert hepatoprotective effects and suppress the hypercholesterolemia-induced oxidative stress in rats.

PubMed

Rezaei-Golmisheh, Ali; Malekinejad, Hassan; Asri-Rezaei, Siamak; Farshid, Amir Abbas; Akbari, Peyman

2015-07-01

The current study was aimed to determine the bioactive constituents and biological effects of the Crataegus monogyna ethanolic extracts from bark, leaves and berries on hypercholesterolemia. Oleanolic acid, ursolic acid, quercetin and lupeol concentrations were quantified by HPLC. Total phenol content and radical scavenging activity of extracts were also measured. The hypocholesterolemic, antioxidant, and hepatoprotective effects of the extracts were examined in hypercholesterolemic rats and compared with orlistat. The highest phenol content, oleanolic acid, quercetin and lupeol levels and free radical scavenging potency were found in the bark extract, and the highest ursolic acid level was found in the berries extract. Orlistat and extracts significantly (P<0.05) lowered the hypercholesterolemia-increased serum level of hepatic enzymes and lipid peroxidation level. Hawthorn's extracts protected from hepatic thiol depletion and improved the lipid profile and hepatic damages. Data suggested that hawthorn's extracts are able to protect from hypercholesterolemia-induced oxidative stress and hepatic injuries. Moreover, the hypocholesterolemic effect of extracts was found comparable to orlistat.

Hepatoprotective effect of ethanol extract from Berchemia lineate against CCl4-induced acute hepatotoxicity in mice.

PubMed

Li, Cong; Yi, Li-Tao; Geng, Di; Han, Yuan-Yuan; Weng, Lian-Jin

2015-05-01

The roots of Berchemia lineate (L.) DC. (Rhamnaceae) have been long used as a remedy for the treatment of some diseases in Guangxi Province, China. The present study investigates the hepatoprotective effect of Berchemia lineate ethanol extract (BELE) on CCl4-induced acute liver damage in mice. Effect of BELE administrated for 7 consecutive days was evaluated in mice by the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), albulin (ALB), globulin (GLB), and total protein (TP) levels, as well as liver superoxide dismutase (SOD) activity and malondialdehyde (MDA) level. Moreover, histopathological examinations were also taken. Compared with the model group, administration of 400 mg/kg BELE for 7 d in mice significantly decreased the serum ALT (56.25 U/L), AST (297.67 U/L), ALP (188.20 U/L), and TBIL (17.90 mol/L), along with the elevation of TP (64.67 g/L). In addition, BELE (100, 200, and 400 mg/kg, i.g.) treated mice recorded a dose-dependent increment of SOD (291.17, 310.32, and 325.67 U/mg prot) and reduction of MDA (7.27, 6.77, and 5.33 nmol/mg prot) levels. Histopathological examinations also confirmed that BELE can ameliorate CCl4-induced liver injuries, characterized by extensive hepatocellular degeneration/necrosis, inflammatory cell infiltration, congestion, and sinusoidal dilatation. The results indicated that BELE possessed remarkable protective effect against acute hepatotoxicity and oxidative injuries induced by CCl4, and that the hepatoprotective effects of BELE may be due to both the inhibition of lipid peroxidation and the increase of antioxidant activity.

Antioxidants of Phyllanthus emblica L. Bark Extract Provide Hepatoprotection against Ethanol-Induced Hepatic Damage: A Comparison with Silymarin

PubMed Central

Chaphalkar, Renuka; Apte, Kishori G.; Talekar, Yogesh

2017-01-01

Phyllanthus emblica L. (amla) has been used in Ayurveda as a potent rasayan for treatment of hepatic disorders. Most of the pharmacological studies, however, are largely focused on PE fruit, while the rest of the parts of PE, particularly, bark, remain underinvestigated. Therefore, we aimed to investigate the protective effect of the hydroalcoholic extract of Phyllanthus emblica bark (PEE) in ethanol-induced hepatotoxicity model in rats. Total phenolic, flavonoid, and tannin content and in vitro antioxidant activities were determined by using H2O2 scavenging and ABTS decolorization assays. Our results showed that PEE was rich in total phenols (99.523 ± 1.91 mg GAE/g), total flavonoids (389.33 ± 1.25 mg quercetin hydrate/g), and total tannins (310 ± 0.21 mg catechin/g), which clearly support its strong antioxidant potential. HPTLC-based quantitative analysis revealed the presence of the potent antioxidants gallic acid (25.05 mg/g) and ellagic acid (13.31 mg/g). Moreover, one-month PEE treatment (500 and 1000 mg/kg, p.o.) followed by 30-day 70% ethanol (10 mL/kg) administration showed hepatoprotection as evidenced by significant restoration of ALT (p < 0.01), AST (p < 0.001), ALP (p < 0.05), and TP (p < 0.001) and further confirmed by liver histopathology. PEE-mediated hepatoprotection could be due to its free radical scavenging and antioxidant activity that may be ascribed to its antioxidant components, namely, ellagic acid and gallic acid. Thus, the results of the present study support the therapeutic claims made in Ayurveda about Phyllanthus emblica. PMID:28168009

Mangiferin exerts hepatoprotective activity against D-galactosamine induced acute toxicity and oxidative/nitrosative stress via Nrf2–NFκB pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Das, Joydeep; Ghosh, Jyotirmoy; Roy, Anandita

Mangiferin, a xanthone glucoside, is well known to exhibit antioxidant, antiviral, antitumor, anti-inflammatory and gene-regulatory effects. In the present study, we isolated mangiferin from the bark of Mangifera indica and assessed its beneficial role in galactosamine (GAL) induced hepatic pathophysiology. GAL (400 mg/kg body weight) exposed hepatotoxic rats showed elevation in the activities of serum ALP, ALT, levels of triglycerides, total cholesterol, lipid-peroxidation and reduction in the levels of serum total proteins, albumin and cellular GSH. Besides, GAL exposure (5 mM) in hepatocytes induced apoptosis and necrosis, increased ROS and NO production. Signal transduction studies showed that GAL exposure significantlymore » increased the nuclear translocation of NFκB and elevated iNOS protein expression. The same exposure also elevated TNF-α, IFN-γ, IL-1β, IL-6, IL-12, IL-18 and decreased IL-10 mRNA expressions. Furthermore, GAL also decreased the protein expression of Nrf2, NADPH:quinine oxidoreductase-1, heme oxygenase-1 and GSTα. However, mangiferin administration in GAL intoxicated rats or coincubation of hepatocytes with mangiferin significantly altered all these GAL-induced adverse effects. In conclusion, the hepatoprotective role of mangiferin was due to induction of antioxidant defense via the Nrf2 pathway and reduction of inflammation via NFκB inhibition. Highlights: ►Galactosamine induces hepatocytes death via oxidative and nitrosative stress. ►Mangiferin exerts hepatoprotective effect/antioxidant defense via Nrf2 pathway. ►Mangiferin exerts anti-inflammatory responses by inhibiting NF-κB. ►Mangiferin suppresses galactosamine-induced repression of IL-10 mRNA.« less

Hepatoprotective activity of Macrothelypteris torresiana (Gaudich.) aerial parts against CCl4-induced hepatotoxicity in rodents and analysis of polyphenolic compounds by HPTLC.

PubMed

Mondal, Sumanta; Ghosh, Debjit; Ganapaty, Seru; Chekuboyina, Surya Vamsi Gokul; Samal, Manisha

2017-06-01

Macrothelypteris torresiana is a fern species belonging to family Thelypteridaceae. The present study was conducted to evaluate hepatoprotective potential of ethanol extract from M. torresiana aerial parts (EEMTAP) and detect the polyphenolic compounds present in the extract using high performance thin layer chromatography (HPTLC). Hepatoprotective potential of EEMTAP were tested at doses of 300 and 600 mg/kg, per os (p.o.), on Wistar albino rats. The extract and silymarin treated animal groups showed significant decrease in activities of different biochemical parameters like serum glutamic oxaloacetic transaminase (SGOT), serum glutamate-pyruvate transaminase (SGPT), alkaline phosphatase (ALP), which were elevated by carbon tetrachloride (CCl 4 ) intoxication. The levels of total bilirubin and total protein alongwith the liver weight were also restored to normalcy by EEMTAP and silymarin treatment. After CCl 4 administration the level of hepatic antioxidant enzymes such as Glutathione (GSH) and Catalase (CAT) were decreased whereas the level of hepatic lipid peroxidation (LPO) was elevated. The level of these hepatic antioxidant enzymes were also brought to normalcy by EEMTAP and silymarin treatment. Histological studies supported the biochemical findings and treatment with EEMTAP at doses 300 and 600 mg/kg, p.o. was found to be effective in restoring CCl 4 -induced hepatotoxicity in rats. A simple HPTLC analysis was conducted for the detection of polyphenolic compounds in EEMTAP, and the result revealed the presence of caffeic acid as phenolic acid and quercetin as flavonoid. The proposed HPTLC method is simple, concise and provides a good resolution of caffeic acid and quercetin from other constituents present in EEMTAP.

Hepatoprotective effects of Micromeria croatica ethanolic extract against CCl4-induced liver injury in mice.

PubMed

Vladimir-Knežević, Sanda; Cvijanović, Olga; Blažeković, Biljana; Kindl, Marija; Štefan, Maja Bival; Domitrović, Robert

2015-07-15

Micromeria croatica (Pers.) Schott is an aromatic plant from Lamiaceae family previously found to possess potent in vitro antioxidant activity which is mainly attributed to the high level of polyphenolic substances. The aim of this study was to investigate the hepatoprotective activity and possible underlying mechanisms of Micromeria croatica ethanolic extract (MC) using a model of carbon tetrachloride (CCl4)-induced liver injury in mice. Male BALB/cN mice were randomly divided into seven groups: control group received saline, MC group received ethanolic extract of M. croatica in 5% DMSO (100 mg/kg b.w., p.o.), and CCl4 group was administered CCl4 dissolved in corn oil (2 mL/kg, 10% v/v, ip). MC50, MC200 and MC400 groups were treated with MC orally at doses of 50, 200 and 400 mg/kg once daily for 2 consecutive days, respectively, 6 h after CCl4 intoxication. The reference group received silymarin at dose of 400 mg/kg. At the end of experiment, blood and liver samples were collected for biochemical, histopathological, immunohistochemical and Western blot analyses. In addition, major phenolic compounds in MC were quantified by HPLC-DAD. CCl4 intoxication resulted in liver cells damage and oxidative stress and triggered inflammatory response in mice livers. MC treatment decreased ALT activity and prevented liver necrosis. Improved hepatic antioxidant status was evident by increased Cu/Zn SOD activity and decreased 4-hydroxynonenal (4-HNE) formation in the livers. Concomitantly, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were overexpressed. The hepatoprotective activity of MC was accompanied by the increase in nuclear factor-kappaB (NF-κB) activation and tumor necrosis factor-alpha (TNF-α) expression, indicating amelioration of hepatic inflammation. Additionally, MC prevented tumor growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) expression, suggesting the potential for suppression of hepatic fibrogenesis. These results of the present study demonstrated that MC possesses in vivo antioxidant and anti-inflammatory activity and exhibits antifibrotic potential, which are comparable to those of standard hepatoprotective compound silymarin.

Protective effect of a polysaccharide from Anoectochilus roxburghii against carbon tetrachloride-induced acute liver injury in mice.

PubMed

Zeng, Biyu; Su, Minghua; Chen, Qingxi; Chang, Qiang; Wang, Wei; Li, Huihua

2017-03-22

Anoectochilus roxburghii (Wall.) Lindl. is traditionally used for the treatment of various types of chronic and acute hepatitis in China. Considering that Anoectochilus roxburghii polysaccharide (ARPT) is the main constituent of Anoectochilus roxburghii, the present study was designed to investigate the hepatoprotective effect of ARPT and its possible mechanism in carbon tetrachloride (CCl 4 )-induced mice. The hepatoprotective activity of ARPT (150, 300 and 500mg/kg) were investigated on CCl 4 -induced acute liver damage in mice. The activities of alanine transaminase (ALT), aspartate transaminase (AST) were determined in serum. The hepatic levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) were measured in liver homogenates. The levels of cytochrome P450 sub family 2E1 (CYP2E1), tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-2 (MIP-2), KC (Murine IL-8 ortholog), transforming growth factor-beta1 (TGF-β1), Bcl-2 and Bax were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The expressions of CYP2E1, nuclear factor-kappa B (NF-κB) p65 and caspase-3 were evaluated by western blot assays. The hepatic levels of TNF-α, IL-6, MIP-2 and TGF-β1 were measured by enzyme-linked immunosorbent assay (ELISA). Furthermore, histopathological observation and terminal-deoxynucleoitidyl transferase mediated nick end labeling assay (TUNEL) were carried out on the separated livers of mice. ARPT significantly decreased serum ALT and AST activities, hepatic MDA level, and markedly enhanced antioxidant enzyme (SOD, CAT and GSH-Px) activities and GSH level in hepatic tissue, in a dose-dependent manner, when compared to the model group. Histopathological observation revealed the hepatoprotective effect of ARPT against the damage. Furthermore, ARPT remarkably inhibited CYP2E1 mRNA expression, decreased NF-κB p65 expression and therefore to prevent the secretion of pro-inflammatory cytokines (TNF-α and IL-6) and chemokines (MCP-1, MIP-2 and KC), suppressed TGF-β1 expression and hepatocytes apoptosis. Moreover, ARPT could prevent DNA fragmentation based on TUNEL assay results. These findings suggested that ARPT possessed hepatoprotective effect against CCl 4 -induced hepatotoxicity in mice and the action might in part be through reducing oxidative stress, inflammation and apoptosis. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Nrf2 activators from Glycyrrhiza inflata and their hepatoprotective activities against CCl4-induced liver injury in mice.

PubMed

Lin, Yan; Kuang, Yi; Li, Kai; Wang, Shuang; Ji, Shuai; Chen, Kuan; Song, Wei; Qiao, Xue; Ye, Min

2017-10-15

Glycyrrhiza inflata (licorice) has been used to treat liver diseases for a long history. However, the bioactive compounds are still not clear. In this work, 77 compounds, including 9 new ones, were isolated from the EtOAc extract of the roots and rhizomes of G. inflata. The Nrf2 activation activities of all compounds were screened using ARE-luciferase reporter assay on HepG2C8 cells. The results indicated a number of chalcones were potent Nrf2 activators, including 11 (licochalcone A, 4.07-fold), 12 (licochalcone B, 5.17-fold), and 19 (echinatin, 4.09-fold). Further studies indicated that 11, 12 and 19 remarkably attenuated CCl 4 -induced acute liver injury in mice (10 or 50mg/kg, 7days, ig.). These compounds could be promising hepatoprotective natural agents. Copyright © 2017 Elsevier Ltd. All rights reserved.

Antioxidant properties of Taraxacum officinale leaf extract are involved in the protective effect against hepatoxicity induced by acetaminophen in mice.

PubMed

Colle, Dirleise; Arantes, Leticia Priscilla; Gubert, Priscila; da Luz, Sônia Cristina Almeida; Athayde, Margareth Linde; Teixeira Rocha, João Batista; Soares, Félix Alexandre Antunes

2012-06-01

Acetaminophen (APAP) hepatotoxicity has been related to several cases of hepatitis, cirrhosis, and hepatic transplant. As APAP hepatotoxicity is related to reactive oxygen species (ROS) formation and excessive oxidative stress, natural antioxidant compounds have been tested as an alternative therapy to diminish the hepatic dysfunction induced by APAP. Taraxacum officinale Weber (Family Asteraceae), commonly known as dandelion, is used for medicinal purposes because of its choleretic, diuretic, antioxidant, anti-inflammatory, and hepatoprotective properties. This study evaluated the hepatoprotective activity of T. officinale leaf extract against APAP-induced hepatotoxicity. T. officinale was able to decrease thiobarbituric acid-reactive substance levels induced by 200 mg/kg APAP (p.o.), as well as prevent the decrease in sulfhydryl levels caused by APAP treatment. Furthermore, histopathological alterations, as well as the increased levels of serum aspartate and alanine aminotransferases caused by APAP, were prevented by T. officinale (0.1 and 0.5 mg/mL). In addition, T. officinale extract also demonstrated antioxidant activity in vitro, as well as scavenger activity against 2,2-diphenyl-1-picrylhydrazyl and nitric oxide radicals. Our results clearly demonstrate the hepatoprotective effect of T. officinale against the toxicity induced by APAP. The possible mechanisms involved include its scavenger activities against ROS and reactive nitrogen species, which are attributed to the content of phenolic compounds in the extract.

Comparative Hepatoprotective Activity of Ethanolic Extracts of Cuscuta australis against Acetaminophen Intoxication in Wistar Rats.

PubMed

Folarin, Rachael O; Omirinde, Jamiu O; Bejide, Ronald; Isola, Tajudeen O; Usende, Levi I; Basiru, Afisu

2014-01-01

This study investigates the comparative hepatoprotective activity of crude ethanol extracts of Cuscuta australis against acetaminophen (APAP) intoxication. Thirty-six rats were randomly divided into six groups of 6 replicates: Group 1 which served as control received water. Group 2 was orally administered 835 mg/kg body wt. of paracetamol on day 8. Groups 3 and 4 were orally administered ethanolic extracts of the seed of Cuscuta australis in doses of 125 mg/kg and 250 mg/kg, respectively, for 7 days and then intoxicated as in Group 2 on the 8th day. Groups 5 and 6 received similar oral doses of Cuscuta australis stem extracts for 7 days and then intoxicated as in Groups 3 and 4. Group 2 rats showed severe periportal hepatic necrosis, significantly elevated serum hepatic injury markers, markedly increased lipid peroxidation, and decreased hepatic antioxidant enzymes activities. Remarkably, Cuscuta australis (seed and stem) extract pretreatments in Groups 3, 4, 5, and 6, most especially, the stem extract pretreatment in Groups 5 and 6, improved better the hepatic histoarchitecture, the hepatocellular, and the oxidative stress injury markers in a dose-dependent manner. Conclusively, ethanol extractions of Cuscuta australis stem appear to protect the liver from acetaminophen intoxication better than the seed counterpart.

Comparative Hepatoprotective Activity of Ethanolic Extracts of Cuscuta australis against Acetaminophen Intoxication in Wistar Rats

PubMed Central

Folarin, Rachael O.; Omirinde, Jamiu O.; Bejide, Ronald; Isola, Tajudeen O.; Usende, Levi I.; Basiru, Afisu

2014-01-01

This study investigates the comparative hepatoprotective activity of crude ethanol extracts of Cuscuta australis against acetaminophen (APAP) intoxication. Thirty-six rats were randomly divided into six groups of 6 replicates: Group 1 which served as control received water. Group 2 was orally administered 835 mg/kg body wt. of paracetamol on day 8. Groups 3 and 4 were orally administered ethanolic extracts of the seed of Cuscuta australis in doses of 125 mg/kg and 250 mg/kg, respectively, for 7 days and then intoxicated as in Group 2 on the 8th day. Groups 5 and 6 received similar oral doses of Cuscuta australis stem extracts for 7 days and then intoxicated as in Groups 3 and 4. Group 2 rats showed severe periportal hepatic necrosis, significantly elevated serum hepatic injury markers, markedly increased lipid peroxidation, and decreased hepatic antioxidant enzymes activities. Remarkably, Cuscuta australis (seed and stem) extract pretreatments in Groups 3, 4, 5, and 6, most especially, the stem extract pretreatment in Groups 5 and 6, improved better the hepatic histoarchitecture, the hepatocellular, and the oxidative stress injury markers in a dose-dependent manner. Conclusively, ethanol extractions of Cuscuta australis stem appear to protect the liver from acetaminophen intoxication better than the seed counterpart. PMID:27433518

Caspase-1 Is Hepatoprotective during Trauma and Hemorrhagic Shock by Reducing Liver Injury and Inflammation

PubMed Central

Menzel, Christoph L; Sun, Qian; Loughran, Patricia A; Pape, Hans-Christoph; Billiar, Timothy R; Scott, Melanie J

2011-01-01

Adaptive immune responses are induced in liver after major stresses such as hemorrhagic shock (HS) and trauma. There is emerging evidence that the inflammasome, the multiprotein platform that induces caspase-1 activation and promotes interleukin (IL)-1β and IL-18 processing, is activated in response to cellular oxidative stress, such as after hypoxia, ischemia and HS. Additionally, damage-associated molecular patterns, such as those released after injury, have been shown to activate the inflammasome and caspase-1 through the NOD-like receptor (NLR) NLRP3. However, the role of the inflammasome in organ injury after HS and trauma is unknown. We therefore investigated inflammatory responses and end-organ injury in wild-type (WT) and caspase-1−/−mice in our model of HS with bilateral femur fracture (HS/BFF). We found that caspase-1−/− mice had higher levels of systemic inflammatory cytokines than WT mice. This result corresponded to higher levels of liver damage, cell death and neutrophil influx in caspase-1−/− liver compared with WT, although there was no difference in lung damage between experimental groups. To determine if hepatoprotection also depended on NLRP3, we subjected NLRP3−/− mice to HS/BFF, but found inflammatory responses and liver damage in these mice was similar to WT. Hepatoprotection was also not due to caspase-1–dependent cytokines, IL-1β and IL-18. Altogether, these data suggest that caspase-1 is hepatoprotective, in part through regulation of cell death pathways in the liver after major trauma, and that caspase-1 activation after HS/BFF does not depend on NLRP3. These findings may have implications for the treatment of trauma patients and may lead to progress in prevention or treatment of multiple organ failure (MOF). PMID:21666957

Phytochemical, antioxidant and protective effect of cactus cladodes extract against lithium-induced liver injury in rats.

PubMed

Ben Saad, Anouar; Dalel, Brahmi; Rjeibi, Ilhem; Smida, Amani; Ncib, Sana; Zouari, Nacim; Zourgui, Lazhar

2017-12-01

Opuntia ficus-indica (L.) Mill. (Castaceae) (cactus) is used in Tunisian medicine for the treatment of various diseases. This study determines phytochemical composition of cactus cladode extract (CCE). It also investigates antioxidant activity and hepatoprotective potential of CCE against lithium carbonate (Li 2 CO 3 )-induced liver injury in rats. Twenty-four Wistar male rats were divided into four groups of six each: a control group given distilled water (0.5 mL/100 g b.w.; i.p.), a group injected with Li 2 CO 3 (25 mg/kg b.w.; i.p.; corresponding to 30% of the LD 50 ) twice daily for 30 days, a group receiving only CCE at 100 mg/kg of b.w. for 60 days and then injected with distilled water during the last 30 days of CCE treatment, and a group receiving CCE and then injected with Li 2 CO 3 during the last 30 days of CCE treatment. The bioactive components containing the CCE were identified using chemical assays. Treatment with Li 2 CO 3 caused a significant change of some haematological parameters including red blood cells (RBC), white blood cells (WBC), haemoglobin content (Hb), haematocrit (Ht) and mean corpuscular volume (VCM) compared to the control group. Moreover, significant increases in the levels of glucose, cholesterol, triglycerides and of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) activities were observed in the blood of Li 2 CO 3 -treated rats. Furthermore, exposure to Li 2 CO 3 significantly increased the LPO level and decreased superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities in the hepatic tissues. CCE possesses a significant hepatoprotective effect.

Protective effect of polysaccharide from maca (Lepidium meyenii) on Hep-G2 cells and alcoholic liver oxidative injury in mice.

PubMed

Zhang, Lijun; Zhao, Qingsheng; Wang, Liwei; Zhao, Mingxia; Zhao, Bing

2017-06-01

To study the characterization and hepatoprotective activity of polysaccharide from maca (Lepidium meyenii), the main polysaccharide from maca (MP-1) was obtained by DEAE-52 cellulose column. The average molecular weight of MP-1 was 1067.3kDa and the polysaccharide purity was 91.63%. In order to assess the antioxidant activities of MP-1, four kinds of methods were used, including scavenging hydroxyl radical, DPPH, superoxide anion radical, and FRAP, and the results indicated high antioxidant activities. Furthermore, hepatoprotective activity of MP-1 was studied both in vitro and vivo. In vitro, the alcohol induced Hep-G2 cells model was established to evaluate the protective effect of MP-1, which demonstrated MP-1 can alleviate alcohol damage in Hep-G2 cells. In vivo, the Institute　of　Cancer　Researcch (ICR) mice were used to evaluate hepatoprotecive effects of MP-1 on alcoholic liver disease (ALD). Supplement with MP-1 supressed the triglyceride level both in serum and in hepatic tissue. In addition, MP-1 ameliorated serous transaminases increase induced by alcohol, including aspartate transaminase, alanine aminotransferase, and γ-glutamyl transpeptidase. Moreover, MP-1 also dramatically increased the superoxide dismutase, glutathione peroxidase, and glutathione s-transferase levels in alcoholic mice. Meantime, histopathologic results MP-1 lighten inflammation induced by alcohol. These results indicate that MP-1 possesses hepatoprotective activity against hepatic injury induced by alcohol. Copyright © 2017 Elsevier B.V. All rights reserved.

Potential antioxidant properties and hepatoprotective effects of an aqueous extract formula derived from three Chinese medicinal herbs against CCl(4)-induced liver injury in rats.

PubMed

Yang, Chi-Ching; Fang, Jong-Yi; Hong, Tuan-Liang; Wang, Tzu-Ching; Zhou, Ya-En; Lin, Ta-Chen

2013-01-01

The hepatoprotective effects of an aqueous extract formula (AEF) derived from Artemisia capillaris, Lonicera japonica and Silybum marianum (ratio 1:1:1) were evaluated by its antioxidant properties and its attenuation of carbon tetrachloride (CCl(4))-induced liver damage in rats. The antioxidant analyses revealed that the AEF showed higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and superoxide anion radical scavenging activities as well as ferric reducing antioxidant potential (FRAP) and Trolox equivalent antioxidant capacity (TEAC) compared with the individual herbs, suggesting a synergism in antioxidation between the three herbs. The animal experiments showed that the CCl(4) treatment increased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, but decreased triglyceride (TG) and glutathione (GSH) levels as well as glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities. However, AEF administration can successfully lower serum ALT and AST activities, restore the GSH level, ameliorate or restore GPx and CAT activities as well as improve SOD action depending on AEF dosage. Histological examination of liver showed that CCl(4) increased the extent of bile duct proliferation, necrosis, fibrosis and fatty vacuolation throughout the liver, but AEF can improve bile duct proliferation, vacuolation and fibrosis, and restore necrosis. The present study demonstrated the hepatoprotective potential of AEF as an alternative to the traditional silymarin. Copyright © 2012 Elsevier B.V. All rights reserved.

Chenopodium bonus-henricus L. - A source of hepatoprotective flavonoids.

PubMed

Kokanova-Nedialkova, Zlatina; Nedialkov, Paraskev; Kondeva-Burdina, Magdalena; Simeonova, Rumyana; Tzankova, Virginia; Aluani, Denitsa

2017-04-01

Three new flavonoid glycosides (7-9) named patuletin-3-O-(5″'-О-Е-feruloyl)-β-d-apiofuranosyl(1→2)[β-d-glucopyranosyl (1→6)]-β-d-glucopyranoside (7), spinacetin-3-O-(5″'-О-Е-feruloyl)-β-d-apiofuranosyl (1→2)[β-d-glucopyranosyl(1→6)]-β-d-glucopyranoside (8) and 6-methoxykaempferol-3-O-(5″'-О-Е-feruloyl)-β-d-apiofuranosyl(1→2)[β-d-glucopyranosyl (1→6)]-β-d-glucopyranoside (9) together with six known flavonoid glycosides of patuletin, spinacetin and 6-methoxykaempferol (1-6) were isolated from the aerial parts of C. bonus-henricus and identified with spectroscopic methods (1D and 2D NMR, UV, IR, HRESIMS). The MeOH extract exerts hepatoprotective and antioxidant activities comparable to those of flavonoid complex silymarin in in vitro (60μg/mL) and in vivo (100mg/kg/daily for 7days) models of hepatotoxicity, induced by CCl 4 . Flavonoids (1-9) (100μM), compared to silybin, significantly reduced the cellular damage caused by CCl 4 in rat hepatocytes, preserved cell viability and GSH level, decreased LDH leakage and reduced lipid damage. High concentrations of compounds (1-9) showed marginal or no cytotoxicity on HepG2 cell line. The experiment data suggest that the glycosides of 6-methoxykaempferol, spinacetin and patuletin are a promising and safe class of hepatoprotective agents. Copyright © 2017 Elsevier B.V. All rights reserved.

Hepatoprotective effect of 10% ethanolic extract from Curdrania tricuspidata leaves against ethanol-induced oxidative stress through suppression of CYP2E1.

PubMed

You, Yanghee; Min, Seoyoung; Lee, Yoo-Hyun; Hwang, Kwontack; Jun, Woojin

2017-10-01

The hepatoprotective effect of 10% ethanolic extract of Curdrania tricuspidata (CTE) was investigated in HepG2/2E1 cells and C57BL/6 J mice. When compared ethanol-only treated HepG2/2E1 cells, pretreatment of CTE prevented increased intra-cellular reactive oxygen species levels and decreased antioxidant activities by ethanol-induced oxidative stress. In C57BL/6 J mice, CTE at a dose of 250 mg/kg/day was administered for 10 days, with ethanol (5 g/kg/day) administered for the final 3 days. Pretreatment with CTE prevented the elevated activities of serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase caused by ethanol-induced hepatic damage. CTE-treated mice displayed a reduced level of malondialdehyde and increased antioxidant activities of catalase, glutathione S-transferase, glutathione peroxidase, and superoxide dismutase, as well as a reduced level of glutathione as compared with ethanol-only-treated mice. CTE-treated mice exhibited significant inhibition of CYP2E1 activities and expression. These results suggest that CTE could be a useful agent for the prevention of ethanol-induced oxidative damage in the liver, elevating antioxidative potentials and alleviating oxidative stress by suppressing CYP2El. Copyright © 2017 Elsevier Ltd. All rights reserved.

Amelioration of Paracetamol-Induced Hepatotoxicity in Rat by the Administration of Methanol Extract of Muntingia calabura L. Leaves

PubMed Central

Mahmood, N. D.; Mamat, S. S.; Kamisan, F. H.; Yahya, F.; Kamarolzaman, M. F. F.; Nasir, N.; Mohtarrudin, N.; Tohid, S. F. Md.; Zakaria, Z. A.

2014-01-01

Muntingia calabura L. is a tropical plant species that belongs to the Elaeocarpaceae family. The present study is aimed at determining the hepatoprotective activity of methanol extract of M. calabura leaves (MEMC) using two models of liver injury in rats. Rats were divided into five groups (n = 6) and received 10% DMSO (negative control), 50 mg/kg N-acetylcysteine (NAC; positive control), or MEMC (50, 250, and 500 mg/kg) orally once daily for 7 days and on the 8th day were subjected to the hepatotoxic induction using paracetamol (PCM). The blood and liver tissues were collected and subjected to biochemical and microscopical analysis. The extract was also subjected to antioxidant study using the 2,2-diphenyl-1-picrylhydrazyl-(DPPH) and superoxide anion-radical scavenging assays. At the same time, oxygen radical antioxidant capacity (ORAC) and total phenolic content were also determined. From the histological observation, lymphocyte infiltration and marked necrosis were observed in PCM-treated groups (negative control), whereas maintenance of hepatic structure was observed in group pretreated with N-acetylcysteine and MEMC. Hepatotoxic rats pretreated with NAC or MEMC exhibited significant decrease (P < 0.05) in ALT and AST enzymes level. Moreover, the extract also exhibited good antioxidant activity. In conclusion, MEMC exerts potential hepatoprotective activity that could be partly attributed to its antioxidant activity and, thus warrants further investigations. PMID:24868543

Anti-fatty liver effects of oils from Zingiber officinale and Curcuma longa on ethanol-induced fatty liver in rats.

PubMed

Nwozo, Sarah Onyenibe; Osunmadewa, Damilola Adeola; Oyinloye, Babatunji Emmanuel

2014-01-01

The present study is aimed at evaluating the protective effects of oils from Zingiber officinale (ginger) and Curcuma longa (turmeric) on acute ethanol-induced fatty liver in male Wistar rats. Ferric reducing antioxidant power activity and oxygen radical absorbance capacity of the oils were evaluated ex vivo. Rats were pretreated for 28 d with standard drug (Livolin Forte) and oils from Z. officinale and C. longa before they were exposed to 45% ethanol (4.8 g/kg) to induce acute fatty liver. Histological changes were observed and the degree of protection was measured by using biochemical parameters such as alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities. Serum triglyceride (TG) level, total cholesterol (TC) level and the effects of both oils on reduced gluthatione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD) and hepatic malondialdehyde (MDA) levels were estimated. Oils from Z. officinale and C. longa at a dose of 200 mg/kg showed hepatoprotection by decreasing the activities of serum enzymes, serum TG, serum TC and hepatic MDA, while they significantly restored the level of GSH as well as GST and SOD activities. Histological examination of rats tissues was related to the obtained results. From the results it may be concluded that oils from Z. officinale and C. longa (200 mg/kg) exhibited hepatoprotective activity in acute ethanol-induced fatty liver and Z. officinale oil was identified to have better effects than C. longa oil.

Hepatoprotective Effects of Chinese Medicinal Herbs: A Focus on Anti-Inflammatory and Anti-Oxidative Activities

PubMed Central

Lam, Puiyan; Cheung, Fan; Tan, Hor Yue; Wang, Ning; Yuen, Man Fung; Feng, Yibin

2016-01-01

The liver is intimately connected to inflammation, which is the innate defense system of the body for removing harmful stimuli and participates in the hepatic wound-healing response. Sustained inflammation and the corresponding regenerative wound-healing response can induce the development of fibrosis, cirrhosis and eventually hepatocellular carcinoma. Oxidative stress is associated with the activation of inflammatory pathways, while chronic inflammation is found associated with some human cancers. Inflammation and cancer may be connected by the effect of the inflammation-fibrosis-cancer (IFC) axis. Chinese medicinal herbs display abilities in protecting the liver compared to conventional therapies, as many herbal medicines have been shown as effective anti-inflammatory and anti-oxidative agents. We review the relationship between oxidative stress and inflammation, the development of hepatic diseases, and the hepatoprotective effects of Chinese medicinal herbs via anti-inflammatory and anti-oxidative mechanisms. Moreover, several Chinese medicinal herbs and composite formulae, which have been commonly used for preventing and treating hepatic diseases, including Andrographis Herba, Glycyrrhizae Radix et Rhizoma, Ginseng Radix et Rhizoma, Lycii Fructus, Coptidis Rhizoma, curcumin, xiao-cha-hu-tang and shi-quan-da-bu-tang, were selected for reviewing their hepatoprotective effects with focus on their anti-oxidative and ant-inflammatory activities. This review aims to provide new insight into how Chinese medicinal herbs work in therapeutic strategies for liver diseases. PMID:27043533

Chemical composition, antioxidant properties and hepatoprotective effects of chamomile (Matricaria recutita L.) decoction extract against alcohol-induced oxidative stress in rat.

PubMed

Sebai, Hichem; Jabri, Mohamed-Amine; Souli, Abdelaziz; Hosni, Karim; Rtibi, Kais; Tebourbi, Olfa; El-Benna, Jamel; Sakly, Mohsen

2015-07-01

The present study assessed the chemical composition, antioxidant properties, and hepatoprotective effects of subacute pre-treatment with chamomile (Matricaria recutita L.) decoction extract (CDE) against ethanol (EtOH)-induced oxidative stress in rats. The colorimetric analysis demonstrated that the CDE is rich in total polyphenols, total flavonoids and condensed tannins, and exhibited an important in vitro antioxidant activity. The use of LC/MS technique allowed us to identify 10 phenolic compounds in CDE. We found that CDE pretreatment, in vivo, protected against EtOH-induced liver injury evident by plasma transaminases activity and preservation of the hepatic tissue structure. The CDE counteracted EtOH-induced liver lipoperoxidation, preserved thiol -SH groups and prevented the depletion of antioxidant enzyme activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). We also showed that acute alcohol administration increased tissue and plasma hydrogen peroxide (H(2)O(2)), calcium and free iron levels. More importantly, CDE pre-treatment reversed all EtOH-induced disturbances in intracellular mediators. In conclusion, our data suggest that CDE exerted a potential hepatoprotective effect against EtOH-induced oxidative stress in rat, at least in part, by negatively regulating Fenton reaction components such as H(2)O(2) and free iron, which are known to lead to cytotoxicity mediated by intracellular calcium deregulation.

Antioxidant and Hepatoprotective Effects of Procyanidins from Wild Grape (Vitis amurensis) Seeds in Ethanol-Induced Cells and Rats

PubMed Central

Bak, Min Ji; Truong, Van-Long; Ko, Se-Yeon; Nguyen, Xuan Ngan Giang; Ingkasupart, Pajaree; Jun, Mira; Shin, Jin Young; Jeong, Woo-Sik

2016-01-01

In the present study, we characterized the antioxidant and hepatoprotective mechanisms underlying of wild grape seed procyanidins (WGP) against oxidative stress damage in ethanol-treated HepG2 cell and Sprague-Dawley (SD)-rat models. In HepG2 cells, WGP not only diminished the ethanol (EtOH, 100 mM)-induced reactive oxygen species (ROS) formation and cytochrome P450 2E1 (CYP2E1) expression, but also renovated both the activity and expression of antioxidant enzymes including catalase, superoxide dismutase, and glutathione peroxidase. Additionally, to investigate the hepatoprotective effect of WGP, rats were orally administered 10 or 50 mg/kg WGP once daily for seven days prior to the single oral administration of EtOH (6 g/kg). The results show that WGP administration decreased the EtOH-induced augment of the levels of serum aspartate transaminase and alanine transaminase as well as serum alcohol and acetaldehyde. WGP treatment upregulated the activities and protein levels of hepatic alcohol dehydrogenase, aldehyde dehydrogenase, and antioxidant enzymes but downregulated the protein expression level of liver CYP2E1 in EtOH-treated rats. Moreover, the decreased phosphorylation levels of mitogen activated protein kinases (MAPKs) by ethanol were induced in both HepG2 cell and rat models. Overall, pretreatment of WGP displayed the protective activity against EtOH-mediated toxicity through the regulation of antioxidant enzymes and alcohol metabolism systems via MAPKs pathways. PMID:27213339

Hepatoprotective Herbs, Avicenna Viewpoint

PubMed Central

Shamsi-Baghbanan, Hamid; Sharifian, Afsaneh; Esmaeili, Somayeh; Minaei, Bagher

2014-01-01

Background: Liver injury or dysfunction is considered as a serious health problem. The available synthetic drugs to treat liver disorders are expensive and cause further damage. Hence, hepatoprotective effects of some herbal drugs have been investigated, and one of the methods to choose herbs in order to study their biological effects is to search in ancient medical texts. Avicenna who is known as the prince of physicians had collected and classified Greek, Persian and Islamic medicine in the best possible way in the book of Canon in Arabic. Objectives: Avicenna’s book of The Canon of Medicine was reviewed to find the hepatoprotective herbs. Patients and Methods: Three different versions of the Canon were prepared and utilized. To find scientific names of plants we took advantage of three botany references. All of the herbs were investigated on the basis of scientific data from hepatoprotective effects point of view. The searched term was “hepatoprotective” without narrowing and limiting. The searched databases included Cochrane library, Web of science, SID, Irandoc and IranMedex. Results: 18 plants were found. 85% of the presented species, genus or families of plants were reported to have hepatoprotective properties and in the remaining 15% there were no reports of hepatoprotective effect. Flowers and fruits were the most used part of the plants. Most of the plants had simultaneous protective effects on multiple organs but the protective effect on the liver was mostly accompanied by protective effect on the stomach (83%). The average temperament of these herbs is "hot" in the 2nd phase of the 2nd grade, and "dry" in the 3rd phase of the 2nd grade. Hepatoprotective herbs mostly prescribed as a part of hepatoprotective compound drugs formula or other formula for liver diseases are Crocus sativus, Pistacia lentiscus, and Cinnamomum spp. Conclusions: Maybe there is common mechanism for protecting both liver and stomach. Aquilaria agallocha, Aquilaria malaccensis, and Ruscus aculeatus whose hepatoprotective effects have not yet been reported are considered as good candidates for future investigations. Given that Crocus sativus, and Cinnamomum spp are used as flavors in most countries, they will be introduced for more investigation in order to produce hepatoprotective drugs. PMID:24719702

Hawthorn ethanolic extracts with triterpenoids and flavonoids exert hepatoprotective effects and suppress the hypercholesterolemia-induced oxidative stress in rats

PubMed Central

Rezaei-Golmisheh, Ali; Malekinejad, Hassan; Asri-Rezaei, Siamak; Farshid, Amir Abbas; Akbari, Peyman

2015-01-01

Objective(s): The current study was aimed to determine the bioactive constituents and biological effects of the Crataegus monogyna ethanolic extracts from bark, leaves and berries on hypercholesterolemia. Materials and Methods: Oleanolic acid, ursolic acid, quercetin and lupeol concentrations were quantified by HPLC. Total phenol content and radical scavenging activity of extracts were also measured. The hypocholesterolemic, antioxidant, and hepatoprotective effects of the extracts were examined in hypercholesterolemic rats and compared with orlistat. Results: The highest phenol content, oleanolic acid, quercetin and lupeol levels and free radical scavenging potency were found in the bark extract, and the highest ursolic acid level was found in the berries extract. Orlistat and extracts significantly (P<0.05) lowered the hypercholesterolemia-increased serum level of hepatic enzymes and lipid peroxidation level. Hawthorn’s extracts protected from hepatic thiol depletion and improved the lipid profile and hepatic damages. Conclusion: Data suggested that hawthorn’s extracts are able to protect from hypercholesterolemia-induced oxidative stress and hepatic injuries. Moreover, the hypocholesterolemic effect of extracts was found comparable to orlistat. PMID:26361538

Antioxidant and anti-hyperlipidemic effects of mycelia zinc polysaccharides by Pleurotus eryngii var. tuoliensis.

PubMed

Xu, Nuo; Ren, Zhenzhen; Zhang, Jianjun; Song, Xinling; Gao, Zheng; Jing, Huijuan; Li, Shangshang; Wang, Shouxian; Jia, Le

2017-02-01

The aims of this work were designed to investigate the hepatoprotective and antioxidant effects of acidic- and alkali-extractable mycelia zinc polysaccharides (AcMZPS, AlMZPS) from Pleurotus eryngii var. tuoliensis on high-fat-high-cholesterol emulsion-induced hyperlipidemic mice. The in vivo experiments demonstrated that both AcMZPS and AlMZPS had potential hepatoprotective effects by significantly decreasing the levels of LDL-C, VLDL-C, TC, TG, ALT, AST, ALP, MDA and LPO, and remarkably increasing the HDL-C, SOD, GSH-Px, and CAT in serum lipid/liver homogenate, respectively. In addition, four polysaccharide fractions of AcMZPS-1, AcMZPS-2, AlMZPS-1, and AlMZPS-2, purified from AcMZPS and AlMZPS using DEAE chromatography, respectively, were subjected to monosaccharide composition analysis and valuated for the in vitro antioxidant activity. The results obtained in present study suggested that AcMZPS, AlMZPS and their purified fractions could be used as functional foods and natural drugs in preventing the hyperlipidemia and non-alcoholic fatty liver. Copyright © 2016 Elsevier B.V. All rights reserved.

Hepatoprotective, antinociceptive and antioxidant activities of cimetidine, ranitidine and famotidine as histamine H2 receptor antagonists.

PubMed

Ahmadi, Amirhossein; Ebrahimzadeh, Mohammad Ali; Ahmad-Ashrafi, Saeb; Karami, Mohammad; Mahdavi, Mohammad Reza; Saravi, Seyed Soheil Saeedi

2011-02-01

The antioxidant, antinociceptive and hepatoprotective effects of H(2) receptor blockers were examined with different experimental models. Antioxidant activities were determined by employing various in vitro assay systems such as 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical-scavenging activity assays, reducing power determination assays, nitric oxide-scavenging activity assays and hydrogen peroxide-scavenging activity assays. Antinociceptive effects were determined using the hot plate test in mice. The hepatoprotective effects of cimetidine, ranitidine and famotidine against hepatotoxicity induced by carbon tetrachloride (CCl(4) ) were determined by measuring the levels of serum enzymes alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) activities in mice. We found that the IC(50) values of cimetidine, ranitidine and famotidine on DPPH radical-scavenging activity were 671±28, 538±21 and 955±43 μg/mL, respectively. Famotidine showed very strong nitric oxide-scavenging activity. All three compounds showed very weak hydrogen peroxide-scavenging activity. Moreover, the compounds did not exhibit any reducing power activity until concentrations of 1.6 mg/mL. All compounds also showed a dose-dependent and marked analgesic activity in mice relative to controls. Pretreatment of mice with cimetidine, ranitidine or famotidine for three consecutive days reduced CCl(4)-induced hepatotoxicity in mice. Treatment with 200 mg/kg ranitidine reduced AST, AST and ALP serum levels, while 200 and 40 mg/kg of cimetidine and famotidine, respectively, reduced AST and ALP serum levels. H(2) blockers exhibited varying levels of antioxidant activities in various assays. Our results indicate that the antioxidant activities of H(2) blockers have an analgesic activity and protective effect on CCl(4)-induced hepatotoxicity in mice. These effects were greater with ranitidine than with the other compounds. © 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.

Hepatoprotective effect of Cichorium intybus L., a traditional Uighur medicine, against carbon tetrachloride-induced hepatic fibrosis in rats

PubMed Central

Li, Guo-Yu; Gao, Hong-Ying; Huang, Jian; Lu, Jin; Gu, Jing-Kai; Wang, Jin-Hui

2014-01-01

AIM: To investigate the hepatoprotective effect of a Cichorium intybus L. extract (CIE) on CCl4-induced hepatic fibrosis in rats. METHODS: Seventy-two male Wistar albino rats were randomly divided into six groups of twelve rats each. The normal control group was allowed free access to food and water. Liver injury was performed in the remaining five groups with an i.p. injection of a 1.0 mL/kg CCl4 and olive oil (2:3 v/v) mixture, twice weekly for 8 weeks. All rats, with the exception of the injury model group, were intragastrically (i.g.,) administered quantum satis (q.s.) dosages [CIE group: 6, 18, and 54 mg/kg, respectively; Fu Fang Bie Jia Ruan Gan Pian (FFBJRGP) group: 780 mg/kg]. The oral administration of different drugs was performed on the day before CCl4 administration and subsequently once per day for 8 wk. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), hexadecenoic acid (HA), laminin (LN), hydroxyproline (Hyp), and glutathione (GSH), malondialdehyde (MDA) and superoxide dismutase (SOD) in the rat livers were measured. Histopathological changes in the liver were assessed for each group using HE staining and a Masson Trichrome examination. The expression of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) was examined by immunohistochemical analysis. RESULTS: CIE at oral doses of 6, 18, and 54 g/kg per day showed a significant hepatoprotective effect, especially at a dose of 54 g/kg per day. CIE doses reduced the levels of AST (149.04 ± 34.44, P < 0.01), ALT (100.72 ± 27.19, P < 0.01), HA (548.50 ± 65.09, P < 0.01), LN (28.69 ± 3.32, P < 0.01) and Hyp (263.33 ± 75.82, P < 0.01). With regards to hepatoprotective activity, the CIE dose of 54 g/kg per day produced the largest significant effect by increasing GSH (3.11 ± 0.81), SOD (269.98 ± 33.77, P < 0.01) and reducing MDA (2.76 ± 0.51, P < 0.01) levels in the liver. The expressions of TGF-β1 and α-SMA were measured by immunohistology and found to be significantly reduced by CIE in a dose-dependent manner. CONCLUSION: CIE may effectively protect against CCl4-induced hepatic fibrosis in rats; thus, it is a promising anti-fibrotic therapeutic agent. PMID:24782629

Hepatoprotective potential of Fumaria indica Pugsley whole plant extracts, fractions and an isolated alkaloid protopine.

PubMed

Rathi, Anshu; Srivastava, Arvind Kumar; Shirwaikar, Annie; Singh Rawat, Ajay Kumar; Mehrotra, Shanta

2008-06-01

The present investigation demonstrates the hepatoprotective potential of 50% ethanolic water extract of whole plant of Fumaria indica and its three fractions viz., hexane, chloroform and butanol against d-galactosamine induced hepatotoxicity in rats. The hepatoprotection was assessed in terms reduction in histological damage, changes in serum enzymes (SGOT, SGPT, ALP) and metabolites bilirubin, reduced glutathione (GSH) and lipid peroxidation (MDA content). Among fractions more than 90% protection was found with butanol fraction in which alkaloid protopine was quantified as highest i.e. about 0.2mg/g by HPTLC. The isolated protopine in doses of 10-20mg p.o. also proved equally effective hepatoprotectants as standard drug silymarine (single dose 25mg p.o.). In general all treatments excluding hexane fraction proved hepatoprotective at par with silymarine (p

Hepatoprotective effect of collagen peptides from cod skin against liver oxidative damage in vitro and in vivo.

PubMed

Han, Yantao; Xie, Jing; Gao, Hui; Xia, Yunqiu; Chen, Xuehong; Wang, Chunbo

2015-03-01

The objective of this study was to investigate the hepatoprotective effect of cod skin collagen peptides (CSCP), isolated from fishing industrial by-products, in vitro and in vivo. Effect of CSCP on cell proliferation of normal and H2O2-damaged Chang liver cells was determined by MTT assay in vitro. Two animal models, CCl4-induced and acetaminophenum-induced acute hepatotoxicity, were established to assess the hepatoprotective effect of CSCP. Liver weight index, serum ALT and AST, antioxidant enzymes, and lipid peroxidation product were used as the markers of liver toxicity. The cell viability in the H2O2-treated Chang liver cells was remarkably increased when pretreated with CSCP from 100 to 1,000 µg/ml in a dose-dependent manner. CSCP pretreatment also alleviated the CCL4-induced liver index loss, while no marked changes were found in acetaminophenum-treated mice. Furthermore, CSCP pulled down serum ALT and AST level, increased the activities of SOD and CAT, and decreased MDA in both murine models of acute liver toxicity. Pretreatment with CSCP protected liver tissue against oxidative injure in vivo and in vitro. The underlying mechanism might involve enhancement in the activities of antioxidant enzymes and reduction in the lipid peroxidation.

Anti-oxidative, anti-inflammatory and hepato-protective effects of Ligustrum robustum.

PubMed

Lau, Kit-Man; He, Zhen-Dan; Dong, Hui; Fung, Kwok-Pui; But, Paul Pui-Hay

2002-11-01

Aqueous extract of processed leaves of Ligustrum robustum could dose-dependently scavenge superoxide radicals, inhibit lipid peroxidation, and prevent AAPH-induced hemolysis of red blood cells. In comparison with green tea, oolong tea and black tea, processed leaves of L. robustum exhibited comparable antioxidant potency in scavenging superoxide radicals and in preventing red blood cell hemolysis. By activity-guided fractionation, a glycoside-rich fraction named fraction B2 was separated and demonstrated to possess strong antioxidant effect. It was evaluated for its anti-inflammatory and hepato-protective activities. A single oral dose of fraction B2 at 0.5 g/kg could provide 51.5% inhibition on the vascular permeability change induced by intraperitoneal injection of acetic acid, but it could not inhibit croton oil-induced ear edema. On the other hand, fraction B2 exhibited moderate hepato-protective effect. Intragastric application of fraction B2 at 1.25, 2.5 or 5 g/kg 6 h after carbon tetrachloride administration could reduce the elevations of serum levels of aminotransferases (AST and ALT). Also, liver integrity was preserved, as liver sections from rats post-treated with fraction B2 showed a milder degree of fatty accumulation and necrosis. These results offer partial support to the traditional uses of the leaves of L. robustum as Ku-Ding-Cha.

Silymarin liposomes improves oral bioavailability of silybin besides targeting hepatocytes, and immune cells.

PubMed

Kumar, Nitesh; Rai, Amita; Reddy, Neetinkumar D; Raj, P Vasanth; Jain, Prateek; Deshpande, Praful; Mathew, Geetha; Kutty, N Gopalan; Udupa, Nayanabhirama; Rao, C Mallikarjuna

2014-10-01

Silymarin, a hepatoprotective agent, has poor oral bioavailability. However, the current dosage form of the drug does not target the liver and inflammatory cells selectively. The aim of the present study was to develop lecithin-based carrier system of silymarin by incorporating phytosomal-liposomal approach to increase its oral bioavailability and to make it target-specific to the liver for enhanced hepatoprotection. The formulation was prepared by film hydration method. Release of drug was assessed at pH 1.2 and 7.4. Formulation was assessed for in vitro hepatoprotection on Chang liver cells, lipopolysaccharide-induced reactive oxygen species (ROS) production by RAW 267.4 (murine macrophages), in vivo efficacy against paracetamol-induced hepatotoxicity and pharmacokinetic study by oral route in Wistar rat. The formulation showed maximum entrapment (55%) for a lecithin-cholesterol ratio of 6:1. Comparative release profile of formulation was better than silymarin at pH 1.2 and pH 7.4. In vitro studies showed a better hepatoprotection efficacy for formulation (one and half times) and better prevention of ROS production (ten times) compared to silymarin. In in vivo model, paracetamol showed significant hepatotoxicity in Wistar rats assessed through LFT, antioxidant markers and inflammatory markers. The formulation was found more efficacious than silymarin suspension in protecting the liver against paracetamol toxicity and the associated inflammatory conditions. The liposomal formulation yielded a three and half fold higher bioavailability of silymarin as compared with silymarin suspension. Incorporating the phytosomal form of silymarin in liposomal carrier system increased the oral bioavailability and showed better hepatoprotection and better anti-inflammatory effects compared with silymarin suspension. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Isoglycyrrhizinate Magnesium Enhances Hepatoprotective Effect of FK506 on Ischemia-Reperfusion Injury Through HMGB1 Inhibition in a Rat Model of Liver Transplantation.

PubMed

Zhang, Weichen; Li, Feibo; Ye, Yufu; Liu, Yuanxing; Yu, Songfeng; Cen, Chao; Chen, Xuliang; Zhou, Lin; Tang, Xiaofeng; Yu, Jun; Zheng, Shusen

2017-12-01

Ischemia-reperfusion injury after liver transplantation (LT) impairs graft function and affects prognosis of recipients. Isoglycyrrhizinate magnesium (Iso) is a hepatoprotective drug usually used after liver injury. In this study, we intended to explore whether Iso alone have protective effect after ischemia-reperfusion injury in a rat model of liver transplantation. We also aimed to study whether Iso could enhance the hepatoprotective effect of FK506 (tacrolimus) and underlying mechanism. Rats after LT were treated with different concentration of FK506 with or without, Iso or lower-dose FK506 plus Iso. Alanine transaminase, aspartate transaminase, and albumin level were measured after 48 hours, 72 hours, and 7 days. A cell ischemic/reperfusion model was established to further study the mechanism of hepatoprotective effect of FK506 and Iso. Iso treatment alone had no effect on liver grafts after LT, but lower-dose FK506 + Iso was better for maintenance of liver function than lower-dose FK506 alone at 48 hours, 72 hours, and 7 days after LT. In terms of mechanism, FK506 induced autophagy which resulted in significantly reduced apoptosis and maintained proliferative potential. However, autophagy induced by FK506 also lead to high-mobility group box (HMGB) 1 release from nuclei, resulting in hepatocyte injury through triggering of p38 phosphorylation and chemokine release. Iso effectively inhibited the release of HMGB1 and downstream inflammatory cytokines. Iso could inhibit release of HMGB1 by FK506 and enhance the hepatoprotective effect of FK506 in rat LT. Combining Iso with FK506 would be promising for the patients after LT.

ERK Signaling Pathway Plays a Key Role in Baicalin Protection Against Acetaminophen-Induced Liver Injury.

PubMed

Liao, Chia-Chih; Day, Yuan-Ji; Lee, Hung-Chen; Liou, Jiin-Tarng; Chou, An-Hsun; Liu, Fu-Chao

2017-01-01

Acetaminophen (APAP) overdose causes hepatocytes necrosis and acute liver failure. Baicalin (BA), a major flavonoid of Scutellariae radix, has potent hepatoprotective properties in traditional medicine. In the present study, we investigated the protective effects of BA on a APAP-induced liver injury in a mouse model. The mice received an intraperitoneal hepatotoxic dose of APAP (300[Formula: see text]mg/kg) and after 30[Formula: see text]min, were treated with BA at concentrations of 0, 15, 30, or 60[Formula: see text]mg/kg. After 16[Formula: see text]h of treatment, the mice were sacrificed for further analysis. APAP administration significantly elevated the serum alanine transferase (ALT) enzyme levels and hepatic myeloperoxidase (MPO) activity when compared with control animals. Baicalin treatment significantly attenuated the elevation of liver ALT levels, as well as hepatic MPO activity in a dose- dependent manner (15-60[Formula: see text]mg/kg) in APAP-treated mice. The strongest beneficial effects of BA were seen at a dose of 30[Formula: see text]mg/kg. BA treatment at 30[Formula: see text]mg/kg after APAP overdose reduced elevated hepatic cytokine (TNF-[Formula: see text] and IL-6) levels, and macrophage recruitment around the area of hepatotoxicity in immunohistochemical staining. Significantly, BA treatment can also decrease hepatic phosphorylated extracellular signal-regulated kinase (ERK) expression, which is induced by APAP overdose. Our data suggests that baicalin treatment can effectively attenuate APAP-induced liver injury by down-regulating the ERK signaling pathway and its downstream effectors of inflammatory responses. These results support that baicalin is a potential hepatoprotective agent.

Hepatoprotective Effects of Chinese Medicine Herbs Decoction on Liver Cirrhosis in Rats

PubMed Central

Lim, Tong-Hye; Nor-Amdan, Nur-Asyura

2017-01-01

Hepatoprotective and curative activities of aqueous extract of decoction containing 10 Chinese medicinal herbs (HPE-XA-08) were evaluated in Sprague–Dawley albino rats with liver damage induced by thioacetamide (TAA). These activities were assessed by investigating the liver enzymes level and also histopathology investigation. Increases in alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) levels were observed in rats with cirrhotic liver. No significant alterations of the liver enzymes were observed following treatment with HPE-XA-08. Histopathology examination of rats treated with HPE-XA-08 at 250 mg/kg body weight, however, exhibited moderate liver protective effects. Reduced extracellular matrix (ECM) proteins within the hepatocytes were noted in comparison to the cirrhotic liver. The curative effects of HPE-XA-08 were observed with marked decrease in the level of ALP (more than 3x) and level of GGT (more than 2x) in cirrhotic rat treated with 600 mg/kg body weight HPE-XA-08 in comparison to cirrhotic rat treated with just water diluent. Reversion of cirrhotic liver to normal liver condition in rats treated with HPE-XA-08 was observed. Results from the present study suggest that HPE-XA-08 treatment assisted in the protection from liver cirrhosis and improved the recovery of cirrhotic liver. PMID:28280515

Bioavailability enhancement of curcumin by complexation with phosphatidyl choline.

PubMed

Gupta, Nishant Kumar; Dixit, Vinod Kumar

2011-05-01

Curcumin is a major constituent of rhizomes of Curcuma longa. Pharmacokinetic studies of curcumin reveal its poor absorption through intestine. Objective of the present study was to enhance bioavailability of curcumin by its complexation with phosphatidyl choline (PC). Complex of curcumin was prepared with PC and characterized on the basis of solubility, melting point, differential scanning calorimetry, thin layer chromatography, and infrared spectroscopic analysis. Everted intestine sac technique was used to study ex vivo drug absorption of curcumin-PC (CU-PC) complex and plain curcumin. Pharmacokinetic studies were performed in rats, and hepatoprotective activity of CU-PC complex was also compared with curcumin and CU-PC physical mixture in isolated rat hepatocytes. Analytical reports along with spectroscopic data revealed the formation of complex. The results of ex vivo study show that CU-PC complex has significantly increased absorption compared with curcumin, when given in equimolar doses. Complex showed enhanced bioavailability, improved pharmacokinetics, and increased hepatoprotective activity as compared with curcumin or CU-PC physical mixture. Enhanced bioavailability of CU-PC complex may be due to the amphiphilic nature of the complex, which greatly enhance the water and lipid solubility of the curcumin. The present study clearly indicates the superiority of complex over curcumin, in terms of better absorption, enhanced bioavailability, and improved pharmacokinetics. Copyright © 2010 Wiley-Liss, Inc.

In vivo evaluation of ethanolic extract of Zingiber officinale rhizomes for its protective effect against liver cirrhosis.

PubMed

Abdulaziz Bardi, Daleya; Halabi, Mohammed Farouq; Abdullah, Nor Azizan; Rouhollahi, Elham; Hajrezaie, Maryam; Abdulla, Mahmood Ameen

2013-01-01

Zingiber officinale is a traditional medicine against various disorders including liver diseases.The aim of this study was to assess the hepatoprotective activity of the ethanolic extract of rhizomes of Z. officinale (ERZO) against thioacetamide-induced hepatotoxicity in rats. Five groups of male Sprague Dawley have been used. In group 1 rats received intraperitoneal (i.p.) injection of normal saline while groups 2-5 received thioacetamide (TAA, 200 mg/kg; i.p.) for induction of liver cirrhosis, thrice weekly for eight weeks. Group 3 received 50 mg/kg of silymarin. The rats in groups 4 and 5 received 250 and 500 mg/kg of ERZO (dissolved in 10% Tween), respectively. Hepatic damage was assessed grossly and microscopically for all of the groups. Results confirmed the induction of liver cirrhosis in group 2 whilst administration of silymarin or ERZO significantly reduced the impact of thioacetamide toxicity. These groups decreased fibrosis of the liver tissues. Immunohistochemistry assessment against proliferating cell nuclear antigen did not show remarkable proliferation in the ERZO-treated rats when compared with group 2. Moreover, factions of the ERZO extract were tested on Hep-G2 cells and showed antiproliferative activity (IC50 38-60 μ g/mL). This study showed hepatoprotective effect of ERZO.

In vitro antioxidant and hepatoprotective potential of Azolla microphylla phytochemically synthesized gold nanoparticles on acetaminophen - induced hepatocyte damage in Cyprinus carpio L.

PubMed

Kunjiappan, Selvaraj; Bhattacharjee, Chiranjib; Chowdhury, Ranjana

2015-06-01

The present study aims to evaluate the hepatoprotective and antioxidant effects of gold nanoparticles (GNaP) biosynthesized through the mediation of Azolla microphylla and A. microphylla extract on acetaminophen-induced hepatocyte damage in common carp fish (Cyprinus carpio L.). The gold nanoparticles (100, 150, 200 μg/ml) and A. microphylla extract powder (100, 200, 400 μg/ml) were added to the primary hepatocytes in different conditions: treatment I (before 12 mM acetaminophen), treatment II (after 12 mM acetaminophen), and treatment III (both before and after 12 mM acetaminophen), and incubated. Among these, control group treated with 12 mM acetaminophen produced significantly elevated levels (50-80%) of lactate dehydrogenase (LDH), catalase (CAT), glutamate oxalate transaminase (GOT), glutamate pyruvate transaminase (GPT), and malondialdehyde (MDA), and significantly decreased the levels (60-75%) of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Treatment with methanol extract of A. microphylla phytochemically biosynthesized gold nanoparticles (100, 150, 200 μg/ml) and A. microphylla methanol extract powder (100, 200, 400 μg/ml) significantly improved the viability of cells in a culture medium. It also significantly reduced the levels of LDH, CAT, GOT, GPT, and MDA, and significantly increased the levels of SOD and GSH-Px. In conclusion, gold nanoparticles biosynthesized through A. microphylla demonstrated effective hepatoprotective and antioxidant effects than methanol extract of A. microphylla.

The Pharmacological Potential of Mushrooms

PubMed Central

2005-01-01

This review describes pharmacologically active compounds from mushrooms. Compounds and complex substances with antimicrobial, antiviral, antitumor, antiallergic, immunomodulating, anti-inflammatory, antiatherogenic, hypoglycemic, hepatoprotective and central activities are covered, focusing on the review of recent literature. The production of mushrooms or mushroom compounds is discussed briefly. PMID:16136207

Hepatoprotective influence of quercetin and ellagic acid on thioacetamide-induced hepatotoxicity in rats.

PubMed

Afifi, Nehal A; Ibrahim, Marwa A; Galal, Mona K

2018-06-01

Despite all the studies performed to date, therapy choices for liver injuries are very few. Therefore, the search for a new treatment that could safely and effectively block or reverse liver injuries remains a challenge. Quercetin (QR) and ellagic acid (EA) had potent antioxidant and anti-inflammatory activities. The current study aimed at evaluating the potential hepatoprotective influence of QR and EA against thioacetamide (TAA)-induced liver toxicity in rats and the underlying mechanism using silymarin as a reference drug. Fifty mature male rats were orally treated daily with EA and QR in separate groups for 45 consecutive days, and then were injected with TAA twice with 24 h intervals in the last 2 days of the experiment. Administration of TAA resulted in marked elevation of liver indices, alteration in oxidative stress parameters, and significant elevation in expression level of fibrosis-related genes (MMP9 and MMP2). Administration of QR and EA significantly attenuated the hepatic toxicity through reduction of liver biomarkers, improving the redox status of the tissue, as well as hampering the expression level of fibrosis-related genes. In this study, QR and EA were proved to attenuate the hepatotoxicity through their antioxidant, metal-chelating capacity, and anti-inflammatory effects.

Methanol extract of Dicranopteris linearis L. leaves impedes acetaminophen-induced liver intoxication partly by enhancing the endogenous antioxidant system.

PubMed

Zakaria, Zainul Amiruddin; Kamisan, Farah Hidayah; Omar, Maizatul Hasyima; Mahmood, Nur Diyana; Othman, Fezah; Abdul Hamid, Siti Selina; Abdullah, Muhammad Nazrul Hakim

2017-05-18

The present study investigated the potential of methanolic extract of Dicranopteris linearis (MEDL) leaves to attenuate liver intoxication induced by acetaminophen (APAP) in rats. A group of mice (n = 5) treated orally with a single dose (5000 mg/kg) of MEDL was first subjected to the acute toxicity study using the OECD 420 model. In the hepatoprotective study, six groups of rats (n = 6) were used and each received as follows: Group 1 (normal control; pretreated with 10% DMSO (extract's vehicle) followed by treatment with 10% DMSO (hepatotoxin's vehicle) (10% DMSO +10% DMSO)), Group 2 (hepatotoxic control; 10% DMSO +3 g/kg APAP (hepatotoxin)), Group 3 (positive control; 200 mg/kg silymarin +3 g/kg APAP), Group 4 (50 mg/kg MEDL +3 g/kg APAP), Group 5 (250 mg/kg MEDL +3 g/kg APAP) or Group 6 (500 mg/kg MEDL +3 g/kg APAP). The test solutions pre-treatment were made orally once daily for 7 consecutive days, and 1 h after the last test solutions administration (on Day 7th), the rats were treated with vehicle or APAP. Blood were collected from those treated rats for biochemical analyses, which were then euthanized to collect their liver for endogenous antioxidant enzymes determination and histopathological examination. The extract was also subjected to in vitro anti-inflammatory investigation and, HPLC and GCMS analyses. Pre-treatment of rats (Group 2) with 10% DMSO failed to attenuate the toxic effect of APAP on the liver as seen under the microscopic examination. This observation was supported by the significant (p < 0.05) increased in the level of serum liver enzymes of alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP), and significant (p < 0.05) decreased in the activity of endogenous antioxidant enzymes of catalase (CAT) and superoxide dismutase (SOD) in comparison to Group 1. Pre-treatment with MEDL, at all doses, significantly (p < 0.05) reduced the level of ALT and AST while the levels of CAT and SOD was significantly (p < 0.05) restored to their normal value. Histopathological studies showed remarkable improvement in the liver cells architecture with increase in dose of the extract. MEDL also demonstrated a low to none inhibitory activity against the respective LOX- and NO-mediated inflammatory activity. The HPLC and GCMS analyses of MEDL demonstrated the presence of several non-volatile (such as rutin, gallic acid etc.) and volatile (such as methyl palmitate, shikimic acid etc.) bioactive compounds. MEDL exerts hepatoprotective activity against APAP-induced intoxication possibly via its ability to partly activate the endogenous antioxidant system and presence of various volatile and non-volatile bioactive compounds that might act synergistically to enhance the hepatoprotective effect.

Hepatoprotective effect of manual acupuncture at acupoint GB34 against CCl4-induced chronic liver damage in rats

PubMed Central

Yim, Yun-Kyoung; Lee, Hyun; Hong, Kwon-Eui; Kim, Young-Il; Lee, Byung-Ryul; Kim, Tae-Han; Yi, Ji-Young

2006-01-01

AIM: To investigate the hepatoprotective effect of manual acupuncture at Yanglingquan (GB34) on CCl4-induced chronic liver damage in rats. METHODS: Rats were injected intraperitoneally with CCl4 (1 mL/kg) and treated with manual acupuncture using reinforcing manipulation techniques at left GB34 (Yanglingquan) 3 times a week for 10 wk. A non-acupoint in left gluteal area was selected as a sham point. To estimate the hepatoprotective effect of manual acupuncture at GB34, measurement of liver index, biochemical assays including serum ALT, AST, ALP and total cholesterol, histological analysis and blood cell counts were conducted. RESULTS: Manual acupuncture at GB34 reduced the liver index, serum ALT, AST, ALP and total cholesterol levels as compared with the control group and the sham acupuncture group. It also increased and normalized the populations of WBC and lymphocytes. CONCLUSION: Manual acupuncture with reinforcing manipulation techniques at left GB34 reduces liver toxicity, protects liver function and liver tissue, and normalizes immune activity in CCl4-intoxicated rats. PMID:16610030

Bioactive compounds, antioxidant potential, and hepatoprotective activity of sea cucumber (Holothuria atra) against thioacetamide intoxication in rats.

PubMed

Esmat, Amr Y; Said, Mahmoud M; Soliman, Amel A; El-Masry, Khaled S H; Badiea, Elham Abdel

2013-01-01

The identification of the active phenolic compounds in the mixed extract of sea cucumber (Holothuria atra) body wall by high-performance liquid chromatography and an assessment of its hepatoprotective activity against thioacetamide-induced liver fibrosis in rats. Female Swiss albino rats were divided into four groups: normal controls; oral administration of a sea cucumber mixed extract (14.4 mg/kg of body weight) on days 2, 4, and 6 weekly for 8 consecutive weeks; intoxication with thioacetamide (200 mg/kg of body weight, intraperitoneally) on days 2 and 6 weekly for 8 wk; and oral administration of a sea cucumber extract and then intoxication with thioacetamide 2 h later for 8 wk. High-performance liquid chromatographic analysis of the sea cucumber mixed extract revealed the presence of some phenolic components, such as chlorogenic acid, pyrogallol, rutin, coumaric acid, catechin, and ascorbic acid. In vitro studies have shown that the extract has a high scavenging activity for the nitric oxide radical, a moderate iron-chelating activity, and a weak inhibitory effect of lipid peroxidation. The subchronic oral administration of sea cucumber extract to the rats did not show any toxic side effects but increased hepatic superoxide dismutase and glutathione peroxidase activities. The coadministration of sea cucumber extract and thioacetamide (protection modality) normalized serum direct bilirubin, alanine and aspartate aminotransferases, hepatic malondialdehyde, and hydroxyproline concentrations and antioxidant enzyme activities. In addition, the histologic examination of liver sections from the protection group that were stained with hematoxylin and eosin showed substantial attenuation of the degenerative cellular changes and regressions in liver fibrosis and necrosis induced by the thioacetamide intoxication. Sea cucumber mixed extract contains physiologically active phenolic compounds with antioxidant activity, which afforded a potential hepatoprotective activity against thioacetamide-induced liver injury in a rat model. Copyright © 2013 Elsevier Inc. All rights reserved.

Hepatoprotective Potential of Some Local Medicinal Plants against 2-Acetylaminoflourene-Induced Damage in Rat.

PubMed

Adetutu, Adewale; Olorunnisola, Olubukola S

2013-01-01

The in vivo micronucleus assay was used to examine the anticlastogenic effects of crude extracts of Bridelia ferruginea, Vernonia amygdalina, Tridax procumbens, Ocimum gratissimum, and Lawsonia inermis in Wistar albino rats. Extracts of doses of 100 mg/kg body weight were given to rats in five groups for seven consecutive days followed by a single dose of 2-AAF (0.5 mmol/kg body weight). The rats were sacrificed after 24 hours and their bone marrow smears were prepared on glass slides stained with Giemsa. The micronucleated polychromatic erythrocyte cells (mPCEs) were thereafter recorded. The hepatoprotective effects of the plant extracts against 2-AAF-induced liver toxicity in rats were evaluated by monitoring the levels of alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and histopathological analysis. The results of the 2-AAF-induced liver toxicity experiments showed that rats treated with the plant extracts (100 mg/kg) showed a significant decrease in mPCEs as compared with the positive control. The rats treated with the plant extracts did not show any significant change in the concentration of ALP and GGT in comparison with the negative control group whereas the 2-AAF group showed a significant increase (P < 0.05) in these parameters. Some of the leaf extracts also showed protective effects against histopathological alterations. This study suggests that the leaf extracts have hepatoprotective potential, thereby justifying their ethnopharmacological uses.

Rectification of impaired adipose tissue methylation status and lipolytic response contributes to hepatoprotective effect of betaine in a mouse model of alcoholic liver disease

PubMed Central

Dou, Xiaobing; Xia, Yongliang; Chen, Jing; Qian, Ying; Li, Songtao; Zhang, Ximei; Song, Zhenyuan

2014-01-01

Background and Purpose Overactive lipolysis in adipose tissue contributes to the pathogenesis of alcoholic liver disease (ALD); however, the mechanisms involved have not been elucidated. We previously reported that chronic alcohol consumption produces a hypomethylation state in adipose tissue. In this study we investigated the role of hypomethylation in adipose tissue in alcohol-induced lipolysis and whether its correction contributes to the well-established hepatoprotective effect of betaine in ALD. Experimental Approach Male C57BL/6 mice were divided into four groups and started on one of four treatments for 5 weeks: isocaloric pair-fed (PF), alcohol-fed (AF), PF supplemented with betaine (BT/AF) and AF supplemented with betaine (BT/AF). Betaine, 0.5% (w v−1), was added to the liquid diet. Both primary adipocytes and mature 3T3-L1 adipocytes were exposed to demethylation reagents and their lipolytic responses determined. Key Results Betaine alleviated alcohol-induced pathological changes in the liver and rectified the impaired methylation status in adipose tissue, concomitant with attenuating lipolysis. In adipocytes, inducing hypomethylation activated lipolysis through a mechanism involving suppression of protein phosphatase 2A (PP2A), due to hypomethylation of its catalytic subunit, leading to increased activation of hormone-sensitive lipase (HSL). In line with in vitro observations, reduced PP2A catalytic subunit methylation and activity, and enhanced HSL activation, were observed in adipose tissue of alcohol-fed mice. Betaine attenuated this alcohol-induced PP2A suppression and HSL activation. Conclusions and Implications In adipose tissue, a hypomethylation state contributes to its alcohol-induced dysfunction and an improvement in its function may contribute to the hepatoprotective effects of betaine in ALD. PMID:24819676

Comparative evaluation of hepatoprotective activity of carotenoids of microalgae.

PubMed

Murthy, K N Chidambara; Rajesha, J; Swamy, M Mahadeva; Ravishankar, G A

2005-01-01

The present study deals with evaluation of the hepatotoprotective activity of carotenoids from two well-known microalgae, Spirulina platensis and Dunaliella salina. Carotenoids were extracted in hexane:isopropyl alcohol (1:1 vol/vol) and fed orally in olive oil to Wistar albino rats at a dose of 100 microg/kg of body weight/day (in terms of carotenoids). The degree of hepatoprotection was measured by estimation of biochemical parameters like serum transaminases [serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT)], serum alkaline phosphatase, total albumin, and total protein. The results were compared with those for a control group, a CCl4-induced hepatic damage group, and a group treated with synthetic beta-carotene (all-trans) at the same dose. The protein content of the CCl4-treated group, which received normal diet and a dose of toxin, showed a significant decrease, i.e., 3.92 mg/mL, whereas the protein levels were higher, i.e., 6.96 and 6.32 mg/mL, in the case of the Dunaliella and Spirulina, respectively, carotenoid-treated groups. The CCl4-treated group shown higher activity of transaminases (128.68 units/mL SGPT and 171.52 units/mL SGOT). However, the activity of SGPT was 62.83 units/mL for Dunaliella and 76.83 units/mL for Spirulina, i.e., carotenoids of Dunaliella showed a higher degree of protection. For serum alkaline phosphatase, the standard beta-carotene value was 81.52 units/mL, compared with 84.46 units/mL for the CCl4-treated group; however, natural algal carotenoids yielded 38.45 units/mL (D. salina) and 44.73 units/mL (Spirulina). The total albumin value diminished with CCl4 treatment (2.46 mg/mL); the effect was highest for Dunaliella, followed by the Spirulina carotenoid-treated group. The results clearly indicate that carotenoids from Dunaliella possess better hepatoprotection compared with those from Spirulina. High-performance liquid chromatography of the carotenoids indicated that Spirulina contains only beta-carotene and Dunaliella contains other carotenoids and xanthophyll. The increase in protection with Dunaliella indicates that mixed carotenoids exhibit better biological activity than beta-carotene alone. The results of this study indicate that carotenoids obtained from an algal source have a higher antihepatotoxic effect, compared with synthetic beta-carotene and with beta-carotene alone from a natural source.

Hepatoprotective, antioxidant, and ameliorative effects of ginger (Zingiber officinale Roscoe) and vitamin E in acetaminophen treated rats.

PubMed

Abdel-Azeem, Amal S; Hegazy, Amany M; Ibrahim, Khadiga S; Farrag, Abdel-Razik H; El-Sayed, Eman M

2013-09-01

Ginger is a remedy known to possess a number of pharmacological properties. This study investigated efficacy of ginger pretreatment in alleviating acetaminophen-induced acute hepatotoxicity in rats. Rats were divided into six groups; negative control, acetaminophen (APAP) (600 mg/kg single intraperitoneal injection); vitamin E (75 mg/kg), ginger (100 mg/kg), vitamin E + APAP, and ginger + APAP. Administration of APAP elicited significant liver injury that was manifested by remarkable increase in plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), arginase activities, and total bilirubin concentration. Meanwhile, APAP significantly decreased plasma total proteins and albumin levels. APAP administration resulted in substantial increase in each of plasma triacylglycerols (TAGs), malondialdhyde (MDA) levels, and total antioxidant capacity (TAC). However, ginger or vitamin E treatment prior to APAP showed significant hepatoprotective effect by lowering the hepatic marker enzymes (AST, ALT, ALP, and arginase) and total bilirubin in plasma. In addition, they remarkably ameliorated the APAP-induced oxidative stress by inhibiting lipid peroxidation (MDA). Pretreatment by ginger or vitamin E significantly restored TAGs, and total protein levels. Histopathological examination of APAP treated rats showed alterations in normal hepatic histoarchitecture, with necrosis and vacuolization of cells. These alterations were substantially decreased by ginger or vitamin E. Our results demonstrated that ginger can prevent hepatic injuries, alleviating oxidative stress in a manner comparable to that of vitamin E. Combination therapy of ginger and APAP is recommended especially in cases with hepatic disorders or when high doses of APAP are required.

Hepatoprotective and immunological functions of Nigella sativa seed oil against hypervitaminosis A in adult male rats.

PubMed

Al-Suhaimi, Ebtesam Abdullah

2012-08-01

The toxic effects of excess vitamin A (VA) intake deserve increased attention. Nigella sativa (NS) seed possesses physiological and pharmacological actions and protects against toxic agents. This work investigated the availability of NS seed oil as a protective agent against the effects of hypervitaminosis A (HVA) on liver function and immunity. Fifty adult albino rats were used and divided into five groups: (G1) control; (G2) experimental HVA rats administered extreme doses (10,000 IU/kg body weight) of VA oil orally, daily for 6 weeks; (G3) rats treated with NS seed oil (800 mg/kg) orally, daily for 6 weeks; (G4) HVA rats simultaneously treated with NS seed oil at the same doses and periods; and (G5) HVA recovery group. Liver function, immunoglobulin (IgG and IgM) levels, and lysosome activity were measured in serum. HVA rats revealed marked elevations in alanine aminotransferase and aspartate aminotransferase activities. This is the first study to demonstrate that NS seed oil possesses significant hepatoprotective activity against HVA. NS seed oil was a potent inducer of IgG and IgM in rat serum either alone or with high doses of VA. These findings may be considered the initial steps of the physiological and humoral immune responses for NS seed oil against HVA, but further studies examining longer periods are needed prior to recommending the use of NS seed oil as an alternative medicine for hepatic and immune diseases.

A Novel AKT Activator, SC79, Prevents Acute Hepatic Failure Induced by Fas-Mediated Apoptosis of Hepatocytes.

PubMed

Liu, Wei; Jing, Zhen-Tang; Wu, Shu-Xiang; He, Yun; Lin, Yan-Ting; Chen, Wan-Nan; Lin, Xin-Jian; Lin, Xu

2018-05-01

Acute liver failure is a serious clinical problem of which the underlying pathogenesis remains unclear and for which effective therapies are lacking. The Fas receptor/ligand system, which is negatively regulated by AKT, is known to play a prominent role in hepatocytic cell death. We hypothesized that AKT activation may represent a strategy to alleviate Fas-induced fulminant liver failure. We report here that a novel AKT activator, SC79, protects hepatocytes from apoptosis induced by agonistic anti-Fas antibody CH11 (for humans) or Jo2 (for mice) and significantly prolongs the survival of mice given a lethal dose of Jo2. Under Fas-signaling stimulation, SC79 inhibited Fas aggregation, prevented the recruitment of the adaptor molecule Fas-associated death domain (FADD) and procaspase-8 [or FADD-like IL-1β-converting enzyme (FLICE)] into the death-inducing signaling complex (DISC), but SC79 enhanced the recruitment of the long and short isoforms of cellular FLICE-inhibitory protein at the DISC. All of the SC79-induced hepatoprotective and DISC-interruptive effects were confirmed to have been reversed by the Akt inhibitor LY294002. These results strongly indicate that SC79 protects hepatocytes from Fas-induced fatal hepatic apoptosis. The potent alleviation of Fas-mediated hepatotoxicity by the relatively safe drug SC79 highlights the potential of our findings for immediate hepatoprotective translation. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Antioxidant and hepatoprotective actions of medicinal herb, Terminalia catappa L. from Okinawa Island and its tannin corilagin.

PubMed

Kinoshita, S; Inoue, Y; Nakama, S; Ichiba, T; Aniya, Y

2007-11-01

The antioxidant and hepatoprotective actions of Terminalia catappa L. collected from Okinawa Island were evaluated in vitro and in vivo using leaves extract and isolated antioxidants. A water extract of the leaves of T. catappa showed a strong radical scavenging action for 1,1-diphenyl-2-picrylhydrazyl and superoxide (O(2)(.-)) anion. Chebulagic acid and corilagin were isolated as the active components from T. catappa. Both antioxidants showed a strong scavenging action for O(2)(.-) and peroxyl radicals and also inhibited reactive oxygen species production from leukocytes stimulated by phorbol-12-myristate acetate. Galactosamine (GalN, 600 mg/kg, s.c.,) and lipopolysaccharide (LPS, 0.5 microg/kg, i.p.)-induced hepatotoxicity of rats as seen by an elevation of serum alanine aminotransferase, aspartate aminotransferase and glutathione S-transferase (GST) activities was significantly reduced when the herb extract or corilagin was given intraperitoneally to rats prior to GalN/LPS treatment. Increase of free radical formation and lipid peroxidation in mitochondria caused by GalN/LPS treatment were also decreased by pretreatment with the herb/corilagin. In addition, apoptotic events such as DNA fragmentation and the increase in caspase-3 activity in the liver observed with GalN/LPS treatment were prevented by the pretreatment with the herb/corilagin. These results show that the extract of T. catappa and its antioxidant, corilagin are protective against GalN/LPS-induced liver injury through suppression of oxidative stress and apoptosis.

Hepatoprotective and Antioxidant Potential of Organic and Conventional Grape Juices in Rats Fed a High-Fat Diet

PubMed Central

Buchner, Iselde; Medeiros, Niara; dos Santos Lacerda, Denise; Normann, Carlos Augusto B. M.; Gemelli, Tanise; Rigon, Paula; Wannmacher, Clovis Milton Duval; Henriques, João Antônio Pegas; Dani, Caroline; Funchal, Cláudia

2014-01-01

The objective of this study was to investigate the antioxidant and hepatoprotective effect of the chronic use of conventional (CGJ) or organic (OGJ) grape juice from the Bordeaux variety grape on oxidative stress and cytoarchitecture in the liver of rats supplemented with a high-fat diet (HFD) for three months. The results demonstrated that HFD induced an increase in thiobarbituric acid-reactive substances (TBARS), catalase (CAT) activity and 2′,7′-dihydrodichlorofluorescein (DCFH) oxidation and a decrease in sulfhydryl content and superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. HFD also induced hepatocellular degeneration and steatosis. These alterations were prevented by CGJ and OGJ, where OGJ was more effective. Therefore, it was concluded that HFD induced oxidative stress and liver damage and that the chronic use of grape juice was able to prevent these alterations. PMID:26784874

Mesenchymal stem cells display hepato-protective activity in lymphoma bearing xenografts.

PubMed

Secchiero, Paola; Corallini, Federica; Zavan, Barbara; Tripodo, Claudio; Vindigni, Vincenzo; Zauli, Giorgio

2012-04-01

A disseminated model of non-Hodgkin's lymphoma with prevalent liver metastasis was generated by intraperitoneal (i.p.) injection of EBV(+) B lymphoblastoid SKW6.4 in nude-SCID mice. The survival of SKW6.4 xenografts (median survival = 27 days) was significantly improved when hyaluronan scaffolds embedded with mesenchimal stem cells (MSC) were implanted in the abdominal area 4 days after SKW6.4 injection (median survival = 39.5 days). Mice implanted with MSC showed a significant improvement of hepatic functionality in lymphoma xenografts, as demonstrated by measurement of serum ALT/AST levels. Co-culture of MSC with lymphoma cells enhanced the release of hepatocyte growth factor (HGF) by MSC. These data suggest that hyaluronan-embedded MSC exert anti-lymphoma activity by ameliorating hepatic functionality.

Hepatoprotectant Ursodeoxycholyl Lysophosphatidylethanolamide Increasing Phosphatidylcholine Levels as a Potential Therapy of Acute Liver Injury

PubMed Central

Chamulitrat, Walee; Zhang, Wujuan; Xu, Weihong; Pathil, Anita; Setchell, Kenneth; Stremmel, Wolfgang

2012-01-01

It has been long known that hepatic synthesis of phosphatidylcholine (PC) is depressed during acute such as carbon tetrachloride-induced liver injury. Anti-hepatotoxic properties of PC as liposomes have been recognized for treatment of acute liver damage. Ursodeoxycholate (UDCA) is a known hepatoprotectant in stabilizing cellular membrane. For therapeutic management of liver injury, we coupled UDCA with a phospholipid known as ursodeoxycholyl lysophosphatidylethanolamide (UDCA-LPE). UDCA-LPE has been shown to first-in-class hepatoprotectant being superior to UDCA or PC. It inhibits mitochondrial damage and apoptosis, elicits survival signaling pathway, and promotes regeneration of hepatocytes. We herein report that a unique contribution of UDCA-LPE in increasing concentrations of PC in vitro and in vivo. UDCA-LPE-treated hepatocytes contained significantly increased PC levels. UDCA-LPE underwent the hydrolysis to LPE which was not the precursor of the increased PC. The levels of PC in the liver and blood were increased rapidly after intraperitoneally administration UDCA-LPE, and were found to be sustained even after 24 h. Among PC synthesis genes tested, UDCA-LPE treatment of mouse hepatocytes increased transcription of CDP-diacylglycerol synthase 1 which is an enzyme catalyzing phosphatidic acid to generate intermediates for PC synthesis. Thus, UDCA-LPE as a hepatoprotectant was able to induce synthesis of protective PC which would supplement for the loss of PC occurring during acute liver injury. This property has placed UDCA-LPE as a candidate agent for therapy of acute hepatotoxicity such as acetaminophen poisoning. PMID:22363296

Antioxidant and hepatoprotective effects of A. cerana honey against acute alcohol-induced liver damage in mice.

PubMed

Zhao, Haoan; Cheng, Ni; He, Liangliang; Peng, Guoxia; Xue, Xiaofeng; Wu, Liming; Cao, Wei

2017-11-01

A. cerana honey, gathered from Apis cerana Fabricius (A. cerana), has not been fully studied. Samples of honey originating from six geographical regions (mainly in the Qinling Mountains of China) were investigated to determine their antioxidant and hepatoprotective effects against acute alcohol-induced liver damage. The results showed that A. cerana honeys from the Qinling Mountains had high total phenolic contents (345.1-502.1mgGAkg -1 ), ascorbic acid contents (153.8-368.4mgkg -1 ), and strong antioxidant activities in DPPH radical scavenging activity assays (87.5-136.2IC50mgmL -1 ), ferric reducing antioxidant powers (191.8-317.4mgTroloxkg -1 ), and ferrous ion-chelating activities (27.5-35.5mgNa 2 EDTAkg -1 ). Pretreatment with A. cerana honey (Qinling Mountains) at 5, 10, or 20gkg -1 twice daily for 12weeks significantly inhibited serum lipoprotein oxidation and increased serum radical absorbance capacity (ORAC) (P<0.05). Moreover, A. cerana honey inhibited acute alcohol-induced increases in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum (P<0.05), reduced the production of hepatic malondialdehyde (MDA) (P<0.05), and promoted superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities (P<0.05). More importantly, it also remarkably inhibited the level of TGF-β1 in the serum and liver (P<0.05). The results of this study indicate that administration of A. cerana honey prevents acute alcohol-induced liver damage likely because of its antioxidant properties and ability to prevent oxidative stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

Amelioration of alcohol-induced hepatotoxicity by the administration of ethanolic extract of Sida cordifolia Linn.

PubMed

Rejitha, S; Prathibha, P; Indira, M

2012-10-01

Sida cordifolia Linn. (Malvaceae) is a plant used in folk medicine for the treatment of the inflammation of oral mucosa, asthmatic bronchitis, nasal congestion and rheumatism. We studied the hepatoprotective activity of 50 % ethanolic extract of S. cordifolia Linn. against alcohol intoxication. The duration of the experiment was 90 d. The substantially elevated levels of toxicity markers such as alanine aminotransferase, aspartate aminotransferase and γ-glutamyl transferase due to the alcohol treatment were significantly lowered in the extract-treated groups. The activity of antioxidant enzymes and glutathione content, which was lowered due to alcohol toxicity, was increased to a near-normal level in the co-administered group. Lipid peroxidation products, protein carbonyls, total collagen and hydroxyproline, which were increased in the alcohol-treated group, were reduced in the co-administered group. The mRNA levels of cytochrome P450 2E1, NF-κB, TNF-α and transforming growth factor-β1 were found to be increased in the alcohol-treated rats, and their expressions were found to be decreased in the co-administered group. These observations were reinforced by histopathological analysis. Thus, the present study clearly indicates that 50 % ethanolic extract of the roots of S. cordifolia Linn. has a potent hepatoprotective action against alcohol-induced toxicity, which was mediated by lowering oxidative stress and by down-regulating the transcription factors.

Molecular Bases Underlying the Hepatoprotective Effects of Coffee

PubMed Central

Salomone, Federico; Galvano, Fabio; Li Volti, Giovanni

2017-01-01

Coffee is the most consumed beverage worldwide. Epidemiological studies with prospective cohorts showed that coffee intake is associated with reduced cardiovascular and all-cause mortality independently of caffeine content. Cohort and case-control studies reported an inverse association between coffee consumption and the degree of liver fibrosis as well as the development of liver cancer. Furthermore, the beneficial effects of coffee have been recently confirmed by large meta-analyses. In the last two decades, various in vitro and in vivo studies evaluated the molecular determinants for the hepatoprotective effects of coffee. In the present article, we aimed to critically review experimental evidence regarding the active components and the molecular bases underlying the beneficial role of coffee against chronic liver diseases. Almost all studies highlighted the beneficial effects of this beverage against liver fibrosis with the most solid results indicating a pivot role for both caffeine and chlorogenic acids. In particular, in experimental models of fibrosis, caffeine was shown to inhibit hepatic stellate cell activation by blocking adenosine receptors, and emerging evidence indicated that caffeine may also favorably impact angiogenesis and hepatic hemodynamics. On the other side, chlorogenic acids, potent phenolic antioxidants, suppress liver fibrogenesis and carcinogenesis by reducing oxidative stress and counteract steatogenesis through the modulation of glucose and lipid homeostasis in the liver. Overall, these molecular insights may have translational significance and suggest that coffee components need clinical evaluation. PMID:28124992

Molecular Bases Underlying the Hepatoprotective Effects of Coffee.

PubMed

Salomone, Federico; Galvano, Fabio; Li Volti, Giovanni

2017-01-23

Coffee is the most consumed beverage worldwide. Epidemiological studies with prospective cohorts showed that coffee intake is associated with reduced cardiovascular and all-cause mortality independently of caffeine content. Cohort and case-control studies reported an inverse association between coffee consumption and the degree of liver fibrosis as well as the development of liver cancer. Furthermore, the beneficial effects of coffee have been recently confirmed by large meta-analyses. In the last two decades, various in vitro and in vivo studies evaluated the molecular determinants for the hepatoprotective effects of coffee. In the present article, we aimed to critically review experimental evidence regarding the active components and the molecular bases underlying the beneficial role of coffee against chronic liver diseases. Almost all studies highlighted the beneficial effects of this beverage against liver fibrosis with the most solid results indicating a pivot role for both caffeine and chlorogenic acids. In particular, in experimental models of fibrosis, caffeine was shown to inhibit hepatic stellate cell activation by blocking adenosine receptors, and emerging evidence indicated that caffeine may also favorably impact angiogenesis and hepatic hemodynamics. On the other side, chlorogenic acids, potent phenolic antioxidants, suppress liver fibrogenesis and carcinogenesis by reducing oxidative stress and counteract steatogenesis through the modulation of glucose and lipid homeostasis in the liver. Overall, these molecular insights may have translational significance and suggest that coffee components need clinical evaluation.

In Vivo Evaluation of Ethanolic Extract of Zingiber officinale Rhizomes for Its Protective Effect against Liver Cirrhosis

PubMed Central

Abdulaziz Bardi, Daleya; Halabi, Mohammed Farouq; Abdullah, Nor Azizan; Rouhollahi, Elham

2013-01-01

Zingiber officinale is a traditional medicine against various disorders including liver diseases.The aim of this study was to assess the hepatoprotective activity of the ethanolic extract of rhizomes of Z. officinale (ERZO) against thioacetamide-induced hepatotoxicity in rats. Five groups of male Sprague Dawley have been used. In group 1 rats received intraperitoneal (i.p.) injection of normal saline while groups 2–5 received thioacetamide (TAA, 200 mg/kg; i.p.) for induction of liver cirrhosis, thrice weekly for eight weeks. Group 3 received 50 mg/kg of silymarin. The rats in groups 4 and 5 received 250 and 500 mg/kg of ERZO (dissolved in 10% Tween), respectively. Hepatic damage was assessed grossly and microscopically for all of the groups. Results confirmed the induction of liver cirrhosis in group 2 whilst administration of silymarin or ERZO significantly reduced the impact of thioacetamide toxicity. These groups decreased fibrosis of the liver tissues. Immunohistochemistry assessment against proliferating cell nuclear antigen did not show remarkable proliferation in the ERZO-treated rats when compared with group 2. Moreover, factions of the ERZO extract were tested on Hep-G2 cells and showed antiproliferative activity (IC50 38–60 μg/mL). This study showed hepatoprotective effect of ERZO. PMID:24396831

The treatment of jaundice with medicinal plants in indigenous communities of the Sub-Himalayan region of Uttarakhand, India.

PubMed

Sharma, Jyotsana; Gairola, Sumeet; Gaur, R D; Painuli, R M

2012-08-30

Inspite of tremendous advances made in allopathic medical practices, herbs still play an important role in the management of various liver diseases. A large number of plants and formulations have been claimed to have hepatoprotective activity. Jaundice is a symptom, indicative of the malfunctioning of the liver. This paper provides ethnomedicinal information on the plants used to treat jaundice by three important indigenous communities, i.e., nomadic Gujjars, Tharu and Bhoxa of Sub-Himalayan region, Uttarakhand, India. To record herbal preparations used by the studied indigenous communities in treatment of jaundice and discuss hepatoprotective properties of the recorded plants. The traditional knowledge of the studied indigenous communities on herbal preparations used for treating jaundice was collected through structured questionnaire and personal interviews. The interviews were conducted with 91 traditional healers (29 Bhoxa, 35 Tharu and 27 nomadic Gujjars) in Sub-Himalayan region of Uttarakhand, India. More than 250 research papers reporting ethnomedicinal information on the hepatoprotective plants used by various communities from different parts of India were extensively reviewed. A total of 40 medicinal plants belonging to 31 families and 38 genera were recorded to be used by the studied communities in 45 formulations as a remedy of jaundice. Bhoxa, nomadic Gujjars and Tharu communities used 15, 23 and 9 plants, respectively. To our knowledge eight plants reported in the present survey viz., Amaranthus spinosus L., Cissampelos pareira L., Ehretia laevis Roxb., Holarrhena pubescens Wall., Ocimum americanum L., Physalis divaricata D. Don, Solanum incanum L. and Trichosanthes cucumerina L. have not been reported earlier as remedy of jaundice in India. Literature review revealed that a total of 214 (belonging to 181 genus and 78 families), 19 (belonging to 18 genus and 12 families) and 14 (belonging to 14 genus and 11 families) plant species are used as internal, external and magico-religious remedies for jaundice, respectively by various communities in different parts of India. Most widely used hepatoprotective plant species for treatment of jaundice in India is Boerhavia diffusa L. followed by Tinospora cordifolia (Willd.) Miers, Saccharum officinarum L., Phyllanthus amarus Schumach. & Thonn., Ricinus communis L., Andrographis paniculata (Burm. f.) Nees., Oroxylum indicum (L.) Kurz, Lawsonia inermis L. and Eclipta prostrata (L.) L. The plants recorded in the present survey have also been discussed in relation to pharmacological studies and hepatoprotective phytoconstituents present in them. Most of the recorded plants have shown hepatoprotective effects on experimental animals in earlier studies but more studies are needed to assess hepatoprotective properties of some recorded medicinal plants viz., Averrhoa carambola L., Ehretia laevis Roxb., Holarrhena pubescens Wall., Mangifera indica L., Ocimum americanum L., Oroxylum indicum (L.) Kurz, Physalis divaricata D. Don, Solanum incanum L., Sphaeranthus senegalensis DC. and Tribulus terrestris L.. The plants enumerated in this study with high number of citations and wider distributions have given some useful leads for further biomedical research. Nevertheless more phytochemical, pharmaceutical and clinical studies are needed to evaluate hepatoprotective properties, efficacy and safety of all the claimed medicinal plants. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Hepatoprotective effect of Taraxacum officinale leaf extract on sodium dichromate-induced liver injury in rats.

PubMed

Hfaiedh, Mbarka; Brahmi, Dalel; Zourgui, Lazhar

2016-03-01

Taraxacum officinale (L.) Weber, commonly known as Dandelion, has been widely used as a folkloric medicine for the treatment of liver and kidney disorders and some women diseases such as breast and uterus cancers. The main objective of the present study was to assess the efficiency of T. officinale leaf extract (TOE) in treating sodium dichromate hazards; it is a major environmental pollutant known for its wide toxic manifestations witch induced liver injury. TOE at a dose of 500 mg/kg b.w was orally administered once per day for 30 days consecutively, followed by 10 mg/kg b.w sodium dichromate was injected (intraperitoneal) for 10 days. Our results using Wistar rats showed that sodium dichromate significantly increased serum biochemical parameters. In the liver, it was found to induce an oxidative stress, evidenced from increase in lipid peroxidation and changes in antioxidative activities. In addition, histopathological observation revealed that sodium dichromate causes acute liver damage, necrosis of hepatocytes, as well as DNA fragmentation. Interestingly, animals that were pretreated with TOE, prior to sodium dichromate administration, showed a significant hepatoprotection, revealed by a significant reduction of sodium dichromate-induced oxidative damage for all tested markers. These finding powerfully supports that TOE was effective in the protection against sodium dichromate-induced hepatotoxicity and genotoxicity and, therefore, suggest a potential therapeutic use of this plant as an alternative medicine for patients with acute liver diseases. © 2014 Wiley Periodicals, Inc.

Hepatoprotective Potential of Some Local Medicinal Plants against 2-Acetylaminoflourene-Induced Damage in Rat

PubMed Central

Adetutu, Adewale; Olorunnisola, Olubukola S.

2013-01-01

The in vivo micronucleus assay was used to examine the anticlastogenic effects of crude extracts of Bridelia ferruginea, Vernonia amygdalina, Tridax procumbens, Ocimum gratissimum, and Lawsonia inermis in Wistar albino rats. Extracts of doses of 100 mg/kg body weight were given to rats in five groups for seven consecutive days followed by a single dose of 2-AAF (0.5 mmol/kg body weight). The rats were sacrificed after 24 hours and their bone marrow smears were prepared on glass slides stained with Giemsa. The micronucleated polychromatic erythrocyte cells (mPCEs) were thereafter recorded. The hepatoprotective effects of the plant extracts against 2-AAF-induced liver toxicity in rats were evaluated by monitoring the levels of alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), and histopathological analysis. The results of the 2-AAF-induced liver toxicity experiments showed that rats treated with the plant extracts (100 mg/kg) showed a significant decrease in mPCEs as compared with the positive control. The rats treated with the plant extracts did not show any significant change in the concentration of ALP and GGT in comparison with the negative control group whereas the 2-AAF group showed a significant increase (P < 0.05) in these parameters. Some of the leaf extracts also showed protective effects against histopathological alterations. This study suggests that the leaf extracts have hepatoprotective potential, thereby justifying their ethnopharmacological uses. PMID:24163694

Protective effect of tea polyphenols against paracetamol-induced hepatotoxicity in mice is significantly correlated with cytochrome P450 suppression.

PubMed

Chen, Xia; Sun, Chang-Kai; Han, Guo-Zhu; Peng, Jin-Yong; Li, Ying; Liu, Yan-Xia; Lv, Yuan-Yuan; Liu, Ke-Xin; Zhou, Qin; Sun, Hui-Jun

2009-04-21

To investigate the hepatoprotective activity of tea polyphenols (TP) and its relation with cytochrome P450 (CYP450) expression in mice. Hepatic CYP450 and CYPb(5) levels were measured by UV-spectrophotometry in mice 2 d after intraperitoneal TP (25, 50 and 100 mg/kg per day). Then the mice were intragastricly pre-treated with TP (100, 200 and 400 mg/kg per day) for six days before paracetamol (1000 mg/kg) was given. Their acute mortality was compared with that of control mice. The mice were pre-treated with TP (100, 200, and 400 mg/kg per day) for five days before paracetamol (500 mg/kg) was given. Hepatic CYP2E1 and CYP1A2 protein and mRNA expression levels were evaluated by Western blotting, immunohistochemical staining and transcriptase-polymerase chain reaction. The hepatic CYP450 and CYPb(5) levels in mice of TP-treated groups (100, 200 and 400 mg/kg per day) were decreased in a dose-dependent manner compared with those in the negative control mice. TP significantly attenuated the paracetamol-induced hepatic injury and dramatically reduced the mortality of paracetamol-treated mice. Furthermore, TP reduced CYP2E1 and CYP1A2 expression at both protein and mRNA levels in a dose-dependent manner. TP possess potential hepatoprotective properties and can suppress CYP450 expression.

The Hepatoprotective Effect of Selenium-Enriched Yeast and Gum Arabic Combination on Carbon Tetrachloride-Induced Chronic Liver Injury in Rats.

PubMed

Hamid, Mohammed; Abdulrahim, Yassin; Liu, Dandan; Qian, Gang; Khan, Alamzeb; Huang, Kehe

2018-02-01

The antioxidant and anti-inflammatory effects of selenium-enriched yeast (SY) and Gum Arabic (GA) have been reported. This study aimed to determine the hepatoprotective effect of SY and GA combination on carbon tetrachloride (CCl 4 )-induced chronic liver injury in rats and to explore their synergistic mechanisms of action. Forty adult male Wistar rats randomly allotted to 5 groups: (A) worked as control, (B) was administered CCl 4 , (C-E) were fed daily by GA, SY, and GA+SY respectively after mixing with basal diet, following CCl 4 -intoxication. GA and SY combination significantly ameliorated CCl 4 -induced reduction in serum total protein with elevation in aspartate transaminase (AST) and alanine transaminase (ALT) in addition to restoring the histopathological changes and hepatic content of hydroxyproline. GA and SY combination was also effective in reducing lipid peroxidation (MDA), consistent with an increase in total antioxidant capacity (T-AOC), glutathione (GSH), superoxide dismutase (SOD) activities, indicating the suppression of liver oxidative stress. Furthermore, liver inflammation was ameliorated by GA and SY combination through inhibition of nuclear factor-kappa (NF-κB), tumor necrosis factor-alpha (TNF-α), cyclooxygenase-2(COX-2), monocyte chemotactic protein-1 (MCP-1), and toll-like receptor 4(TLR-4) over expression in the liver. Moreover, the up-regulation of proliferating cell nuclear antigen (PCNA) expression by GA and SY combination enhanced the regeneration of liver tissue after CCl 4 -administration. The expression of Collagen1, alpha-smooth muscle actin (α-SMA), and transforming growth factor-beta1 (TGFβ1), was obviously ameliorated by GA and SY combination, suggesting the amelioration of profibrotic response of the liver. Taken together, our current study suggests that GA and SY combination exhibit a significant hepatoprotective activity, which more efficient than GA or SY alone. Chronic liver diseases are the serious health problems, which increase the morbidity and mortality in the world today. Selenium-enriched yeast (SY) and Gum Arabic (GA) combination might be potential dietary agents could obviously ameliorate chronic liver damage, higher than GA and SY alone. They act to suppress the inflammation and inhibit the profibrotic response as well as support the liver regeneration. © 2018 Institute of Food Technologists®.

Antcin H Protects Against Acute Liver Injury Through Disruption of the Interaction of c-Jun-N-Terminal Kinase with Mitochondria

PubMed Central

Huo, Yazhen; Win, Sanda; Than, Tin Aung; Yin, Shutao; Ye, Min

2017-01-01

Abstract Aim: Antrodia Camphorate (AC) is a mushroom that is widely used in Asian countries to prevent and treat various diseases, including liver diseases. However, the active ingredients that contribute to the biological functions remain elusive. The purpose of the present study is to test the hepatoprotective effect of Antcin H, a major triterpenoid chemical isolated from AC, in murine models of acute liver injury. Results: We found that Antcin H pretreatment protected against liver injury in both acetaminophen (APAP) and galactosamine/tumor necrosis factor (TNF)α models. More importantly, Antcin H also offered a significant protection against acetaminophen-induced liver injury when it was given 1 h after acetaminophen. The protection was verified in primary mouse hepatocytes. Antcin H prevented sustained c-Jun-N-terminal kinase (JNK) activation in both models. We excluded an effect of Antcin H on acetaminophen metabolism and TNF receptor signaling and excluded a direct effect as a free radical scavenger or JNK inhibitor. Since the sustained JNK activation through its interaction with mitochondrial Sab, leading to increased mitochondrial reactive oxygen species (ROS), is pivotal in both models, we examined the effect of Antcin H on p-JNK binding to mitochondria and impairment of mitochondrial respiration. Antcin H inhibited the direct effect of p-JNK on isolated mitochondrial function and binding to isolated mitochondria. Innovation and Conclusion: Our study has identified Antcin H as a novel active ingredient that contributes to the hepatoprotective effect of AC, and Antcin H protects against liver injury through disruption of the binding of p-JNK to Sab, which interferes with the ROS-dependent self-sustaining activation of MAPK cascade. Antioxid. Redox Signal. 26, 207–220. PMID:27596680

Bioactive alkaloids from the aerial parts of Houttuynia cordata.

PubMed

Ma, Qinge; Wei, Rongrui; Wang, Zhiqiang; Liu, Wenmin; Sang, Zhipei; Li, Yaping; Huang, Hongchun

2017-01-04

Houttuynia cordata is an important traditional Chinese medicine used in heat-clearing and detoxifying, swelling and discharging pus, promoting diuresis and relieving stranguria which recorded in Pharmacopoeia of the people's Republic of China (2015 Edition). H. cordata has been recorded in the book Bencaogangmu which was written by Shizhen Li for the treatment of pyretic toxicity, carbuncle swelling, haemorrhoids, and rectocele diseases. Phytochemical investigation of the aerial parts of H. cordata and evaluation of their PTP1B inhibitory activities and hepatoprotective activities. The dried aerial parts of H. cordata were fractionated by liquid-liquid extraction to obtain CHCl 3 , ethyl acetate, and n-butanolic fractions. The CHCl 3 fraction was confirmed active fraction by the bioactivity-guided investigation, which was isolated and purified by chromatographing over silica gel, Sephadex LH-20, MPLC, and preparative HPLC. The chemical structures of the purified compounds were identified by their spectroscopic data and references. Eight new compounds (1-8), together with fourteen known compounds (9-22) were isolated from the aerial parts of H. cordata. The known compounds (9-22) were obtained from this plant for the first time. Among them, some compounds exhibited moderate bioactivities. Compounds (1-8) were identified as new alkaloids, and the known alkaloids (9-22) were isolated from this plant for the first time. Compounds 1, 4, 14, and 19 showed significant PTP1B inhibitory activities with IC 50 values of 1.254, 2.016, 2.672, and 1.862µm, respectively. Compounds 1, 3, 6, 11, 17, and 20 (10µm) exhibited moderate hepatoprotective activities against D-galactosamine-induced WB-F344 cells damage. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A comparative study on the anti-schistosomal and hepatoprotective effects of vinpocetine and isosorbide-5-mononitrate on Schistosoma mansoni-infected mice.

PubMed

Alhusseiny, Samar M; El-Beshbishi, Samar N; Hashim, Maha M Abu; El-Nemr, Hosam El-Dein E; Handoussa, Aya E

2017-12-01

Schistosomiasis is a remarkable public health problem in developing countries. Presently, praziquantel is the optional drug for all human schistosomiasis. Owing to the increased praziquantel resistance, there is an urgent need to develop new alternatives. This study aims at determining the anti-schistosomal and/or the hepatoprotective effects of the anti-inflammatory drug; vinpocetine, and the vasodilator and the nitric oxide donor; isosorbide-5-mononitrate, in comparison to praziquantel. In the present research, the therapeutic efficacies of these drugs were assessed in Swiss albino female mice (CD-I strain) experimentally infected with an Egyptian strain of Schistosoma mansoni, using some general, parasitological, and histopathological parameters. In this work, praziquantel significantly reduced worm burden and hepatic egg load, increased the percentage of dead eggs in the small intestine and decreased granuloma count, but did not reduce granuloma diameter. While, either vinpocetine or isosorbide-5-mononitrate monotherapy did not induce significant reduction in the worm count, hepatic egg load or shift in the oogram pattern, but significantly reduced granuloma count and diameter. Moreover, isosorbide-5-mononitrate significantly reduced hepatic inflammation and necrosis. The best results were obtained in the mice groups treated with isosorbide-5-mononitrate combined with praziquantel or vinpocetine. Our results point to vinpocetine and isosorbide-5-mononitrate as a convenient and promising adjuvant to praziquantel for ameliorating schistosomal liver pathology. Further studies are recommended to reveal the actual pathways responsible for the different activities of vinpocetine and isosorbide-5-mononitrate. Copyright © 2017 Elsevier B.V. All rights reserved.

Pretreatment Hepatoprotective Effect of the Marine Fungus Derived from Sponge on Hepatic Toxicity Induced by Heavy Metals in Rats

PubMed Central

Abdel-Monem, Nehad M.; Abdel-Azeem, Ahmed M.; El-Ashry, El-Sayed H.; Ghareeb, Doaa A.; Nabil-adam, Asmaa

2013-01-01

The aim of this study was to evaluate the pretreatment hepatoprotective effect of the extract of marine-derived fungus Trichurus spiralis Hasselbr (TS) isolated from Hippospongia communis sponge on hepatotoxicity. Twenty-eight male Sprague-Dawley rats were divided into four groups (n = 7). Group I served as −ve control, group II served as the induced group receiving subcutaneously for seven days 0.25 mg heavy metal mixtures, group III received (i.p.) TS extract of dose 40 mg for seven days, and group IV served as the protected group pretreated with TS extract for seven days as a protection dose, and then treated with the heavy metal-mixture. The main pathological changes within the liver after heavy-metal mixtures administrations marked hepatic damage evidenced by foci of lobular necrosis with neutrophilic infiltration, adjacent to dysplastic hepatocytes. ALT and AST measurements show a significant increase in group II by 46.20% and 45.12%, respectively. Total protein, elevated by about 38.9% in induction group compared to the −ve control group, in contrast to albumin, decreased as a consequence of metal administration with significant elevation on bilirubin level. The results prove that TS extract possesses a hepatoprotective property due to its proven antioxidant and free-radical scavenging properties. PMID:23484129

Buckwheat Honey Attenuates Carbon Tetrachloride-Induced Liver and DNA Damage in Mice

PubMed Central

Cheng, Ni; Wu, Liming; Zheng, Jianbin; Cao, Wei

2015-01-01

Buckwheat honey, which is widely consumed in China, has a characteristic dark color. The objective of this study was to investigate the protective effects of buckwheat honey on liver and DNA damage induced by carbon tetrachloride in mice. The results revealed that buckwheat honey had high total phenolic content, and rutin, hesperetin, and p-coumaric acid were the main phenolic compounds present. Buckwheat honey possesses super DPPH radical scavenging activity and strong ferric reducing antioxidant power. Administration of buckwheat honey for 10 weeks significantly inhibited serum lipoprotein oxidation and increased serum oxygen radical absorbance capacity. Moreover, buckwheat honey significantly inhibited aspartate aminotransferase and alanine aminotransferase activities, which are enhanced by carbon tetrachloride. Hepatic malondialdehyde decreased and hepatic antioxidant enzymes (superoxide dismutase and glutathione peroxidase) increased in the presence of buckwheat honey. In a comet assay, lymphocyte DNA damage induced by carbon tetrachloride was significantly inhibited by buckwheat honey. Therefore, buckwheat honey has a hepatoprotective effect and inhibits DNA damage, activities that are primarily attributable to its high antioxidant capacity. PMID:26508989

Buckwheat Honey Attenuates Carbon Tetrachloride-Induced Liver and DNA Damage in Mice.

PubMed

Cheng, Ni; Wu, Liming; Zheng, Jianbin; Cao, Wei

2015-01-01

Buckwheat honey, which is widely consumed in China, has a characteristic dark color. The objective of this study was to investigate the protective effects of buckwheat honey on liver and DNA damage induced by carbon tetrachloride in mice. The results revealed that buckwheat honey had high total phenolic content, and rutin, hesperetin, and p-coumaric acid were the main phenolic compounds present. Buckwheat honey possesses super DPPH radical scavenging activity and strong ferric reducing antioxidant power. Administration of buckwheat honey for 10 weeks significantly inhibited serum lipoprotein oxidation and increased serum oxygen radical absorbance capacity. Moreover, buckwheat honey significantly inhibited aspartate aminotransferase and alanine aminotransferase activities, which are enhanced by carbon tetrachloride. Hepatic malondialdehyde decreased and hepatic antioxidant enzymes (superoxide dismutase and glutathione peroxidase) increased in the presence of buckwheat honey. In a comet assay, lymphocyte DNA damage induced by carbon tetrachloride was significantly inhibited by buckwheat honey. Therefore, buckwheat honey has a hepatoprotective effect and inhibits DNA damage, activities that are primarily attributable to its high antioxidant capacity.

Pharmacological safety evaluation of a traditional herbal medicine "Zereshk-e-Saghir" and assessment of its hepatoprotective effects on carbon tetrachloride induced hepatic damage in rats.

PubMed

Sarhadynejad, Zarrin; Sharififar, Fariba; Pardakhty, Abbas; Nematollahi, Mohammad-Hadi; Sattaie-Mokhtari, Saeedeh; Mandegary, Ali

2016-08-22

"Zereshk-e-Saghir" (ZES), one of the traditional herbal medicines in old manuscripts of Persian hakims, has been used for the treatment of liver disorders. This current study is aimed to evaluate ZES effects on animal model to investigate its safety and hepatoprotective activity. ZES was prepared according to a traditional method by blending aqueous extracts of Berberis vulgaris L., with fine particles of other plants including Rosa damascene Mill, Cichorium intybus L., Cucumis sativus L., Portulaca oleracea L., Rheum palmatum L., and Nardostachys jatamansi DC.. The lethality of ZES was determined in male NMRI mice. Acute organ toxicity of ZES (750 and 1500mg/kg for 15 days, orally) was evaluated by measuring the cell blood count, liver marker enzymes, creatinine, antioxidant status and histopathological examinations in rats. CCl4-induced liver toxicity was used to examine the hepatoprotective effects of the preparation. The rats were pretreated with 250, 500, 750 and 1500mg/kg ZES by gavage for 15 days. At day 16, the rats were intraperitoneally injected 1ml/kg CCl4 in olive oil. Forty-eight hours after CCl4 injection, the animals were sacrificed and their liver samples and blood were collected for determination of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase (ALT, AST, and ALP), histopathological examinations and antioxidant status. Treatment of the mice with a single dose of ZES up to 2g/kg did not cause mortality. Treatment of the rats with doses of 750 and 1500mg/kg for 15 days showed no significant hematotoxicity and hepatotoxicity. Treatment of the rats with ZES reduced the increased serum levels of ALT, AST, and ALP induced by CCl4 at the doses of 250, 500, and 750mg/kg. This was almost confirmed by histopathological examinations. Pretreatment with ZES also decreased lipid peroxidation and maintained the levels of glutathione and total antioxidant capacity. The present in vivo study revealed that the long term usage of ZES was safe for organs in laboratory animals. Meanwhile, prescribing the traditionally-recommended dose of ZES can be probably used against the liver injuries induced by xenobiotics. Further studies in other models of liver injuries are recommended for finding the exact hepatoprotective mechanism of ZES. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Hepatoprotective activity of sea cucumber Phyllophorus sp. extract in carp (Cyprinus carpio)

NASA Astrophysics Data System (ADS)

Sulmartiwi, Laksmi; Triastuti, Juni; Andriyono, Sapto; Umami, Mardiah Rahma

2017-02-01

Many procedures continuously in aquaculture and scientific research like tagging and vaccinating cause pain, involving damaging tissue and also cause stress responses in fish. Stress responses in fish influence liver because liver have vital role to supply energy and metabolism. Histology alteration in liver is caused by stress response like changes of vacuolation hepatocyte and characteristic colour. Triterpenoid was known had hepatoprotective activity. One of marine organism contained triterpenoid was sea cucumber. Result of research showed that liver tissue in fish with injected acetic acid 5 % (in upper lip) as pain stimulus have histopathology damages such as pyknosis (medium damage level) and oedema (heavy damage level) after 8 hour injection. Injected Lidocaine 1mg/fish as analgesic drug have histopathology damages such as oedema (heavy damages level), necrosis and pyknosis (low damages level). Injected acetic acid 5 % (in upper lip) and ethanolic extract of sea cucumber Phyllophorus sp. dose 5 mg/50 gr body weight shown histopathology damages such as necrosis, edema (medium damage level) and pyknosis (low damage level).

Pharmacognostic evaluation of leaf of Cordia macleodii Hook., An ethnomedicinally important plant.

PubMed

Bhide, Bhargav; Pillai, A P G; Shukla, V J; Acharya, R N

2011-04-01

Plants of ethnomedicinal importance have contributed for the development of many new pharmacologically effective molecules/chemical entities to modern medicine. India, the country having one of the richest biodiversity of its flora in its forest, with numerous tribal inhabitants, is able to contribute a lot from ethnomedicine to the ailing humanity. Cordia macleodii Hook. (Boraginaceae), an ethnomedicinal plant has been highlighted for its wound healing, aphrodisiac and hepatoprotective activities. It is a medium-sized tree, known as Panki/Shikari by the tribals, rarely found in the forests of Orissa, Chhattisgarh and Madhya Pradesh. So far, the plant has been studied neither for its pharmacognostical characters nor for its pharmacological actions except its hepatoprotective activity. Hence, it has been selected for a detailed investigation which includes pharmacognostic study of its leaf to find out the diagnostic characters and preliminary physicochemical analysis. Results of the study will help in identifying the plant pharmacognostically. Presence of alkaloids, glycosides and tannins were found during the study.

Pharmacognostic evaluation of leaf of Cordia macleodii Hook., An ethnomedicinally important plant

PubMed Central

Bhide, Bhargav; Pillai, A. P. G.; Shukla, V. J.; Acharya, R. N.

2011-01-01

Plants of ethnomedicinal importance have contributed for the development of many new pharmacologically effective molecules/chemical entities to modern medicine. India, the country having one of the richest biodiversity of its flora in its forest, with numerous tribal inhabitants, is able to contribute a lot from ethnomedicine to the ailing humanity. Cordia macleodii Hook. (Boraginaceae), an ethnomedicinal plant has been highlighted for its wound healing, aphrodisiac and hepatoprotective activities. It is a medium-sized tree, known as Panki/Shikari by the tribals, rarely found in the forests of Orissa, Chhattisgarh and Madhya Pradesh. So far, the plant has been studied neither for its pharmacognostical characters nor for its pharmacological actions except its hepatoprotective activity. Hence, it has been selected for a detailed investigation which includes pharmacognostic study of its leaf to find out the diagnostic characters and preliminary physicochemical analysis. Results of the study will help in identifying the plant pharmacognostically. Presence of alkaloids, glycosides and tannins were found during the study. PMID:22408312

Hepatoprotective effect of silymarin

PubMed Central

Vargas-Mendoza, Nancy; Madrigal-Santillán, Eduardo; Morales-González, Ángel; Esquivel-Soto, Jaime; Esquivel-Chirino, Cesar; García-Luna y González-Rubio, Manuel; Gayosso-de-Lucio, Juan A; Morales-González, José A

2014-01-01

The use of medicinal plants in treating illnesses has been reported since ancestral times. In the case of hepatic diseases, several species such as Silybum marianum, Phyllanthus niruri, and Panus giganteus (Berk.) have been shown to ameliorate hepatic lesions. Silymarin is a natural compound derived from the species Silybum marianum, which is commonly known as Milk thistle. This plant contains at least seven flavoligands and the flavonoid taxifolin. The hepatoprotective and antioxidant activity of silymarin is caused by its ability to inhibit the free radicals that are produced from the metabolism of toxic substances such as ethanol, acetaminophen, and carbon tetrachloride. The generation of free radicals is known to damage cellular membranes and cause lipoperoxidation. Silymarin enhances hepatic glutathione and may contribute to the antioxidant defense of the liver. It has also been shown that silymarin increases protein synthesis in hepatocytes by stimulating RNA polymerase I activity. A previous study on humans reported that silymarin treatment caused a slight increase in the survival of patients with cirrhotic alcoholism compared with untreated controls. PMID:24672644

Senna singueana: Antioxidant, Hepatoprotective, Antiapoptotic Properties and Phytochemical Profiling of a Methanol Bark Extract.

PubMed

Sobeh, Mansour; Mahmoud, Mona F; Hasan, Rehab A; Cheng, Haroan; El-Shazly, Assem M; Wink, Michael

2017-09-08

Natural products are considered as an important source for the discovery of new drugs to treat aging-related degenerative diseases and liver injury. The present study profiled the chemical constituents of a methanol extract from Senna singueana bark using HPLC-PDA-ESI-MS/MS and 36 secondary metabolites were identified. Proanthocyanidins dominated the extract. Monomers, dimers, trimers of (epi)catechin, (epi)gallocatechin, (epi)guibourtinidol, (ent)cassiaflavan, and (epi)afzelechin represented the major constituents. The extract demonstrated notable antioxidant activities in vitro: In DPPH (EC 50 of 20.8 µg/mL), FRAP (18.16 mM FeSO₄/mg extract) assays, and total phenolic content amounted 474 mg gallic acid equivalent (GAE)/g extract determined with the Folin-Ciocalteu method. Also, in an in vivo model, the extract increased the survival rate of Caenorhabditis elegans worms pretreated with the pro-oxidant juglone from 43 to 64%, decreased intracellular ROS inside the wild-type nematodes by 47.90%, and induced nuclear translocation of the transcription factor DAF-16 in the transgenic strain TJ356. Additionally, the extract showed a remarkable hepatoprotective activity against d-galactosamine (d-GalN) induced hepatic injury in rats. It significantly reduced elevated AST (aspartate aminotransferase), and total bilirubin. Moreover, the extract induced a strong cytoplasmic Bcl-2 expression indicating suppression of apoptosis. In conclusion, the bark extract of S. sengueana represents an interesting candidate for further research in antioxidants and liver protection.

Protective effect of black garlic extracts on tert-Butyl hydroperoxide-induced injury in hepatocytes via a c-Jun N-terminal kinase-dependent mechanism

PubMed Central

Lee, Ko-Chao; Teng, Chih-Chuan; Shen, Chien-Heng; Huang, Wen-Shih; Lu, Chien-Chang; Kuo, Hsing-Chun; Tung, Shui-Yi

2018-01-01

Black garlic has been reported to show multiple bioactivities against the development of different diseases. In the present study, the hepatoprotective effect of black garlic on injured liver cells was investigated. Rat clone-9 hepatocytes were used for all experiments; tert-Butyl hydroperoxide (tBHP) was used to induce injury of rat clone-9 hepatocytes. The contents of malondialdehyde (MDA) and glutathione (GSH); anti-oxidative enzyme activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx); and mRNA expression levels of interleukin (IL)-6 and IL-8 in rat clone-9 hepatocytes were determined to evaluate the level of cell damage. Black garlic extracts were demonstrated to significantly attenuate tBHP-induced cell death of rat clone-9 hepatocytes (P<0.05). Pretreatment with black garlic extracts antagonized GSH depletion, tBHP-increased MDA accumulation and the mRNA expression level of IL-6/IL-8, and tBHP-decreased antioxidative enzyme activities (all P<0.05). Moreover, the present study revealed that c-Jun N-terminal kinase signaling regulated black garlic-inhibited tBHP effects in rat clone-9 hepatocytes. Our findings demonstrate that black garlic has the hepatoprotective potential to block tBHP-damaged effects on cell death, lipid peroxidation, oxidative stress, and inflammation in rat clone-9 hepatocytes. Thus, the present study indicates that black garlic may be an excellent natural candidate in the development of adjuvant therapy and healthy foods for liver protection. PMID:29456651

Spirulina exhibits hepatoprotective effects against lead induced oxidative injury in newborn rats.

PubMed

Gargouri, M; Ben Saad, H; Ben Amara, I; Magné, C; El Feki, A

2016-08-31

Lead is a toxic metal that induces a wide range of biochemical and physiological effects. The present investigation was designed at evaluating the toxic effects of a prenatal exposure to lead of mothers on hepatic tissue of newborn rats, and potent protective effects of spirulina. Female rats were randomly divided into 4 groups which were given a normal diet (control),a diet enriched with spirulina (S), lead acetate administered through drinking water (Pb), or a diet enriched with spirulina and lead contaminated water (S Pb), respectively. The duration of treatments was from the 5th day of gestation to 14 days postpartum. Lead toxicity was assessed by measuring body and liver weights, blood and stomach lead levels, hepatic DNA, RNA and protein amounts, blood enzyme activities (AST and ALT), as well as lipid peroxidation level and activities of antioxidant enzymes in hepatic tissues of neonates. Lead intoxication of mothers caused reduction of liver weight as well as of hepatic DNA, mRNA and protein levels in newborns. Moreover, oxidative stress and changes in antioxidant enzyme activities were recorded. Conversely, supplementation of mothers with spirulina mitigated these effects induced by lead. These results substantiated the potential hepatoprotective and antioxidant activity of spirulina.

Hepatoprotective activity of Eugenia jambolana Lam. in carbon tetrachloride treated rats

PubMed Central

Sisodia, S.S.; Bhatnagar, M.

2009-01-01

Objective: To estimate the hepatoprotective effects of the methanolic seed extract of Eugenia jambolana Lam. (Myrtaceae), in Wistar albino rats treated with carbon tetrachloride (CCl4). Materials and Methods: Liver damage in rats treated with CCl4 (1ml/kg/Bw, administered subcutaneously, on alternate days for one week) was studied by assessing parameters such as serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase (ALP), acid phosphatase (ACP) and bilirubin (total and direct). The effect of co-administration of Eugenia jambolana Lam. (doses 100, 200 and 400 mg/kg p. o.) on the above parameters was investigated. These biochemical observations were supplemented by weight and histological examination of liver sections. Liv.52® was used as positive control. Data were analyzed by one way ANOVA, followed by Scheff's/Dunnett's test. Results: Administration of Eugenia jambolana Lam. (doses 100, 200 and 400 mg/kg p. o.) significantly prevented carbon tetrachloride induced elevation of serum SGOT, SGPT, ALP, ACP and bilirubin (total and direct) level. Histological examination of the liver section revealed hepatic regeneration, after administration of various doses of Eugenia jambolana Lam. The results were comparable to that of Liv.52®. Conclusion: The study suggests preventive action of Eugenia jambolana Lam. in carbon tetrachloride induced liver toxicity. Hepatic cell regeneration process was dose dependent. PMID:20177577

The hepatoprotective effect of Phyllanthus emblica L. fruit on high fat diet-induced non-alcoholic fatty liver disease (NAFLD) in SD rats.

PubMed

Huang, Cheng-Ze; Tung, Yu-Tang; Hsia, Shih-Min; Wu, Chi-Hao; Yen, Gow-Chin

2017-02-22

Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease, is closely associated with metabolic syndrome and refers to the accumulation of hepatic steatosis not due to excess alcohol consumption. Phyllanthus emblica L. is a rich source of gallic acid and many known medicinally phytochemicals such as tannins, lignans, flavonoids, alkaloids, vitamin C, mucic acid, and ellagic acid. Our previous study has revealed that P. emblica exhibits inhibitory effects on hepatic steatosis and liver fibrosis in vitro, as well as gallic acid improves high fat diet (HFD)-induced dyslipidaemia, hepatosteatosis, and oxidative stress in vivo. Therefore, the aim of this study was to investigate the hepatoprotective effect of the water extract of P. emblica L. fruit (WEPE) on NAFLD in an animal model. The results showed that WEPE could significantly decrease body weight, peritoneal fat and epididymal fat, enhance the antioxidant enzyme activities, and improve steatosis through elevating adiponectin in adipocytes and PPAR-α in the liver as well as lowering SREBP-1c in the liver of rats fed with a high fat diet (HFD). This might be an explanation for the hepatic fat deposition-lowering effect of WEPE. These results demonstrate that WEPE could be beneficial for the amelioration of HFD-induced steatosis.

The thalidomide analog 3-phthalimido-3-(3,4-dimethoxyphenyl)-propanoic acid improves the biliary cirrhosis in the rat.

PubMed

Fernández-Martínez, Eduardo; Pérez-Hernández, Nury; Muriel, Pablo; Pérez-Alvarez, Víctor; Shibayama, Mineko; Tsutsumi, Víctor

2009-09-01

Chronic cholestasis and cholangitis may lead to the last phase known as biliary cirrhosis, characterized by cellular necrosis, apoptosis, tissue damage, local regeneration, inflammation and fibrosis. Such events are mediated by cytokines. Thalidomide and its analogs have shown to be effective immunomodulatory and hepatoprotective agents. The aim of this work was to evaluate the hepatoprotective properties of a thalidomide analog, the 3-phthalimido-3-(3,4-dimethoxyphenyl)-propanoic acid (PDA), on bile duct obstruction-induced cirrhosis. Vehicle or PDA (67 mg/kg) was orally administered twice a day to sham (Sham) or bile duct-ligated (BDL) male Wistar rats. The animals were sacrificed 28 days after treatments. Alkaline phosphatase (AP), gamma-glutamyl transpeptidase (GGTP) and alanine aminotransferase (ALT) enzyme activities as well as direct and total bilirubins concentration were determined in plasma. Lipid peroxidation (LP), glycogen and collagen were quantified in liver; in addition, histopathology was performed. PDA improved cholestasis, necrosis and fibrosis by significantly diminishing most of liver injury markers (P<0.05). Histopathology also showed remarkable liver damage amelioration. PDA effectiveness may be due to its water-solubility, stability, phosphodiesterase-4 inhibitory and immunomodulatory actions. Thalidomide and its analogs seem to be promising drugs for further treatment of biliary cirrhosis.

Mechanisms of the hepatoprotective effects of tamoxifen against drug-induced and chemical-induced acute liver injuries

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoshikawa, Yukitaka; Miyashita, Taishi; Higuchi, Satonori

Although estrogen receptor (ER)α agonists, such as estradiol and ethinylestradiol (EE2), cause cholestasis in mice, they also reduce the degree of liver injury caused by hepatotoxicants as well as ischemia–reperfusion. The functional mechanisms of ERα have yet to be elucidated in drug-induced or chemical-induced liver injury. The present study investigated the effects of an ERα agonist, selective ER modulators (SERMs) and an ER antagonist on drug-induced and chemical-induced liver injuries caused by acetaminophen, bromobenzene, diclofenac, and thioacetamide (TA). We observed hepatoprotective effects of EE2, tamoxifen (TAM) and raloxifene pretreatment in female mice that were exposed to a variety of hepatotoxicmore » compounds. In contrast, the ER antagonist did not show any hepatoprotective effects. DNA microarray analyses suggested that monocyte to macrophage differentiation-associated 2 (Mmd2) protein, which has an unknown function, is commonly increased by TAM and RAL pretreatment, but not by pretreatment with the ER antagonist. In ERα-knockout mice, the hepatoprotective effects of TAM and the increased expression of Mmd2 mRNA were not observed in TA-induced liver injury. To investigate the function of Mmd2, the expression level of Mmd2 mRNA was significantly knocked down to approximately 30% in mice by injection of siRNA for Mmd2 (siMmd2). Mmd2 knockdown resulted in a reduction of the protective effects of TAM on TA-induced liver injury in mice. This is the first report of the involvement of ERα in drug-induced or chemical-induced liver injury. Upregulation of Mmd2 protein in the liver was suggested as the mechanism of the hepatoprotective effects of EE2 and SERMs. -- Highlights: ► Liver injury induced by drugs or chemicals was investigated in mice. ► Liver injury was suppressed by pretreatment with tamoxifen in female mice. ► Mmd2, whose function was unknown, could be a candidate gene for liver protection. ► Tamoxifen up-regulated Mmd2 mRNA expression via ERα.« less

Cryopreservation of in vitro-grown shoot tips of Chinese medicinal plant Atractylodes macrocephala Koidz. using a droplet-vitrification method

USDA-ARS?s Scientific Manuscript database

BACKGROUND: Atractylodes macrocephala Koidz. is an important medicinal species from China and has been used for thousands of years because of pharmacological antioxidant, hepatoprotective, anti-inflammatory, anti-allergic, antithrombotic, antiviral, and anticarcinogenic activities. OBJECTIVE: The ai...

Andrographis paniculata ameliorates carbon tetrachloride (CCl(4))-dependent hepatic damage and toxicity: diminution of oxidative stress.

PubMed

Koh, Pei Hoon; Mokhtar, Ruzaidi Azli Mohd; Iqbal, Mohammad

2011-01-01

Andrographis paniculata (hempedu bumi) is a plant that possesses many medicinal values in treating several diseases and for health care maintenance. However, its hepatoprotective activity and mechanism of action have not been fully investigated. Therefore, this study aimed to evaluate the hepatoprotective effects of A. paniculata and its mechanism of action in rats. Carbon tetrachloride (CCl(4)) challenge of rats at a dose of 1.2 ml/kg body weight-induced oxidative stress in the liver. This was evidenced by augmentation in lipid peroxidation, which was accompanied by a decrease in the activities of antioxidant enzymes and depletion in the level of reduced glutathione (P < 0.05). Parrallel to these changes, CCl(4) challenge too, enhanced hepatic damage as evidenced by sharp increase in serum transaminases (e.g. alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase) (P < 0.05). Additionally, the impairment of liver function corresponded to histolopathological changes. However, most of these changes were reversed in a dose-dependent fashion by pre-treatment of animals with A. paniculata (P < 0.05). The ability of A. paniculata to scavenge the 2,2-Diphenyl-2-picrylhydrazyl radical was determined through its EC(50) value. The EC(50) value of A. paniculata was 583.60 ± 4.25 µg/ml. In addition, A. paniculata was found to contain 65.37 ± 1.20 mg/g total phenolics expressed as gallic acid equivalent. From these studies, it is concluded that A. paniculata could be used as a hepatoprotective agent and possesses the potential to treat or prevent degenerative diseases where oxidative stress is implicated.

In vitro and in vivo evaluation of an oral sustained release hepatoprotective caffeine loaded w/o Pickering emulsion formula - containing wheat germ oil and stabilized by magnesium oxide nanoparticles.

PubMed

Elmotasem, Heba; Farag, Hala K; Salama, Abeer A A

2018-05-16

The objective of this study was to innovate an effective oral sustained release hepatoprotective formula for - the water soluble drug - caffeine. Caffeine is rapidly absorbed and eliminated which dictates frequent administration to achieve adequate therapeutic effect. A w/o Pickering emulsion incorporating caffeine in the internal phase was primed. It contained wheat germ oil and was stabilized by synthesized magnesium oxide nanoparticles (MgO NPs). Components selection was based on their antioxidant, hepatoprotective and anticarcinogenic effects. The MgO NPs were prepared via sol-gel method, and then were characterized using X-ray diffractometry, transmission electron microscopy, contact angle and cytotoxicity. The Pickering emulsion formula stabilized by MgO NPs (F1) was compared to another stabilized by conventional MgO particles (F2). Both were evaluated regarding droplet size, stability and caffeine release. F1 was stable against phase separation for a 2 months period. Its droplets mean size was 665.9 ± 90 nm. F1 afforded sustained release for caffeine that reached 70% within 48 h that followed zero order kinetics. 100 ppm of F1 showed nearly 36% growth inhibition of hepatocellular carcinoma (HEPG2). In vivo and histopathalogical evaluations were conducted on CCl 4 intoxicated rats. Biochemical analysis for liver enzymes - (ALT and AST), oxidative stress biomarkers and the inflammation marker (protein kinase C) - revealed that the selected formula elicited significant hepatoprotection. This formula acted as an economical approach to multiple therapy and afforded safe effective sustained level for caffeine. Copyright © 2018. Published by Elsevier B.V.

Hepatoprotective effects of litchi (Litchi chinensis) procyanidin A2 on carbon tetrachloride-induced liver injury in ICR mice

PubMed Central

Chen, Lih-Geeng; Chang, Cheng-Wei; Tsay, Jwu-Guh; Weng, Brian Bor-Chun

2017-01-01

Drug tolerance, lacking liver regenerative activity and inconclusive inhibition of steatosis and cirrhosis by silymarin treatment during chronic liver injury have increased the demand for novel alternative or synergistic treatments for liver damage. Litchi fruit is abundant in polyphenolic compounds and is used in traditional Chinese medicine for treatments that include the strengthening of hepatic and pancreatic functions. Unique polyphenolic compounds obtained from litchi pericarp extract (LPE) were studied in vitro and in vivo for hepatoprotection. Epicatechin (EC) and procyanidin A2 (PA2) of LPE were obtained by fractionated-extraction from pulverized litchi pericarps. All fractions, including LPE, were screened against silymarin in carbon tetrachloride (CCl4)-treated murine embryonic liver cell line (BNL). The effects of daily gavage-feeding of LPE, silymarin (200 mg/kg body weight) or H2O in CCl4-intoxicated male ICR mice were evaluated by studying serum chemicals, liver pathology and glutathione antioxidative enzymes. The effects of EC and PA2 on liver cell regenerative activity were investigated using a scratch wound healing assay and flow cytometric cell cycle analysis; the results of which demonstrated that LPE protected BNL from CCl4-intoxication. Gavage-feeding of LPE decreased serum glutamic oxaloacetate transaminase and glutamic pyruvic transaminase levels, and exhibited superior retention of the hexagonal structure of hepatocytes and reduced necrotic cells following liver histopathological examinations in CCl4-intoxicated ICR mice. Glutathione peroxidise and glutathione reductase activities were preserved as the normal control level in LPE groups. EC and PA2 were principle components of LPE. PA2 demonstrated liver cell regenerative activity in scratch wound healing assays and alcohol-induced liver cell injury in vitro. The present findings suggest that litchi pericarp polyphenolic extracts, including EC and PA2, may be a synergistic alternative to silymarin in hepatoprotection and liver cell regeneration. PMID:28587348

Hepatoprotective effects of litchi (Litchi chinensis) procyanidin A2 on carbon tetrachloride-induced liver injury in ICR mice.

PubMed

Chen, Lih-Geeng; Chang, Cheng-Wei; Tsay, Jwu-Guh; Weng, Brian Bor-Chun

2017-06-01

Drug tolerance, lacking liver regenerative activity and inconclusive inhibition of steatosis and cirrhosis by silymarin treatment during chronic liver injury have increased the demand for novel alternative or synergistic treatments for liver damage. Litchi fruit is abundant in polyphenolic compounds and is used in traditional Chinese medicine for treatments that include the strengthening of hepatic and pancreatic functions. Unique polyphenolic compounds obtained from litchi pericarp extract (LPE) were studied in vitro and in vivo for hepatoprotection. Epicatechin (EC) and procyanidin A2 (PA2) of LPE were obtained by fractionated-extraction from pulverized litchi pericarps. All fractions, including LPE, were screened against silymarin in carbon tetrachloride (CCl 4 )-treated murine embryonic liver cell line (BNL). The effects of daily gavage-feeding of LPE, silymarin (200 mg/kg body weight) or H 2 O in CCl 4 -intoxicated male ICR mice were evaluated by studying serum chemicals, liver pathology and glutathione antioxidative enzymes. The effects of EC and PA2 on liver cell regenerative activity were investigated using a scratch wound healing assay and flow cytometric cell cycle analysis; the results of which demonstrated that LPE protected BNL from CCl 4 -intoxication. Gavage-feeding of LPE decreased serum glutamic oxaloacetate transaminase and glutamic pyruvic transaminase levels, and exhibited superior retention of the hexagonal structure of hepatocytes and reduced necrotic cells following liver histopathological examinations in CCl 4- intoxicated ICR mice. Glutathione peroxidise and glutathione reductase activities were preserved as the normal control level in LPE groups. EC and PA2 were principle components of LPE. PA2 demonstrated liver cell regenerative activity in scratch wound healing assays and alcohol-induced liver cell injury in vitro . The present findings suggest that litchi pericarp polyphenolic extracts, including EC and PA2, may be a synergistic alternative to silymarin in hepatoprotection and liver cell regeneration.

Thymoquinone: an emerging natural drug with a wide range of medical applications

PubMed Central

Khader, Mohannad; Eckl, Peter M

2014-01-01

Nigella sativa has attracted healers in ancient civilizations and researchers in recent times. Traditionally, it has been used in different forms to treat many diseases including asthma, hypertension, diabetes, inflammation, cough, bronchitis, headache, eczema, fever, dizziness and influenza. Experimentally, it has been demonstrated that N. sativa extracts and the main constituent of their volatile oil, thymoquinone, possess antioxidant, anti-inflammatory and hepatoprotective properties. In this review we aimed at summarizing the most recent investigations related to a few and most important effects of thymoquinone. It is concluded that thymoquinone has evidently proved its activity as hepatoprotective, anti-inflammatory, antioxidant, cytotoxic and anti-cancer chemical, with specific mechanisms of action, which provide support to consider this compound as an emerging drug. Further research is required to make thymoquinone a pharmaceutical preparation ready for clinical trials. PMID:25859298

Association of caffeine intake and histological features of chronic hepatitis C.

PubMed

Costentin, Charlotte E; Roudot-Thoraval, Françoise; Zafrani, Elie-Serge; Medkour, Fatiha; Pawlotsky, Jean-Michel; Mallat, Ariane; Hézode, Christophe

2011-06-01

The severity of chronic hepatitis C (CHC) is modulated by host and environmental factors. Several reports suggest that caffeine intake exerts hepatoprotective effects in patients with chronic liver disease. The aim of this study was to evaluate the impact of caffeine consumption on activity grade and fibrosis stage in patients with CHC. A total of 238 treatment-naïve patients with histologically-proven CHC were included in the study. Demographic, epidemiological, environmental, virological, and metabolic data were collected, including daily consumption of alcohol, cannabis, tobacco, and caffeine during the six months preceding liver biopsy. Daily caffeine consumption was estimated as the sum of mean intakes of caffeinated coffee, tea, and caffeine-containing sodas. Histological activity grade and fibrosis stage were scored according to Metavir. Patients (154 men, 84 women, mean age: 45±11 years) were categorized according to caffeine consumption quartiles: group 1 (<225 mg/day, n=59), group 2 (225-407 mg/day, n=57), group 3 (408-678 mg/day, n=62), and group 4 (>678 mg/day, n=60). There was a significant inverse relationship between activity grade and daily caffeine consumption: activity grade>A2 was present in 78%, 61%, 52%, and 48% of patients in group 1, 2, 3, and 4, respectively (p<0.001). By multivariate analysis, daily caffeine consumption greater than 408 mg/day was associated with a lesser risk of activity grade>A2 (OR=0.32 (0.12-0.85). Caffeine intake showed no relation with fibrosis stage. Caffeine consumption greater than 408 mg/day (3 cups or more) is associated with reduced histological activity in patients with CHC. These findings support potential hepatoprotective properties of caffeine in chronic liver diseases. Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Hepatoprotective effects of ethanol extracts from Folium Syringae against acetaminophen-induced hepatotoxicity in vitro and in vivo.

PubMed

Shi, Chen-Xi; Lin, Yue-Xia; Liu, Fang-Ping; Chang, Yi-Cong; Li, Rui; Li, Chang-Wen; Li, Ying; He, Jing-Shan; Ma, Xin; Li, Zhi

2017-10-01

The leaves of Folium Syringae (FS) have been long used as a traditional Chinese folk medicine for their anti-inflammatory effect, utilized as an antibacterial and antiviral treatment. The purpose of this study was to investigate the potential hepatoprotective effects of FS on acetaminophen-induced hepatic injury in primary hepatocytes and mice. Hepatocytes obtained by the inverse perfusion method were divided randomly into five groups. Prior to acetaminophen exposure, 3 different doses of FS ethanol extracts were given to hepatocytes and mice, respectively. Thereafter, transaminases, glutathione S-transferase A1 (GSTA1) and some hepatic indices were determined. FS ethanol extracts (200 μg/mL) pretreatment prevented all of the alterations, returning their levels to nearly those levels observed in the control group in vitro. Treatment with FS ethanol extracts (200 mg/kg) significantly reduced the toxicity induced by acetaminophen in vivo, which manifested as a decrease in transaminases, and the hepatoprotective effects of FS were similar to Silymarin (positive group). GSTA1 represented the same change trend as transaminases and hepatic indices, and at a dose of 100 μg/mL FS ethanol extracts in vitro and 100 mg/kg in vivo, GSTA1 content changed significantly (p < 0.01), but transaminases were insignificant (p > 0.05). The results of our investigation suggested that FS ethanol extracts possess significant protective effects against hepatotoxicity induced by acetaminophen both in vitro and in vivo. In addition, GSTA1 could be used as an indicator assessing the extents of hepatic injury, which is more sensitive than transaminases. Copyright © 2017. Published by Elsevier Taiwan LLC.

Nanosuspension of Phyllanthus amarus extract for improving oral bioavailability and prevention of paracetamol induced hepatotoxicity in Sprague-Dawley rats

NASA Astrophysics Data System (ADS)

Bhushan Mishra, Shanti; Pandey, Himanshu; Pandey, Avinash C.

2013-09-01

Phyllanthus amarus (P. amarus) is commonly used for traditional Indian medicine and as dietary adjuncts for the treatment of numerous physiological disorders including hepatic disorders. Due to the poor water solubility of its major constituents such as lignans and flavonoids, its absorption upon oral administration could be limited. The present study was designed to evaluate and compare the hepatoprotective effects of the ethanolic extract of P. amarus (PAE) and its nanoparticles (PAN) on paracetamol induced acute liver toxicity in Sprague-Dawley rats. An oral dose of PAE at 125 and 250 mg kg-1 and PAN at 25 and 50 mg kg-1 showed a significant hepatoprotective effect relatively to the same extent (P < 0.001) by reducing levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and bile salts. These biochemical assessments were supported by rat hepatic biopsy examinations. Moreover, the results also indicated that the hepatoprotective effect of 50 mg kg-1 PAN was effectively better than 125 mg kg-1 PAE (P < 0.001), and an oral dose of PAN that is five times less than PAE could exhibit similar levels of outcomes. In conclusion, we suggest that the nanoparticles system can be applied to overcome other poorly water soluble herbal medicines and furthermore to decrease the treatment dosage.

Protective effects from Houttuynia cordata aqueous extract against acetaminophen-induced liver injury.

PubMed

Chen, Wei-Ting; Yang, Chieh-Ling; Yin, Mei-Chin

2014-01-01

Protective effects of Houttuynia cordata aqueous extract (HCAE) against acetaminophen-induced hepatotoxicity in Balb/cA mice were examined. HCAE, at 1 or 2 g/L, was added into the drinking water for 4 weeks. Acute liver injury was induced by acetaminophen treatment intraperitoneally (350 mg/kg body weight). Acetaminophen treatment significantly depleted hepatic glutathione (GSH) content, increased hepatic malonyldialdehyde (MDA), reactive oxygen species (ROS) and oxidized glutathione (GSSG) levels, and decreased hepatic activity of glutathione peroxidase (GPX), catalase and superoxide dismutase (SOD) ( p <0.05). The pre-intake of HCAE alleviated acetaminophen-induced oxidative stress by retaining GSH content, decreasing MDA, ROS and GSSG production, and maintaining activity of GPX, catalase and SOD in liver ( p <0.05). The pre-intake of HCAE also significantly lowered acetaminophen-induced increase in cytochrome P450 2E1 activity ( p <0.05). Acetaminophen treatment increased hepatic release of interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-alpha and monocyte chemoattractant protein-1 ( p <0.05). HCAE intake significantly diminished acetaminophen-induced elevation of these cytokines ( p <0.05). These results support that HCAE could provide hepato-protection.

Hepatoprotective evaluation and isolation of the major secondary metabolites from the ethyl acetate extract of liquid culture filtrate of Chaetomium globosum.

PubMed

Awad, Nagwa E; Kassem, Hanaa A; Hamed, Manal A; El-Feky, Amal M; El-Naggar, Mohamed A A

2018-01-01

The aim of the present study was to evaluate the hepatoprotective activity of ethyl acetate extract of the liquid culture filtrate of Chaetomium globosum fungus (family Chaetomiaceae). Rats were intraperitoneally injected by CCl4 (0.5ml/kg) twice a week for six consecutive weeks. Treatment tacks (250mg/kg) place at the same time of CCl4 induction and with the same duration. The evaluation was done through determination of liver function indices; aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total serum protein content. In addition, the oxidative stress markers; hepatic glutathione content (GSH), hepatic malondialdehyde (MDA), hepatic superoxide dismutase (SOD), and hepatic total protein were estimated. Moreover, the liver architectures were also examined. Isolation and identification of the main secondary metabolites were identified. Seven volatile compounds were identified from the plain chloroform fraction where, 1-Cyclopentyl-2,2-dimethyl-1-propanol (54.63%) was presented as the major compound. Eleven compounds were also identified from the fraction eluted by chloroform: methanol (85:15). 1,5,5-Trimethyl-6-methylene-1-cyclohexene (25.79%) and Norbornan-2-one (26.84%) are presented as the major compounds of this fraction. In conclusion, the extract recorded hepatoprotective effect by ameliorating the biochemical parameters under investigation. The liver histopathological pictures confirmed our results. Copyright © 2017. Published by Elsevier Masson SAS.

Hepatoprotective effects of lycopene on liver enzymes involved in methionine and xenobiotic metabolism in hyperhomocysteinemic rats.

PubMed

Yefsah-Idres, Aicha; Benazzoug, Yasmina; Otman, Amel; Latour, Alizée; Middendorp, Sandrine; Janel, Nathalie

2016-06-15

Hyperhomocysteinemia, defined by an increased plasma homocysteine level, is commonly associated with chronic liver diseases. A link between the elevated homocysteine level and oxidative stress has been demonstrated. Indeed the pathogenesis of liver diseases in the case of hyperhomocysteinemia could be due to this production of oxidative stress. Many studies have demonstrated the antioxidative properties of lycopene, a carotenoid. Therefore, the present study was designed to induce hyperhomocysteinemia in male Wistar rats in order to analyze the effect of lycopene supplementation on homocysteine metabolism, on phase I and phase II xenobiotic-metabolizing enzyme activities, and on liver injury by histological examination and analysis of biochemical markers. We found that rats with a high methionine diet showed abnormal histological features, with an increase of serum homocysteine, alanine aminotransferase and aspartate aminotransferase levels, decreased hepatic cystathionine beta synthase and S-adenosyl-homocysteine hydrolase activities and an increased hepatic malondialdehyde level. We demonstrated the reversal effect of lycopene supplementation on hyperhomocysteinemia. Taken together, these findings provide additional clues on the hepatoprotective effects of lycopene.

Hepatoprotective effect of silyamarin in individuals chronically exposed to hydrogen sulfide; modulating influence of TNF-α cytokine genetic polymorphism

PubMed Central

2013-01-01

Background and the purpose of the study Silymarin, a standardized extract of the milk thistle (Silybum marianum), is believed to exert some of its hepatoprotective effects though inhibition of free radicals and inflammation. In this study the effect of some pro- and anti-inflammatory cytokines and also antioxidant genes polymorphisms on the hepatoprotective effects of silymarin in the occupationally exposed individuals to hydrogen sulfide (H2S) in the sour natural gas refinery was investigated. Methods We genotyped seven polymorphisms in six genes reported by others as modifiers of oxidative stress (NQO1, mEPXH1, GSTT1 and GSTM1) and inflammation (TNF-α and TGF-β1) for an association in effect of decreasing in liver function tests (LFTs). The LFTs of 77 sour gas refinery workers were measured before and after administration of silymarin (140 mg, three times per day for 1 month). Results A significant reduction of blood AST, ALT and ALP was observed after 30 days of consumption (p < 0.001). The decreasing effect of silymarin on ALT in the subjects with high producer genotype (A allele carriers) was less than low producers. There were no significant associations between TGF-β1 and the studied genes of oxidative stress pathway and the effectiveness of silymarin. Conclusion This is the first report about the effectiveness of silymarin in the subjects exposed chronically to H2S. Meanwhile, the modulatory effect of TNF-α on the effectiveness of silymarin might be used for individualize therapy. PMID:23566372

Hepatoprotective and Antioxidant Effect of Mangifera Indica Leaf Extracts against Mercuric Chloride-induced Liver Toxicity in Mice.

PubMed

Karuppanan, Muthupillai; Krishnan, Manigandan; Padarthi, Pavankumar; Namasivayam, Elangovan

2014-01-01

To explore the antioxidant and hepatoprotective effect of ethanolic Mangifera indica (EMI) and methanolic Mangifera indica (MMI) leaf extracts in mercuric chloride (HgCl 2 ) induced toxicity in Swiss albino mice. Toxicity in mice was induced with HgCl 2 (5.0 mg/kg, i.p.), followed by oral intervention with EMI and MMI extracts (25 mg and 50 mg/kg. body wt.) for 30 days. The extent of liver damage was assessed from the extents of histopathological, morphological, antioxidant and liver enzymes. Mercuric chloride-induced mice showed an increased cellular damage whereas leaf extracts of EMI and MMI-treated mice showed recovery of damaged hepatocytes. Mercuric chloride intoxicated mice exhibited a significant (p < 0.05) elevation in the liver enzymes (Aspartate amino transferase and Alanine amino transferase) and gradual decline in the cellular radical scavenging enzyme levels (Catalase, Glutathione-s-transferase and Glutathione peroxidase. The combined treatment with EMI and MMI leaf extracts significantly (p < 0.05) reversed these parameters. However, the effects of MMI leaf extract (50 mg/kg) were superior to those of EMI- treated mice possibly due to its potent radical scavenging property. These results suggest that oral supplementation of Mangifera indica extract remarkably reduces hepatotoxicity in mice possibly through its antioxidant potentials. How to cite this article: Karuppanan M, Krishnan M, Padarthi P, Namasivayam E. Hepatoprotec-tive and Antioxidant Effect of Mangifera Indica Leaf Extracts against Mercuric Chloride-induced Liver Toxicity in Mice. Euroasian J Hepato-Gastroenterol 2014;4(1):18-24.

Hepatoprotective and Antioxidant Effect of Mangifera Indica Leaf Extracts against Mercuric Chloride-induced Liver Toxicity in Mice

PubMed Central

Karuppanan, Muthupillai; Krishnan, Manigandan; Padarthi, Pavankumar

2014-01-01

ABSTRACT Background To explore the antioxidant and hepatoprotective effect of ethanolic Mangifera indica (EMI) and methanolic Mangifera indica (MMI) leaf extracts in mercuric chloride (HgCl2) induced toxicity in Swiss albino mice. Materials and methods Toxicity in mice was induced with HgCl2 (5.0 mg/kg, i.p.), followed by oral intervention with EMI and MMI extracts (25 mg and 50 mg/kg. body wt.) for 30 days. Results and discussion The extent of liver damage was assessed from the extents of histopathological, morphological, antioxidant and liver enzymes. Mercuric chloride-induced mice showed an increased cellular damage whereas leaf extracts of EMI and MMI-treated mice showed recovery of damaged hepatocytes. Mercuric chloride intoxicated mice exhibited a significant (p < 0.05) elevation in the liver enzymes (Aspartate amino transferase and Alanine amino transferase) and gradual decline in the cellular radical scavenging enzyme levels (Catalase, Glutathione-s-transferase and Glutathione peroxidase. The combined treatment with EMI and MMI leaf extracts significantly (p < 0.05) reversed these parameters. However, the effects of MMI leaf extract (50 mg/kg) were superior to those of EMI- treated mice possibly due to its potent radical scavenging property. These results suggest that oral supplementation of Mangifera indica extract remarkably reduces hepatotoxicity in mice possibly through its antioxidant potentials. How to cite this article: Karuppanan M, Krishnan M, Padarthi P, Namasivayam E. Hepatoprotec-tive and Antioxidant Effect of Mangifera Indica Leaf Extracts against Mercuric Chloride-induced Liver Toxicity in Mice. Euroasian J Hepato-Gastroenterol 2014;4(1):18-24. PMID:29264314

Hepatoprotective effect of Matrine salvianolic acid B salt on Carbon Tetrachloride-Induced Hepatic Fibrosis

PubMed Central

2012-01-01

The aim of this study was to investigate the hepatoprotective effect of Matrine salvianolic acid B salt on carbon tetrachloride (CCl4)-induced hepatic fibrosis in rats. Salvianolic acid B and Matrine has long been used to treat liver fibrosis. Matrine salvianolic acid B salt is a new compound containing Salvianolic acid B and Matrine. Hepatic fibrosis induced by CCl4 was studied in animal models using Wistar rats. Organ coefficient, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), hexadecenoic acid (HA), laminin (LN), hydroxyproline (Hyp), and glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) in liver tissues were measured, respectively. Histopathological changes in the livers were studied by hematoxylin-eosin (H&E) staining and Masson Trichrome (MT) examination. The expression of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) was observed by immunohistochemical analysis. A significant reduction in serum levels of AST, ALT, HA, LN and Hyp was observed in the Matrine salvianolic acid B salt treated groups, suggesting that the salt had hepatoprotective effects. The depletion of GSH and SOD, as well as MDA accumulation in liver tissues was suppressed by Matrine salvianolic acid B salt too. The expression of TGF-β1 and α-SMA measured by immunohistology was significantly reduced by Matrine salvianolic acid B salt in a dose-dependent manner. Matrine salvianolic acid B salt treatment attenuated the necro-inflammation and fibrogenesis induced by CCl4 injection, and thus it is promising as a therapeutic anti-fibrotic agent against hepatic fibrosis. PMID:22559721

Hepatoprotective effect of Matrine salvianolic acid B salt on Carbon Tetrachloride-Induced Hepatic Fibrosis.

PubMed

Gao, Hong-Ying; Li, Guo-Yu; Lou, Meng-Meng; Li, Xiao-Yu; Wei, Xiu-Yan; Wang, Jin-Hui

2012-05-04

The aim of this study was to investigate the hepatoprotective effect of Matrine salvianolic acid B salt on carbon tetrachloride (CCl4)-induced hepatic fibrosis in rats. Salvianolic acid B and Matrine has long been used to treat liver fibrosis. Matrine salvianolic acid B salt is a new compound containing Salvianolic acid B and Matrine. Hepatic fibrosis induced by CCl4 was studied in animal models using Wistar rats. Organ coefficient, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), hexadecenoic acid (HA), laminin (LN), hydroxyproline (Hyp), and glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) in liver tissues were measured, respectively. Histopathological changes in the livers were studied by hematoxylin-eosin (H&E) staining and Masson Trichrome (MT) examination. The expression of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA) was observed by immunohistochemical analysis. A significant reduction in serum levels of AST, ALT, HA, LN and Hyp was observed in the Matrine salvianolic acid B salt treated groups, suggesting that the salt had hepatoprotective effects. The depletion of GSH and SOD, as well as MDA accumulation in liver tissues was suppressed by Matrine salvianolic acid B salt too. The expression of TGF-β1 and α-SMA measured by immunohistology was significantly reduced by Matrine salvianolic acid B salt in a dose-dependent manner. Matrine salvianolic acid B salt treatment attenuated the necro-inflammation and fibrogenesis induced by CCl4 injection, and thus it is promising as a therapeutic anti-fibrotic agent against hepatic fibrosis.

Oxidative Stress Alleviation by Sage Essential Oil in Co-amoxiclav induced Hepatotoxicity in Rats.

PubMed

El-Hosseiny, L S; Alqurashy, N N; Sheweita, S A

2016-06-01

Clinical studies have shown that several classes of antibiotics are evidenced in drug induced liver injury. The combination of amoxicillin with clavulanic acid is commonly cited in such cases. Accordingly, the present study investigated the potential hepatoprotective and in vivo antioxidant efficacy of sage essential oil in Co-amoxiclav induced hepatotoxicity in rats. Sage essential oil was hydrodistilled from the aerial parts of Salvia officinalis L. and its compositional analysis was characterized by Gas chromatography-Mass spectroscopy. Rats were treated singly or concomitantly with Co-amoxiclav and sage essential oil for a period of seven days. The major components of sage oil as identified by GC-MS were 1,8-cineole, β-pinene, camphor, β-caryophyllene, α-pinene and α-caryophyllene comprising 26.3%, 14.4%, 10.9%, 7.8%, 6% and 2.5% respectively. The in vivo exposure of rats to Co-amoxiclav resulted in hepatotoxicity biochemically evidenced by the significant elevation of serum AST, ALT, ALP, γ-GT, total bilirubin and histologically conveyed by hydropic, inflammatory and cholestatic changes in rats' liver. Oxidative stress mediated the hepatic injury as indicated by the significant escalation in lipid peroxidation, as well as, the significant depletion of both glutathione level and glutathione dependent enzymes' activities. The concomitant administration of sage essential oil with Co-amoxiclav exerted a hepatoprotective effect via inducing an in vivo antioxidant defense response eventually regressing, to some extent, the hepatoarchitectural changes induced by Co-amoxiclav. Results suggest that sage essential oil is a potential candidate for counteracting hepatic injury associating Co-amoxiclav and this effect is in part related to the complexity of its chemical composition.

Oxidative Stress Alleviation by Sage Essential Oil in Co-amoxiclav induced Hepatotoxicity in Rats

PubMed Central

El-Hosseiny, L. S.; Alqurashy, N. N.; Sheweita, S. A.

2016-01-01

Clinical studies have shown that several classes of antibiotics are evidenced in drug induced liver injury. The combination of amoxicillin with clavulanic acid is commonly cited in such cases. Accordingly, the present study investigated the potential hepatoprotective and in vivo antioxidant efficacy of sage essential oil in Co-amoxiclav induced hepatotoxicity in rats. Sage essential oil was hydrodistilled from the aerial parts of Salvia officinalis L. and its compositional analysis was characterized by Gas chromatography-Mass spectroscopy. Rats were treated singly or concomitantly with Co-amoxiclav and sage essential oil for a period of seven days. The major components of sage oil as identified by GC-MS were 1,8-cineole, β-pinene, camphor, β-caryophyllene, α-pinene and α-caryophyllene comprising 26.3%, 14.4%, 10.9%, 7.8%, 6% and 2.5% respectively. The in vivo exposure of rats to Co-amoxiclav resulted in hepatotoxicity biochemically evidenced by the significant elevation of serum AST, ALT, ALP, γ-GT, total bilirubin and histologically conveyed by hydropic, inflammatory and cholestatic changes in rats’ liver. Oxidative stress mediated the hepatic injury as indicated by the significant escalation in lipid peroxidation, as well as, the significant depletion of both glutathione level and glutathione dependent enzymes’ activities. The concomitant administration of sage essential oil with Co-amoxiclav exerted a hepatoprotective effect via inducing an in vivo antioxidant defense response eventually regressing, to some extent, the hepatoarchitectural changes induced by Co-amoxiclav. Results suggest that sage essential oil is a potential candidate for counteracting hepatic injury associating Co-amoxiclav and this effect is in part related to the complexity of its chemical composition. PMID:27493593

Hepatoprotective effects of Flagellaria indica are mediated through the suppression of pro-inflammatory cytokines and oxidative stress markers in rats.

PubMed

Gnanaraj, Charles; Shah, Muhammad Dawood; Makki, Jaafar Sadeq; Iqbal, Mohammad

2016-08-01

Context The antioxidative properties of plants or plant derivative products are well known for their free radical scavenging effects. Flagellaria indica L. (Flagellariaceae) (FI) is a tropical medicinal plant used by the natives of Sabah as medication for semi-paralysis. Objective This study evaluates the hepatoprotective mechanism of FI against carbon tetrachloride (CCl4)-mediated liver damage. Materials and methods Aqueous extract of FI leaves was orally administered to adult Sprague-Dawley rats once daily for 14 consecutive days at 300, 400, and 500 mg/kg b.w. prior to CCl4 treatment (1.0 mL/kg b.w.) on the 13th and 14th days. Results Total phenolic content in the aqueous extract of FI leaves was 65.88 ± 1.84 mg gallic acid equivalent/g. IC50 value for free radical scavenging activity of FI aqueous extract was reached at the concentration of 400 μg/mL. Biochemical studies show that the aqueous extract of FI was able to prevent the increase in levels of serum transaminases, alanine aminotransferase, and aspartate aminotransferase (38-74% recovery), and malondialdehyde formation (25-87% recovery) in a dose-dependent manner. Immunohistochemical results evidenced the suppression of oxidative stress markers (4-hydroxynonenal and 8-hydroxydeoxyguanosine) and pro-inflammatory markers (tumour necrosis factor-α, interleukin-6, prostaglandin E2). Histopathological and hepatocyte ultrastructural alterations proved that there were protective effects in FI against CCl4-mediated liver injury. Signs of toxicity were not present in rats treated with FI alone (500 mg/kg b.w.). Discussion and conclusion It can be concluded that the presence of phenolic constituents and their antioxidative effects can be credited to the hepatoprotective activity of FI.

Commensal microbiota is hepatoprotective and prevents liver fibrosis in mice

PubMed Central

Mazagova, Magdalena; Wang, Lirui; Anfora, Andrew T.; Wissmueller, Max; Lesley, Scott A.; Miyamoto, Yukiko; Eckmann, Lars; Dhungana, Suraj; Pathmasiri, Wimal; Sumner, Susan; Westwater, Caroline; Brenner, David A.; Schnabl, Bernd

2015-01-01

Translocation of bacteria and their products across the intestinal barrier is common in patients with liver disease, and there is evidence that experimental liver fibrosis depends on bacterial translocation. The purpose of our study was to investigate liver fibrosis in conventional and germ-free (GF) C57BL/6 mice. Chronic liver injury was induced by administration of thioacetamide (TAA) in the drinking water for 21 wk or by repeated intraperitoneal injections of carbon tetrachloride (CCl4). Increased liver fibrosis was observed in GF mice compared with conventional mice. Hepatocytes showed more toxin-induced oxidative stress and cell death. This was accompanied by increased activation of hepatic stellate cells, but hepatic mediators of inflammation were not significantly different. Similarly, a genetic model using Myd88/Trif-deficient mice, which lack downstream innate immunity signaling, had more severe fibrosis than wild-type mice. Isolated Myd88/Trif-deficient hepatocytes were more susceptible to toxin-induced cell death in culture. In conclusion, the commensal microbiota prevents fibrosis upon chronic liver injury in mice. This is the first study describing a beneficial role of the commensal microbiota in maintaining liver homeostasis and preventing liver fibrosis.—Mazagova, M., Wang, L., Anfora, A. T., Wissmueller, M., Lesley, S. A., Miyamoto, Y., Eckmann, L., Dhungana, S., Pathmasiri, W., Sumner, S., Westwater, C., Brenner, D. A., Schnabl, B. Commensal microbiota is hepatoprotective and prevents liver fibrosis in mice. PMID:25466902

The Effect of Artichoke Leaf Extract on Alanine Aminotransferase and Aspartate Aminotransferase in the Patients with Nonalcoholic Steatohepatitis.

PubMed

Rangboo, Vajiheh; Noroozi, Mostafa; Zavoshy, Roza; Rezadoost, Seyed Amirmansoor; Mohammadpoorasl, Asghar

2016-01-01

Background. Based on recent basic and clinical investigations, the extract of artichoke (Cynara scolymus) leaf has been revealed to be used for hepatoprotective and cholesterol reducing purposes. We aimed to assess the therapeutic effects of artichoke on biochemical and liver biomarkers in patients with nonalcoholic steatohepatitis (NASH). Methods. In a randomized double blind clinical trial, 60 consecutive patients suffering NASH were randomly assigned to receive Cynara scolymus extract (as 6 tablets per day consisting of 2700 mg extract of the herb) as the intervention group or placebo as the control group for two months. Results. Comparing changes in study markers following interventions showed improvement in liver enzymes. The levels of triglycerides and cholesterol were significantly reduced in the group treated with Cynara scolymus when compared to placebo group. To compare the role of Cynara scolymus use with placebo in changes in study parameters, multivariate linear regression models were employed indicating higher improvement in liver enzymes and also lipid profile particularly triglycerides and total cholesterol following administration of Cynara scolymus in comparison with placebo use. Conclusion. This study sheds light on the potential hepatoprotective activity and hypolipidemic effect of Cynara scolymus in management of NASH. This clinical trial is registered in the IRCT, Iranian Registry of Clinical Trials, by number IRCT2014070218321N1.

The Effect of Artichoke Leaf Extract on Alanine Aminotransferase and Aspartate Aminotransferase in the Patients with Nonalcoholic Steatohepatitis

PubMed Central

Rangboo, Vajiheh; Noroozi, Mostafa; Zavoshy, Roza; Rezadoost, Seyed Amirmansoor; Mohammadpoorasl, Asghar

2016-01-01

Background. Based on recent basic and clinical investigations, the extract of artichoke (Cynara scolymus) leaf has been revealed to be used for hepatoprotective and cholesterol reducing purposes. We aimed to assess the therapeutic effects of artichoke on biochemical and liver biomarkers in patients with nonalcoholic steatohepatitis (NASH). Methods. In a randomized double blind clinical trial, 60 consecutive patients suffering NASH were randomly assigned to receive Cynara scolymus extract (as 6 tablets per day consisting of 2700 mg extract of the herb) as the intervention group or placebo as the control group for two months. Results. Comparing changes in study markers following interventions showed improvement in liver enzymes. The levels of triglycerides and cholesterol were significantly reduced in the group treated with Cynara scolymus when compared to placebo group. To compare the role of Cynara scolymus use with placebo in changes in study parameters, multivariate linear regression models were employed indicating higher improvement in liver enzymes and also lipid profile particularly triglycerides and total cholesterol following administration of Cynara scolymus in comparison with placebo use. Conclusion. This study sheds light on the potential hepatoprotective activity and hypolipidemic effect of Cynara scolymus in management of NASH. This clinical trial is registered in the IRCT, Iranian Registry of Clinical Trials, by number IRCT2014070218321N1. PMID:27293900

Protective effect of rutin in comparison to silymarin against induced hepatotoxicity in rats.

PubMed

Reddy, M Kasi; Reddy, A Gopala; Kumar, B Kala; Madhuri, D; Boobalan, G; Reddy, M Anudeep

2017-01-01

The aim of this study is to evaluate the hepatoprotective effect of rutin (RTN) in comparison to silymarin (SLM) against acetaminophen (APAP)-induced hepatotoxicity in rats. Male Wistar albino rats (n=24) of 3 months age were equally divided into four groups. Group 1 served as normal control. Hepatotoxicity was induced in the remaining three groups with administration of 500 mg/kg po APAP from day 1-3. Groups 2, 3, and 4 were subsequently administered orally with distilled water, 25 mg/kg of SLM, and 20 mg/kg of RTN, respectively, for 11 days. The mean body weights and biomarkers of hepatotoxicity were estimated on day 0, 4 (confirmation of toxicity), and 15 (at the end of treatment). Hematological parameters were evaluated on day 4 and 15. Antioxidant profile and adenosine triphosphatases (ATPases) were assessed at the end of the experiment. Liver tissues were subjected to histopathology and transmission electron microscopy after the sacrifice on day 15. Antioxidant profile, ATPases, and hematological and sero-biochemical parameters were significantly altered, and histopathological changes were noticed in the liver of toxic control group. These changes were reversed in groups 3 and 4 that were administered with SLM and RTN, respectively. The results of the present investigation enunciated that SLM has potent hepatoprotective activity though the RTN was found superior in restoring the pathological alterations in paracetamol-induced hepatotoxicity in Wistar albino rats.

Hepatoprotective properties in the rat of Mitracarpus scaber (Rubiaceae).

PubMed

Germanò, M P; Sanogo, R; Costa, C; Fulco, R; D'Angelo, V; Torre, E A; Viscomi, M G; De Pasquale, R

1999-06-01

The effect of Mitracarpus scaber on carbon tetrachloride-induced acute liver damage in the rat has been evaluated. Results showed that treatment with Mitracarpus scaber decoction resulted in significant hepatoprotection against CCl4-induced liver injury both in-vivo and in-vitro. In-vivo, Mitracarpus scaber pretreatment reduced levels of serum glutamate-oxalate-transaminase (P < 0.01 for 250, 500 and 1000 mg kg(-1)) and serum glutamate-pyruvate-transaminase (P < 0.05 for 250 mg kg(-1) and P < 0.01 for 1000 mg kg(-1)) previously increased by administration of CCl4. In-vitro results indicated that addition to the culture medium of Mitracarpus scaber extracts significantly reduced glutamate-oxalate-transaminase (P < 0.05 for 100 microg mL(-1) and P < 0.01 for 10 and 1000 microg mL(-1)) and lactate dehydrogenase activity (P < 0.05 for 10 microg mL(-1)). Mitracarpus treatment also resulted in a good ( > 93%) survival rate for the CCl4-intoxicated hepatocytes as demonstrated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Moreover, as in the in-vitro assay, Mitracarpus scaber had radical-scavenging properties, shown by its reaction with the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical (EC50, the extract concentration resulting in a 50% reduction in the absorbance of DPPH blank solution, = 41.64+/-1.5 microg mL(-1)). The results of this study showed that Mitracarpus scaber had antihepatotoxic potential, a finding which supports the validity of traditional usage of this drug in Mali for the treatment of liver diseases.

Hepatoprotective effect of engineered silver nanoparticles coated bioactive compounds against diethylnitrosamine induced hepatocarcinogenesis in experimental mice.

PubMed

Prasannaraj, Govindaraj; Venkatachalam, Perumal

2017-02-01

Nanoparticle based drug delivery can rapidly improves the therapeutic potential of anti-cancer agents. The present study focused to evaluate the hepatoprotective activity of silver nanoparticles (AgNPs) synthesized using aqueous extracts of Andrographis paniculata leaves (ApAgNPs) and Semecarpus anacardium nuts (SaAgNPs) against diethylnitrosamine (DEN) induced liver cancer in mice model. The physico-chemical properties of synthesized AgNPs were characterized by Fourier transform infrared (FTIR) spectroscopy, Transmission Electron Microscopy (TEM), Selected Area Electron Diffraction (SAED), X-ray Diffraction (XRD), Energy Dispersive X-ray (EDX) spectrum, Zeta potential and Dynamic Light Scattering (DLS) analysis. The surface plasmon resonance (SPR) absorption spectrum revealed a strong peak at 420nm for both SaAgNPs and ApAgNPs. FTIR results exhibited the presence of possible functional groups in the synthesized AgNPs. TEM analysis determined the hexagonal, and spherical shape of the synthesized silver nanoparticles. The XRD and SAED pattern confirmed the crystalline nature and crystalline size of the AgNPs. EDX result clearly showed strong silver signals in the range between 2 and 4keV. Zeta potential measurements indicated a sharp peak at -3.93 and -13.8mV for ApAgNPs and SaAgNPs, respectively. DLS measurement expressed the particle size distribution was 70 and 60nm for ApAgNPs and SaAgNPs, respectively. DEN (20mg/kg b.wt.) was subjected to induce liver cancer in mice for 8weeks and treated with biosynthesized silver nanoparticles. Interestingly, ApAgNPs and SaAgNPs treated DEN induced animal groups show a decreased level of aspartate amino transferase (AST), alanine amino transferase (ALT), serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) activity and elevated level of catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST) and superoxide dismutase (SOD) activity over untreated DEN control animals group. Histopathological investigation reveals decreased fat accumulation, appearance of binucleated cells in nanoparticle treated animals and showed mere normal cells induced by DEN. Argyrophilic nucleolar organiser region (AgNORs) had a significant decrease in number of acidic proteins and mast cells assay showed decrease of metachromatic cells in nanoparticles treated animal groups over control. Present results strongly suggest that biomolecule coated silver nanoparticles exposure showed potential hepatoprotective effect against DEN induced liver cancer and could be used as an effective anticancer nanodrug. Copyright © 2017. Published by Elsevier B.V.

Silymarin Constituents Enhance ABCA1 Expression in THP-1 Macrophages

PubMed Central

Wang, Limei; Rotter, Susanne; Ladurner, Angela; Heiss, Elke H.; Oberlies, Nicholas H.; Dirsch, Verena M.; Atanasov, Atanas G.

2016-01-01

Silymarin is a hepatoprotective mixture of flavonolignans and flavonoids extracted from the seeds of milk thistle (Silybum marianum L. Gaertn). This study investigates the effect of major bioactive constituents from silymarin, silybin A, silybin B, isosilybin A, isosilybin B, silydianin, silychristin, isosilychristin, and taxifolin, on the expression of ABCA1, an important cholesterol efflux transporter, in THP-1-derived macrophages. Four of the studied compounds, isosilybin A, silybin B, silychristin and isosilychristin, were found to significantly induce ABCA1 protein expression without affecting cell viability. Moreover, isosilybin A, a partial PPARγ agonist, was found to promote cholesterol efflux from THP-1 macrophages in a concentration-dependent manner. These findings first show ABCA1 protein up-regulating activity of active constituents of silymarin and provide new avenues for their further study in the context of cardiovascular disease. PMID:26729088

Silymarin Constituents Enhance ABCA1 Expression in THP-1 Macrophages.

PubMed

Wang, Limei; Rotter, Susanne; Ladurner, Angela; Heiss, Elke H; Oberlies, Nicholas H; Dirsch, Verena M; Atanasov, Atanas G

2015-12-31

Silymarin is a hepatoprotective mixture of flavonolignans and flavonoids extracted from the seeds of milk thistle (Silybum marianum L. Gaertn). This study investigates the effect of major bioactive constituents from silymarin, silybin A, silybin B, isosilybin A, isosilybin B, silydianin, silychristin, isosilychristin, and taxifolin, on the expression of ABCA1, an important cholesterol efflux transporter, in THP-1-derived macrophages. Four of the studied compounds, isosilybin A, silybin B, silychristin and isosilychristin, were found to significantly induce ABCA1 protein expression without affecting cell viability. Moreover, isosilybin A, a partial PPARγ agonist, was found to promote cholesterol efflux from THP-1 macrophages in a concentration-dependent manner. These findings first show ABCA1 protein up-regulating activity of active constituents of silymarin and provide new avenues for their further study in the context of cardiovascular disease.

Antihyperglycemic and Antihyperlipidemic Activity of Hydroponic Stevia rebaudiana Aqueous Extract in Hyperglycemia Induced by Immobilization Stress in Rabbits

PubMed Central

Aghajanyan, Anush; Movsisyan, Zaruhi

2017-01-01

Diabetes mellitus (DM) is a serious worldwide problem related to human hyperglycemia. Thus, herbal preparations with antihyperglycemic properties especially leaf extracts of hydroponic Stevia rebaudiana (SR) would be useful in hyperglycemia treatment. The antihyperglycemic potential of this medicinal plant grown using hydroponics methods has been evaluated. Significant reduction of some biochemical characteristics for sugars and fatty acids in blood, liver, and muscle especially fasting glucose levels, serum triglycerides, LDL-cholesterol, total cholesterol levels, and increased HDL-cholesterol ones was shown with SR aqueous extract treatment. Therefore, the aqueous extract of SR is suggested to have antihyperglycemic and antihyperlipidemic activity and to restore liver and muscle glycogen levels (hepatoprotective effects) in hyperglycemia induced by immobilization stress in rabbits and might be recommended for treatment of DM (hyperglycemia). PMID:28758125

An Antioxidant Extract of the Insectivorous Plant Drosera burmannii Vahl. Alleviates Iron-Induced Oxidative Stress and Hepatic Injury in Mice

PubMed Central

Das, Abhishek; Panja, Sourav; Mandal, Nripendranath

2015-01-01

Free iron typically leads to the formation of excess free radicals, and additional iron deposition in the liver contributes to the oxidative pathologic processes of liver disease. Many pharmacological properties of the insectivorous plant Drosera burmannii Vahl. have been reported in previous studies; however, there is no evidence of its antioxidant or hepatoprotective potential against iron overload. The antioxidant activity of 70% methanolic extract of D. burmannii (DBME) was evaluated. DBME showed excellent DPPH, hydroxyl, hypochlorous, superoxide, singlet oxygen, nitric oxide, peroxynitrite radical and hydrogen peroxide scavenging activity. A substantial iron chelation (IC50 = 40.90 ± 0.31 μg/ml) and supercoiled DNA protection ([P]50 = 50.41 ± 0.55 μg) were observed. DBME also displayed excellent in vivo hepatoprotective activity in iron-overloaded Swiss albino mice compared to the standard desirox treatment. Administration of DBME significantly normalized serum enzyme levels and restored liver antioxidant enzymes levels. DBME lowered the raised levels of liver damage parameters, also reflected from the morphological analysis of the liver sections. DBME also reduced liver iron content by 115.90% which is also seen by Perls’ staining. A phytochemical analysis of DBME confirms the presence of various phytoconstituents, including phenols, flavonoids, carbohydrates, tannins, alkaloids and ascorbic acid. Alkaloids, phenols and flavonoids were abundantly found in DBME. An HPLC analysis of DBME revealed the presence of purpurin, catechin, tannic acid, reserpine, methyl gallate and rutin. Purpurin, tannic acid, methyl gallate and rutin displayed excellent iron chelation but exhibited cytotoxicity toward normal (WI-38) cells; while DBME found to be non-toxic to the normal cells. These findings suggest that the constituents present in DBME contributed to its iron chelation activity. Additional studies are needed to determine if DBME can be used as a treatment for iron overload diseases. PMID:26010614

Quality assessment of Penthorum chinense Pursh through multicomponent qualification and fingerprint, chemometric, and antihepatocarcinoma analyses.

PubMed

Sun, Zong-Liang; Zhang, Yu-Zhen; Zhang, Feng; Zhang, Jia-Wei; Zheng, Guo-Can; Tan, Ling; Wang, Chong-Zhi; Zhou, Lian-Di; Zhang, Qi-Hui; Yuan, Chun-Su

2018-06-22

An efficient method combined with fingerprint and chemometric analyses was developed to evaluate the quality of the traditional Chinese medicine plant Penthorum chinense Pursh. Nine samples were collected from different regions during different harvest periods, and 17 components in the form of extracts were simultaneously examined to assess quality by using high-performance liquid chromatography. The hepatoprotective effects of components were investigated by assessing the inhibition of SMMC-7721 cell growth. The results indicated that the quality control method was accurate, stable, and reliable, and the hierarchical heat-map cluster and the principle component analyses confirmed that the classification of all nine samples was consistent. Quercetin and ellagitannins including pinocembrin-7-O-[3''-O-galloyl-4'',6''-hexahydroxydiphenoyl]-β-glucose (PGHG), thonningianin A, thonningianin B, and other flavonoids were abundant in the extracts, and significantly contributed to the hepatoprotective effects.

Andrographis paniculata Leaf Extract Prevents Thioacetamide-Induced Liver Cirrhosis in Rats

PubMed Central

Bardi, Daleya Abdulaziz; Halabi, Mohammed Farouq; Hassandarvish, Pouya; Rouhollahi, Elham; Paydar, Mohammadjavad; Moghadamtousi, Soheil Zorofchian; Al-Wajeeh, Nahla Saeed; Ablat, Abdulwali; Abdullah, Nor Azizan; Abdulla, Mahmood Ameen

2014-01-01

This study investigated the hepatoprotective effects of ethanolic Andrographis paniculata leaf extract (ELAP) on thioacetamide-induced hepatotoxicity in rats. An acute toxicity study proved that ELAP is not toxic in rats. To examine the effects of ELAP in vivo, male Sprague Dawley rats were given intraperitoneal injections of vehicle 10% Tween-20, 5 mL/kg (normal control) or 200 mg/kg TAA thioacetamide (to induce liver cirrhosis) three times per week. Three additional groups were treated with thioacetamide plus daily oral silymarin (50 mg/kg) or ELAP (250 or 500 mg/kg). Liver injury was assessed using biochemical tests, macroscopic and microscopic tissue analysis, histopathology, and immunohistochemistry. In addition, HepG2 and WRL-68 cells were treated in vitro with ELAP fractions to test cytotoxicity. Rats treated with ELAP exhibited significantly lower liver/body weight ratios and smoother, more normal liver surfaces compared with the cirrhosis group. Histopathology using Hematoxylin and Eosin along with Masson’s Trichrome stain showed minimal disruption of hepatic cellular structure, minor fibrotic septa, a low degree of lymphocyte infiltration, and minimal collagen deposition after ELAP treatment. Immunohistochemistry indicated that ELAP induced down regulation of proliferating cell nuclear antigen. Also, hepatic antioxidant enzymes and oxidative stress parameters in ELAP-treated rats were comparable to silymarin-treated rats. ELAP administration reduced levels of altered serum liver biomarkers. ELAP fractions were non-cytotoxic to WRL-68 cells, but possessed anti-proliferative activity on HepG2 cells, which was confirmed by a significant elevation of lactate dehydrogenase, reactive oxygen species, cell membrane permeability, cytochrome c, and caspase-8,-9, and, -3/7 activity in HepG2 cells. A reduction of mitochondrial membrane potential was also detected in ELAP-treated HepG2 cells. The hepatoprotective effect of 500 mg/kg of ELAP is proposed to result from the reduction of thioacetamide-induced toxicity, normalizing reactive oxygen species levels, inhibiting cellular proliferation, and inducing apoptosis in HepG2 cells. PMID:25280007

Andrographis paniculata leaf extract prevents thioacetamide-induced liver cirrhosis in rats.

PubMed

Abdulaziz Bardi, Daleya; Halabi, Mohammed Farouq; Hassandarvish, Pouya; Rouhollahi, Elham; Paydar, Mohammadjavad; Moghadamtousi, Soheil Zorofchian; Al-Wajeeh, Nahla Saeed; Ablat, Abdulwali; Abdullah, Nor Azizan; Abdulla, Mahmood Ameen

2014-01-01

This study investigated the hepatoprotective effects of ethanolic Andrographis paniculata leaf extract (ELAP) on thioacetamide-induced hepatotoxicity in rats. An acute toxicity study proved that ELAP is not toxic in rats. To examine the effects of ELAP in vivo, male Sprague Dawley rats were given intraperitoneal injections of vehicle 10% Tween-20, 5 mL/kg (normal control) or 200 mg/kg TAA thioacetamide (to induce liver cirrhosis) three times per week. Three additional groups were treated with thioacetamide plus daily oral silymarin (50 mg/kg) or ELAP (250 or 500 mg/kg). Liver injury was assessed using biochemical tests, macroscopic and microscopic tissue analysis, histopathology, and immunohistochemistry. In addition, HepG2 and WRL-68 cells were treated in vitro with ELAP fractions to test cytotoxicity. Rats treated with ELAP exhibited significantly lower liver/body weight ratios and smoother, more normal liver surfaces compared with the cirrhosis group. Histopathology using Hematoxylin and Eosin along with Masson's Trichrome stain showed minimal disruption of hepatic cellular structure, minor fibrotic septa, a low degree of lymphocyte infiltration, and minimal collagen deposition after ELAP treatment. Immunohistochemistry indicated that ELAP induced down regulation of proliferating cell nuclear antigen. Also, hepatic antioxidant enzymes and oxidative stress parameters in ELAP-treated rats were comparable to silymarin-treated rats. ELAP administration reduced levels of altered serum liver biomarkers. ELAP fractions were non-cytotoxic to WRL-68 cells, but possessed anti-proliferative activity on HepG2 cells, which was confirmed by a significant elevation of lactate dehydrogenase, reactive oxygen species, cell membrane permeability, cytochrome c, and caspase-8,-9, and, -3/7 activity in HepG2 cells. A reduction of mitochondrial membrane potential was also detected in ELAP-treated HepG2 cells. The hepatoprotective effect of 500 mg/kg of ELAP is proposed to result from the reduction of thioacetamide-induced toxicity, normalizing reactive oxygen species levels, inhibiting cellular proliferation, and inducing apoptosis in HepG2 cells.

Self-nanoemulsifying drug delivery system for enhanced bioavailability and improved hepatoprotective activity of biphenyl dimethyl dicarboxylate.

PubMed

El-Laithy, Hanan M

2008-07-01

Biphenyl Dimethyl Dicarboxylate (BDD) is insoluble in aqueous solution and the bioavailability after oral administration is low. Self-nanoemulsifying drug delivery system (SNEDDS) containing BDD has been successfully prepared using carefully selected ingredients which are less affected by pH and ionic strength changes to improve its bioavailability. SNEDDS is an isotropic mixture of lipid, surfactant, and cosurfactant which are spontaneously emulsified in aqueous medium under gentle digestive motility in the gastrointestinal tract. Pseudo ternary phase diagrams composed of various excipients were plotted to identify self -nano -emulsifying area. Droplet size changes upon dilution with aqueous media and in vitro release of BDD from SNEDDS in 0.1N HCl and phosphate buffer (pH 7.4) were studied and compared with commercial chinese pilules and Pennel capsules. The hepatoprotective activity upon oral administration of SNEDDS against carbon tetrachloride-induced oxidative stress in albino rats was assessed by measuring biochemical parameters like serum glutamic oxalacetate transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT) and lactate dehydrogenase (LDH). Results showed that using a proper ratio of Tween 80 to Transcutol as surfactant and co-surfactant respectively and Miglyol 812 as oil to surfactants mixture resulted in production of infinitely diluted formulations in nano droplet size range. BDD self nano emulsified formula composed of 20% Miglyol 812, 60% Tween 80 and 20% Transcutol released 99% of the drug very rapidly within 10-15 minutes regardless of the pH condition. The oral absorption and bioavailability of BDD self nano emulsified formula in albino rats were significantly enhanced (P<0.01) with an average improvement of 1.7 and 6-folds that of commercial chinese pilules and Pennel capsules respectively. This improvement was also confirmed histopathologically in chemically injured rats and by the significant decrease in elevated liver enzymes level.

Hepatoprotective effects of parsley, basil, and chicory aqueous extracts against dexamethasone-induced in experimental rats

PubMed Central

Soliman, Hanan A.; El-Desouky, Mohamed A.; Hozayen, Walaa G.; Ahmed, Rasha R.; Khaliefa, Amal K.

2016-01-01

Aim: The objective of this study is to investigate the hypoglycemic, hypolipidemic, and hepatoprotective effects of the aqueous extract of parsley, basil, and chicory whole plant in normal and dexamethasone (Dex) rats. Materials and Methods: 50 female albino rats were used in this study and divided into 5 groups (for each 10). Group (1) fed basal diet and maintained as negative control group. Group (2) received Dex in a dose of (0.1 mg/kg b. wt.). Groups 3, 4, and 5 were treated with Dex along with three different plant extracts of parsley, basil, and chicory (2 g/kg b. wt.), (400 mg/kg b. wt.), and (100 mg/kg b. wt.), respectively. Results: All these groups were treated given three times per week for 8 consecutive weeks. Dex-induced alterations in the levels of serum glucose, triglyceride, cholesterol, low-density lipoprotein-cholesterol levels and cardiovascular indices and serum alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities, liver thiobarbituric acid (TBARS) levels increased, while high-density lipoprotein-cholesterol, total protein, albumin, and liver glutathione (GSH) levels decreased. On the other hand, plant extracts succeeded to modulate these observed abnormalities resulting from Dex as indicated by the reduction of glucose, cholesterol, TBARS, and the pronounced improvement of the investigated biochemical and antioxidant parameters. Conclusions: It was concluded that probably, due to its antioxidant property, parsley, basil, and chicory extracts have hepatoprotective effects in Dex-induced in rats. PMID:27069727

A study on effects of glutathione s-transferase from silkworm on CCL4-induced mouse liver injury.

PubMed

Yan, Hui; Gui, Zhongzheng; Wang, Bochu

2011-01-01

To assess the hepatoprotective activity of Glutathione S-transferase(GSTsw), extracted and purified from silkworm, in experimental acute mice liver injury and explore mechanisms. Mice were divided into five groups: control group, carbon tetrachloride (CCl4) group, and three treatment groups that received CCl4 and GSTsw at doses of 0.083 mg•g(-1), 0.0415 mg•g(-1) and 0.0207 mg•g(-1) for 3 days. ALT in serum, GST, SOD and T-AOC in liver tissue homogenate, and changes in liver pathology in the five groups were studied. CCl4 administration led to pathological and biochemical evidence of liver injury as compared to untreated controls. GSTsw administration led to significant protection against CCl4-induced changes in liver pathology. It was also associatedwith significantly lower serum ALT levels, higher GST-SOD and T-AOC level in live tissue homogenate. Thus, GSTsw showed protective activity against CCl4-induced hepatotoxicity in mice.

Reduction of oxidative stress by an ethanolic extract of leaves of Piper betle (Paan) Linn. decreased methotrexate-induced toxicity.

PubMed

De, Soumita; Sen, Tuhinadri; Chatterjee, Mitali

2015-11-01

Methotrexate (MTX), a folate antagonist, is currently used as first line therapy for autoimmune diseases like rheumatoid arthritis and psoriasis, but its use is limited by the associated hepatotoxicity. As leaves of Piper betle, belonging to family Piperaceae, have antioxidant and anti-inflammatory properties, the present study was undertaken to investigate the potential of Piper betle leaf extract (PB) in attenuating MTX-induced hepatotoxicity. Rats pre-treated with PB (50 or 100 mg kg(-1) b.w., p.o.) were administered with a single dose of MTX (20 mg kg(-1), b.w., i.p.) and its hepatoprotective efficacy was compared with folic acid (1 mg kg(-1) b.w., i.p.), conventionally used to minimize MTX-induced toxicity. MTX-induced hepatotoxicity was confirmed by increased activities of marker enzymes, alanine transaminase, aspartate transaminase, and alkaline phosphatase which were remitted by pre-treatment with PB and corroborated with histopathology. Additionally, MTX-induced hepatic oxidative stress which included increased generation of reactive oxygen species, enhanced lipid peroxidation, depleted levels of glutathione and decreased activities of antioxidant enzymes was effectively mitigated by PB, indicative that its promising antioxidant-mediated hepatoprotective activity was worthy of future pharmacological consideration.

Protective effect of crocin on BPA-induced liver toxicity in rats through inhibition of oxidative stress and downregulation of MAPK and MAPKAP signaling pathway and miRNA-122 expression.

PubMed

Vahdati Hassani, Faezeh; Mehri, Soghra; Abnous, Khalil; Birner-Gruenberger, Ruth; Hosseinzadeh, Hossein

2017-09-01

Bisphenol A (BPA) is an artificial environmental endocrine disrupting chemical and commonly used as a monomer of polycarbonate plastics and epoxy resins. The aim of the present study is to investigate the hepatoprotective effects of crocin, a constituent of saffron, against BPA-induced liver toxicity. We showed that treatment of male Wistar rats with 0.5 mg/kg BPA for 30 days increased the level of 8-isoprostane, decreased the level of reduced glutathione, elevated serum levels of aspartate aminotransferase, lactate dehydrogenase, triglyceride, and glucose, and induced periportal inflammation. Western blot results revealed that BPA increased the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK1/2), and mitogen-activated protein kinase-activated protein kinase (MAPKAPK), but not p38. BPA also reduced the Akt signaling activation and upregulated microRNA (miR-122) expression. Moreover, we showed here that crocin 20 mg/kg administration ameliorated liver damage and improved elevated levels of TG and liver enzymes of BPA-treated rats possibly though antioxidant activity, downregulation of miR-122 transcript level and lowering the phosphorylation of JNK, ERK1/2, and MAPKAPK and subsequently their activities. Overall, the findings suggest that crocin possesses hepatoprotective effects against BPA-induced liver toxicity by enhancing the antioxidative defense system and regulation of important signaling pathway activities and miR-122 expression. Copyright © 2017 Elsevier Ltd. All rights reserved.

Low-molecular-weight lignin-rich fraction in the extract of cultured Lentinula edodes mycelia attenuates carbon tetrachloride-induced toxicity in primary cultures of rat hepatocytes.

PubMed

Yoshioka, Yasuko; Kojima, H; Tamura, A; Tsuji, K; Tamesada, M; Yagi, K; Murakami, N

2012-01-01

The extract of cultured Lentinula edodes mycelia (LEM) is a medicinal food ingredient that has hepatoprotective effects. In this study, we fractionated the LEM extract to explore novel active compounds related to hepatoprotection by using primary cultures of rat hepatocytes exposed to carbon tetrachloride (CCl(4)). The LEM extract and the fractions markedly inhibited the release of alanine aminotransferase (ALT) from hepatocytes damaged by CCl(4) into the culture medium. The strongest hepatocyte-protective activity was seen in a fraction (Fr. 2) in which a 50% ethanol extract was further eluted with 50% methanol and separated using reverse-phase HPLC. Fr. 2 had an average molecular weight of 2753, and the main components are lignin (49%) and saccharides (36%, of which xylose comprises 41%). Therefore, Fr. 2 was presumed to be a low-molecular-weight compound consisting mainly of lignin and xylan-like polysaccharides. The hepatocyte-protective activity was observed even after digestion of xylan-like polysaccharides in Fr.2 and confirmed with low-molecular-weight lignin (LM-lignin) alone. In addition, Fr. 2, the xylan-digested Fr. 2 and LM-lignin showed higher superoxide dismutase (SOD)-like activity than the LEM extract. These results suggested that the effective fraction in the LEM extract related to hepatocyte protection consisted mainly of LM-lignin, and its antioxidant activity partially contributes to the hepatocyte-protective activity of the LEM extract.

The hepatoprotective role of Silymarin in isoniazid induced liver damage of rabbits.

PubMed

Jahan, Sarwat; Khan, Moosa; Imran, Sana; Sair, Mohammad

2015-06-01

To evaluate the hepatoprotective role of Silymarin against isonicotinylhydrazine-induced hepatotoxicity in rabbit model. The experimental animal study was held at Jinnah Postgraduate Medical Centre, Karachi, from April to September 2013 and comprised rabbits weighing 1-1.5kgof either gender. The animals were divided randomly into equal groups: group I underwent liver function test without any drug; in group II effects of Silymarin (50mg/kg/day orally) was observed; in group III isoniazid (50mg/kg/dayorally) was administered; and in group IV combined effects of isoniazid and silymarin were observed. Liver function tests were performed at day0 and after the treatment at day19. SPSS 16 was used for statistical analysis. The 28 rabbits in the study were divided in four groups of 7(25%) each. No mortality was recorded in any group. In group III, bilirubin level was increased and alanine transaminase was decreased significantly (p<0.05 each). In group IV, there was significant improvement in serum billirubin and serum alanine transaminase (p<0.05 each). Isonicotinylhydrazine-induced hepatotoxicity was well treated by concurrent administration of Silymarin.

The Effect of Geraniol on Liver Regeneration Αfter Hepatectomy in Rats

PubMed Central

CANBEK, MEDIHA; UYANOGLU, MUSTAFA; CANBEK, SELCUK; CEYHAN, EMRE; OZEN, AHMET; DURMUS, BASAK; TURGAK, OZGE

2017-01-01

Geraniol is a monoterpenoid alcohol that has a hepatoprotective effect. We investigated the regenerative effects of geraniol in rats after a 70% partial hepatectomy (PH). Using Wistar albino rats, nine groups were created: Group I was the control group, while the remaining groups received a single intraperitoneal dose of saline, Silymarin, or geraniol after PH. A 70% PH was performed on all groups except for groups II and III. Blood serum samples were obtained for alanine amino transferase (ALT) analysis. Then liver tissues were harvested for histological and real-time polymerase chain reaction (PCR) analyses. Tumor necrosis factor-α (TNFα) and interleukin 6 (IL6) gene expression were examined 24 and 48 h after PH. ALT levels were found to be statistically significantly increased in all PH-treated groups. TNFα and IL6 gene expression levels were elevated in geraniol-treated groups. Histological evaluation revealed a hepatoprotective effect for geraniol-treated groups. Our results suggest that geraniol plays a significant role during liver regeneration, which involves the elevated expression of TNFα and IL6 48 h after PH. PMID:28358702

[Hepatoprotective effect of deanol aceglumate on experimental stress-induced gastropathy and diabetes mellitus].

PubMed

Blinov, D S; Gogina, E D; Krupnova, T S; Balashov, V P; blinova, E V; Sadovnikov, V N; Lebedev, A B; Nikitina, O I

2012-01-01

Experiments on mice with streptozotocin-induced diabetes mellitus and stress-induced erosive ulcerous damage of the mucous membrane of stomach showed evidence of the preventive activity of deanol aceglumate in the course of peroral introduction at a dose of 250 mg/kg per 24 h during 4 days. This effect is accompanied by activation of the peristalsis of bowels and by an increase in the blood flow in the wall of stomach.

The Potential Protective Effect of Physalis peruviana L. against Carbon Tetrachloride-Induced Hepatotoxicity in Rats Is Mediated by Suppression of Oxidative Stress and Downregulation of MMP-9 Expression

PubMed Central

Al-Olayan, Ebtisam M.; El-Khadragy, Manal F.; Aref, Ahmed M.; Othman, Mohamed S.; Kassab, Rami B.; Abdel Moneim, Ahmed E.

2014-01-01

The active constituent profile in Cape gooseberry (Physalis peruviana L.) juice was determined by GC-MS. Quercetin and kaempferol were active components in the juice. In this study we have evaluated its potential protective effect on hepatic injury and fibrosis induced by carbon tetrachloride (CCl4). Twenty-eight rats divided into 4 groups: Group I served as control group, and Group II received weekly i.p. injection of 2 mL CCl4/kg bwt for 12 weeks. Group III were supplemented with Physalis juice via the drinking water. The animals of Group IV received Physalis juice as Group III and also were intraperitoneally injected weekly with 2 mL CCl4/kg bwt for 12 weeks. Hepatoprotective effect was evaluated by improvement in liver enzymes serum levels, reduction in collagen areas, downregulation in expression of the fibrotic marker MMP-9, reduction in the peroxidative marker malonaldehyde and the inflammatory marker nitric oxide, and restoration of the activity of antioxidant enzymatic and nonenzymatic systems, namely, glutathione content, superoxide dismutase, catalase, glutathione-S-transferase, glutathione peroxidase, and glutathione reductase activities. The results show that the potential hepatoprotective effects of Physalis peruviana may be due to physalis acts by promotion of processes that restore hepatolobular architecture and through the inhibition of oxidative stress pathway. PMID:24876910

The potential protective effect of Physalis peruviana L. against carbon tetrachloride-induced hepatotoxicity in rats is mediated by suppression of oxidative stress and downregulation of MMP-9 expression.

PubMed

Al-Olayan, Ebtisam M; El-Khadragy, Manal F; Aref, Ahmed M; Othman, Mohamed S; Kassab, Rami B; Abdel Moneim, Ahmed E

2014-01-01

The active constituent profile in Cape gooseberry (Physalis peruviana L.) juice was determined by GC-MS. Quercetin and kaempferol were active components in the juice. In this study we have evaluated its potential protective effect on hepatic injury and fibrosis induced by carbon tetrachloride (CCl4). Twenty-eight rats divided into 4 groups: Group I served as control group, and Group II received weekly i.p. injection of 2 mL CCl4/kg bwt for 12 weeks. Group III were supplemented with Physalis juice via the drinking water. The animals of Group IV received Physalis juice as Group III and also were intraperitoneally injected weekly with 2 mL CCl4/kg bwt for 12 weeks. Hepatoprotective effect was evaluated by improvement in liver enzymes serum levels, reduction in collagen areas, downregulation in expression of the fibrotic marker MMP-9, reduction in the peroxidative marker malonaldehyde and the inflammatory marker nitric oxide, and restoration of the activity of antioxidant enzymatic and nonenzymatic systems, namely, glutathione content, superoxide dismutase, catalase, glutathione-S-transferase, glutathione peroxidase, and glutathione reductase activities. The results show that the potential hepatoprotective effects of Physalis peruviana may be due to physalis acts by promotion of processes that restore hepatolobular architecture and through the inhibition of oxidative stress pathway.

Improved Chemotherapeutic Activity by Morus alba Fruits through Immune Response of Toll-Like Receptor 4.

PubMed

Chang, Bo Yoon; Kim, Seon Beom; Lee, Mi Kyeong; Park, Hyun; Kim, Sung Yeon

2015-10-13

Morus alba L. fruits have long been used in traditional medicine by many cultures. Their medicinal attributes include cardiovascular, hepatoprotective, neuroprotective and immunomodulatory actions. However, their mechanism of macrophage activation and anti-cancer effects remain unclear. The present study investigated the molecular mechanisms of immune stimulation and improved chemotherapeutic effect of M. alba L. fruit extract (MFE). MFE stimulated the production of cytokines, nitric oxide (NO) and tumor necrosis factor-α (TNF-α) and tumoricidal properties of macrophages. MFE activated macrophages through the mitogen-activated protein kinase (MAPKinase) and nuclear factor-κB (NF-κB) signaling pathways downstream from toll-like receptor (TLR) 4. MFE was shown to exhibit cytotoxicity of CT26 cells via the activated macrophages, even though MFE did not directly affect CT26 cells. In a xenograft mouse model, MFE significantly enhanced anti-cancer activity combined with 5-fluorouracil and markedly promoted splenocyte proliferation, natural killer (NK) cell activity, cytotoxic T lymphocyte (CTL) activity and IFN-γ production. Immunoglobulin G (IgG) antibody levels were significantly increased. These results indicate the indirect anti-cancer activity of MFE through improved immune response mediated by TLR4 signaling. M. alba L. fruit extract might be a potential anti-tumor immunomodulatory candidate chemotherapy agent.

Improved Chemotherapeutic Activity by Morus alba Fruits through Immune Response of Toll-Like Receptor 4

PubMed Central

Chang, Bo Yoon; Kim, Seon Beom; Lee, Mi Kyeong; Park, Hyun; Kim, Sung Yeon

2015-01-01

Morus alba L. fruits have long been used in traditional medicine by many cultures. Their medicinal attributes include cardiovascular, hepatoprotective, neuroprotective and immunomodulatory actions. However, their mechanism of macrophage activation and anti-cancer effects remain unclear. The present study investigated the molecular mechanisms of immune stimulation and improved chemotherapeutic effect of M. alba L. fruit extract (MFE). MFE stimulated the production of cytokines, nitric oxide (NO) and tumor necrosis factor-α (TNF-α) and tumoricidal properties of macrophages. MFE activated macrophages through the mitogen-activated protein kinase (MAPKinase) and nuclear factor-κB (NF-κB) signaling pathways downstream from toll-like receptor (TLR) 4. MFE was shown to exhibit cytotoxicity of CT26 cells via the activated macrophages, even though MFE did not directly affect CT26 cells. In a xenograft mouse model, MFE significantly enhanced anti-cancer activity combined with 5-fluorouracil and markedly promoted splenocyte proliferation, natural killer (NK) cell activity, cytotoxic T lymphocyte (CTL) activity and IFN-γ production. Immunoglobulin G (IgG) antibody levels were significantly increased. These results indicate the indirect anti-cancer activity of MFE through improved immune response mediated by TLR4 signaling. M. alba L. fruit extract might be a potential anti-tumor immunomodulatory candidate chemotherapy agent. PMID:26473845

20(R)-ginsenoside Rg3, a rare saponin from red ginseng, ameliorates acetaminophen-induced hepatotoxicity by suppressing PI3K/AKT pathway-mediated inflammation and apoptosis.

PubMed

Zhou, Yan-Dan; Hou, Jin-Gang; Liu, Wei; Ren, Shen; Wang, Ying-Ping; Zhang, Rui; Chen, Chen; Wang, Zi; Li, Wei

2018-06-01

Although ginsenoside Rg3 was isolated as a major component of Korea red ginseng and confirmed to exert potential hepatoprotective effect on acetaminophen (APAP)-induced liver injury via induction of glutathione S-transferase (GST) in vitro, thein vivo hepatoprotective effect of Rg3 and the underlying molecular mechanism of action remain unclear. The current study was aimed to explore whether 20(R)-Ginsenoside Rg3 (20(R)-Rg3) could alleviate acetaminophen-induced liver injury in mice and to determine the involvement of PI3K/AKT signaling pathway. Our findings demonstrated that a single injection of APAP (250 mg/kg) increased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β); such increases were attenuated by pretreatment of mice with 20(R)-Rg3 for seven days. The depletion of glutathione (GSH), generation of malondialdehyde (MDA) and the over expression of cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) caused by APAP exposure were also inhibited by 20(R)-Rg3 pretreatment. Moreover, 20(R)-Rg3 pretreatment significantly alleviated APAP-induced apoptosis, necrosis, and inflammatory infiltration in liver tissues. Importantly, 20(R)-Rg3 effectively attenuated APAP-induced liver injury in part via activating PI3K/AKT signaling pathway. In summary, 20(R)-Rg3 exerted liver protection against APAP-caused hepatotoxicity evidenced by inhibition of oxidative stress and inflammatory response, alleviation of hepatocellular necrosis and apoptosis via activation of PI3K/AKT signaling pathway, showing potential as a novel therapeutic agent to prevent liver damage. Copyright © 2018 Elsevier B.V. All rights reserved.

Hepatoprotective evaluation of the total flavonoids extracted from flowers of Abelmoschus manihot (L.) Medic: In vitro and in vivo studies.

PubMed

Ai, Guo; Liu, Qingchuan; Hua, Wei; Huang, Zhengming; Wang, Dewen

2013-04-19

The decoction of the flowers of Abelmoschus manihot (L.) Medic is traditionally used for the treatment of jaundice and various types of chronic and acute hepatitis in Anhui and Jiangsu Provinces of China. Phytochemical studies have indicated that total flavonoids extracted from flowers of Abelmoschus manihot (L.) Medic (TFA) were the major constituents of the flowers. The present study was designed to investigate the hepatoprotective effect of the plant extracts against carbon tetrachloride (CCl4) induced hepatocyte damage in vitro and liver injury in vivo. In the in vitro studies, freshly isolated rat hepatocytes were exposed to CCl4 (1%) along with/without various concentrations of TFA (4.5-72mg/L). Cell damage was assessed by the trypan blue exclusion method and alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in the medium were analyzed. In the in vivo studies, the hepatoprotective activity of TFA (125, 250 and 500mg/kg) were investigated on CCl4-induced liver damages in mice. The levels of ALT, AST and ALP, gamma glutamyltransferase (γ-GT), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and nitric oxide (NO) were determined in serum. Hepatic malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and glutathione transferase (GST) were measured in the liver homogenates. Cytokine transcript levels of TNF-α, IL-1β and inducible nitric oxide synthase (iNOS) in the liver tissues of mice were measured using reverse transcription-polymerase chain reaction (RT-PCR). Livers were dissected out and evaluated for histomorphological changes. A concentration-dependent increase in the percentage viability was observed when CCl4-exposed hepatocytes were treated with different concentrations of TFA. Levels of ALT, AST and ALP in the medium were significantly decreased. In the animal studies, TFA showed significant protection with the depletion of ALT, AST, ALP and γ-GT in serum as was raised by the induction of CCl4. Moreover, TFA decreased the MDA level and elevated the content of GSH in the liver as compared to those in the CCl4 group. Furthermore, activities of antioxidative enzymes, including SOD, GPx, CAT and GST, were enhanced dose dependently with TFA. Meanwhile, the inflammatory mediators (e.g., TNF-α, IL-1β and NO) were inhibited by TFA treatment both at the serum and mRNA levels. Additionally, histological analyses also showed that TFA reduced the extent of liver lesions induced by CCl4. These results suggested that TFA protected mice against CCl4-induced liver injury through antioxidant stress and antiinflammatory effects. This finding justified the use of this plant in traditional medicine for the treatment of liver disease. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Free Radical-Scavenging, Anti-Inflammatory/Anti-Fibrotic and Hepatoprotective Actions of Taurine and Silymarin against CCl4 Induced Rat Liver Damage.

PubMed

Abdel-Moneim, Ashraf M; Al-Kahtani, Mohammed A; El-Kersh, Mohamed A; Al-Omair, Mohammed A

2015-01-01

The present study aims to investigate the hepatoprotective effect of taurine (TAU) alone or in combination with silymarin (SIL) on CCl4-induced liver damage. Twenty five male rats were randomized into 5 groups: normal control (vehicle treated), toxin control (CCl4 treated), CCl4+TAU, CCl4+SIL and CCl4+TAU+SIL. CCl4 provoked significant increases in the levels of hepatic TBARS, NO and NOS compared to control group, but the levels of endogenous antioxidants such as SOD, GPx, GR, GST and GSH were significantly decreased. Serum pro-inflammatory and fibrogenic cytokines including TNF-α, TGF-β1, IL-6, leptin and resistin were increased while the anti-inflammatory (adiponectin) cytokine was decreased in all treated rats. Our results also showed that CCl4 induced an increase in liver injury parameters like serum ALT, AST, ALP, GGT and bilirubin. In addition, a significant increase in liver tissue hydroxyproline (a major component of collagen) was detected in rats exposed to CCl4. Moreover, the concentrations of serum TG, TC, HDL-C, LDL-C, VLDL-C and FFA were significantly increased by CCl4. Both TAU and SIL (i.e., antioxidants) post-treatments were effectively able to relieve most of the above mentioned imbalances. However, the combination therapy was more effective than single applications in reducing TBARS levels, NO production, hydroxyproline content in fibrotic liver and the activity of serum GGT. Combined treatment (but not TAU- or SIL-alone) was also able to effectively prevent CCl4-induced decrease in adiponectin serum levels. Of note, the combined post-treatment with TAU+SIL (but not monotherapy) normalized serum FFA in CCl4-treated rats. The biochemical results were confirmed by histological and ultrastructural changes as compared to CCl4-poisoned rats. Therefore, on the basis of our work, TAU may be used in combination with SIL as an additional adjunct therapy to cure liver diseases such as fibrosis, cirrhosis and viral hepatitis.

Hepatoprotective effect of fucoidan isolated from the seaweed Turbinaria decurrens in ethanol intoxicated rats.

PubMed

Meenakshi, Selvaraju; Umayaparvathi, Shanmugam; Saravanan, Ravichandran; Manivasagam, Tamilarasan; Balasubramanian, Thangavel

2014-06-01

Fucoidan is the sulfated polysaccharide which is present in the cell wall of the brown seaweeds with high nutritive value. It is widely known for its pharmacological activity and hence it is added as a main ingredient in the food supplements. A water soluble crude polysaccharide was extracted from Turbinaria decurrens. Ethanol has been used as a hepatotoxin in vivo and its administration increased oxidative stress, decreased antioxidant defence and liver injury. Fucoidan treatment increased the body weight, food intake and serum protein levels, it decreases the level of hepatic markers. Fucoidan improved the antioxidant status of alcoholic rats, which is evaluated by the decreased levels of lipid peroxidation markers and increased level of enzymatic antioxidants were observed in liver. Histopathological observations and protein expression were also in correlation with the biochemical parameters. The hepatoprotective effect of fucoidan is probably due to its antioxidant effect. Copyright © 2014 Elsevier B.V. All rights reserved.

Recent Updates on Acetaminophen Hepatotoxicity: The Role of Nrf2 in Hepatoprotection

PubMed Central

Gum, Sang Il

2013-01-01

Acetaminophen (APAP) known as paracetamol is the main ingredient in Tylenol, which has analgesic and anti-pyretic properties. Inappropriate use of APAP causes major morbidity and mortality secondary to hepatic failure. Overdose of APAP depletes the hepatic glutathione (GSH) rapidly, and the metabolic intermediate leads to hepatocellular death. This article reviews the mechanisms of hepatotoxicity and provides an overview of current research studies. Pharmacokinetics including metabolism (activation and detoxification), subsequent transport (efflux)-facilitating excretion, and some other aspects related to toxicity are discussed. Nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated gene battery plays a critical role in the multiple steps associated with the mitigation of APAP toxicity. The role of Nrf2 as a protective target is described, and potential natural products inhibiting APAP toxicity are outlined. This review provides an update on the mechanism of APAP toxicity and highlights the beneficial role of Nrf2 and specific natural products in hepatoprotection. PMID:24386516

Genistein modulates the expression of NF-κB and MAPK (p-38 and ERK1/2), thereby attenuating D-Galactosamine induced fulminant hepatic failure in Wistar rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ganai, Ajaz A., E-mail: ganaikashmir@gmail.com; Khan, Athar A., E-mail: atharbiotech@gmail.com; Malik, Zainul A., E-mail: mzabdin@rediffmail.com

2015-03-01

Genistein is an isoflavanoid abundantly found in soy. It has been found to play an important role in the prevention of various chronic diseases including cancer. In this study, we evaluated potential therapeutic properties of Genistein against D-Galactosamine (D-GalN) induced inflammation and hepatotoxicity in male Wistar rats. Fulminant hepatic failure (FHF) was induced in rats by intraperitoneal injection of D-GalN (700 mg/kgBW). Genistein (5 mg/kgBW/day) was given as pre-treatment for 30 days via intra-gastric route followed by D-GalN (700 mg/kgBW) injection. The hepatoprotective and curative effects of Genistein were evident from a significant decrease in the serum aspartate aminotransferase (AST)more » and alanine aminotransferase (ALT) levels as well as prevention of histological damage by pre-treatment of Genistein. Genistein pre-treatment significantly inhibited the increased protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), thereby reducing nitric oxide (NO) and prostaglandin-E2 (PGE) levels, respectively. In addition Genistein significantly suppressed the production of D-GalN-induced proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin (IL)-1β. These inhibitory effects were associated with the suppression of nuclear factor-kappa B (NF-ĸB) activation, IKKα/β and Mitogen activated protein kinase (MAPK) phosphorylation by Genistein in D-GalN-treated animals. In conclusion, our results suggest that Genistein may serve as a potential supplement in the prevention of hepatic and inflammatory diseases. Furthermore Genistein is able to maintain the redox potential and strengthens the antioxidant defense system of a cell. - Highlights: • First study to evaluate hepatoprotective effect of Genistein against D-GalN • Genistein prevents oxidative damage induced by D-GalN. • Genistein blunts iNOS, COX-2, NF-ĸB, IKKα/β and MAPK expression. • Genistein prevents D-GalN induced apoptosis and necrosis.« less

Biochemical studies in experimentally Escherichia coli infected broiler chicken supplemented with neem (Azadirachta indica) leaf extract

PubMed Central

Sharma, Vikash; Jakhar, K. K.; Nehra, Vikas; Kumar, Sarvan

2015-01-01

Aim: An experimental study was conducted on 192-day-old broiler chicks for evaluating the effect of 10% neem leaf extract (NLE) supplementationon biochemical parameters in chickens experimentally infected with Escherichia coli O78 at 107 CFU/0.5 ml at 7 days of age. Materials and Methods: The 192-day-old broiler chicks were procured. These chicks were divided into two groups (A and B) containing 96 birds each on the 1st day. Diet of all the chicks of Group A was supplemented with 10%NLE in water, whereas chicks of Group B were given feed and water devoid of NLE supplementation throughout the experiment. After rearing for 1 week, chicks of both the groups (A and B) were again divided into two subgroups (Group A into A1 and A2 and Group B into B1 and B2) of 54 and 42 birds, respectively. At the age of 7 days all the chicks of groups A1 and B1 were injected with E. coli O78 at 107 CFU/0.5 ml intraperitoneally. Blood samples were collected from six chicks from each group at day 0, 2, 4, 7, 14, 21, 28 days post-infection and serum was separated for biochemical studies. Results: There was a significant increase in serum alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH) activities, globulin concentration and a decrease in total protein (TP), albumin concentrations, and alkaline phosphatase (ALP) activity in both the infected groups. However, the changes in biochemical values, i.e., ALT, AST, LDH, ALP, TP, albumin, and globulin wereof lower magnitude in NLE supplemented group suggesting hepatoprotective and cardioprotective effect of NLE. Conclusions: Fromthe present study, it is reasonable to conclude that significant increase in the value of ALT, AST, LDH, globulin, and significant decrease in the value of ALP, TP, and albumin was of lower magnitude in supplemented infected group (A1) as compared to non-supplemented infected group (B1) suggesting hepatoprotective and cardioprotective effect of NLE. PMID:27047040

AMELIORATIVE ROLE OF Vernonia cinerea IN CARBON TETRACHLORIDE INDUCED HEPATIC DYSFUNCTION IN RATS.

PubMed

Gokilaveni, C; Nishadh, A; Selvi, V

2006-01-01

The ameliorative activity of herbal powder prepared from Veronia cinerea leaves on CCl(4) (0.2ml/kg body wt. intraperitoneally (ip) and liquid paraffin (0.2 ml / kg body wt:ip) induced hepatotoxicity was studied in rats. The liver marker enzymes namely alanine transmainase (ALT), aspartate transaminase (AST), acid phosphatase and alkaline phosphatase (ALP) activities were decreased in 10% w/v liver homogenates of hepatotoxicity induced rats. The results of both post treated and pre treated groups suggest the hepatoprotective activity of Veronia cinerea in CCl(4) induced rats.

Hepatoprotective effects of kaempferol 3-O-rutinoside and kaempferol 3-O-glucoside from Carthamus tinctorius L. on CCl4-induced oxidative liver injury in mice.

PubMed

Wang, Yu; Tang, Changyun; Zhang, Hao

2015-06-01

Safflower (Carthamus tinctorius L.) is a traditional medicinal and edible herb with a long history of use in China. In this study, a model of hepatotoxicity induced by carbon tetrachloride (CCl 4 ) in mice was used to investigate the hepatoprotective effects of kaempferol 3-O-rutinoside (K-3-R) and kaempferol 3-O-glucoside (K-3-G), two kaempferol glycosides isolated from C. tinctorius L. K-3-R and K-3-G, at doses of 200 mg/kg and 400 mg/kg, were given orally to male mice once/d for 7 days before they received CCl 4 intraperitoneally. Our results showed that K-3-R and K-3-G treatment increased the level of total protein (TP) and prevented the CCl 4 -induced increases in serum aspartate aminotransferase (AST), serum alkaline phosphatase (ALP), and hepatic malondialdehyde (MDA) levels. Additionally, mice treated with K-3-R and K-3-G had significantly restored glutathione (GSH) levels and showed normal catalase (CAT) and superoxide dismutase (SOD) activities, compared to CCl 4 -treated mice. K-3-R and K-3-G also mitigated the CCl 4 -induced liver histological alteration, as indicated by histopathological evaluation. These findings demonstrate that K-3-R and K-3-G have protective effects against acute CCl 4 -induced oxidative liver damage. Copyright © 2014. Published by Elsevier B.V.

Pharmacology and potential therapeutic applications of nitric oxide-releasing non-steroidal anti-inflammatory and related nitric oxide-donating drugs

PubMed Central

Keeble, J E; Moore, P K

2002-01-01

This review examines the biological significance, therapeutic potential and mechanism(s) of action of a range of nitric oxide-releasing non-steroidal anti-inflammatory drugs (NO-NSAID) and related nitric oxide-releasing donating drugs (NODD). The slow release of nitric oxide (NO) from these compounds leads to subtle changes in the profile of pharmacological activity of the parent, non-steroidal anti-inflammatory drugs (NSAID). For example, compared with NSAID, NO-NSAID cause markedly diminished gastrointestinal toxicity and improved anti-inflammatory and anti-nociceptive efficacy. In addition, nitroparacetamol exhibits hepatoprotection as opposed to the hepatotoxic activity of paracetamol. The possibility that NO-NSAID or NODD may be of therapeutic benefit in a wide variety of disease states including pain and inflammation, thrombosis and restenosis, neurodegenerative diseases of the central nervous system, colitis, cancer, urinary incontinence, liver disease, impotence, bronchial asthma and osteoporosis is discussed. PMID:12237248

Silibinin ameliorates Aβ25-35-induced memory deficits in rats by modulating autophagy and attenuating neuroinflammation as well as oxidative stress.

PubMed

Song, Xiaoyu; Zhou, Biao; Cui, Lingyu; Lei, Di; Zhang, Pingping; Yao, Guodong; Xia, Mingyu; Hayashi, Toshihiko; Hattori, Shunji; Ushiki-Kaku, Yuko; Tashiro, Shin-Ichi; Onodera, Satoshi; Ikejima, Takashi

2017-04-01

Alzheimer's disease (AD) is a progressive, neurodegenerative disease. Accumulating evidence suggests that inflammatory response, oxidative stress and autophagy are involved in amyloid β (Aβ)-induced memory deficits. Silibinin (silybin), a flavonoid derived from the herb milk thistle, is well known for its hepatoprotective activities. In this study, we investigated the neuroprotective effect of silibinin on Aβ 25-35 -injected rats. Results demonstrated that silibinin significantly attenuated Aβ 25-35 -induced memory deficits in Morris water maze and novel object-recognition tests. Silibinin exerted anxiolytic effect in Aβ 25-35 -injected rats as determined in elevated plus maze test. Silibinin attenuated the inflammatory responses, increased glutathione (GSH) levels and decreased malondialdehyde (MDA) levels, and upregulated autophagy levels in the Aβ 25-35 -injected rats. In conclusion, silibinin is a potential candidate for AD treatment because of its anti-inflammatory, antioxidant and autophagy regulating activities.

Enhanced oral bioavailability and in vivo antioxidant activity of chlorogenic acid via liposomal formulation.

PubMed

Feng, Yingshu; Sun, Congyong; Yuan, Yangyang; Zhu, Yuan; Wan, Jinyi; Firempong, Caleb Kesse; Omari-Siaw, Emmanuel; Xu, Yang; Pu, Zunqin; Yu, Jiangnan; Xu, Ximing

2016-03-30

In the present study, a formulation system consisting of cholesterol and phosphatidyl choline was used to prepare an effective chlorogenic acid-loaded liposome (CAL) with an improved oral bioavailability and an increased antioxidant activity. The developed liposomal formulation produced regular, spherical and multilamellar-shaped distribution nanoparticles. The pharmacokinetic analysis of CAL compared with chlorogenic acid (CA), showed a higher value of Cmax(6.42 ± 1.49 min versus 3.97 ± 0.39 min) and a delayed Tmax(15 min versus 10 min), with 1.29-fold increase in relative oral bioavailability. The tissue distribution in mice also demonstrated that CAL predominantly accumulated in the liver which indicated hepatic targeting potential of the drug. The increased activities of antioxidant enzymes (Total Superoxide Dismutase (T-SOD) and Glutathione Peroxidase (GSH-Px)) and total antioxidant capacity (T-AOC), in addition to decreased level of malondialdehyde (MDA) in CCl4-induced hepatotoxicity study further revealed that CAL exhibited significant hepatoprotective and antioxidant effects. Collectively, these findings present a liposomal formulation with significantly improved oral bioavailability and an increased in vivo antioxidant activity of CA. Copyright © 2016 Elsevier B.V. All rights reserved.

CCl4 induced genotoxicity and DNA oxidative damages in rats: hepatoprotective effect of Sonchus arvensis.

PubMed

Alkreathy, Huda Mohammad; Khan, Rahmat Ali; Khan, Muhammad Rashid; Sahreen, Sumaira

2014-11-21

Sonchus arvesis is traditionally reported in various human ailments including hepatotoxicity in Pakistan. Presently we designed to assess the protective effects of methanolic extract of Sonchus arvesis against carbon tetrachloride induced genotoxicity and DNA oxidative damages in hepatic tissues of experimental rats. 36 male Sprague-Dawley rats were randomly divided into 6 groups to evaluate the hepatoprotective effects of Sonchus arvensis against CCl4 induced genotoxicity, DNA damages and antioxidant depletion. Rats of normal control group were given free access of food and water add labitum. Group II rats received 3 ml/kg of CCl4 (30% in olive oil v/v) via the intraperitoneal route twice a week for four weeks. Group III and IV received 1 ml of 100 mg/kg b.w. and 200 mg/kg b.w. SME via gavage after 48 h of CCl4 treatment whereas group V was given 1 ml of silymarin (100 mg/kg b.w.) after 48 h of CCl4 treatment. Group VI only received 200 mg/kg b.w. SME. Protective effects of SME were checked by measuring serum markers, activities of antioxidant enzymes, genotoxicity and DNA dmages. Results of the present study showed that treatment of SME reversed the activities of serum marker enzymes and cholesterol profile as depleted with CCl4 treatment. Activities of endogenous antioxidant enzymes of liver tissue homogenate; catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSHpx), glutathione-S-transferase (GST) and glutathione reductase (GSR) were reduced with administration of CCl4, which were returned to the control level with SME treatment. CCl4-induced hepatic cirrhosis decreased hepatic glutathione (GSH) and increased lipid peroxidative products (TBARS), were normalized by treatment with SME. Moreover, administration of CCl4 caused genotoxicity and DNA fragmentation which were significantly restored towards the normal level with SME. These results reveal that treatment of SME may be useful in the prevention of hepatic stress.

Hepatoprotective Potential of Chestnut Bee Pollen on Carbon Tetrachloride-Induced Hepatic Damages in Rats

PubMed Central

Yıldız, Oktay; Can, Zehra; Saral, Özlem; Yuluğ, Esin; Öztürk, Ferhat; Aliyazıcıoğlu, Rezzan; Canpolat, Sinan; Kolaylı, Sevgi

2013-01-01

Bee pollen has been used as an apitherapy agent for several centuries to treat burns, wounds, gastrointestinal disorders, and various other diseases. The aim of our study was to investigate the hepatoprotective effects of chestnut bee pollen against carbon tetrachloride (CCI4)-induced liver damage. Total phenolic content, flavonoid, ferric reducing/antioxidant power, and DPPH radical activity measurements were used as antioxidant capacity determinants of the pollen. The study was conducted in rats as seven groups. Two different concentrations of chestnut bee pollens (200 and 400 mg/kg/day) were given orally and one group was administered with silibinin (50 mg/kg/day, i.p.) for seven days to the rats following the CCI4 treatment. The protective effect of the bee pollen was monitored by aspartate transaminase (AST) and alanine transaminase (AST) activities, histopathological imaging, and antioxidant parameters from the blood and liver samples of the rats. The results were compared with the silibinin-treated and untreated groups. We detected that CCI4 treatment induced liver damage and both the bee pollen and silibinin-treated groups reversed the damage; however, silibinin caused significant weight loss and mortality due, severe diarrhea in the rats. The chestnut pollen had showed 28.87 mg GAE/g DW of total phenolic substance, 8.07 mg QUE/g DW of total flavonoid, 92.71 mg Cyn-3-glu/kg DW of total anthocyanins, and 9 mg β-carotene/100 g DW of total carotenoid and substantial amount of antioxidant power according to FRAP and DPPH activity. The results demonstrated that the chestnut bee pollen protects the hepatocytes from the oxidative stress and promotes the healing of the liver damage induced by CCI4 toxicity. Our findings suggest that chestnut bee pollen can be used as a safe alternative to the silibinin in the treatment of liver injuries. PMID:24250716

Identification of Hepatoprotective Constituents in Limonium tetragonum and Development of Simultaneous Analysis Method using High-performance Liquid Chromatography

PubMed Central

Lee, Jae Sun; Kim, Yun Na; Kim, Na-Hyun; Heo, Jeong-Doo; Yang, Min Hye; Rho, Jung-Rae; Jeong, Eun Ju

2017-01-01

Background: Limonium tetragonum, a naturally salt-tolerant halophyte, has been studied recently and is of much interest to researchers due to its potent antioxidant and hepatoprotective activities. Objective: In the present study, we attempted to elucidate bioactive compounds from ethyl acetate (EtOAc) soluble fraction of L. tetragonum extract. Furthermore, the simultaneous analysis method of bioactive EtOAc fraction of L. tetragonum has been developed using high-performance liquid chromatography (HPLC). Materials and Methods: Thirteen compounds have been successfully isolated from EtOAc fraction of L. tetragonum, and the structures of 1–13 were elucidated by extensive one-dimensional and two-dimensional spectroscopic methods including 1H-NMR, 13C-NMR, 1H-1H COSY, heteronuclear single quantum coherence, heteronuclear multiple bond correlation, and nuclear Overhauser effect spectroscopy. Hepatoprotection of the isolated compounds against liver fibrosis was evaluated by measuring inhibition on hepatic stellate cells (HSCs) undergoing proliferation. Results: Compounds 1–13 were identified as gallincin (1), apigenin-3-O-β-D-galactopyranoside (2), quercetin (3), quercetin-3-O-β-D-galactopyranoside (4), (−)-epigallocatechin (5), (−)-epigallocatechin-3-gallate (6), (−)-epigallocatechin-3-(3″-O-methyl) gallate (7), myricetin-3-O-β-D-galactopyranoside (8), myricetin-3-O-(6″-O-galloyl)-β-D-galactopyranoside (9), myricetin-3-O-α-L-rhamnopyranoside (10), myricetin-3-O-(2″-O-galloyl)-α-L-rhamnopyranoside (11), myricetin-3-O-(3″-O-galloyl)-α-L-rhamnopyranoside (12), and myricetin-3-O-α-L-arabinopyranoside (13), respectively. All compounds except for 4, 8, and 10 are reported for the first time from this plant. Conclusion: Myricetin glycosides which possess galloyl substituent (9, 11, and 12) showed most potent inhibitory effects on the proliferation of HSCs. SUMMARY In the present study, we have successfully isolated 13 compounds from bioactive fraction of Limonium tetragonum. The structures of compounds isolated have been fully elucidated, and hepatoprotective activities of compounds against liver fibrosis were evaluated by measuring inhibition on hepatic stellate cells undergoing proliferation. Furthermore, the simultaneous analysis method of bioactive ethyl acetate fraction of L. tetragonum has been developed using HPLC. Ten compounds identified herein are reported for the first time from this plant. Abbreviations used: HSQC: Heteronuclear single quantum coherence; HMBC: Heteronuclear multiple bond correlation; NOESY: Nuclear Overhauser effect spectroscopy; EGCG: Epigallocatechin-3-gallate; EGC: Epigallocatechin; HSC: Hepatic stellate cell; MTT: 3-(4,5-dimethylthiazol-2-yl)-2.5-diphenyltetrazolium bromide. PMID:29200710

Ginseng essence, a medicinal and edible herbal formulation, ameliorates carbon tetrachloride-induced oxidative stress and liver injury in rats.

PubMed

Lu, Kuan-Hung; Weng, Ching-Yi; Chen, Wei-Cheng; Sheen, Lee-Yan

2017-07-01

Ginseng essence (GE) is a formulation comprising four medicinal and edible herbs including ginseng ( Panax ginseng ), American ginseng ( Panax quinquefolius ), lotus seed ( Nelumbo nucifera ), and lily bulb ( Lilium longiflorum ). This study was aimed at investigating the hepatoprotective effect of GE against carbon tetrachloride (CCl 4 )-induced liver injury in rats. We treated Wistar rats daily with low, medium, and high [0.625 g/kg body weight (bw), 1.25 g/kg bw, and 3.125 g/kg bw, respectively] doses of GE for 9 wk. After the 1 st wk of treatment, rats were administered 20% CCl 4 (1.5 mL/kg bw) two times a week to induce liver damage until the treatment ended. Serum biochemical analysis indicated that GE ameliorated the elevation of aspartate aminotransferase and alanine aminotransferase and albumin decline in CCl 4 -treated rats. Moreover, CCl 4 -induced accumulation of hepatic total cholesterol and triglyceride was inhibited. The hepatoprotective effects of GE involved enhancing the hepatic antioxidant defense system including glutathione, glutathione peroxidase, glutathione reductase, glutathione S -transferase, superoxide dismutase, and catalase. In addition, histological analysis using hematoxylin and eosin and Masson's trichrome staining showed that GE inhibited CCl 4 -induced hepatic inflammation and fibrosis. Furthermore, immunohistochemical staining of alpha-smooth muscle actin indicated that CCl 4 -triggered activation of hepatic stellate cells was reduced. These findings demonstrate that GE improves CCl 4 -induced liver inflammation and fibrosis by attenuating oxidative stress. Therefore, GE could be a promising hepatoprotective herbal formulation for future development of phytotherapy.

Chemotaxonomic Diversity of Three Ficus Species: Their Discrimination Using Chemometric Analysis and Their Role in Combating Oxidative Stress.

PubMed

Al-Musayeib, Nawal; Ebada, Sherif S; Gad, Haidy A; Youssef, Fadia S; Ashour, Mohamed Lotfy

2017-10-01

Genus Ficus (Moraceae) constitutes more than 850 species and about 2000 varieties and it acts as a golden mine that could afford effective and safe remedies combating many health disorders. Discrimination of Ficus cordata , Ficus ingens , and Ficus palmata using chemometric analysis and assessment of their role in combating oxidative stress. Phytochemical profiling of the methanol extracts of the three Ficus species and their successive fractions was performed using high-performance liquid chromatography/electrospray ionization mass spectrometry. Their discrimination was carried out using the obtained spectral data applying chemometric unsupervised pattern-recognition techniques, namely, principal component analysis and hierarchical cluster analysis. In vitro hepatoprotective and antioxidant evaluation of the samples was performed using human hepatocellular carcinoma cells challenged by carbon tetrachloride (CCl 4 ). Altogether, 22 compounds belonging to polyphenolics, flavonoids, and furanocoumarins were identified in the three Ficus species. Aviprin is the most abundant compound in F. cordata while chlorogenic acid and psoralen were present in high percentages in F. ingens and F. palmata , respectively. Chemometric analyses showed that F. palmata and F. cordata are more closely related chemically to each other rather than F. ingens . The ethyl acetate fractions of all the examined species showed a marked hepatoprotective efficacy accounting for 54.78%, 55.46%, and 56.42% reduction in serum level of alanine transaminase and 56.82%, 54.16%, and 57.06% suppression in serum level of aspartate transaminase, respectively, at 100 μg/mL comparable to CCl 4 -treated cells. Ficus species exhibited a no table antioxidant and hepatoprotective activity owing to their richness in polyphenolics and furanocoumarins. Ficus cordata , Ficus ingens , and Ficus palmata were analyzed using high-performance liquid chromatography/electrospray ionization mass spectrometry that revealed their richness with polyphenolics and furanocoumarinsDiscrimination of the three species was performed using spectral data coupled with chemometrics that showed that F. palmata and F. cordata are chemically related to each other rather than F. ingens In vitro hepatoprotective and antioxidant evaluation was performed using human hepatocellular carcinoma cells. The ethyl acetate fractions of all the examined species showed a marked hepatoprotective efficacy Ficus species exhibited notable activities due to polyphenolics and furanocoumarins. Abbreviations used: ALT: Alanine transaminase, AST: Aspartate transaminase, CCl 4: Carbon tetrachloride, DMEM: Dulbecco's Modified Eagle's medium, DMSO: Dimethyl sulfoxide, EDTA: Ethylenediaminetetraacetic acid, FBS: Fetal bovine serum, FCA: Ficus cordata remaining aqueous fraction, FCB: Ficus cordata n -butanol fraction, FCE: Ficus cordata ethyl acetate fraction, FCP: Ficus cordata petroleum ether fraction, FCT: Ficus cordata total methanol extract, FIA: Ficus ingens remaining aqueous fraction, FIB: Ficus ingens n -butanol fraction, FIE: Ficus ingens ethyl acetate fraction, FIP: Ficus ingens petroleum ether fraction, FIT: Ficus ingens total methanol extract, FPA: Ficus palmata remaining aqueous fraction, FPB: Ficus palmata n -butanol fraction, FPE: Ficus palmata ethyl acetate fraction, FPP: Ficus palmata petroleum ether fraction, FPT: Ficus palmata total methanol extract, GSH: Reduced glutathione, HepG2 cells: Human hepatocellular carcinoma, HPLC-ESI-MS: High-performance liquid chromatography/electrospray ionization mass spectrometry, and SOD: Superoxide dismutase.

Hepatoprotective Effects of Grape Seed Procyanidin B2 in Rats With Carbon Tetrachloride-induced Hepatic Fibrosis.

PubMed

Wang, Zhenli; Zhang, Zemin; Du, Ning; Wang, Kai; Li, Lei

2015-01-01

Infectious hepatitis is a serious problem affecting millions of people worldwide, particularly in China and other developing countries, and it is the major risk factor for hepatic cirrhosis. To date, the pathogenesis of hepatic cirrhosis is complex and unclear. Traditional Chinese medicine (TCM) has long been used in its treatment; however, little is known to date about the effects of grape seed procyanidin B2 (GSPB2) on liver fibrosis. Using a rat model of carbon tetrachloride (CCl4)-induced hepatic fibrosis, the study intended to investigate the hepatoprotective effects of GSPB2 and to determine the possible pathway by which GSPB2 exerts its activities. Design • Thirty-six male, Sprague-Dawley rats were used in the study. Rats in a model (CCl4 only) group and the GSPB2 group were given CCl4 to induce hepatic fibrosis. Simultaneously, animals in the GSPB2 group were treated with GSPB2 by intragastric administration for 12 wk. In addition, the rat's Kupffer cells were cultured with CCl4 and GSPB2. The study took place at the central laboratory of Qilu Hospital at Shandong University in Jinan, China. The following parameters were investigated: (1) hepatic function; (2) the liver fibrosis index-serum hyaluronic acid (HA), laminin (LN), type 3 procollagen (PC-3), collagen 4, and hepatic hydroxyproline; (3) the expression in the liver of transforming growth factor β-1 (TGF-β1); (4) inflammatory cytokines in the liver and cell culture medium-tumor necrosis factor α (TNF-α), interleukin (IL) 1-β (IL-1β), IL-6, and IL-17; (5) oxidative stress markers in the liver and cell culture medium-malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), total superoxide dismutase (T-SOD), and total antioxidant capacity (T-AOC); and (6) levels of angiotensin 2 (Ang 2) in the liver. The CCl4 induced (1) significant hepatic-function damage; (2) elevated levels of the measures of the liver fibrosis index, TGF-β1, inflammatory cytokines, MDA, and 8-OHdG; (3) a reduction in the activities of T-SOD and T-AOC; and (4) no effect on the level of expression of hepatic Ang 2. GSPB2 treatment partially reversed the changes induced by CCl4. The cell culture also showed that CCl4 elevated the levels of inflammatory cytokines and MDA in the Kupffer cell culture medium, whereas it reduced the activities of T-SOD and T-AOC in the medium. GSPB2 treatment partially reversed the changes induced by CCl4. GSPB2 had hepatoprotective effects on CCl4-induced hepatic fibrosis in Sprague-Dawley rats and inhibited the inflammatory response and oxidative stress in vivo and in vitro.

DOE Office of Scientific and Technical Information (OSTI.GOV)

MadanKumar, Perumal; NaveenKumar, Perumal; Manikandan, Samidurai

The anti-fibrotic effect of morin was examined in LX-2 cells (culture-activated human hepatic stellate cells) and in diethylnitrosamine induced rat model of liver fibrosis. The in vitro study was designed to determine whether morin affects the survival of cultured LX-2 cells, while the in vivo study was designed to evaluate the antioxidant and anti-fibrotic efficacy of morin on diethylnitrosamine induced liver fibrosis in male albino Wistar rat. The activities of liver function enzymes in serum, liver lipid peroxide levels, activities of serum antioxidant enzymes and liver architecture were monitored to cast light on the antioxidant and hepatoprotective nature of morin.more » To establish the anti-fibrotic effects of morin, the levels of key Wnt signaling molecules which are strongly associated with the signal transduction pathway of HSC activation were measured. Overall, from the in vitro results, it was observed that morin at 50 μM concentration inhibited the proliferation of cultured LX-2 cells, inhibited Wnt signaling and induced G1 cell cycle arrest. The in vivo results further confirmed that morin by downregulating the expressions of GSK-3β, β-catenin and cyclin D1 ameliorated DEN-induced liver fibrosis. Hence morin could be employed as a promising chemopreventive natural supplement for liver fibrosis. - Highlights: • In vivo and in vitro results revealed the active participation of Wnt signaling. • Morin at 50 μM inhibited LX-2 cell proliferation by suppressing Wnt signaling. • Morin exhibited hepatoprotective effects against DEN induced liver fibrosis. • Morin inhibited HSC activation in vivo by downregulating Wnt/β-catenin signaling.« less

Aqueous and ethanolic leaf extracts of Ocimum basilicum (sweet basil) protect against sodium arsenite-induced hepatotoxicity in Wistar rats.

PubMed

Gbadegesin, M A; Odunola, O A

2010-11-25

We evaluated the effects of aqueous and ethanolic leaf extracts of Ocimum basilicum (sweet basil) on sodium arsenite-induced hepatotoxicity in Wistar rats. We observed that treatment of the animals with the extracts before or just after sodium arsenite administration significantly (p < 0.05) reduced mean liver and serum γ-Glutamyl transferase (γGT), and serum alkaline phosphatase (ALP) activities when compared with the group administered the toxin alone. In addition, treatments of the animals with aqueous or ethanolic extract of O. basilicum before the administration of sodium arsenite resulted in the attenuation of the sodium arsenite-induced aspartate and alanine aminotransferase activities: ALT (from 282.6% to 167.7% and 157.8%), AST (from 325.1% to 173.5% and 164.2%) for the group administered sodium arsenite alone, the aqueous extracts plus sodium arsenite, and ethanolic extracts plus sodium arsenite respectively, expressed as percentage of the negative control. These findings support the presence of hepatoprotective activity in the O.basilicum extracts.

Monascus-fermented red mold dioscorea protects mice against alcohol-induced liver injury, whereas its metabolites ankaflavin and monascin regulate ethanol-induced peroxisome proliferator-activated receptor-γ and sterol regulatory element-binding transcription factor-1 expression in HepG2 cells.

PubMed

Cheng, Chih-Fu; Pan, Tzu-Ming

2018-03-01

Alcoholic hepatitis is a necroinflammatory process that is associated with fibrosis and leads to cirrhosis in 40% of cases. The hepatoprotective effects of red mold dioscorea (RMD) from Monascus purpureus NTU 568 were evaluated in vivo using a mouse model of chronic alcohol-induced liver disease (ALD). ALD mice were orally administered vehicle (ALD group) or vehicle plus 307.5, 615.0 or 1537.5 mg kg -1 (1 ×, 2 × and 5 ×) RMD for 5 weeks. RMD lowered serum leptin, hepatic total cholesterol, free fatty acid and hepatic triglyceride levels and increased serum adiponectin, hepatic alcohol dehydrogenase and antioxidant enzyme levels. Furthermore, ankaflavin (AK) and monascin (MS), metabolites of RMD fermented with M. purpureus 568, induced peroxisome proliferator-activated receptor-γ expression and the concomitant suppression of ethanol-induced elevation of sterol regulatory element-binding transcription factor-1 and TG in HepG2 cells. These results indicate the hepatoprotective effect of Monascus-fermented RMD. Moreover, AK and MS were identified as the active constituents of RMD for the first time and were shown to protect against ethanol-induced liver damage. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Chemistry and Biological Activities of Flavonoids: An Overview

PubMed Central

Kumar, Shashank; Pandey, Abhay K.

2013-01-01

There has been increasing interest in the research on flavonoids from plant sources because of their versatile health benefits reported in various epidemiological studies. Since flavonoids are directly associated with human dietary ingredients and health, there is need to evaluate structure and function relationship. The bioavailability, metabolism, and biological activity of flavonoids depend upon the configuration, total number of hydroxyl groups, and substitution of functional groups about their nuclear structure. Fruits and vegetables are the main dietary sources of flavonoids for humans, along with tea and wine. Most recent researches have focused on the health aspects of flavonoids for humans. Many flavonoids are shown to have antioxidative activity, free radical scavenging capacity, coronary heart disease prevention, hepatoprotective, anti-inflammatory, and anticancer activities, while some flavonoids exhibit potential antiviral activities. In plant systems, flavonoids help in combating oxidative stress and act as growth regulators. For pharmaceutical purposes cost-effective bulk production of different types of flavonoids has been made possible with the help of microbial biotechnology. This review highlights the structural features of flavonoids, their beneficial roles in human health, and significance in plants as well as their microbial production. PMID:24470791

[Coffee as hepatoprotective factor].

PubMed

Szántová, Mária; Ďurkovičová, Zuzana

The mind about the coffee did change upon the recent studies and metaanalysis of the last years. Consensual protective effect of coffee on the progression of chronic liver diseases (NASH, viral hepatitis, liver cirrhosis, hepatocelullar carcinoma) was detected in experimental, clinical and large population studies together with decrease of mortality. Antioxidant, antifibrotic, insulinsensitizing and anticarcinogenic effect of coffee were detected. Modulation of genetic expression of key enzymes of fatty acid synthesis, modulation of mRNA included in autophagia, reduction of stress of endoplasmatic reticulum together with decrease of proinflammatory cytokines and decrease of fibrogenesis are main mechanisms. Chlorogenic acids, diterpens (cafestol, kahweol), caffein, polyfenols and melanoidins are key protective components of coffee. Inverse dose-dependent correlation of coffee consumption with liver diseases was found in clinical and population studies. Coffee is non-pharmacological tool of primary and secondary prevention of chronic liver diseases. Review of published data together with supposed mechanisms of hepatoprotection are given.Key words: coffee - hepatoprotective effect - metaanalysis.

The Effect of Geraniol on Liver Regeneration After Hepatectomy in Rats.

PubMed

Canbek, Mediha; Uyanoglu, Mustafa; Canbek, Selcuk; Ceyhan, Emre; Ozen, Ahmet; Durmus, Basak; Turgak, Ozge

2017-01-01

Geraniol is a monoterpenoid alcohol that has a hepatoprotective effect. We investigated the regenerative effects of geraniol in rats after a 70% partial hepatectomy (PH). Using Wistar albino rats, nine groups were created: Group I was the control group, while the remaining groups received a single intraperitoneal dose of saline, Silymarin, or geraniol after PH. A 70% PH was performed on all groups except for groups II and III. Blood serum samples were obtained for alanine amino transferase (ALT) analysis. Then liver tissues were harvested for histological and real-time polymerase chain reaction (PCR) analyses. Tumor necrosis factor-α (TNFα) and interleukin 6 (IL6) gene expression were examined 24 and 48 h after PH. ALT levels were found to be statistically significantly increased in all PH-treated groups. TNFα and IL6 gene expression levels were elevated in geraniol-treated groups. Histological evaluation revealed a hepatoprotective effect for geraniol-treated groups. Our results suggest that geraniol plays a significant role during liver regeneration, which involves the elevated expression of TNFα and IL6 48 h after PH. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Hepatoprotective effects of Vaccinium arctostaphylos against CCl4-induced acute liver injury in rats.

PubMed

Ravan, Alireza Pouyandeh; Bahmani, Mahdi; Ghasemi Basir, Hamid Reza; Salehi, Iraj; Oshaghi, Ebrahim Abbasi

2017-09-26

This study was carried out to evaluate the antioxidant and hepatoprotective effects of Vaccinium arctostaphylos (V.a) methanolic extract on carbon tetrachloride (CCl4)-induced acute liver injury in Wistar rats. Total phenolic and total flavonoid contents as well as antioxidant activity of V.a were determined. Extracts of V.a at doses of 200 and 400 mg/kg were administered by oral gavage to rats once per day for 7 days and then were given an intraperitoneal injection of 1 mL/kg CCl4 (1:1 in olive oil) for 3 consecutive days. Serum biochemical markers of liver injury, oxidative markers, as well as hydroxyproline (HP) content and histopathology of liver were evaluated. The obtained results showed that V.a had strong antioxidant activity. Treatment of rats with V.a blocked the CCl4-induced elevation of serum markers of liver function and enhanced albumin and total protein levels. The level of hepatic HP content was also reduced by the administration of V.a treatment. Histological examination of the liver section revealed that V.a prevented the occurrence of pathological changes in CCl4-treated rats. These findings suggested that V.a may be useful in the treatment and prevention of hepatic injury induced by CCl4.

Sweet Marjoram

PubMed Central

Bina, Fatemeh; Rahimi, Roja

2016-01-01

Origanum majorana L. commonly known as sweet marjoram has been used for variety of diseases in traditional and folklore medicines, including gastrointestinal, ocular, nasopharyngeal, respiratory, cardiac, rheumatologic, and neurological disorders. Essential oil containing monoterpene hydrocarbons and oxygenated monoterpenes as well as phenolic compounds are chemical constituents isolated and detected in O majorana. Wide range of pharmacological activities including antioxidant, hepatoprotective, cardioprotective, anti-platelet, gastroprotective, antibacterial and antifungal, antiprotozoal, antiatherosclerosis, anti-inflammatory, antimetastatic, antitumor, antiulcer, and anticholinesterase inhibitory activities have been reported from this plant in modern medicine. This article summarizes comprehensive information concerning traditional uses, phytochemistry, and pharmacological activities of sweet marjoram. PMID:27231340

AMELIORATIVE ROLE OF Vernonia cinerea IN CARBON TETRACHLORIDE INDUCED HEPATIC DYSFUNCTION IN RATS

PubMed Central

Gokilaveni, C.; Nishadh, A.; Selvi, V.

2006-01-01

The ameliorative activity of herbal powder prepared from Veronia cinerea leaves on CCl4 (0.2ml/kg body wt. intraperitoneally (ip) and liquid paraffin (0.2 ml / kg body wt:ip) induced hepatotoxicity was studied in rats. The liver marker enzymes namely alanine transmainase (ALT), aspartate transaminase (AST), acid phosphatase and alkaline phosphatase (ALP) activities were decreased in 10% w/v liver homogenates of hepatotoxicity induced rats. The results of both post treated and pre treated groups suggest the hepatoprotective activity of Veronia cinerea in CCl4 induced rats. PMID:22557198

Antitumor Activity of Ethanolic Extract of Dendrobium formosum in T-Cell Lymphoma: An In Vitro and In Vivo Study

PubMed Central

Prasad, Ritika; Koch, Biplob

2014-01-01

Dendrobium, a genus of orchid, was found to possess useful therapeutic activities like anticancer, hypoglycaemic, antimicrobial, immunomodulatory, hepatoprotective, antioxidant, and neuroprotective activities. The study was aimed to evaluate the anticancer property of the ethanolic extract of Dendrobium formosum on Dalton's lymphoma. In vitro cytotoxicity was determined by MTT assay, apoptosis was determined by fluorescence microscopy, and cell cycle progression was analysed using flow cytometry; in vivo antitumor activity was performed in Dalton's lymphoma bearing mice. The IC50 value of ethanolic extract was obtained at 350 μg/mL in Dalton's lymphoma cells. Fluorescence microscopy analysis showed significant increase in apoptotic cell death in dose- and time-dependent manner which was further confirmed through the resulting DNA fragmentation. Further, flow cytometry analysis showed that the ethanolic extract arrests the cells in G2/M phase of the cell cycle. The in vivo anticancer activity study illustrates significant increase in the survival time of Dalton's lymphoma bearing mice on treatment with ethanolic extract when compared to control. These results substantiate the antitumor properties of ethanolic extract of Dendrobium formosum and suggest an alternative in treatment of cancer. Further studies are required regarding the isolation and characterization of bioactive components along with the analysis of molecular mechanism involved. PMID:24959588

Effect of adrenergic blockers, carvedilol, prazosin, metoprolol and combination of prazosin and metoprolol on paracetamol-induced hepatotoxicity in rabbits.

PubMed

Zubairi, Maysaa B; Ahmed, Jawad H; Al-Haroon, Sawsan S

2014-01-01

To evaluate hepatoprotective potential of carvedilol, prazosin, metoprolol and prazosin plus metoprolol in paracetamol-induced hepatotoxicity. Thirty-six male rabbits were divided into six groups, six in each, group 1 received distilled water, group 2 were treated with paracetamol (1 g/kg/day, orally), group 3, 4,5 and 6 were treated at a dose in (mg/kg/day) of the following: Carvedilol (10 mg), prazosin (0.5 mg), metoprolol (10 mg), and a combination of metoprolol (10 mg) and prazosin (0.5 mg) respectively 1 h before paracetamol treatment. All treatments were given for 9 days; animals were sacrificed at day 10. Liver function tests, malondialdehyde (MDA) and glutathione (GSH) in serum and liver homogenates were estimated. Histopathological examinations of liver were performed. Histopathological changes of hepatotoxicity were found in all paracetamol-treated rabbits. The histopathological findings of paracetamol toxicity disappeared in five rabbits on prazosin, very mild in one. In carvedilol group paracetamol toxicity completely disappeared in three, while mild in three rabbits. Paracetamol hepatotoxicity was not changed by metoprolol. In metoprolol plus prazosin treated rabbits, moderate histopathological changes were observed. Serum liver function tests and MDA in serum and in liver homogenate were elevated; GSH was depleted after paracetamol treatment and returned back to the control value on prior treatment with prazosin. MDA in serum and liver homogenate, alkaline phosphatase, total bilirubin were significantly decreased after carvedilol and prazosin plus metoprolol treatments. Carvedilol and prazosin are hepatoprotective in paracetamol hepatotoxicity, combination of prazosin and metoprolol have moderate, and metoprolol has a little hepatoprotection.

Ameliorative efficacy of quercetin against cisplatin‑induced mitochondrial dysfunction: Study on isolated rat liver mitochondria.

PubMed

Waseem, Mohammad; Tabassum, Heena; Bhardwaj, Monica; Parvez, Suhel

2017-09-01

The present study aimed to investigate the hepatoprotective effects of the bioflavonoid quercetin (QR) on cisplatin (CP)‑induced mitochondrial oxidative stress in the livers of rats, to elucidate the role of mitochondria in CP‑induced hepatotoxicity, and its underlying mechanism. Isolated liver mitochondria were incubated with 100 µg/ml CP and/or 50 µM QR in vitro. CP treatment triggered a significant increase in membrane lipid peroxidation (LPO) levels, protein carbonyl (PC) contents, and a decrease in reduced glutathione (GSH) and non‑protein thiol (NP‑SH) levels. In addition, CP caused a marked decline in the activities of enzymatic antioxidants and mitochondrial complexes (I, II, III and V) in liver mitochondria. QR pre‑treatment significantly modulated the activities of enzymatic antioxidants and mitochondrial complex enzymes. Furthermore, QR reversed the alterations in LPO and PC levels, and GSH and NP‑SH contents in liver mitochondria. The results of the present study suggested that QR supplementation may suppress CP‑induced mitochondrial toxicity during chemotherapy, and provides a potential prophylactic and defensive candidate for anticancer agent‑induced oxidative stress.

Antimalarial and hepatoprotective effects of crude ethanolic extract of Lingzhi or Reishi medicinal mushroom, Ganoderma lucidum (W.Curt.:Fr.)P.Karst. (higher Basidiomycetes), in Plasmodium berghei-infected mice.

PubMed

Oluba, Olarewaju M; Olusola, Augustine O; Fagbohunka, Bamidele S; Onyeneke, E

2012-01-01

This study was aimed at investigating the in vivo antimalarial activity (using some biochemical indices) of crude aqueous extracts of the fruiting bodies of Ganoderma lucidum, a mushroom with well-established medicinal properties. A rodent malaria parasite, Plasmodium berghei (1 × 107), was inoculated intraperitoneally into Swiss albino mice. The test groups were administered G. lucidum extract and chloroquine (CQ, as standard drug), while the control groups were administered the same amount of distilled water by an intragastric tube once daily. The antimalarial activity of the extract was investigated from the suppressive, curative, and prophylactic effects of the extract on parasite growth. Serum aminotransferases (AST and ALT), alkaline phosphatase (ALP), and gamma glutamine transpeptidase (γ-GT) levels monitored following the 4-day suppressive test were significantly reduced, with a corresponding significant increase in the livers of mice treated with the extract compared with infected untreated mice. The results obtained from this study provide scientific justification in an animal model of malaria that an ethanolic extract of G. lucidum possesses potent antimalarial activity and also could help ameliorate the attendant Plasmodium-induced liver damage due to malarial infection.

Short-term therapy with peroxisome proliferation-activator receptor-alpha agonist Wy-14,643 protects murine fatty liver against ischemia-reperfusion injury.

PubMed

Teoh, Narci C; Williams, Jacqueline; Hartley, Jennifer; Yu, Jun; McCuskey, Robert S; Farrell, Geoffrey C

2010-03-01

Steatosis increases operative morbidity/mortality from ischemia-reperfusion injury (IRI); few pharmacological approaches have been protective. Using novel genetic/dietary models of nonalcoholic steatohepatitis (NASH) and simple steatosis (SS) in Alms1 mutant (foz/foz) mice, we characterized severity of IRI in NASH versus SS and lean liver and tested our hypothesis that the lipid-lowering effects of the peroxisome proliferation-activator receptor (PPAR)-alpha agonist Wy-14,643 would be hepatoprotective. Mice were subjected to 60-minute partial hepatic IRI. Microvascular changes were assessed at 15-minute reperfusion by in vivo microscopy, injury at 24 hours by serum alanine aminotransferase (ALT), and hepatic necrosis area. Injury and inflammation mediators were determined by way of immunoblotting for intercellular cellular adhesion molecule, vascular cellular adhesion molecule, p38, c-jun N-terminal kinase, IkappaB-alpha, interleukin (IL)-1a, IL-12, tumor necrosis factor-alpha (TNF-alpha) and IL-6, cell cycle by cyclin D1 and proliferating cell nuclear antigen immunohistochemistry. In foz/foz mice fed a high-fat diet (HFD) to cause NASH or chow (SS), IRI was exacerbated compared with HFD-fed or chow-fed wild-type littermates by ALT release; corresponding necrotic areas were 60 +/- 22% NASH, 29 +/- 9% SS versus 7 +/- 1% lean. Microvasculature of NASH or SS livers was narrowed by enormous lipid-filled hepatocytes, significantly reducing numbers of perfused sinusoids, all exacerbated by IRI. Wy-14,643 reduced steatosis in NASH and SS livers, whereas PPAR-alpha stimulation conferred substantial hepatoprotection against IRI by ALT release, with reductions in vascular cellular adhesion molecule-1, IL-1a, TNF-alpha, IL-12, activated nuclear factor-kappaB (NF-kappaB), p38, IL-6 production and cell cycle entry. NASH and SS livers are both more susceptible to IRI. Mechanisms include possible distortion of the microvasculature by swollen fat-laden hepatocytes, and enhanced production of several cytokines. The beneficial effects of Wy-14,643 may be exerted by dampening adhesion molecule and cytokine responses, and activating NF-kappaB, IL-6 production, and p38 kinase to effect cell cycle entry.

Hepatoprotective and antioxidant effects of lycopene on non-alcoholic fatty liver disease in rat.

PubMed

Jiang, Wei; Guo, Mei-Hua; Hai, Xin

2016-12-14

To evaluate the hepatoprotective effect of lycopene (Ly) on non-alcoholic fatty liver disease (NAFLD) in rat. A rat model of NAFLD was first established by feeding a high-fat diet for 14 wk. Sixty-five rats were randomly divided into normal group, model group and Ly treatment groups. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), total cholesterol (TC) in serum and low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), free fatty acid (FFA), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) in liver tissue were evaluated, respectively. While the hepatoprotective effect was also confirmed by histopathological analysis, the expression levels of TNF-α and cytochrome P 450 (CYP) 2E1 in rat liver were determined by immunohistochemistry analysis. A significant decrease was observed in the levels of serum AST (2.07-fold), ALT (2.95-fold), and the blood lipid TG (2.34-fold) and TC (1.66-fold) in the dose of 20 mg/kg Ly-treated rats ( P < 0.01), compared to the model group. Pretreatment with 5, 10 and 20 mg/kg of Ly significantly raised the levels of antioxidant enzyme SOD in a dose-dependent manner, to 90.95 ± 9.56, 109.52 ± 11.34 and 121.25 ± 10.68 ( P < 0.05, P < 0.01), as compared with the model group. Similarly, the levels of GSH were significantly increased ( P < 0.05, P < 0.01) after the Ly treatment. Meanwhile, pretreatment with 5, 10 and 20 mg/kg of Ly significantly reduced MDA amount by 30.87, 45.51 and 54.49% in the liver homogenates, respectively ( P < 0.01). The Ly treatment group showed significantly decreased levels of lipid products LDL-C ( P < 0.05, P < 0.01), improved HDL-C level and significantly decreased content of FFA, compared to the model group ( P < 0.05, P < 0.01). Furthermore, the Ly-treated group also exhibited a down-regulated TNF-α and CYP2E1 expression, decreased infiltration of liver fats and reversed histopathological changes, all in a dose-dependent manner ( P < 0.05, P < 0.01). This study suggests that Ly has a protective effect on NAFLD, down-regulates expression of TNF-α, and that CYP2E1 may be one of the action mechanisms for Ly.

Anti-influenza A virus activity of rhein through regulating oxidative stress, TLR4, Akt, MAPK, and NF-κB signal pathways

PubMed Central

Wang, Qian-Wen; Su, Yun; Sheng, Jiang-Tao; Gu, Li-Ming; Zhao, Ying; Chen, Xiao-Xuan; Chen, Cheng; Li, Wei-Zhong; Li, Kang-Sheng

2018-01-01

Rhein, an anthraquinone compound existing in many traditional herbal medicines, has anti-inflammatory, antioxidant, antitumor, antiviral, hepatoprotective, and nephroprotective activities, but its anti-influenza A virus (IAV) activity is ambiguous. In the present study, through plaque inhibition assay, time-of-addition assay, antioxidant assay, qRT-PCR, ELISA, and western blotting assays, we investigated the anti-IAV effect and mechanism of action of rhein in vitro and in vivo. The results showed that rhein could significantly inhibit IAV adsorption and replication, decrease IAV-induced oxidative stress, activations of TLR4, Akt, p38, JNK MAPK, and NF-κB pathways, and production of inflammatory cytokines and matrix metalloproteinases in vitro. Oxidant H2O2 and agonists of TLR4, Akt, p38/JNK and IKK/NF-κB could significantly antagonize the inhibitory effects of rhein on IAV-induced cytopathic effect (CPE) and IAV replication. Through an in vivo test in mice, we also found that rhein could significantly improve the survival rate, lung index, pulmonary cytokines, and pulmonary histopathological changes. Rhein also significantly decreased pulmonary viral load at a high dose. In conclusion, rhein can inhibit IAV adsorption and replication, and the mechanism of action to inhibit IAV replication may be due to its ability to suppress IAV-induced oxidative stress and activations of TLR4, Akt, p38, JNK MAPK, and NF-κB signal pathways. PMID:29385192

Anti-influenza A virus activity of rhein through regulating oxidative stress, TLR4, Akt, MAPK, and NF-κB signal pathways.

PubMed

Wang, Qian-Wen; Su, Yun; Sheng, Jiang-Tao; Gu, Li-Ming; Zhao, Ying; Chen, Xiao-Xuan; Chen, Cheng; Li, Wei-Zhong; Li, Kang-Sheng; Dai, Jian-Ping

2018-01-01

Rhein, an anthraquinone compound existing in many traditional herbal medicines, has anti-inflammatory, antioxidant, antitumor, antiviral, hepatoprotective, and nephroprotective activities, but its anti-influenza A virus (IAV) activity is ambiguous. In the present study, through plaque inhibition assay, time-of-addition assay, antioxidant assay, qRT-PCR, ELISA, and western blotting assays, we investigated the anti-IAV effect and mechanism of action of rhein in vitro and in vivo. The results showed that rhein could significantly inhibit IAV adsorption and replication, decrease IAV-induced oxidative stress, activations of TLR4, Akt, p38, JNK MAPK, and NF-κB pathways, and production of inflammatory cytokines and matrix metalloproteinases in vitro. Oxidant H2O2 and agonists of TLR4, Akt, p38/JNK and IKK/NF-κB could significantly antagonize the inhibitory effects of rhein on IAV-induced cytopathic effect (CPE) and IAV replication. Through an in vivo test in mice, we also found that rhein could significantly improve the survival rate, lung index, pulmonary cytokines, and pulmonary histopathological changes. Rhein also significantly decreased pulmonary viral load at a high dose. In conclusion, rhein can inhibit IAV adsorption and replication, and the mechanism of action to inhibit IAV replication may be due to its ability to suppress IAV-induced oxidative stress and activations of TLR4, Akt, p38, JNK MAPK, and NF-κB signal pathways.

Synergistic activity of curcumin with methotrexate in ameliorating Freund's Complete Adjuvant induced arthritis with reduced hepatotoxicity in experimental animals.

PubMed

Banji, David; Pinnapureddy, Jyothi; Banji, Otilia J F; Saidulu, A; Hayath, Md Sikinder

2011-10-01

Methotrexate is employed in low doses for the treatment of rheumatoid arthritis. One of the major drawbacks with methotrexate is hepatotoxicity resulting in poor compliance of therapy. Curcumin is an extensively used spice possessing both anti-arthritic and hepatoprotective potential. The present study was aimed at investigating the effect of curcumin (30 and 100 mg/kg) in combination with subtherapeutic dose of methotrexate (1 mg/kg) is salvaging hepatotoxicity, oxidative stress and producing synergistic anti-arthritic action with methotrexate. Wistar albino rats were induced with arthritis by subplantar injection of Freund's Complete Adjuvant and pronounced arthritis was seen after 9 days of injection. Groups of animals were treated with subtherapeutic dose of methotrexate followed half an hour later with 30 and 100mg/kg of curcumin from day 9 up to days 45 by intraperitoneal route. Methotrexate treatment in Freund's Complete Adjuvant induced arthritic animals produced elevation in the levels of aminotransferases, alkaline phosphatase, total and direct bilirubin. Enhanced oxidative stress in terms of measured lipid peroxides was observed in the methotrexate treated group. Curcumin significantly circumvented hepatotoxicity induced by methotrexate as evidenced by a change in biochemical markers possibly due to its strong anti-oxidant action. Hepatoprotective potential of curcumin was also confirmed from histological evaluation. Sub-therapeutic dose of methotrexate elicited substantial anti-arthritic action when used in combination with curcumin implying that the latter potentiated its action. Concomitant administration of curcumin with methotrexate was also found to minimize liver damage. Copyright © 2011 Elsevier B.V. All rights reserved.

Ethanol extract and its dichloromethane fraction of Alpinia oxyphylla Miquel exhibited hepatoprotective effects against CCl4-induced oxidative damage in vitro and in vivo with the involvement of Nrf2.

PubMed

Zhang, Qiao; Hu, Xiaolong; Hui, Fuhai; Song, Qi; Cui, Can; Wang, Changli; Zhao, Qingchun

2017-07-01

Alpinia oxyphylla Miq. (A. oxyphylla), as a kind of medicine which also be used as food, is widely used in East Asian for the treatment of dyspepsia, diarrhea, abdominal pain and deficiency cold of spleen and stomach. This study aimed to investigate the protective effects of ethanol extract (EE) and its dichloromethane fraction (DM) of A. oxyphylla, which are rich in phenolic compounds, against CCl 4 -induced hepatic injury in vitro and in vivo. EE, DM and silymarin ameliorated CCl 4 -induced decrease of cell viability and increase of reactive oxygen species (ROS) in HepG2 cells. The CCl 4 -induced changes of glutathione (GSH) and methane dicarboxylic aldehyde (MDA) levels, and the decrease of superoxide dismutase (SOD) and catalase (CAT) activities were all restored with the pretreatment of EE, DM and silymarin. The results in liver injury model in rats showed that EE, DM and silymarin could significant decrease the levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin than the model group. Liver histopathology revealed that EE and DM attenuated the incidence of liver lesions triggered by CCl 4 intoxication. They also effectively relieved CCl 4 -induced oxidative damage. Western blot analysis indicated NF-E2-related factor (Nrf2) pathway played an critical role in the protection of EE and DM against CCl 4 -induced oxidative stress. In conclusion, the extracts from A. oxyphylla might be used as hepatoprotective agents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Hepatoprotective efficacy of Spirulina platensis against lead-induced oxidative stress and genotoxicity in catfish; Clarias gariepinus.

PubMed

Sayed, Alaa El-Din H; El-Sayed, Yasser S; El-Far, Ali H

2017-09-01

Lead (Pb) is a toxic environmental pollutant that induces a broad range of biochemical and physiological hazards in living organisms. We investigated the possible hepatoprotective effects of Spirulina platensis (SP) in counteracting the Pb-induced oxidative damage. Ninety-six adult African catfish were allocated into four equal groups. The 1st group (control) fed basal diet while the 2nd group (Pb-treated) fed on basal diet and exposed to 1mg Pb(NO 3 ) 2 /L. The 3rd and 4th groups fed SP-supplemented basal diets at levels of 0.25% and 0.5%, respectively and exposed to Pb. Serum samples were used to analyze hepatic function biomarkers, electrolytes, and oxidant and antioxidant status. Lipid peroxidation and DNA fragmentation were determined in the liver tissues. Pb exposure induced hepatic dysfunction, electrolytes (Na + , K + , Ca +2 , and Cl - ) imbalance, as well a significant decrease in GSH content, and LDH, AChE, SOD, CAT and GST enzymes activity. SP supplementation reverted these biochemical and genetic alterations close to control levels. This amelioration was higher with 0.5% SP and at the 4th week of exposure, showing concentration- and time-dependency. Thus, the current study suggests that SP could protect the catfish liver against lead-induced injury by scavenging ROS, sustaining the antioxidant status and diminishing DNA oxidative damage. The dietary inclusion of SP can be used as a promising protective agent to counteract oxidative stress-mediated diseases and toxicities. Copyright © 2017 Elsevier Inc. All rights reserved.

Reduction of the DNA damages, Hepatoprotective Effect and Antioxidant Potential of the Coconut Water, ascorbic and Caffeic Acids in Oxidative Stress Mediated by Ethanol.

PubMed

Bispo, Vanderson S; Dantas, Lucas S; Chaves, Adriano B; Pinto, Isabella F D; Silva, Railmara P DA; Otsuka, Felipe A M; Santos, Rodrigo B; Santos, Aline C; Trindade, Danielle J; Matos, Humberto R

2017-01-01

Hepatic disorders such as steatosis and alcoholic steatohepatitis are common diseases that affect thousands of people around the globe. This study aims to identify the main phenol compounds using a new HPLC-ESI+-MS/MS method, to evaluate some oxidative stress parameters and the hepatoprotective action of green dwarf coconut water, caffeic and ascorbic acids on the liver and serum of rats treated with ethanol. The results showed five polyphenols in the lyophilized coconut water spiked with standards: chlorogenic acid (0.18 µM), caffeic acid (1.1 µM), methyl caffeate (0.03 µM), quercetin (0.08 µM) and ferulic acid (0.02 µM) isomers. In the animals, the activity of the serum γ-glutamyltranspeptidase (γ-GT) was reduced to 1.8 I.U/L in the coconut water group, 3.6 I.U/L in the ascorbic acid group and 2.9 I.U/L in the caffeic acid groups, when compared with the ethanol group (5.1 I.U/L, p<0.05). Still in liver, the DNA analysis demonstrated a decrease of oxidized bases compared to ethanol group of 36.2% and 48.0% for pretreated and post treated coconut water group respectively, 42.5% for the caffeic acid group, and 34.5% for the ascorbic acid group. The ascorbic acid was efficient in inhibiting the thiobarbituric acid reactive substances (TBARS) in the liver by 16.5% in comparison with the ethanol group. These data indicate that the green dwarf coconut water, caffeic and ascorbic acids have antioxidant, hepatoprotective and reduced DNA damage properties, thus decreasing the oxidative stress induced by ethanol metabolism.

Influence of diabetes on liver injury induced by antitubercular drugs and on silymarin hepatoprotection in rats.

PubMed

Srivastava, R K; Sharma, S; Verma, S; Arora, B; Lal, H

2008-12-01

Isoniazid, rifampicin and pyrazinamide during short-course chemotherapy for tuberculosis can result in liver injury. The coexistence of tuberculosis and diabetes is common in patients who receive inadequate treatment. The risk of hepatotoxicity from many toxicants is increased in diabetic rats. Silymarin provides protection against liver injury caused by many hepatotoxicants, including antitubercular drugs (ATDs). In the wake of increased severity of ATD-induced hepatotoxicity in diabetes we report here the results of a study on the influence of diabetes on silymarin hepatoprotection in rats. Rats with diabetes induced via intraperitoneally injected streptozotocin (50 mg/kg), nondiabetic rats and insulin-treated diabetic rats received isoniazid (7.5 mg/kg/day), rifampicin (10 mg/kg/day) and pyrazinamide (35 mg/kg/day) orally (p.o.) with or without silymarin (100 mg/kg/day p.o.) treatment for 45 days. Compared to nondiabetic rats, liver function tests and histological changes of liver revealed exaggerated liver injury in diabetic rats caused by ATDs which was evident by 5- to 8-fold increases in serum levels of marker enzymes (aspartate and alanine aminotransferase, alkaline phosphatase and gamma-glutamyltranspeptidase) and 1- to 2-fold increases in bilirubin accompanied by a 2-fold decrease in total serum proteins, intense fatty and inflammatory infiltrations, necrosis and fibrosis. Coadministration of silymarin provided protection against ATD hepatotoxicity in all animals. However, insulin-treated diabetic animals showed greater silymarin-induced hepatoprotection against ATD-induced liver injury, which was characterized by near normal levels of marker enzymes, an increase in total proteins and normal hepatic structure. These results thus indicate that diabetes exaggerates ATD-induced liver injury and attenuates silymarin-induced hepatoprotection. However, insulin treatment for diabetes offers greater silymarin-induced hepatoprotection against ATD-induced liver injury. Copyright (c) 2008 Prous Science, S.A.U. or its licensors. All rights reserved.

Histological and immunohistochemical effects of Curcuma longa on activation of rat hepatic stellate cells after cadmium induced hepatotoxicity.

PubMed

El-Mansy, A A; Mazroa, S A; Hamed, W S; Yaseen, A H; El-Mohandes, E A

2016-01-01

The liver is a target for toxic chemicals such as cadmium (Cd). When the liver is damaged, hepatic stellate cells (HSC) are activated and transformed into myofibroblast-like cells, which are responsible for liver fibrosis. Curcuma longa has been reported to exert a hepato-protective effect under various pathological conditions. We investigated the effects of C. longa administration on HSC activation in response to Cd induced hepatotoxicity. Forty adult male albino rats were divided into: group 1 (control), group 2 (Cd treated), group 3 (C. longa treated) and group 4 (Cd and C. longa treated). After 6 weeks, liver specimens were prepared for light and electron microscopy examination of histological changes and immunohistochemical localization of alpha smooth muscle actin (αSMA) as a specific marker for activated HSC. Activated HSC with a positive αSMA immune reaction were not detected in groups 1 and 3. Large numbers of activated HSC with αSMA immune reactions were observed in group 2 in addition to Cd induced hepatotoxic changes including excess collagen deposition in thickened portal triads, interlobular septa with hepatic lobulation, inflammatory cell infiltration, a significant increase in Kupffer cells and degenerated hepatocytes. In group 4, we observed a significant decrease in HSC that expressed αSMA with amelioration of the hepatotoxic changes. C. longa administration decreased HSC activation and ameliorated hepatotoxic changes caused by Cd in adult rats.

Rutin exhibits hepatoprotective effects in a mouse model of non-alcoholic fatty liver disease by reducing hepatic lipid levels and mitigating lipid-induced oxidative injuries.

PubMed

Liu, Qingsheng; Pan, Ran; Ding, Lei; Zhang, Fuli; Hu, Linfeng; Ding, Bin; Zhu, Linwensi; Xia, Yongliang; Dou, Xiaobing

2017-08-01

Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive accumulation of hepatic lipids and oxidative injury of hepatocytes. Rutin is a natural flavonoid with significant roles in combating cellular oxidative stress and regulating lipid metabolism. The current study aims to investigate the molecular mechanisms underlying rutin's hypolipidemic and hepatoprotective effects in nonalcoholic fatty liver disease. Rutin treatment was applied to male C57BL/6 mice maintained on a high-fat diet and HepG2 cells challenged with oleic acid. Hepatic lipid accumulation was evaluated by triglyceride assay and Oil Red O staining. Oxidative hepatic injury was assessed by malondialdehyde assay, superoxide dismutase assay and reactive oxygen species assay. The expression levels of various lipogenic and lipolytic genes were determined by quantitative real-time polymerase chain reactions. In addition, liver autophagy was investigated by enzyme-linked immunosorbent assay. In both fat-challenged murine liver tissues and HepG2 cells, rutin treatment was shown to significantly lower triglyceride content and the abundance of lipid droplets. Rutin was also found to reduce cellular malondialdehyde level and restore superoxide dismutase activity in hepatocytes. Among the various lipid-related genes, rutin treatment was able to restore the expression of peroxisome proliferator-activated receptor alpha (PPAR-α) and its downstream targets, carnitine palmitoyltransferase 1 and 2 (CPT-1 and CPT-2), while suppressing those of sterol regulatory element-binding protein 1c (SREBP-1c), diglyceride acyltransfase 1 and 2 (DGAT-1 and 2), as well as acyl-CoA carboxylase (ACC). In addition, rutin was shown to repress the autophagic function of liver tissues by down-regulating key autophagy biomarkers, including tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β). The experimental data demonstrated that rutin could reduce triglyceride content and mitigate oxidative injuries in fat-enriched hepatocytes. The hypolipidemic properties of rutin could be attributed to its ability to simultaneously facilitate fatty acid metabolism and inhibit lipogenesis. Copyright © 2017 Elsevier B.V. All rights reserved.

Hepatoprotective effect of chrysin on prooxidant-antioxidant status during ethanol-induced toxicity in female albino rats.

PubMed

Sathiavelu, Jayanthi; Senapathy, Giftson Jebakkan; Devaraj, Rajkumar; Namasivayam, Nalini

2009-06-01

To evaluate the effect of chrysin, a natural, biologically active compound extracted from many plants, honey and propolis, on the tissue and circulatory antioxidant status, and lipid peroxidation in ethanol-induced hepatotoxicity in rats. Rats were divided into four groups. Groups 1 and 2 received isocaloric glucose. Groups 3 and 4 received 20% ethanol, equivalent to 5 g/kg bodyweight every day. Groups 2 and 4 received chrysin (20 mg/kg bodyweight) dissolved in 0.5% dimethylsulfoxide. The results showed significantly elevated levels of tissue and circulatory thiobarbituric acid reactive substances, conjugated dienes and lipid hydroperoxides, and significantly lowered enzymic and non-enzymic antioxidant activity of superoxide dismutase, catalase and glutathione-related enzymes such as glutathione peroxidase, glutathione reductase, glutathione-S-transferase, reduced glutathione, vitamin C and vitamin E in ethanol-treated rats compared with the control. Chrysin administration to rats with ethanol-induced liver injury significantly decreased the levels of thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes, and significantly elevated the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and the levels of reduced glutathione, vitamin C and vitamin E in the tissues and circulation compared with those of the unsupplemented ethanol-treated rats. The histological changes observed in the liver and kidney correlated with the biochemical findings. Chrysin offers protection against free radical-mediated oxidative stress in rats with ethanol-induced liver injury.

Hepatoprotective effect of fermented ginseng and its major constituent compound K in a rat model of paracetamol (acetaminophen)-induced liver injury.

PubMed

Igami, Kentaro; Shimojo, Yosuke; Ito, Hisatomi; Miyazaki, Toshitsugu; Kashiwada, Yoshiki

2015-04-01

This work aimed at evaluating the effect of fermented ginseng (FG) and fermented red ginseng (FRG) against rat liver injury caused by paracetamol (acetaminophen (APAP)). Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the serum and histopathological changes in the liver were analysed to determine the degree of liver injury. Deoxyribonucleic acid (DNA) microarray analysis was performed to compare gene expression levels altered in the rat livers. Phosphorylated Jun-N-terminal kinase (JNK) in human hepatocellular carcinoma (HepG2) cells were detected using western blot analysis to investigate the anti-inflammatory activity of compound K. Pretreatment with FG, containing compound K at high concentration, attenuated AST as well as ALT levels in rats, while no obvious effect was observed in the group that received FRG, whose content of compound K was lower than that of FG. In addition, the results of our histopathological analysis were consistent with changes in the serum biochemical analysis. DNA microarray analysis indicated that JNK- and glutathione S-transferase (GST)-related genes were involved in the hepatotoxicity. Notably, compound K, a major ginsenoside in FG, inhibited the phosphorylation of JNK in HepG2 cells. FG was shown to possess hepatoprotective activity against paracetamol (APAP)-induced liver injury better than FRG. Compound K might play an important role for an anti-inflammatory activity of FG by inhibiting JNK signalling in the liver. © 2014 Royal Pharmaceutical Society.

Hepatoprotective effects of pecan nut shells on ethanol-induced liver damage.

PubMed

Müller, Liz Girardi; Pase, Camila Simonetti; Reckziegel, Patrícia; Barcelos, Raquel C S; Boufleur, Nardeli; Prado, Ana Cristina P; Fett, Roseane; Block, Jane Mara; Pavanato, Maria Amália; Bauermann, Liliane F; da Rocha, João Batista Teixeira; Burger, Marilise Escobar

2013-01-01

The hepatoprotective activity of the aqueous extract of the shells of pecan nut was investigated against ethanol-induced liver damage. This by-product of the food industry is popularly used to treat toxicological diseases. We evaluated the phytochemical properties of pecan shell aqueous extract (AE) and its in vitro and ex vivo antioxidant activity. The AE was found to have a high content of total polyphenols (192.4±1.9 mg GAE/g), condensed tannins (58.4±2.2 mg CE/g), and antioxidant capacity, and it inhibited Fe(2+)-induced lipid peroxidation (LP) in vitro. Rats chronically treated with ethanol (Et) had increased plasmatic transaminases (ALT, AST) and gamma glutamyl transpeptidase (GGT) levels (96%, 59.13% and 465.9%, respectively), which were effectively prevented (87; 41 and 383%) by the extract (1:40, w/v). In liver, ethanol consumption increased the LP (121%) and decreased such antioxidant defenses as glutathione (GSH) (33%) and superoxide dismutase (SOD) (47%) levels, causing genotoxicity in erythrocytes. Treatment with pecan shell AE prevented the development of LP (43%), GSH and SOD depletion (33% and 109%, respectively) and ethanol-induced erythrocyte genotoxicity. Catalase activity in the liver was unchanged by ethanol but was increased by the extract (47% and 73% in AE and AE+Et, respectively). Therefore, pecan shells may be an economic agent to treat liver diseases related to ethanol consumption. Copyright © 2011 Elsevier GmbH. All rights reserved.

Chemical characteristics and enhanced hepatoprotective activities of Maillard reaction products derived from milk protein-sugar system.

PubMed

Oh, Nam Su; Young Lee, Ji; Lee, Hyun Ah; Joung, Jae Yeon; Shin, Yong Kook; Kim, Sae Hun; Kim, Younghoon; Lee, Kwang Won

2016-02-01

The objective of this study was to investigate the characteristics, antioxidative properties, and hepatoprotective effects of Maillard reaction products (MRP) from milk protein reacted with sugars. The MRP were obtained from milk protein, whey protein concentrates and sodium caseinate, using 2 types of sugars, lactose and glucose, by heating the mixture at 55°C for 7d in a sodium phosphate buffer (pH 7.4). Changes in the chemical modification of the milk protein were monitored by measuring the protein-bound carbonyls and PAGE protein profiles. The results showed that the amount of protein-bound carbonyls increased after Maillard reaction (MR). In addition, sodium dodecyl sulfate-PAGE analysis indicated a formation of high-molecular weight complexes through MR. The modification sites induced by MR of milk protein were monitored by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis of tryptic-digested gel spots of MRP. As a result, modification and their localization in AA sequence of MRP was identified. Also, the MRP showed higher antioxidant activities than the intact milk protein, and they reduced intracellular reactive oxygen species production and inhibited the depletion of the reduced glutathione concentrations in the HepG2 cells. In particular, glucose-sodium caseinate MRP showed the highest biological activities among all MRP. Therefore, these results suggest that the MRP from milk protein reacting with sugars possess effective antioxidant activity and have a protective ability against oxidative damage. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Free Radical-Scavenging, Anti-Inflammatory/Anti-Fibrotic and Hepatoprotective Actions of Taurine and Silymarin against CCl4 Induced Rat Liver Damage

PubMed Central

Abdel-Moneim, Ashraf M.; Al-Kahtani, Mohammed A.; El-Kersh, Mohamed A.; Al-Omair, Mohammed A.

2015-01-01

The present study aims to investigate the hepatoprotective effect of taurine (TAU) alone or in combination with silymarin (SIL) on CCl4-induced liver damage. Twenty five male rats were randomized into 5 groups: normal control (vehicle treated), toxin control (CCl4 treated), CCl4+TAU, CCl4+SIL and CCl4+TAU+SIL. CCl4 provoked significant increases in the levels of hepatic TBARS, NO and NOS compared to control group, but the levels of endogenous antioxidants such as SOD, GPx, GR, GST and GSH were significantly decreased. Serum pro-inflammatory and fibrogenic cytokines including TNF-α, TGF-β1, IL-6, leptin and resistin were increased while the anti-inflammatory (adiponectin) cytokine was decreased in all treated rats. Our results also showed that CCl4 induced an increase in liver injury parameters like serum ALT, AST, ALP, GGT and bilirubin. In addition, a significant increase in liver tissue hydroxyproline (a major component of collagen) was detected in rats exposed to CCl4. Moreover, the concentrations of serum TG, TC, HDL-C, LDL-C, VLDL-C and FFA were significantly increased by CCl4. Both TAU and SIL (i.e., antioxidants) post-treatments were effectively able to relieve most of the above mentioned imbalances. However, the combination therapy was more effective than single applications in reducing TBARS levels, NO production, hydroxyproline content in fibrotic liver and the activity of serum GGT. Combined treatment (but not TAU- or SIL-alone) was also able to effectively prevent CCl4-induced decrease in adiponectin serum levels. Of note, the combined post-treatment with TAU+SIL (but not monotherapy) normalized serum FFA in CCl4-treated rats. The biochemical results were confirmed by histological and ultrastructural changes as compared to CCl4-poisoned rats. Therefore, on the basis of our work, TAU may be used in combination with SIL as an additional adjunct therapy to cure liver diseases such as fibrosis, cirrhosis and viral hepatitis. PMID:26659465

The hepatoprotective activity of olive oil and Nigella sativa oil against CCl4 induced hepatotoxicity in male rats.

PubMed

Al-Seeni, Madeha N; El Rabey, Haddad A; Zamzami, Mazin A; Alnefayee, Abeer M

2016-11-04

Liver disease is the major cause of serious health problem leading to morbidity and mortality worldwide and the problem has increased in search for hepatotherapeutic agents from plants. The present study was designed to compare the probable hepatoprotective activity of olive oil and N. sativa oil on CCl 4 induced liver damage in male rats. Forty males of a new model of albino rats (Wistar strain) (175-205 g) were divided into four groups. The 1st Group (G1) was the negative control group, the remaining rats were injected with CCl 4 (1 ml/kg body weight) with equal amount of olive oil on the 1st and 4th day of every week for 4 weeks. The 2nd group (G2) was the positive control, the 3rd group (G3) and the fourth group (G4) were treated orally with N. sativa oil and olive oils using stomach tube. The positive control group showed an increase in hepatic enzymes, total bilirubin, creatinine, uric acid, lipid peroxide total cholesterol, triglyceride, low density lipoprotein, very low density lipoproteins, interleukin-6, and a decrease in antioxidant enzymes, high density lipoprotein cholesterol, a decrease in total protein and albumin an when compared with negative control group. Histology of the CCl 4 treated group revealed inflammation and damage of liver cells. Treating the hepatotoxic rats with olive oil and N. sativa oil showed a significant improvement in all biochemical tests compared with the positive CCl 4 control group. In addition, the liver tissues of olive oil treated group showed mild improvement in inflammatory infiltration and in N. sativa oil treated group showed normal hepatocytes with no evidence of inflammation. This study revealed that olive oil and N. sativa oil have a protective effect against CCl 4 -induced hepatotoxicity in male rats. Nigella sativa oil was more effective than olive oil.

Review of the Pharmacological Effects of Vitis vinifera (Grape) and its Bioactive Constituents: An Update.

PubMed

Nassiri-Asl, Marjan; Hosseinzadeh, Hossein

2016-09-01

Vitis vinifera fruit (grape) contains various phenolic compounds, flavonoids and stilbenes. In recent years, active constituents found in the fruits, seeds, stems, skin and pomaces of grapes have been identified and some have been studied. In this review, we summarize the active constituents of different parts of V. vinifera and their pharmacological effects including skin protection, antioxidant, antibacterial, anticancer, antiinflammatory and antidiabetic activities, as well as hepatoprotective, cardioprotective and neuroprotective effects in experimental studies published after our 2009 review. Clinical and toxicity studies have also been examined. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The hepatoprotective activity of blue green algae in Schistosoma mansoni infected mice.

PubMed

Mohamed, Azza H; Osman, Gamalat Y; Salem, Tarek A; Elmalawany, Alshimaa M

2014-10-01

This study aims to evaluate the immunomodulatory effects of a natural product, blue green algae (BGA) (100 mg/kg BW), alone or combined with praziquantel PZQ (250 mg/kg BW) on granulomatous inflammation, liver histopathology, some biochemical and immunological parameters in mice infected with Schistosoma mansoni. Results showed that the diameter and number of egg granuloma were significantly reduced after treatment of S. mansoni-infected mice with BGA, PZQ and their combination. The histopathological alterations observed in the liver of S. mansoni-infected mice were remarkably inhibited after BGA treatments. BGA decreased the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) as well as the level of total protein (TP) while the level of albumin was increased. Treatment of infected mice with BGA, PZQ as well as their combination led to significant elevation in the activities of hepatic antioxidant enzymes glutathione peroxidase (GPX) and glutathione-S-transferase (GST) as compared with control group. Combination of BGA and PZQ resulted in significant reduction in the level of intercellular adhesion molecules-1 (ICAM-1), vascular adhesion molecules-1 (VCAM-1) and tumor necrosis factor-alpha (TNF-α) when compared to those of the S. mansoni-infected group. Overall, BGA significantly inhibited the liver damage accompanied with schistosomiasis, exhibited a potent antioxidant and immunoprotective activities. This study suggests that BGA can be considered as promising for development a complementary and/or alternative medicine against schistosomiasis. Copyright © 2014 Elsevier Inc. All rights reserved.

Effect of adrenergic blockers, carvedilol, prazosin, metoprolol and combination of prazosin and metoprolol on paracetamol-induced hepatotoxicity in rabbits

PubMed Central

Zubairi, Maysaa B.; Ahmed, Jawad H.; Al-Haroon, Sawsan S.

2014-01-01

Objectives: To evaluate hepatoprotective potential of carvedilol, prazosin, metoprolol and prazosin plus metoprolol in paracetamol-induced hepatotoxicity. Materials and Methods: Thirty-six male rabbits were divided into six groups, six in each, group 1 received distilled water, group 2 were treated with paracetamol (1 g/kg/day, orally), group 3, 4,5 and 6 were treated at a dose in (mg/kg/day) of the following: Carvedilol (10 mg), prazosin (0.5 mg), metoprolol (10 mg), and a combination of metoprolol (10 mg) and prazosin (0.5 mg) respectively 1 h before paracetamol treatment. All treatments were given for 9 days; animals were sacrificed at day 10. Liver function tests, malondialdehyde (MDA) and glutathione (GSH) in serum and liver homogenates were estimated. Histopathological examinations of liver were performed. Results: Histopathological changes of hepatotoxicity were found in all paracetamol-treated rabbits. The histopathological findings of paracetamol toxicity disappeared in five rabbits on prazosin, very mild in one. In carvedilol group paracetamol toxicity completely disappeared in three, while mild in three rabbits. Paracetamol hepatotoxicity was not changed by metoprolol. In metoprolol plus prazosin treated rabbits, moderate histopathological changes were observed. Serum liver function tests and MDA in serum and in liver homogenate were elevated; GSH was depleted after paracetamol treatment and returned back to the control value on prior treatment with prazosin. MDA in serum and liver homogenate, alkaline phosphatase, total bilirubin were significantly decreased after carvedilol and prazosin plus metoprolol treatments. Conclusion: Carvedilol and prazosin are hepatoprotective in paracetamol hepatotoxicity, combination of prazosin and metoprolol have moderate, and metoprolol has a little hepatoprotection. PMID:25538338

Isolating the metabolic pathways involved in the hepatoprotective effect of Muntingia calabura against CCl4-induced liver injury using LC/MS Q-TOF.

PubMed

Rofiee, M S; Yusof, M I M; Abdul Hisam, E E; Bannur, Z; Zakaria, Z A; Somchit, M N; Teh, L K; Salleh, M Z

2015-05-26

Muntingia calabura L. has been used in Southeast Asia and tropical America as antipyretic, antiseptic, analgesic, antispasmodic and liver tonic. This study aims to determine the acute toxicity and the metabolic pathways involved in the hepatoprotective mechanism of M. calabura. CCl4-induced hepatotoxic rat model was developed and a dose dependent effect of M. calabura was conducted. Body weight, food and water consumption were measured every day and rats were sacrificed to collect the serum samples at the end of the 10-days treatment. Liquid chromatography-mass spectrometry quadrapole time of flight (LC/MS-QTOF) combined with principal component analysis (PCA) were used to determine differentially expressed metabolites due to treatment with CCl4 and M. calabura extracts. Metabolomics Pathway Analysis (MetPA) was used for analysis and visualization of pathways involved. Body weight, food and water consumption were significantly decreased and histopathological study revealed steatosis in CCl4-induced rats. PCA score plots show distinct separation in the metabolite profiles of the normal group, CCl4-treated group and extract of M. calabura (MCME) pre-treated groups. Biomarkers network reconstruction using MetPA had identified 2 major pathways which were involved in the protective mechanism of MCME. These include the (i) biosynthesis of the primary bile acid, (ii) metabolism of arachidonic acid. This study has successfully isolated 2 major pathways involved in the hepatoprotecive effect of MCME against CCl4-induced liver injury using the LC/MS Q-TOF metabolomics approach. The involvement of archidonic acid and purine metabolism in hepatoprotection has not been reported previously and may provide new therapeutic targets and/or options for the treatment of liver injury. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Analysis of the liver mitochondrial proteome in response to ethanol and S-adenosylmethionine treatments: novel molecular targets of disease and hepatoprotection.

PubMed

Andringa, Kelly K; King, Adrienne L; Eccleston, Heather B; Mantena, Sudheer K; Landar, Aimee; Jhala, Nirag C; Dickinson, Dale A; Squadrito, Giuseppe L; Bailey, Shannon M

2010-05-01

S-adenosylmethionine (SAM) minimizes alcohol hepatotoxicity; however, the molecular mechanisms responsible for SAM hepatoprotection remain unknown. Herein, we use proteomics to determine whether the hepatoprotective action of SAM against early-stage alcoholic liver disease is linked to alterations in the mitochondrial proteome. For this, male rats were fed control or ethanol-containing liquid diets +/- SAM and liver mitochondria were prepared for proteomic analysis. Two-dimensional isoelectric focusing (2D IEF/SDS-PAGE) and blue native gel electrophoresis (BN-PAGE) were used to determine changes in matrix and oxidative phosphorylation (OxPhos) proteins, respectively. SAM coadministration minimized alcohol-dependent inflammation and preserved mitochondrial respiration. SAM supplementation preserved liver SAM levels in ethanol-fed rats; however, mitochondrial SAM levels were increased by ethanol and SAM treatments. With use of 2D IEF/SDS-PAGE, 30 proteins showed significant changes in abundance in response to ethanol, SAM, or both. Classes of proteins affected by ethanol and SAM treatments were chaperones, beta oxidation proteins, sulfur metabolism proteins, and dehydrogenase enzymes involved in methionine, glycine, and choline metabolism. BN-PAGE revealed novel changes in the levels of 19 OxPhos proteins in response to ethanol, SAM, or both. Ethanol- and SAM-dependent alterations in the proteome were not linked to corresponding changes in gene expression. In conclusion, ethanol and SAM treatment led to multiple changes in the liver mitochondrial proteome. The protective effects of SAM against alcohol toxicity are mediated, in part, through maintenance of proteins involved in key mitochondrial energy conserving and biosynthetic pathways. This study demonstrates that SAM may be a promising candidate for treatment of alcoholic liver disease.

Ameliorative effect of alkaloid extract of Cyclea peltata (Poir.) Hook. f. & Thoms. roots (ACP) on APAP/CCl4 induced liver toxicity in Wistar rats and in vitro free radical scavenging property.

PubMed

Shine, Varghese Jancy; Latha, Panikamparambil Gopalakrishnan; Suja, Somasekharan Nair Rajam; Anuja, Gangadharan Indira; Raj, Gopan; Rajasekharan, Sreedharan Nair

2014-02-01

To evaluate the hepatoprotective and antioxidant properties of alkaloid extract of Cyclea peltata (C. peltata) against paracetamol/carbon tetra chloride induced liver damage in Wistar rats. In vivo paracetamol/carbon tetrachloride induced liver damage in Wistar rats, in vitro free radical scavenging studies, HPTLC estimation of tetrandrine and direct analysis in real time- mass spectrometry of alkaloid extract of C. peltata were used for the validation. The results showed that pretreatment with alkaloid extract of C. peltata caused significant reduction of serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, serum alkaline phosphatase, serum cholesterol, liver malondialdehyde levels. The reduced glutathione, catalase, superoxide dismutase levels in liver were increased with alkaloid extract of C. peltata treatment. These results were almost comparable to silymarin and normal control. Histopathological studies also substantiated the biochemical findings. The in vitro hydroxyl, superoxide and DPPH scavenging study of alkaloid extract of C. peltata showed significant free radical scavenging property. The hepatoprotective property of alkaloid extract of C. peltata against paracetamol/carbon tetrachloride may be due the synergistic action of alkaloids especially tetrandrine, fangchinoline through free radical scavenging and thus preventing oxidative stress.

Prevention of CCl4-induced liver damage by ginger, garlic and vitamin E.

PubMed

Patrick-Iwuanyanwu, K C; Wegwu, M O; Ayalogu, E O

2007-02-15

The hepatoprotective effects of garlic (Allium sativum), ginger (Zingiber officinale) and vitamin E pre-treatment against carbon tetrachloride (CCl4)-induced liver damage in male wistar albino rats were investigated. Carbon tetrachloride (0.5 mL kg(-1) body weight) was administered after 28 days of feeding animals with diets containing ginger, garlic, vitamin E and various mixtures of ginger and garlic. Serum alanine amino transferase, aspartate amino transferase and alkaline phosphatase levels, 24 h after CCl4 administration, decreased significantly (p < or = 0.05) in rats pre-treated with garlic, ginger, vitamin E and various mixtures of garlic and ginger than in CCl4-treated rats only. Lipid peroxidation expressed by serum malondialdehyde (MDA) concentration was assayed to assess the extent of liver damage by CCl4; including the extent of hepatoprotection by garlic, ginger and vitamin E. MDA concentration was significantly decreased (p < or = 0.05) in rats pretreated with garlic, ginger, vitamin E and various mixtures of garlic and ginger than in rats administered CCl4-alone. Histological examination of the liver revealed severe infiltration of inflammatory cells in rats treated with CCl4 alone. However, the observed alteration in the normal architecture of the hepatic cells decreased remarkably in pre-treated rats.

Hepatoprotective effect of grape seed oil against carbon tetrachloride induced oxidative stress in liver of γ-irradiated rat.

PubMed

Ismail, Amel F M; Salem, Asmaa A M; Eassawy, Mamdouh M T

2016-07-01

Carbon tetrachloride (CCl4) and ionizing radiation are well known environmental pollutants that generate free radicals and induce oxidative stress. The liver is the primary and major target organ responsible for the metabolism of drugs, toxic chemicals and affected by irradiation. This study investigated the effect of grape seed oil (GSO) on acute liver injury induced by carbon tetrachloride (CCl4) in γ-irradiated rats (7Gy). CCl4-intoxicated rats exhibited an elevation of ALT, AST activities, IL-6 and TNF-α level in the serum. Further, the levels of MDA, NO, NF-κB and the gene expression of CYP2E1, iNOS and Caspase-3 were increased, and SOD, CAT, GSH-Px, GST activities and GSH content were decreased. Furthermore, silent information regulator protein 1 (SIRT1) gene expression was markedly down-regulated. Additionally, alterations of the trace elements; copper, manganese, zinc and DNA fragmentation was observed in the hepatic tissues of the intoxicated group. These effects were augmented in CCl4-intoxicated-γ-irradiated rats. However, the administration of GSO ameliorated these parameters. GSO exhibit protective effects on CCl4 induced acute liver injury in γ-irradiated rats that could be attributed to its potent antioxidant, anti-inflammatory and anti-apoptotic activities. The induction of the antioxidant enzymes activities, down-regulation of the CYP2E1, iNOS, Caspase-3 and NF-κB expression, up-regulation of the trace elements concentration levels and activation of SIRT1 gene expression are responsible for the improvement of the antioxidant and anti-inflammatory status in the hepatic tissues and could be claimed to be the hepatoprotective mechanism of GSO. Copyright © 2016 Elsevier B.V. All rights reserved.

Antioxidant and hepatoprotective effects of Crataegus songarica methanol extract.

PubMed

Ganie, Showkat Ahmad; Dar, Tanveer Ali; Zargar, Bilal; Hamid, Rabia; Zargar, Ovais; Dar, Parvaiz Ahmad; Abeer, Shayaq Ul; Masood, Akbar; Amin, Shajrul; Zargar, Mohammad Afzal

2014-01-01

The protective activity of the methanolic extract of the Crataegus songarica leaves was investigated against CCl4- and paracetamol-induced liver damage. On folklore levels, this plant is popularly used to treat various toxicological diseases. We evaluated both in vitro and ex vivo antioxidant activity of C. songarica. At higher concentration of plant extract (700 µg/ml), 88.106% inhibition on DPPH radical scavenging activity was observed and reducing power of extract was increased in a concentration-dependent manner. We also observed its inhibition on Fe2+/ascorbic acid-induced lipid peroxidation on rat liver microsomes in vitro. In addition, C. songarica extract exhibited antioxidant effects on calf thymus DNA damage induced by Fenton reaction. Hepatotoxicity was induced by challenging the animals with CCl4 (1 ml/kg body weight, i.p.) and paracetamol (500 mg/kg body weight) and the extract was administered at three concentrations (100, 200, and 300 mg/kg body weight). Hepatoprotection was evaluated by determining the activities of liver function marker enzymes and antioxidant status of liver. Administration of CCl4 elevated the levels of liver function enzymes, SGOT, SGPT, and LDH. We also observed a dramatic increase in ALT, AST, bilirubin, and alkaline phosphatase levels in rats administered 500 mg/kg body weight of paracetamol. Decreased antioxidant defense system as glutathione (GSH), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR), glutathione-S-transferase (GST), and superoxide dismutase (SOD) were observed in rats treated with CCl4 and paracetamol. Pretreatment with the extract decreased the elevated serum GOT, GPT, LDH, bilirubin, and alkaline phosphatase activities and increased the antioxidant enzymes in a dose-dependent manner. Therefore, C. songarica methanol extract may be an effective hepatic protective agent and viable candidate for treating hepatic disorders and other oxidative stress-related diseases.

Modulatory role of Co-enzyme Q10 on methionine and choline deficient diet-induced non-alcoholic steatohepatitis (NASH) in albino rats.

PubMed

Saleh, Dalia O; Ahmed, Rania F; Amin, Mohamed M

2017-03-01

The present study aimed to evaluate the hepato-protective and neuro-protective activity of Co-enzyme Q10 (CoQ10) on non-alcoholic steatohepatitis (NASH) in albino rats induced by methionine and choline-deficient (MCD) diet. Rats were fed an MCD diet for 8 weeks to induce non-alcoholic steatohepatitis. CoQ10 (10 mg/(kg·day) -1 ) was orally administered for 2 consecutive weeks. Twenty-four hours after the last dose of the drug, the behavioral test, namely the activity cage test, was performed and the activity counts were recorded. Serum alanine transaminase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, total/direct bilirubin, and albumin were valued to assess liver function. Moreover, hepatic cytokines interleukin-6 as well as its modulator nuclear factor kappa-light-chain-enhancer of activated B cells were determined. In addition, brain biomarkers, viz ammonia, nitric oxide, and brain-derived neurotrophic factor (BDNF), were measured as they are reliable indices to assess brain damage. Histopathological and immunohistochemical examination of brain proliferating cell nuclear antigen in brain and liver tissues were also evaluated. Results revealed that MCD-induced NASH showed impairment in the liver functions with an increase in the liver inflammatory markers. Moreover, NASH resulted in pronounced brain dysfunction as evidenced by hyper-locomotor activity, a decrease in the BDNF level, as well as an increase in the brain nitric oxide and ammonia contents. Oral treatment of MCD-diet-fed rats with CoQ10 for 14 days showed a marked improvement in all the assigned parameters. Finally, it can be concluded that CoQ10 has a hepatoprotective and neuroprotective role in MCD-diet-induced NASH in rats.

Guajavadimer A, a Dimeric Caryophyllene-Derived Meroterpenoid with a New Carbon Skeleton from the Leaves of Psidium guajava.

PubMed

Li, Chuang-Jun; Ma, Jie; Sun, Hua; Zhang, Dan; Zhang, Dong-Ming

2016-01-15

Guajavadimer A (1), a dimeric sesquiterpene-based meroterpenoid which possessed an unprecedented two caryophyllenes, a benzylphlorogulcinol, and a flavonone-fused complicated stereochemical skeleton, was isolated from the leaves of Psidium guajava L. Its structure and absolute configuration were elucidated on the basis of spectroscopic data and X-ray crystallography. Guajavadimer A (1) showed moderate hepatoprotective activity against N-acetyl-p-aminophenol (APAP)-induced toxicity in HepG2 cells.

Glycyrrhetinic acid suppressed NF-κB activation in TNF-α-induced hepatocytes.

PubMed

Chen, Hong-Jhang; Kang, Shih-Pei; Lee, I-Jung; Lin, Yun-Lian

2014-01-22

Tumor necrosis factor-alpha (TNF-α) is a crucial inflammatory cytokine when hepatocytes are damaged. Glycyrrhiza uralensis Fisch. (Chinese licorice) has been widely used in Chinese herbal prescriptions for the treatment of liver diseases and as a food additive. Nuclear factor-kappa B (NF-κB) reporter gene assay in TNF-α-induced HepG2 was used as a screening platform. IκBα phosphorylation and p65 translocation were measured by Western blotting, and nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) gene expression were further confirmed in rat primary hepatocytes. Results showed that TNF-α enhanced NF-κB activity was significantly attenuated by glycyrrhetinic acid in a concentration-dependent manner in the NF-κB reporter gene assay. Glycyrrhetinic acid decreased the gene expression of iNOS through inhibited IκBα phosphorylation and p65 translocation in protein level. Furthermore, NO production and iNOS expression were reduced by glycyrrhetinic acid in TNF-α-induced rat primary hepatocytes. These results suggest that glycyrrhetinic acid may provide hepatoprotection against chronic liver inflammation through attenuating NF-κB activation to alleviate the inflammation.

Protective role of polyphenols from Bauhinia hookeri against carbon tetrachloride-induced hepato- and nephrotoxicity in mice.

PubMed

Al-Sayed, Eman; Abdel-Daim, Mohamed M; Kilany, Omnia E; Karonen, Maarit; Sinkkonen, Jari

2015-08-01

The hepatoprotective and nephroprotective activity of a polyphenol-rich fraction (BHPF) obtained from Bauhinia hookeri was investigated against CCl4-induced acute hepatorenal toxicity in mice. BHPF was administered (100, 200 and 400 mg/kg/day) for 5 days, then CCl4 was administered. BHPF pretreatment significantly (p < 0.001) inhibited the CCl4-induced increase in ALT, AST, ALP, LDH, total bilirubin, cholesterol, creatinine, uric acid, urea and malondialdehyde in a dose-dependent manner. In contrast, BHPF pretreatment markedly increased the contents of glutathione and superoxide dismutase in the liver and kidney tissues, indicating the strong in vivo antioxidant activity of BHPF. Pretreatment with BHPF preserved the hepatic architecture and conferred marked protection against necrosis and ballooning degeneration. Pretreatment with BHPF reduced the inflammatory cell aggregation and degenerative changes in the lining epithelium of the kidney tubules. It can be concluded that BHPF has a remarkable hepato- and nephroprotective activity by enhancing the antioxidant defense status, reducing lipid peroxidation and protecting against the histopathological changes induced by CCl4 in the liver and kidney tissues.

Apitherapy products enhance the recovery of CCL4-induced hepatic damages in rats.

PubMed

Saral, Özlem; Yildiz, Oktay; Aliyazicioğlu, Rezzan; Yuluğ, Esin; Canpolat, Sinan; Öztürk, Ferhat; Kolayli, Sevgi

2016-01-05

Our objective was to identify the antioxidant properties of honeybee products from Turkey, chestnut honey, pollen, propolis, and royal jelly, and their hepatoprotective activity against CCl4-induced hepatic damage in rats. Animals were fed with honeybee products for 7 days following CCl4 injection. Development of liver damage and oxidative stress were monitored by measuring the activities of the enzymes alanine transaminase, aspartate transaminase, malondialdehyde, superoxide dismutase, and catalase. Antioxidant capacities of the bee products were identified using FRAP and DPPH assays, as well as by measuring total phenolic and flavonoid contents. The antioxidant activities of the honeybee products were highest in propolis, followed, in order, by pollen, honey, and royal jelly. Despite their different levels of antioxidant capacity, their roles in the prevention of liver damage induced by CCl4 were very similar, which can be explained through their bioavailability to the treated animals. Our results suggest that honey, propolis, pollen, and royal jelly significantly enhanced the healing of CCl4-induced liver damage, partially due to their antioxidant properties and bioavailability.

Protective effect of boric acid against carbon tetrachloride-induced hepatotoxicity in mice.

PubMed

Ince, Sinan; Keles, Hikmet; Erdogan, Metin; Hazman, Omer; Kucukkurt, Ismail

2012-07-01

The protective effect of boric acid against liver damage was evaluated by its attenuation of carbon tetrachloride (CCl(4))-induced hepatotoxicity in mice. Male albino mice were treated intraperitoneally (i.p.) with boric acid (50, 100, and 200 mg/kg) or silymarin daily for 7 days and received 0.2% CCl(4) in olive oil (10 mL/kg, i.p.) on day 7. Results showed that administration of boric acid significantly reduced the elevation in serum levels of aspartate aminotransferase, alkaline phosphatase, alanine aminotransferase, and the level of malondialdehyde in the liver that were induced by CCl(4) in mice. Boric acid treatment significantly increased glutathione content, as well as the activities of superoxide dismutase and catalase in the liver. Boric acid treatment improved the catalytic activity of cytochrome P450 2E1 and maintained activation of nuclear factor kappa light-chain enhancer of activated B cell gene expression, with no effect on inducible nitric oxide synthase gene expression in the livers of mice. Histopathologically, clear decreases in the severity of CCl(4)-induced lesions were observed, particularly at high boric acid concentrations. Results suggest that boric acid exhibits potent hepatoprotective effects on CCl(4)-induced liver damage in mice, likely the result of both the increase in antioxidant-defense system activity and the inhibition of lipid peroxidation.

Taurine zinc solid dispersions attenuate doxorubicin-induced hepatotoxicity and cardiotoxicity in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yu; Mei, Xueting; Yuan, Jingquan

2015-11-15

The clinical efficacy of anthracycline anti-neoplastic agents is limited by cardiac and hepatic toxicities. The aim of this study was to assess the hepatoprotective and cardioprotective effects of taurine zinc solid dispersions, which is a newly-synthesized taurine zinc compound, against doxorubicin-induced toxicity in Sprague–Dawley rats intraperitoneally injected with doxorubicin hydrochloride (3 mg/kg) three times a week (seven injections) over 28 days. Hemodynamic parameters, levels of liver toxicity markers and oxidative stress were assessed. Taurine zinc significantly attenuated the reductions in blood pressure, left ventricular pressure and ± dp/dtmax, increases in serum alanine aminotransferase and aspartate aminotransferase activities, and reductions inmore » serum Zn{sup 2+} and albumin levels (P < 0.05 or 0.01) induced by doxorubicin. In rats treated with doxorubicin, taurine zinc dose-dependently increased liver superoxide dismutase activity and glutathione concentration, and decreased malondialdehyde level (P < 0.01). qBase{sup +} was used to evaluate the stability of eight candidate reference genes for real-time quantitative reverse-transcription PCR. Taurine zinc dose-dependently increased liver heme oxygenase-1 and UDP-glucuronyl transferase mRNA and protein expression (P < 0.01). Western blotting demonstrated that taurine zinc inhibited c-Jun N-terminal kinase phosphorylation by upregulating dual-specificity phosphoprotein phosphatase-1. Additionally, taurine zinc inhibited cardiomyocyte apoptosis as there was decreased TUNEL/DAPI positivity and protein expression of caspase-3. These results indicate that taurine zinc solid dispersions prevent the side-effects of anthracycline-based anticancer therapy. The mechanisms might be associated with the enhancement of antioxidant defense system partly through activating transcription to synthesize endogenous phase II medicine enzymes and anti-apoptosis through inhibiting JNK phosphorylation. - Highlights: • Dissolution of taurine zinc complex can be increased by solid dispersions (SDs). • Taurine zinc SDs blocked doxorubicin-induced hepatotoxicity and cardiotoxicity. • Taurine zinc SDs can alleviate oxidative stress and dampen JNK phosphorylation. • Taurine zinc SDs increased the expression of UGT, HO-1 at mRNA and protein level. • Taurine zinc SDs revealed greater hepatoprotective effects than silymarin.« less

Antioxidant activity of the oyster mushroom, Pleurotus ostreatus, on CCl(4)-induced liver injury in rats.

PubMed

Jayakumar, T; Ramesh, E; Geraldine, P

2006-12-01

This study was undertaken to investigate the putative antioxidant activity of the oyster mushroom Pleurotus ostreatus on CCl(4)-induced liver damage in male Wistar rats. Intraperitoneal administration of CCl(4) (2ml/kg) to rats for 4 days resulted in significantly elevated (p<0.05) serum levels of glutamic oxaloacetic transaminase (SGOT), glutamic pyruvate transaminase (SGPT) and alkaline phosphatase (SALP) compared to controls. In the liver, significantly elevated levels (p<0.05) of malondialdehyde (MDA) and lowered levels (p<0.05) of reduced glutathione (GSH) were observed following CCl(4) administration. Quantitative and qualitative analysis of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (Gpx) revealed lower activities of these antioxidant enzymes in the liver of CCl(4)-administered rats. An analysis of the isozyme pattern of these enzymes revealed variations in relative concentration presumably due to hepatotoxicity. When rats with CCl(4)-induced hepatotoxicity were treated with the extract of P. ostreatus, the serum SGOT, SGPT and SALP levels reverted to near normal, while the hepatic concentration of GSH, CAT, SOD and Gpx were significantly increased (p<0.05) and that of MDA significantly (p<0.05) lowered, when compared to CCl(4)-exposed untreated rats. Histopathological studies confirmed the hepatoprotective effect conferred by the extract of P. ostreatus. These results suggest that an extract of P. ostreatus is able to significantly alleviate the hepatotoxicity induced by CCl(4) in the rat.

Hepatoprotective Effects of Corilagin Following Hemorrhagic Shock are Through Akt-Dependent Pathway

PubMed Central

Liu, Fu-Chao; Chaudry, Irshad H.; Yu, Huang-Ping

2017-01-01

ABSTRACT Corilagin, a component of Phyllanthus urinaria extract, possesses antioxidant, thrombolytic, antiatherogenic, and hepatoprotective properties, but the mechanism underlying these effects remains unclear. Previous studies showed that the Akt (protein kinase B) signaling pathway exerts anti-inflammatory and organ protective effects. The aim of this study was to investigate the mechanism of action of corilagin and determine whether these effects are mediated through the Akt-dependent pathway in a trauma-hemorrhagic shock-induced liver injury rodent model. Hemorrhagic shock was induced in male Sprague–Dawley rats; mean blood pressure was maintained at 35 mm Hg to 40 mm Hg for 90 min, followed by fluid resuscitation. During resuscitation, three doses of corilagin alone (1 mg/kg, 5 mg/kg, or 10 mg/kg, intravenously) were administered. Furthermore, a single dose of corilagin (5 mg/kg) with and without Wortmannin (1 mg/kg, PI3K inhibitor), Wortmannin alone, or vehicle was administered. Twenty-four hours after resuscitation, plasma alanine aminotransferase and aspartate aminotransferase concentration and hepatic parameters were measured. One-way ANOVA was used for statistical analysis. Hepatic myeloperoxidase activity and the concentrations of plasma alanine aminotransferase and aspartate aminotransferase, interleukin-6, tumor necrosis factor-α, intercellular adhesion molecule-1, and cytokine-induced neutrophil chemoattractant-1 (CINC-1) and CINC-3 increased following hemorrhagic shock. These parameters were significantly attenuated in corilagin-treated rats following hemorrhagic shock. Hepatic phospho-Akt expression was also higher in corilagin-treated rats than in vehicle-treated rats. The elevation of phospho-Akt was abolished by combined treatment with Wortmannin and corilagin. Our results suggest that corilagin exerts its protective effects on hemorrhagic shock-induced liver injury, at least, via the Akt-dependent pathway. PMID:27559697

Protective effects of Lycium barbarum polysaccharides against carbon tetrachloride-induced hepatotoxicity in precision-cut liver slices in vitro and in vivo in common carp (Cyprinus carpio L.).

PubMed

Liu, Yingjuan; Cao, Liping; Du, Jinliang; Jia, Rui; Wang, Jiahao; Xu, Pao; Yin, Guojun

2015-03-01

The protective effects of Lycium barbarum polysaccharides (LBPs) against carbon tetrachloride-induced hepatotoxicity in common carp were investigated in vitro and in vivo. Precision-cut liver slices (PCLSs) were employed as an in vitro model system. LBPs (0.1, 0.3 and 0.6 mg/ml) was added to PCLSs culture system before (pre-treatment), after (post-treatment) and both before and after (pre- and post-treatment) the exposure of PCLSs to 12 mM CCl4. The supernatants and PCLSs were collected for biochemical analyses. Results showed that LBPs inhibited the elevations of the marker enzymes (GOT, GPT, LDH and AKP) and MDA induced by CCl4 in all LBPs treatments and it also enhanced the suppressed antioxidant enzymes (SOD, CAT, GSH-Px, GST) and GSH, in the pre-treatment and pre- and post-treatment. In vivo, fish were fed diets containing LBPs at 0.1, 0.5 and 1% for 60 d before an intraperitoneal injection of 30% CCl4 in olive oil at a volume of 0.05 ml/10 g body weight. At 72 h post-injection, blood and liver samples were taken for biochemical analyses. Results showed that LBPs at 0.5 and 1% significantly reduced the levels of GOT, GPT and LDH in the serum; the decreases of the antioxidant enzymes and the increase of MDA in the liver tissue were inhibited markedly. Moreover, LBPs even at lower concentration exerted a potent DPPH scavenging activity. Overall results prove the hepatoprotective and antioxidant effects of LBPs and support the use of LBPs as a hepatoprotective agent in fish. Copyright © 2015 Elsevier Inc. All rights reserved.

Consumption of Goats’ Milk Protects Mice From Carbon Tetrachloride-Induced Acute Hepatic Injury and Improves the Associated Gut Microbiota Imbalance

PubMed Central

Zhang, Jiachao; Wang, Zhaoxia; Huo, Dongxue; Shao, Yuyu

2018-01-01

Drugs used to treat liver diseases have serious side effects; it is important to search for safe functional foods with hepatoprotective functions and few side effects. In this study, potential hepatoprotective effects of goats’ milk and cows’ milk on mice with CCl4-induced acute hepatic injury were evaluated. We also elucidated the role of goats’ and cows’ milk on the regulation of CCl4-induced gut microbiota imbalance. In mice with liver damage induced by CCl4, administration of goats’ milk for 7 days prior to injection of CCl4 had beneficial effects on the indicators of liver damage within 1 day: the area of liver necrosis was small; activity of alanine transaminase (ALT) and aspartate transaminase (AST) and expression of the genes CYP2E1 and TNF-α were lower than that of model group of mice. By 7 days after CCl4 injection, there were no significant differences in liver damage indicators (ALT, AST, malondialdehyde, superoxide dismutase, and glutathione) between the goats’ milk group, which continued to receive goats’ milk, and the untreated control group of mice showing that goats’ milk continued to protect against liver damage. Throughout the entire experiment, the community of gut microbes from mice in the goats’ milk treatment was more similar to the untreated control group than to the cows’ milk group and the model group, indicating that intake of goats’ milk prior and post-CCl4 injection effectively prevented and alleviated the intestinal microbial disorder that caused by CCl4 in mice. Our research suggests that goats’ milk could be developed as a potential functional food to prevent/protect against liver injury. PMID:29867999

Cistanches Herba: An overview of its chemistry, pharmacology, and pharmacokinetics property.

PubMed

Fu, Zhifei; Fan, Xiang; Wang, Xiaoying; Gao, Xiumei

2018-06-12

Cistanches Herba is an Orobanchaceae parasitic plant. As a commonly used Traditional Chinese Medicine (TCM), its traditional functions include treating kidney deficiency, impotence, female infertility and senile constipation. Chemical analysis of Cistanches Herba revealed that phenylethanoid glycosides, iridoids, lignans, oligosaccharides, and polysaccharides were the main constituents. Pharmacological studies demonstrated that Cistanches Herba exhibited neuroprotective, immunomodulatory, hormonal balancing, anti-fatigue, anti-inflammatory, hepatoprotection, anti-oxidative, anti-bacterial, anti-viral, and anti-tumor effects, etc. The aim of this review is to provide updated, comprehensive and categorized information on the phytochemistry, pharmacological research and pharmacokinetics studies of the major constituents of Cistanches Herba. The literature search was conducted by systematic searching multiple electronic databases including SciFinder, ISI Web of Science, PubMed, Google Scholar and CNKI. Information was also collected from journals, local magazines, books, monographs. To date, more than 100 compounds have been isolated from this genus, include phenylethanoid glycosides, carbohydrates, lignans, iridoids, etc. The crude extracts and isolated compounds have exhibited a wide range of in vitro and in vivo pharmacologic effects, such as neuroprotective, immunomodulatory, anti-inflammatory, hepatoprotection, anti-oxidative, anti-bacterial, and anti-tumor effects. The phenylethanoid glycosides, echinacoside and acteoside have attracted the most attention for their significantly neuropharmacology effects. Pharmacokinetic studies of echinacoside and acteoside also have also been summarized. Phenylethanoid glycosides have demonstrated wide pharmacological actions and have great clinical value if challenges such as poor bioavailability, fast and extensive metabolism are addressed. Apart from phenylethanoid glycosides, other constituents of Cistanches Herba, their pharmacological activities and underlying mechanisms are also need to be studied further. Copyright © 2017. Published by Elsevier B.V.

The lipid lowering drug lovastatin protects against doxorubicin-induced hepatotoxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Henninger, Christian; Institute of Toxicology, University Duesseldorf, Medical Faculty, Universitätsstrasse 1, D-40225 Duesseldorf; Huelsenbeck, Johannes

2012-05-15

Liver is the main detoxifying organ and therefore the target of high concentrations of genotoxic compounds, such as environmental carcinogens and anticancer drugs. Here, we investigated the usefulness of lovastatin, which is nowadays widely used for lipid lowering purpose, as a hepatoprotective drug following the administration of the anthracycline derivative doxorubicin in vivo. To this end, BALB/c mice were exposed to either a single high dose or three consecutive low doses of doxorubicin. Acute and subacute hepatotoxicities were analyzed with or without lovastatin co-treatment. Lovastatin protected the liver against doxorubicin-induced acute pro-inflammatory and pro-fibrotic stress responses as indicated by anmore » attenuated mRNA expression of tumor necrosis factor alpha (TNFα) and connective tissue growth factor (CTGF), respectively. Hepatoprotection by lovastatin was due to a reduced induction of DNA damage following doxorubicin treatment. The statin also mitigated subacute anthracycline-provoked hepatotoxicity as shown on the level of doxorubicin- and epirubicin-stimulated CTGF mRNA expression as well as histopathologically detectable fibrosis and serum concentration of marker enzymes of hepatotoxicity (GPT/GLDH). Kidney damage following doxorubicin exposure was not detectable under our experimental conditions. Moreover, lovastatin showed multiple inhibitory effects on doxorubicin-triggered hepatic expression of genes involved in oxidative stress response, drug transport, DNA repair, cell cycle progression and cell death. Doxorubicin also stimulated the formation of ceramides. Ceramide production, however, was not blocked by lovastatin, indicating that hepatoprotection by lovastatin is independent of the sphingolipid metabolism. Overall, the data show that lovastatin is hepatoprotective following genotoxic stress induced by anthracyclines. Based on the data, we hypothesize that statins might be suitable to lower hepatic injury following anthracycline-based anticancer therapy. -- Highlights: ► Normal tissue damage is the therapy limiting side effect of anthracyclines. ► The effect of lovastatin on doxorubicin-induced hepatic damage was analyzed in vivo. ► Lovastatin protects the liver against DNA damage induced by doxorubicin. ► Lovastatin protects against acute and subacute doxorubicin-induced hepatotoxicity. ► Hepatoprotection by lovastatin is independent of the shingolipid metabolism.« less

Protective Effect of Free and Bound Polyphenol Extracts from Ginger (Zingiber officinale Roscoe) on the Hepatic Antioxidant and Some Carbohydrate Metabolizing Enzymes of Streptozotocin-Induced Diabetic Rats

PubMed Central

Kazeem, Mutiu Idowu; Akanji, Musbau Adewunmi; Yakubu, Musa Toyin; Ashafa, Anofi Omotayo Tom

2013-01-01

This study investigated the hepatoprotective effects of polyphenols from Zingiber officinale on streptozotocin-induced diabetic rats by assessing liver antioxidant enzymes, carbohydrate-metabolizing enzymes and liver function indices. Initial oral glucose tolerance test was conducted using 125 mg/kg, 250 mg/kg, and 500 mg/kg body weight of both free and bound polyphenols from Z. officinale. 28 day daily oral administration of 500 mg/kg body weight of free and bound polyphenols from Z. officinale to streptozotocin-induced (50 mg/kg) diabetic rats significantly reduced (P < 0.05) the fasting blood glucose compared to control groups. There was significant increase (P < 0.05) in the antioxidant enzymes activities in the animals treated with both polyphenols. Similarly, the polyphenols normalised the activities of some carbohydrate metabolic enzymes (hexokinase and phosphofructokinase) in the liver of the rats treated with it and significantly reduced (P < 0.05) the activities of liver function enzymes. The results from the present study have shown that both free and bound polyphenols from Z. officinale especially the free polyphenol could ameliorate liver disorders caused by diabetes mellitus in rats. This further validates the use of this species as medicinal herb and spice by the larger population of Nigerians. PMID:24367390

Protective Effect of Free and Bound Polyphenol Extracts from Ginger (Zingiber officinale Roscoe) on the Hepatic Antioxidant and Some Carbohydrate Metabolizing Enzymes of Streptozotocin-Induced Diabetic Rats.

PubMed

Kazeem, Mutiu Idowu; Akanji, Musbau Adewunmi; Yakubu, Musa Toyin; Ashafa, Anofi Omotayo Tom

2013-01-01

This study investigated the hepatoprotective effects of polyphenols from Zingiber officinale on streptozotocin-induced diabetic rats by assessing liver antioxidant enzymes, carbohydrate-metabolizing enzymes and liver function indices. Initial oral glucose tolerance test was conducted using 125 mg/kg, 250 mg/kg, and 500 mg/kg body weight of both free and bound polyphenols from Z. officinale. 28 day daily oral administration of 500 mg/kg body weight of free and bound polyphenols from Z. officinale to streptozotocin-induced (50 mg/kg) diabetic rats significantly reduced (P < 0.05) the fasting blood glucose compared to control groups. There was significant increase (P < 0.05) in the antioxidant enzymes activities in the animals treated with both polyphenols. Similarly, the polyphenols normalised the activities of some carbohydrate metabolic enzymes (hexokinase and phosphofructokinase) in the liver of the rats treated with it and significantly reduced (P < 0.05) the activities of liver function enzymes. The results from the present study have shown that both free and bound polyphenols from Z. officinale especially the free polyphenol could ameliorate liver disorders caused by diabetes mellitus in rats. This further validates the use of this species as medicinal herb and spice by the larger population of Nigerians.

Antioxidant, Hepatoprotective Potential and Chemical Profiling of Propolis Ethanolic Extract from Kashmir Himalaya Region Using UHPLC-DAD-QToF-MS

PubMed Central

Wali, Adil F.; Avula, Bharathi; Ali, Zulfiqar; Khan, Ikhlas A.; Mushtaq, Ahlam; Rehman, Muneeb U.; Akbar, Seema; Masoodi, Mubashir Hussain

2015-01-01

The aim of this study was to examine hepatoprotective effect of ethanolic extract of propolis (KPEt) from Kashmir Himalaya against isoniazid and rifampicin (INH-RIF) induced liver damage in rats. Hepatic cellular injury was initiated by administration of INH-RIF combination (100 mg/kg) intraperitoneal (i.p.) injection for 14 days. We report the protective effects of KPEt against INH-RIF induced liver oxidative stress, inflammation, and enzymatic and nonenzymatic antioxidants. Oral administration of KPEt at both doses (200 and 400 mg/kg body weight) distinctly restricted all modulating oxidative liver injury markers and resulted in the attenuation of INH-RIF arbitrated damage. The free radical scavenging activity of KPEt was evaluated by DPPH, nitric oxide, and superoxide radical scavenging assay. The components present in KPEt identified by ultra high performance liquid chromatography diode array detector time of flight-mass spectroscopy (UHPLC-DAD-QToF-MS) were found to be flavonoids and phenolic acids. The protective efficacy of KPEt is possibly because of free radical scavenging and antioxidant property resulting from the presence of flavonoids and phenolic acids. PMID:26539487

Purification, Preliminary Characterization and Hepatoprotective Effects of Polysaccharides from Dandelion Root.

PubMed

Cai, Liangliang; Wan, Dongwei; Yi, Fanglian; Luan, Libiao

2017-08-25

In this study, purification, preliminary characterization and hepatoprotective effects of water-soluble polysaccharides from dandelion root (DRP) were investigated. Two polysaccharides, DRP1 and DRP2, were isolated from DRP. The two polysaccharides were α-type polysaccharides and didn't contain protein. DRP1, with a molecular weight of 5695 Da, was composed of glucose, galactose and arabinose, whereas DRP2, with molecular weight of 8882 Da, was composed of rhamnose, galacturonic acid, glucose, galactose and arabinose. The backbone of DRP1 was mainly composed of (1→6)-linked-α-d-Glc and (1→3,4)-linked-α-d-Glc. DRP2 was mainly composed of (1→)-linked-α-d-Ara and (1→)-linked-α-d-Glc. A proof-of-concept study was performed to assess the therapeutic potential of DRP1 and DRP2 in a mouse model that mimics acetaminophen (APAP) -induced liver injury (AILI) in humans. The present study shows DRP1 and DRP2 could protect the liver from APAP-induced hepatic injury by activating the Nrf2-Keap1 pathway. These conclusions demonstrate that the DRP1 and DRP2 might be suitable as functional foods and natural drugs in preventing APAP-induced liver injury.

Phenolic compounds analysis, antioxidant, and hepatoprotective effects of Periploca angustifolia extract on cadmium-induced oxidative damage in HepG2 cell line and rats.

PubMed

Athmouni, Khaled; Belhaj, Dalel; Mkadmini Hammi, Khaoula; El Feki, Abdelfattah; Ayadi, Habib

2017-11-20

A total of five components (Catechin, Caffeic acid, Ferulic acid, Rosmarinic acid, and Amentoflavone) were identified in Periploca angustifolia leaf methanolic extract. This extract did not cause any cytotoxic effect on HepG2 cell line within the range of concentrations tested (0-400 µg mL -1 ). Thus, pre-treatment with 100 µg mL -1 of P. angustifolia leaf methanolic extract (PAE) significantly (p < .05) protective HepG2 cells against cytotoxicity induced by cadmium exposure. However, Cd-intoxication significantly (p < .05) increased alanine and aspartate amino transferases serum activities (ALT and AST) and bilirubin content by 1.85-, 1.13-, and 3.55-fold, respectively. The levels of hepatic antioxidant parameters including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were significantly (p < .05) decreased in Cd-intoxicated rats with concomitant enhancement of lipid peroxidation. Our results showed that P. angustifolia leaf methanolic extract can induce antioxidant effects and also exerts beneficial effects for the treatment of Cd-induced hepatotoxicity.

Evaluation of Sedative and Hypnotic Activity of Ethanolic Extract of Scoparia dulcis Linn.

PubMed Central

Moniruzzaman, Md.; Atikur Rahman, Md.; Ferdous, Afia

2015-01-01

Scoparia dulcis Linn. (SD) is a perennial herb that has been well studied for its antioxidant, anti-inflammatory, antidiabetic, and hepatoprotective effects. However, scientific information on SD regarding the neuropharmacological effect is limited. This study evaluated the sedative and hypnotic effect of the ethanolic extract of whole plants of Scoparia dulcis (EESD). For this purpose, the whole plants of S. dulcis were extracted with ethanol following maceration process and tested for the presence of phytochemical constituents. The sedative and hypnotic activity were then investigated using hole cross, open field, hole-board, rota-rod, and thiopental sodium-induced sleeping time determination tests in mice at the doses of 50, 100, and 200 mg/kg of EESD. Diazepam at the dose of 1 mg/kg was used as a reference drug in all the experiments. We found that EESD produced a significant dose-dependent inhibition of locomotor activity of mice both in hole cross and open field tests (P < 0.05). Besides, it also decreased rota-rod performances and the number of head dips in hole-board test. Furthermore, EESD significantly decreased the induction time to sleep and prolonged the duration of sleeping, induced by thiopental sodium. Taken together, our study suggests that EESD may possess sedative principles with potent hypnotic properties. PMID:25861372

Evaluation of Sedative and Hypnotic Activity of Ethanolic Extract of Scoparia dulcis Linn.

PubMed

Moniruzzaman, Md; Atikur Rahman, Md; Ferdous, Afia

2015-01-01

Scoparia dulcis Linn. (SD) is a perennial herb that has been well studied for its antioxidant, anti-inflammatory, antidiabetic, and hepatoprotective effects. However, scientific information on SD regarding the neuropharmacological effect is limited. This study evaluated the sedative and hypnotic effect of the ethanolic extract of whole plants of Scoparia dulcis (EESD). For this purpose, the whole plants of S. dulcis were extracted with ethanol following maceration process and tested for the presence of phytochemical constituents. The sedative and hypnotic activity were then investigated using hole cross, open field, hole-board, rota-rod, and thiopental sodium-induced sleeping time determination tests in mice at the doses of 50, 100, and 200 mg/kg of EESD. Diazepam at the dose of 1 mg/kg was used as a reference drug in all the experiments. We found that EESD produced a significant dose-dependent inhibition of locomotor activity of mice both in hole cross and open field tests (P < 0.05). Besides, it also decreased rota-rod performances and the number of head dips in hole-board test. Furthermore, EESD significantly decreased the induction time to sleep and prolonged the duration of sleeping, induced by thiopental sodium. Taken together, our study suggests that EESD may possess sedative principles with potent hypnotic properties.

Anticancer activity of Cynodon dactylon L. root extract against diethyl nitrosamine induced hepatic carcinoma

PubMed Central

Kowsalya, R.; Kaliaperumal, Jagatheesh; Vaishnavi, M.; Namasivayam, Elangovan

2015-01-01

Background: Hepatocellular carcinoma is one of the most common cancers and a lethal disease. In view of the limited treatment and a grave prognosis of liver cancer, preventive control has been emphasized. Materials and Methods: The methanolic extract of roots of Cynodon dactylon was screened for its hepato-protective activity in diethyl nitrosamine (DEN) induced liver cancer in Swiss albino mice. The plant extract at a dose of 50 mg/kg was administered orally once a week, up to 30 days after DEN administration. The animals were sacrificed; blood sample and liver tissue were collected and used for enzyme assay such as, asparatate amino transferase (AST), alanine aminotransferase (ALT), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST). The liver marker enzymes AST and ALT produced significant results in the protective action. Results: The antioxidant enzyme assay results concerning the improved activity of GPx, GST and CAT. These results concluded that enhanced levels of antioxidant enzyme and reduced amount of serum amino transaminase, which are suggested to be the major mechanisms of C. dactylon root extract in protecting the mice from hepatocarcinoma induced by DEN. These biochemical observations were supplemented by histopathological examination of liver sections. Conclusion: The methanolic extract of C. dactylon possesses significant anticancer properties PMID:25992348

Anticancer activity of Cynodon dactylon L. root extract against diethyl nitrosamine induced hepatic carcinoma.

PubMed

Kowsalya, R; Kaliaperumal, Jagatheesh; Vaishnavi, M; Namasivayam, Elangovan

2015-01-01

Hepatocellular carcinoma is one of the most common cancers and a lethal disease. In view of the limited treatment and a grave prognosis of liver cancer, preventive control has been emphasized. The methanolic extract of roots of Cynodon dactylon was screened for its hepato-protective activity in diethyl nitrosamine (DEN) induced liver cancer in Swiss albino mice. The plant extract at a dose of 50 mg/kg was administered orally once a week, up to 30 days after DEN administration. The animals were sacrificed; blood sample and liver tissue were collected and used for enzyme assay such as, asparatate amino transferase (AST), alanine aminotransferase (ALT), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST). The liver marker enzymes AST and ALT produced significant results in the protective action. The antioxidant enzyme assay results concerning the improved activity of GPx, GST and CAT. These results concluded that enhanced levels of antioxidant enzyme and reduced amount of serum amino transaminase, which are suggested to be the major mechanisms of C. dactylon root extract in protecting the mice from hepatocarcinoma induced by DEN. These biochemical observations were supplemented by histopathological examination of liver sections. The methanolic extract of C. dactylon possesses significant anticancer properties.

Spondias mombin L. (Anacardiaceae) enhances detoxification of hepatic and macromolecular oxidants in acetaminophen-intoxicated rats.

PubMed

Saheed, Sabiu; Taofik, Sunmonu Olatunde; Oladipo, Ajani Emmanuel; Tom, Ashafa Anofi Omotayo

2017-11-01

Oxidative stress is a common pathological condition associated with drug-induced hepatotoxicity. This study investigated Spondias mombin L. aqueous leaf extract on reactive oxygen species and acetaminophen-mediated oxidative onslaught in rats' hepatocytes. Hepatotoxic rats were orally administered with the extract and vitamin C for 4 weeks. The extract dose-dependently scavenged DPPH, hydrogen peroxide and hydroxyl radicals, with IC 50 values of 0.13, 0.66, and 0.64 mg/mL, and corresponding % inhibitions of 89, 80, and 90%, respectively at 1.0 mg/mL. Ferric ion was also significantly reduced. The marked (p<0.05) increases in the activities of alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase were reduced following treatment with the extract. The extract also significantly (p<0.05) induced the activities of antioxidant enzymes. These inductions reversed the acetaminophen-enhanced reduction in the specific activities of these enzymes as well as attenuated the observed elevated concentrations of autooxidized products and rived DNA in the acetaminophen-intoxicated animals. The observed effects competed with those of vitamin C and are suggestive of hepatoprotective and antioxidative attributes of the extract. Overall, the data from the present findings suggest that S. Mombin aqueous leaf extract is capable of ameliorating acetaminophen-mediated oxidative hepatic damage via enhancement of antioxidant defense systems.

Diet Supplementation with Allicin Protects against Alcoholic Fatty Liver Disease in Mice by Improving Anti-inflammation and Antioxidative Functions.

PubMed

Panyod, Suraphan; Wu, Wei-Kai; Ho, Chi-Tang; Lu, Kuan-Hung; Liu, Chun-Ting; Chu, Yung-Lin; Lai, Yi-Syuan; Chen, Wei-Cheng; Lin, Yu-En; Lin, Shih-Hang; Sheen, Lee-Yan

2016-09-28

This study investigated the liver-protective effects of allicin, an active compound in fresh garlic, against alcoholic fatty liver disease (AFLD) and liver inflammation. Its effects were investigated in an AFLD model in male C57BL/6 mice, which were fed Lieber-DeCarli liquid diet containing ethanol. Allicin (5 and 20 mg/kg bw/day) was orally administered daily in the AFLD mice for 4 weeks. The results indicate that allicin promotes hepatoprotection by significantly reducing aspartate transaminase (AST) and alanine transaminase (ALT) levels (p < 0.05) in the plasma, which are key indicators of liver damage. Allicin reduced fat accumulation, increased glutathione and catalase levels, and decreased microsomal protein cytochrome P450 2E1 (CYP2E1) expression (p < 0.05) in the livers of the AFLD mice. Furthermore, allicin supplementation significantly decreased the levels of proinflammatory tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 and suppressed the expression of sterol regulatory element-binding protein-1 (SREBP-1) (p < 0.05). Additionally, it improved the hepatic alcohol dehydrogenase (ADH) activity (p < 0.05). Collectively, these findings demonstrate that allicin attenuates liver oxidative stress and inflammation.

Hepatoprotective and curative properties of Kombucha tea against carbon tetrachloride-induced toxicity.

PubMed

Murugesan, G S; Sathishkumar, M; Jayabalan, R; Binupriya, A R; Swaminathan, K; Yun, S E

2009-04-01

Kombucha tea (KT) is sugared black tea fermented with a symbiotic culture of acetic acid bacteria and yeasts, which is said to be tea fungus. KT is claimed to have various beneficial effects on human health, but there is very little scientific evidence available in the literature. In the present study, KT along with black tea (BT) and black tea manufactured with tea fungus enzymes (enzyme-processed tea, ET) was evaluated for hepatoprotective and curative properties against CCl4-induced toxicity, using male albino rats as an experimental model by analyzing aspartate transaminase, alanine transaminase, and alkaline phosphatase in plasma and malondialdehyde content in plasma and liver tissues. Histopathological analysis of liver tissue was also included. Results showed that BT, ET, and KT have the potential to revert the CCl4-induced hepatotoxicity. Among the three types of teas tried, KT was found to be more efficient than BT and ET. Antioxidant molecules produced during the fermentation period could be the reason for the efficient hepatoprotective and curative properties of KT against CCI4-induced hepatotoxicity.

Advance on the Flavonoid C-glycosides and Health Benefits.

PubMed

Xiao, Jianbo; Capanoglu, Esra; Jassbi, Amir Reza; Miron, Anca

2016-07-29

The dietary flavonoids, especially their glycosides, are the most vital phytochemicals in diets and are of great general interest due to their diverse bioactivity. Almost all natural flavonoids exist as their O-glycoside or C-glycoside forms in plants. The dietary flavonoid C-glycosides have received less attention than their corresponding O-glycosides. This review summarizes current knowledge regarding flavonoid C-glycosides and their influence on human health. Among the flavonoid C-glycosides, flavone C-glycosides, especially vitexin, isoorientin, orientin, isovitexin and their multiglycosides are more frequently mentioned than others. Flavonoid C-monoglycosides are poorly absorbed in human beings with very few metabolites in urine and blood and are deglycosylated and degraded by human intestinal bacteria in colon. However, flavonoid C-multiglycosides are absorbed unchanged in the intestine and distributed to other tissues. Flavonoid C-glycosides showed significant antioxidant activity, anticancer and antitumor activity, hepatoprotective activity, anti-inflammatory activity, anti-diabetes activity, antiviral activity, antibacterial and antifungal activity, and other biological effects. It looks like that the C-glycosylflavonoids in most cases showed higher antioxidant and anti-diabetes potential than their corresponding O-glycosylflavonoids and aglycones. However, there is a lack of in vivo data on the biological benefits of flavonoid C-glycosides. It is necessary to investigate more on how flavonoid C-glycosides prevent and handle the diseases.

Effect of infliximab on acute hepatic ischemia/reperfusion injury in rats.

PubMed

Yucel, Ahmet Fikret; Pergel, Ahmet; Aydin, Ibrahim; Alacam, Hasan; Karabicak, Ilhan; Kesicioglu, Tugrul; Tumkaya, Levent; Kalkan, Yildiray; Ozer, Ender; Arslan, Zakir; Sehitoglu, Ibrahim; Sahin, Dursun Ali

2015-01-01

This study aimed to investigate the hepatoprotective and antioxidant effects of infliximab (IFX) against liver ischemia/reperfusion (I/R) injury in rats. A total of 30 male Wistar albino rats were divided into three groups: sham, I/R, and I/R+IFX. IFX was given at a dose of 3 mg/kg for three days before I/R. Rat livers were subjected to 60 min of ischemia followed by 90 h of reperfusion. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), TNF-α, malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels were measured in the serum. The liver was removed to evaluate the histopathologic changes. The I/R group had a significant increase in AST, ALT, MDA, and TNF-α levels, and a decrease in GSH-Px activity compared with the sham group. The use of IFX significantly reduced the ALT, AST, MDA and TNF-α levels and significantly increased GSH-Px activity. IFX attenuated the histopathologic changes. IFX has a protective effect on liver I/R injury. This liver protective effect may be related to antioxidant and anti-TNF-α effects. We propose that, for the relief of liver injury subsequent to transplantation, liver resection, trauma, and shock, tentative treatments can be incorporated with IFX, which is already approved for clinical use.

Effect of infliximab on acute hepatic ischemia/reperfusion injury in rats

PubMed Central

Yucel, Ahmet Fikret; Pergel, Ahmet; Aydin, Ibrahim; Alacam, Hasan; Karabicak, Ilhan; Kesicioglu, Tugrul; Tumkaya, Levent; Kalkan, Yildiray; Ozer, Ender; Arslan, Zakir; Sehitoglu, Ibrahim; Sahin, Dursun Ali

2015-01-01

This study aimed to investigate the hepatoprotective and antioxidant effects of infliximab (IFX) against liver ischemia/reperfusion (I/R) injury in rats. A total of 30 male Wistar albino rats were divided into three groups: sham, I/R, and I/R+IFX. IFX was given at a dose of 3 mg/kg for three days before I/R. Rat livers were subjected to 60 min of ischemia followed by 90 h of reperfusion. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), TNF-α, malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels were measured in the serum. The liver was removed to evaluate the histopathologic changes. The I/R group had a significant increase in AST, ALT, MDA, and TNF-α levels, and a decrease in GSH-Px activity compared with the sham group. The use of IFX significantly reduced the ALT, AST, MDA and TNF-α levels and significantly increased GSH-Px activity. IFX attenuated the histopathologic changes. IFX has a protective effect on liver I/R injury. This liver protective effect may be related to antioxidant and anti-TNF-α effects. We propose that, for the relief of liver injury subsequent to transplantation, liver resection, trauma, and shock, tentative treatments can be incorporated with IFX, which is already approved for clinical use. PMID:26885068

Taraxacum official (dandelion) leaf extract alleviates high-fat diet-induced nonalcoholic fatty liver.

PubMed

Davaatseren, Munkhtugs; Hur, Haeng Jeon; Yang, Hye Jeong; Hwang, Jin-Taek; Park, Jae Ho; Kim, Hyun-Jin; Kim, Min Jung; Kwon, Dae Young; Sung, Mi Jeong

2013-08-01

The purpose of this study is to determine the protective effect of Taraxacum official (dandelion) leaf extract (DLE) on high-fat-diet (HFD)-induced hepatic steatosis, and elucidate the molecular mechanisms behind its effects. To determine the hepatoprotective effect of DLE, we fed C57BL/6 mice with normal chow diet (NCD), high-fat diet (HFD), HFD supplemented with 2g/kg DLE DLE (DL), and HFD supplemented with 5 g/kg DLE (DH). We found that the HFD supplemented by DLE dramatically reduced hepatic lipid accumulation compared to HFD alone. Body and liver weights of the DL and DH groups were significantly lesser than those of the HFD group, and DLE supplementation dramatically suppressed triglyceride (TG), total cholesterol (TC), insulin, fasting glucose level in serum, and Homeostatic Model Assessment Insulin Resistance (HOMA-IR) induced by HFD. In addition, DLE treatment significantly increased activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) in liver and muscle protein. DLE significantly suppressed lipid accumulation in the liver, reduced insulin resistance, and lipid in HFD-fed C57BL/6 mice via the AMPK pathway. These results indicate that the DLE may represent a promising approach for the prevention and treatment of obesity-related nonalcoholic fatty liver disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Investigation of the Hepatoprotective Effect of Prunus mume Sieb. et Zucc Extract in a Mouse Model of Alcoholic Liver Injury Through High-Resolution Metabolomics.

PubMed

Khan, Adnan; Pan, Jeong Hoon; Cho, Seongha; Lee, Sojung; Kim, Young Jun; Park, Youngja H

2017-08-01

This study aimed to identify the changes in the metabolomics profile of liver damage caused by alcohol consumption and verify the beneficial effect of Prunus mume Sieb. et Zucc extract (PME) in protection of alcohol-induced injury by attenuating the level of identified metabolites. Mice were treated with PME and saline or untreated once daily for 5 days, followed by alcohol injection. The plasma samples were analyzed using liquid chromatography-mass spectrometry-based high-resolution metabolomics followed by a multivariate statistical analysis using MetaboAnalyst 3.0 to obtain significantly expressed metabolites, using a false discovery rate threshold of q = 0.05. Metabolites were annotated using Metlin database and mapped through Kyoto Encyclopedia of Genes and Genomes (KEGG). Among 4999 total features, 101 features were significant among alcohol- and PME-treated mice groups. All the samples cluster showed a clear separation in the heat map, and the scores plot of orthogonal partial least squares-discriminant analysis (OPLS-DA) model discriminated the three groups. Phosphatidylcholine, Saikosaponin BK1, Ganoderiol I, and N-2-[4-(3,3-dimethylallyloxy) phenyl] ethylcinnamide were among the significant compounds with a low intensity in alcohol group compared to PME group, suggesting that these compounds have a relation in the development of PME's protective effect. The study confirms the hepatoprotective, antioxidant, and anti-inflammatory effects of PME against alcohol-induced liver steatosis, inflammation, and apoptosis.

Therapeutic potential and health benefits of Sargassum species

PubMed Central

Yende, Subhash R.; Harle, Uday N.; Chaugule, Bhupal B.

2014-01-01

Sargassum species are tropical and sub-tropical brown macroalgae (seaweed) of shallow marine meadow. These are nutritious and rich source of bioactive compounds such as vitamins, carotenoids, dietary fibers, proteins, and minerals. Also, many biologically active compounds like terpenoids, flavonoids, sterols, sulfated polysaccharides, polyphenols, sargaquinoic acids, sargachromenol, pheophytine were isolated from different Sargassum species. These isolated compounds exhibit diverse biological activities like analgesic, anti-inflammatory, antioxidant, neuroprotective, anti-microbial, anti-tumor, fibrinolytic, immune-modulatory, anti-coagulant, hepatoprotective, anti-viral activity etc., Hence, Sargassum species have great potential to be used in pharmaceutical and neutralceutical areas. This review paper explores the current knowledge of phytochemical, therapeutic potential, and health benefits of different species of genus Sargassum. PMID:24600190

Advances in the use of milk thistle (Silybum marianum).

PubMed

Post-White, Janice; Ladas, Elena J; Kelly, Kara M

2007-06-01

Milk thistle (Silybum marianum) is an herbal supplement used to treat liver and biliary disorders. Silymarin, a mixture of flavanoid complexes, is the active component that protects liver and kidney cells from toxic effects of drugs, including chemotherapy. Although milk thistle has not significantly altered the course of chronic liver disease, it has reduced liver enzyme levels and demonstrated anti-inflammatory and T cell-modulating effects. There is strong preclinical evidence for silymarin's hepatoprotective and anticarcinogenic effects, including inhibition of cancer cell growth in human prostate, skin, breast, and cervical cells. Milk thistle is considered safe and well-tolerated, with gastrointestinal upset, a mild laxative effect, and rare allergic reaction being the only adverse events reported when taken within the recommended dose range. More clinical trials of rigorous methodology, using standardized and well-defined products and dosages, are needed to evaluate the potential of silymarin against liver toxicity, chronic liver disease, and human cancers.

Comparative study on the hepatoprotection to heavy metals of Zingiber officinale

PubMed Central

Nwokocha, Chukwuemeka R.; Owu, Daniel U.; Nwokocha, Magdalene I.; Ufearo, Chibueze S.; Iwuala, Moses O. E.

2012-01-01

Context: Zingiber officinale (Zingiberaceae) is a herb used for culinary and therapeutic purposes due to its anti-inflammatory and antioxidant potentials. Objectives: We examined its protective ability against mercury (Hg), lead (Pb) and cadmium (Cd) accumulation in the liver. Materials & Methods: Ground Zingiber officinale (7%, w/w of feed) was administered to rats either at the same time with the exposure ofheavy metals (group 2), a week after exposure to heavy metals (group 3) or given a week before heavy metal exposure (group 4) for six weeks. Animals were exposed to either of Hg (10 ppm), Cd (200 ppm) and Pb (100 ppm) in drinking water. The heavy metal accumulations in the liver were determined using AAS. Results: Weight losses induced by these metals were not reversed by Zingiber officinale administration. There was a significant (P<0.01) increase in protection to Pb (97%) and Cd (63%) accumulation when compared to Hg (32%) at week 2. The protective ability was significantly (P<0.01) decreased at week 4 when compared to week 2 for Cd and Pb but not to Hg in groups 3 (50%) and 4 (52%). At week 6, hepatoprotection to Hg (44%) and Cd (85%) was significantly (P<0.01) different but not to Pb which was only significant (P<0.05) in week 2 of treatment for all groups. Discussion and Conclusion: Zingiber officinale affected the bioavailability, elimination and uptake of these metals in a time-dependent way with highest beneficial reducing effect to Cd followed by Hg and least protection to Pb in the liver. PMID:23225964

Comparative study on the hepatoprotection to heavy metals of Zingiber officinale.

PubMed

Nwokocha, Chukwuemeka R; Owu, Daniel U; Nwokocha, Magdalene I; Ufearo, Chibueze S; Iwuala, Moses O E

2012-10-01

Zingiber officinale (Zingiberaceae) is a herb used for culinary and therapeutic purposes due to its anti-inflammatory and antioxidant potentials. We examined its protective ability against mercury (Hg), lead (Pb) and cadmium (Cd) accumulation in the liver. MATERIALS #ENTITYSTARTX00026; Ground Zingiber officinale (7%, w/w of feed) was administered to rats either at the same time with the exposure ofheavy metals (group 2), a week after exposure to heavy metals (group 3) or given a week before heavy metal exposure (group 4) for six weeks. Animals were exposed to either of Hg (10 ppm), Cd (200 ppm) and Pb (100 ppm) in drinking water. The heavy metal accumulations in the liver were determined using AAS. Weight losses induced by these metals were not reversed by Zingiber officinale administration. There was a significant (P<0.01) increase in protection to Pb (97%) and Cd (63%) accumulation when compared to Hg (32%) at week 2. The protective ability was significantly (P<0.01) decreased at week 4 when compared to week 2 for Cd and Pb but not to Hg in groups 3 (50%) and 4 (52%). At week 6, hepatoprotection to Hg (44%) and Cd (85%) was significantly (P<0.01) different but not to Pb which was only significant (P<0.05) in week 2 of treatment for all groups. Zingiber officinale affected the bioavailability, elimination and uptake of these metals in a time-dependent way with highest beneficial reducing effect to Cd followed by Hg and least protection to Pb in the liver.

Hepatoprotective activity of bacoside A against N-nitrosodiethylamine-induced liver toxicity in adult rats.

PubMed

Janani, Panneerselvam; Sivakumari, Kanakarajan; Parthasarathy, Chandrakesan

2009-10-01

N-Nitrosodiethylamine (DEN) is a notorious carcinogen, present in many environmental factors. DEN induces oxidative stress and cellular injury due to enhanced generation of reactive oxygen species; free radical scavengers protect the membranes from DEN-induced damage. The present study was designed to evaluate the protective effect of bacoside A (the active principle isolated from Bacopa monniera Linn.) on carcinogen-induced damage in rat liver. Adult male albino rats were pretreated with 15 mg/kg body weight/day of bacoside A orally (for 14 days) and then intoxicated with single necrogenic dose of N-nitrosodiethylamine (200 mg/kg bodyweight, intraperitonially) and maintained for 7 days. The liver weight, lipid peroxidation (LPO), and activity of serum marker enzymes (aspartate transaminases, alanine transaminases, lactate dehydrogenase, alkaline phosphatase, and gamma-glutamyl transpeptidase) were markedly increased in carcinogen-administered rats, whereas the activities of marker enzymes were near normal in bacoside A-pretreated rats. Activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutatione-S-transferase, and reduced glutathione) in liver also decreased in carcinogen-administered rats, which were significantly elevated in bacoside A-pretreated rats. It is concluded that pretreatment of bacoside A prevents the elevation of LPO and activity of serum marker enzymes and maintains the antioxidant system and thus protects the rats from DEN-induced hepatotoxicity.

Involvement of catalase in the protective benefits of metformin in mice with oxidative liver injury.

PubMed

Dai, Jie; Liu, Mingwei; Ai, Qing; Lin, Ling; Wu, Kunwei; Deng, Xinyu; Jing, Yuping; Jia, Mengying; Wan, Jingyuan; Zhang, Li

2014-06-05

Metformin is a commonly used anti-diabetic drug with AMP-activated protein kinase (AMPK)-dependent hypoglycemic activities. Recent studies have revealed its anti-inflammatory and anti-oxidative properties. In the present study, the anti-oxidative potential of metformin and its potential mechanisms were investigated in a mouse model with carbon tetrachloride (CCl₂)-induced severe oxidative liver injury. Our results showed that treatment with metformin significantly attenuated CCl₂-induced elevation of serum aminotransferases and hepatic histological abnormalities. The alleviated liver injury was associated with decreased hepatic contents of oxidized glutathione (GSSG) and malondialdehyde (MDA). In addition, metformin treatment dose-dependently enhanced the activities of catalase (CAT) and decreased CCl₄-induced elevation of hepatic H₂O₂ levels, but it had no obvious effects on the protein level of CAT. We also found that metformin increased the level of phosphorylated AMP-activated protein kinase (AMPK), but treatment with AMPK activator AICAR had no obvious effects on CAT activity. A molecular docking analysis indicated that metformin might interact with CAT via hydrogen bonds. These data suggested that metformin effectively alleviated CCl₄-induced oxidative liver injury in mice and these hepatoprotective effects might be associated with CAT. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Study of Silymarin and Vitamin E Protective Effects on Silver Nanoparticle Toxicity on Mice Liver Primary Cell Culture.

PubMed

Faedmaleki, Firouz; Shirazi, Farshad H; Ejtemaeimehr, Shahram; Anjarani, Soghra; Salarian, Amir-Ahmad; Ahmadi Ashtiani, Hamidreza; Rastegar, Hossein

2016-02-01

Nanotechnology is a most promising field for generating new applications in medicine, although, only few nano products are currently in use for medical purposes. A most prominent nanoproduct is nanosilver. Nano-silver has biological properties which are significant for consumer products, food technology, textiles, and medical applications (e.g. wound care products, implantable medical devices, in diagnosis, drug delivery, and imaging). For their antibacterial activity, silver nanoparticles (Ag NPs) are largely used in various commercially available products. The use of nano-silver is becoming more and more widespread in medicine and related applications, and due to its increasing exposure, toxicological and environmental issues need to be raised. Cytotoxicity induced by silver nanoparticles (AgNPs) and the role that oxidative stress plays in this process were demonstrated in human hepatoma cells AgNPs agglomerated in the cytoplasm and nuclei of treated cells, and they induced intracellular oxidative stress. AgNP reduced ATP content of the cell and caused damage to mitochondria and increased production of reactive oxygen species (ROS) in a dose-dependent manner. Silymarin was known as a hepatoprotective agent that is used in the treatment of hepatic diseases including viral hepatitis, alcoholic liver diseases, Amanita mushroom poisoning, liver cirrhosis, toxic and drug-induced liver diseases. It promotes protein synthesis, helps in regenerating liver tissue, controls inflammation, enhances glucuronidation, and protects against glutathione depletion. Vitamin E is a well-known antioxidant and has hepatoprotective effect in liver diseases. In this study, we investigated the cytotoxic effects of Ag NPs on primary liver cells of mice. Cell viability (cytotoxicity) was examined with MTT assay after primary liver cells of mice exposure to AgNPs at 1, 10, 50, 100, 150, 200, 400 ppm for 24h. AgNPs caused a concentration- dependent decrease of cell viability (IC50 value = 121.7 ppm or µg/ml). Then the hepatoprotective effect of silymarin and vitamin E were experimented on silver nanoparticle toxicity on mice liver primary cell culture. The results showed that silymarin at 600 µg/ml and vitamin E at 2500 µmol/l have protective effects on silver nanoparticle toxicity on mice liver primary cell culture. Viability percentage of the primary liver cell of the mouse were exposed to silver nanoparticles at 121.7 ppm and co-treatment of silymarin, and vitamin E is more than viability percentage of the primary liver cell of the mouse were exposed to silver nanoparticles and silymarin or silver nanoparticles and vitamin E.

Beneficial effects of Lagenaria siceraria (Mol.) Standley fruit epicarp in animal models.

PubMed

Deshpande, J R; Choudhari, A A; Mishra, M R; Meghre, V S; Wadodkar, S G; Dorle, A K

2008-04-01

Lagenaria siceraria (Mol.) Standley fruit (bottle gourd), a commonly used vegetable in India is described as cardiotonic and as a general tonic in Ayurveda. Keeping in view the presence of free radical scavenging activity in L. siceraria and involvement of free radicals in the development of various disorders, present studies were designed to evaluate the ethanolic extract of L. siceraria fruit against the disorders where free radicals play a major role in pathogenesis. The extract was found effective as hepatoprotective, antioxidant, antihyperglycemic, immunomodulatory, antihyperlipidemic and cardiotonic agent. The results showed that the radical scavenging capacity of L. siceraria fruit may be responsible for various biological activities studied.

[Pharmaceutical and formulation aspects of Petroselinum crispum extract].

PubMed

Pápay, Zsófia Edit; Kósa, Annamária; Boldizsár, Imre; Ruszkai, Akos; Balogh, Emese; Klebovich, Imre; Antal, István

2012-01-01

Parsley (Petroselinum crispum L.) is a very popular spice and vegetable in Europe, it is widely spread and easy to grow. It's herb and fruits are known to be diuretic, smooth muscle relaxant and hepatoprotective. The most important identified active ingredients are flavonoids, cumarins and vitamin C. Apigenin and its glycosides are the main flavonoids in parsley, it can be found relatively large amounts in the leaves. The bioactive flavonoid apigenin has antiinflammatory, antioxidant and anticancer activities. The objectives of this study were the preparation and detemination of the apigenin content of the parsley extract and the formulation using inert pellets by layering the apigenin in fluid-bed process.

The medicinal and pharmaceutical importance of Dendrobium species.

PubMed

Teixeira da Silva, Jaime A; Ng, Tzi Bun

2017-03-01

Plants of the Dendrobium genus, one of the largest in the Orchidaceae, manifest a diversity of medicinal effects encompassing antiangiogenic, immunomodulating, antidiabetic, cataractogenesis-inhibiting, neuroprotective, hepatoprotective, anti-inflammatory, antiplatelet aggregation, antifungal, antibacterial, antiherpetic, antimalarial, aquaporin-5 stimulating, and hemagglutininating activities and also exert beneficial actions on colonic health and alleviate symptoms of hyperthyroidism. The active principles include a wide range of proteinaceous and non-proteinaceous molecules. This mini-review discusses the latest advances in what is known about the medicinal and pharmaceutical properties of members of the Dendrobium genus and explores how biotechnology can serve as a conduit to mass propagate valuable germplasm for sustainable exploration for the pharmaceutical industry.

Pinelliae Rhizoma Praeparatum Involved in the Regulation of Bile Acids Metabolism in Hepatic Injury.

PubMed

Guo, Shun; Zhang, Song; Liu, Linna; Yang, Peng; Dang, Xueliang; Wei, Huamei; Hu, Na; Shi, Lei; Zhang, Yan

2018-06-01

Pinelliae Rhizoma Praeparatum (PRP) as traditional Chinese medicine had been used for hepatic diseases in combinative forms. However, the effect of PRP was not clear when used alone. So to explore the hepatoprotective/hepatotoxin of PRP is necessary. The activities of PRP were investigated in acetaminophen-induced hepatic injury mice. Liver function markers, hepatic oxidative stress markers were evaluated. Bile acids metabolic transports and nuclear factor erythroid 2-related factor 2 (Nrf2) were detected. As a drug for the treatment of liver diseases, PRP slightly restored the parameters towards normal in model mice only in low dosage, and also had no antioxidant activity and regulate Nrf2. Cholestasis was significantly elevated in model mice when pretreatment with routine or high dosage of PRP, but had no effect on normal mice. Bile salt export pump (Bsep) and multidrug resistance-associated protein 2 (Mrp2) in model mice were markedly increased when pretreatment with low dose PRP, but significantly decreased when pretreatment in routine or high dosage. Mrp3 was significantly induced in model mice after pretreatment of PRP. But the adjustment effect to bile acids transporters by PRP was not significant in normal mice. These results reveal that PRP has the different effects on bile acids transporter in hepatic injury mice, and therefore, the dosage of PRP need to be paid attention to when it is used in clinical hepatic injury.

A subset of IL-10-producing gammadelta T cells protect the liver from Listeria-elicited, CD8(+) T cell-mediated injury.

PubMed

Rhodes, Katherine A; Andrew, Elizabeth M; Newton, Darren J; Tramonti, Daniela; Carding, Simon R

2008-08-01

Although gammadelta T cells play a role in protecting tissues from pathogen-elicited damage to bacterial, viral and parasitic pathogens, the mechanisms involved in the damage and in the protection have not been clearly elucidated. This has been addressed using a murine model of listeriosis, which in mice lacking gammadelta T cells (TCRdelta(-/-)) is characterised by severe and extensive immune-mediated hepatic necrosis. We show that these hepatic lesions are caused by Listeria-elicited CD8(+) T cells secreting high levels of TNF-alpha that accumulate in the liver of Listeria-infected TCRdelta(-/-) mice. Using isolated populations of gammadelta T cells from wild-type and cytokine-deficient strains of mice to reconstitute TCRdelta(-/-) mice, the TCR variable gene 4 (Vgamma4)(+) subset of gammadelta T cells was shown to protect against liver injury. Hepatoprotection was dependent upon their ability to produce IL-10 after TCR-mediated interactions with Listeria-elicited macrophages and CD8(+) T cells. IL-10-producing Vgamma4(+) T cells also contribute to controlling CD8(+) T cell expansion and to regulating and reducing TNF-alpha secretion by activated CD8(+) T cells. This effect on TNF-alpha production was directly attributed to IL-10. These findings identify a novel mechanism by which pathogen-elicited CD8(+) T cells are regulated via interactions with, and activation of, IL-10-producing hepatoprotective gammadelta T cells.

Synergistic Hepatoprotective and Antioxidant Effect of Artichoke, Fig, Blackberry Herbal Mixture on HepG2 Cells and Their Metabolic Profiling Using NMR Coupled with Chemometrics.

PubMed

Youssef, Fadia S; Labib, Rola M; Eldahshan, Omayma A; Singab, Abdel Nasser B

2017-12-01

The edible plants have long been reported to possess a lot of biological activities. Herein, the hepatoprotective and the antioxidant activities of the aqueous infusion of the edible parts of Cynara cardunculus, Ficus carica, and Morus nigra and their herbal mixture (CFM) was investigated in vitro using CCl 4 induced damage in HepG2 cells. The highest amelioration was observed via the consumption of CFM at 1 mg/ml showing 47.00% and 37.09% decline in aspartate transaminase and alanine transaminase and 77.32% and 101.02% increase in reduced glutathione and superoxide dismutase comparable to CCl 4 treated cells. Metabolic profiling of their aqueous infusions was done using nuclear magnetic resonance spectroscopic experiments coupled with chemometrics particularly hierarchical cluster analysis (HCA) and principal component analysis (PCA). The structural closeness of the various metabolites existing in black berry and the mixture as reflected in the PCA score plot and HCA processed from the 1 H-NMR spectral data could eventually explained the close values in their biological behavior. For fig and artichoke, the existence of different phenolic metabolites that act synergistically could greatly interpret their potent biological behavior. Thus, it can be concluded that a herbal mixture composed of black berry, artichoke, and fig could afford an excellent natural candidate to combat oxidative stress and counteract hepatic toxins owing to its phenolic compounds. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

Hepatoprotective effects of polysaccharide isolated from Agaricus bisporus industrial wastewater against CCl₄-induced hepatic injury in mice.

PubMed

Huang, Jiafu; Ou, Yixin; Yew, Tai Wai David; Liu, Jingna; Leng, Bo; Lin, Zhichao; Su, Yi; Zhuang, Yuanhong; Lin, Jiaofen; Li, Xiumin; Xue, Yu; Pan, Yutian

2016-01-01

During the industrial production of canned mushroom (Agaricus bisporus), a large quantity of wastewater is produced. In this study, the wastewater generated during the canning of mushroom was analyzed. From this wastewater, four polysaccharide components (Abnp1001, Abnp1002, Abap1001, and Abap1002) with hepatic-protective activity were isolated by ultrafiltration, DEAE cellulose-52 chromatography and Sephadex G-200 size-exclusion chromatography. Results of ultraviolet spectra analysis and molecular weight determination showed that Abnp1001, Abnp1002, Abap1001 and Abap1002 were uniform with average molecular weights of 336, 12.8, 330 and 15.8kDa, respectively. The monosaccharide composition analysis using gas chromatography (GC) showed that the four fractions were heteropolysaccharides and mainly composed of glucose. Fourier transform-infrared (FT-IR) analysis showed that the isolated fractions were all composed of β-glycoside linkages. Additionally, the potential hepatoprotective activities of these polysaccharides against CCl4-induced hepatic injury in mice were studied. Notably, Abnp1002 and Abap1002 could lower the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations in serum in a dose dependent manner and reduce the hepatocellular degeneration and necrosis, as well as inflammatory infiltration. These results indicate that these two polysaccharides had protective effects on acute hepatic injury induced by CCl4 in mice and suggest that the polysaccharides extracted from A. bisporus industrial wastewater might have potential in therapeutics of acute hepatic injury. Copyright © 2015 Elsevier B.V. All rights reserved.

Evaluation of Hepatoprotective Effect of Curcumin on Liver Cirrhosis Using a Combination of Biochemical Analysis and Magnetic Resonance-Based Electrical Conductivity Imaging

PubMed Central

Kyung, Eun Jung; Kim, Hyun Bum; Hwang, Eun Sang; Lee, Seok; Choi, Bup Kyung; Lim, Sang Moo; Kwon, Oh In

2018-01-01

In oriental medicine, curcumin is used to treat inflammatory diseases, and its anti-inflammatory effect has been reported in recent research. In this feasibility study, the hepatoprotective effect of curcumin was investigated using a rat liver cirrhosis model, which was induced with dimethylnitrosamine (DMN). Together with biochemical analysis, we used a magnetic resonance-based electrical conductivity imaging method to evaluate tissue conditions associated with a protective effect. The effects of curcumin treatment and lactulose treatment on liver cirrhosis were compared. Electrical conductivity images indicated that liver tissues damaged by DMN showed decreased conductivity compared with normal liver tissues. In contrast, cirrhotic liver tissues treated with curcumin or lactulose showed increased conductivity than tissues in the DMN-only group. Specifically, conductivity of cirrhotic liver after curcumin treatment was similar to that of normal liver tissues. Histological staining and immunohistochemical examination showed significant levels of attenuated fibrosis and decreased inflammatory response after both curcumin and lactulose treatments compared with damaged liver tissues by DMN. The conductivity imaging and biochemical examination results indicate that curcumin's anti-inflammatory effect can prevent the progression of irreversible liver dysfunction. PMID:29887757

Fabrication of surfactant-free quercetin-loaded PLGA nanoparticles: evaluation of hepatoprotective efficacy by nuclear scintigraphy

NASA Astrophysics Data System (ADS)

Ganguly, Soumya; Gaonkar, Raghuvir H.; Sinha, Samarendu; Gupta, Amit; Chattopadhyay, Dipankar; Chattopadhyay, Sankha; Sachdeva, Satbir S.; Ganguly, Shantanu; Debnath, Mita C.

2016-07-01

The purpose of this study was to develop surfactant-free quercetin-loaded PLGA nanoparticles (Qr-NPs) and investigate the hepatoprotective efficacy of the product non-invasively by nuclear scintigraphy. The nanoparticles were prepared using PLGA by dialysis method and ranged in size between 50 and 250 nm with a narrow range of distribution. They were found to arrive at the fenestra of liver sinusoidal epithelium for accumulation. The sizes of nanoparticles (batch S1) were optimal to reach the target and offer enough protection of the hepatocytes degenerated by CCl4 intoxication as determined by various biochemical and histopathological tests. In vitro studies exhibited the cytotoxic effect of the formulation against HepG2 cell line. The hepatoprotective efficacy of Qr-NPs evaluated non-invasively by nuclear scintigraphic technique using 99mTc-labelled sulphur colloid revealed abnormality in liver at the area of decreased uptake in rats of CCl4-treated group, which disappeared in Qr-NP-treated group. In dynamic studies with 99mTc-mebrofenin, excretion was severely impaired in CCl4-treated group but was moderate in drug-treated group, proving the recovery of animals from damage.

Hepatoprotective effects of Arctium lappa on carbon tetrachloride- and acetaminophen-induced liver damage.

PubMed

Lin, S C; Chung, T C; Lin, C C; Ueng, T H; Lin, Y H; Lin, S Y; Wang, L Y

2000-01-01

The root of Arctium lappa Linne (A. lappa) (Compositae), a perennial herb, has been cultivated for a long time as a popular vegetable. In order to investigate the hepatoprotective effects of A. lappa, male ICR mice were injected with carbon tetrachloride (CCl4, 32 microl/kg, i.p.) or acetaminophen (600 mg/kg, i.p.). A. lappa suppressed the SGOT and SGPT elevations induced by CCl4 or acetaminophen in a dose-dependent manner and alleviated the severity of liver damage based on histopathological observations. In an attempt to elucidate the possible mechanism(s) of this hepatoprotective effect, glutathione (GSH), cytochrome P-450 (P-450) and malondialdehyde (MDA) contents were studied. A. lappa reversed the decrease in GSH and P-450 induced by CCl4 and acetaminophen. It was also found that A. lappa decreased the malondialdehyde (MDA) content in CCl4 or acetaminophen-intoxicated mice. From these results, it was suggested that A. lappa could protect the liver cells from CCl4 or acetaminophen-induced liver damages, perhaps by its antioxidative effect on hepatocytes, hence eliminating the deleterious effects of toxic metabolites from CCl4 or acetaminophen.

Marine collagen peptides protect against early alcoholic liver injury in rats.

PubMed

Lin, Bing; Zhang, Feng; Yu, Yongchao; Jiang, Qinghao; Zhang, Zhaofeng; Wang, Junbo; Li, Yong

2012-04-01

Marine collagen peptides (MCP) have been reported to exhibit antioxidative activity, which is the common property of numerous hepatoprotective agents. Previous studies have shown that MCP have biological functions including anti-hypertension, anti-ulcer, anti-skin ageing and extending the life span. However, its role in alcoholic liver injury remains unknown. The present study aimed to investigate the effects of MCP on early alcoholic liver injury in rats. Rats were administered with alcohol at a dose of 6 g/kg body weight intragastrically per d to induce early liver injury, which was then evaluated by serum markers and histopathological examination. Treatment with MCP could reverse the increased level of serum aminotransferase and reduce hepatic histological damage. In addition, MCP attenuated the alteration in serum superoxide dismutase and malondialdehyde levels. MCP also counteracted the increased levels of total cholesterol and TAG. However, no significant difference was observed in the contents of alcohol dehydrogenase both in liver and serum protein of rats. These findings suggest that MCP have a protective effect on early alcoholic liver injury in rats by their antioxidative activity and improving lipid metabolism.

Isopropyl Caffeate: A Caffeic Acid Derivative—Antioxidant Potential and Toxicity

PubMed Central

Montenegro, Camila de Albuquerque; de Oliveira, Kardilandia Mendes; de Oliveira Filho, Abrahão Alves; da Paz, Alexandre Rolim; de Araújo, Marianna Oliveira; Lima, Caliandra Maria Bezerra Luna; Diniz, Margareth de Fátima Formiga Melo; Pessôa, Hilzeth de Luna Freire

2018-01-01

Phenolic compounds, among them isopropyl caffeate, possess antioxidant potential, but not without toxicity and/or adverse effects. The present study aimed to evaluate the antioxidant activity and toxicity of isopropyl caffeate through in silico, in vitro and in vivo testing. The results showed that isopropyl caffeate presents no significant theoretical risk of toxicity, with likely moderate bioactivity: GPCR binding, ion channel modulation, nuclear receptor binding, and enzyme inhibition. Isopropyl caffeate induced hemolysis only at the concentrations of 500 and 1000 μg/ml. We observed types A and O erythrocyte protection from osmotic stress, no oxidation of erythrocytes, and even sequestrator and antioxidant behavior. However, moderate toxicity, according to the classification of GHS, was demonstrated through depressant effects on the central nervous system, though there was no influence on water and food consumption or on weight gain, and it did present possible hepatoprotection. We conclude that the effects induced by isopropyl caffeate are due to its antioxidant activity, capable of preventing production of free radicals and oxidative stress, a promising molecule with pharmacological potential. PMID:29849905

Protective effect of ethanolic extract of polyherbal formulation on carbon tetrachloride induced liver injury

PubMed Central

Gurusamy, K; Kokilavani, R; Arumugasamy, K; Sowmia, C

2009-01-01

Protective effect of ethanolic extract of polyherbalformulation (PHF) of three medicinalplants was studied on carbon tetrachloride induced liver damage in rats. Treatment with 250mg I kg b.w. of ethanolic extract of PHF protected rats against carbon tetrachloride liver injury by significantly lowering 5’NT, GGF, GDH and SDH and bilirubin levels compared to control group of rats. Normalising the effect of these parameters indicates strong hepatoprotective property of the PHF extract. PMID:22557313

Antagonistic effects of Spirulina platensis against sub-acute deltamethrin toxicity in mice: Biochemical and histopathological studies.

PubMed

Abdel-Daim, Mohamed; El-Bialy, Badr E; Rahman, Haidy G Abdel; Radi, Abeer M; Hefny, Hany A; Hassan, Ahmed M

2016-02-01

Spirulina platensis (SP); a microalga with high antioxidant and anti-inflammatory activities, acts as a food supplement in human and as many animal species. Deltamethrin (DLM) is a synthetic pyrethroid with broad spectrum activities against acaricides and insects and widely used for veterinary and agricultural purposes. Exposure to DLM leads to hepatotoxic, nephrotoxic and neurotoxic side effects for human and many species, including birds and fish. The present study was undertaken to examine the potential hepatoprotective, nephroprotective, neuroprotective and antioxidant effects of SP against sub-acute DLM toxicity in male mice. DLM intoxicated animals revealed a significant increase in serum hepatic and renal injury biomarkers as well as TNF-α level and AChE activity. Moreover, liver, kidney and brain lipid peroxidation and oxidative stress markers were altered due to DLM toxicity. Spirulina normalized the altered serum levels of AST, ALT, APL, LDH, γ-GT, cholesterol, uric acid, urea, creatinine AChE and TNF-α. Furthermore, it reduced DLM-induced tissue lipid peroxidation, nitric oxide and oxidative stress in a dose-dependent manner. Collectively, that Spirulina supplementation could overcome DLM-induced hepatotoxicty, nephrotoxicity and neurotoxicity by abolishing oxidative tissue injuries. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Phytopharmacology of Tribulus terrestris.

PubMed

Shahid, M; Riaz, M; Talpur, M M A; Pirzada, T

2016-01-01

Tribulus terrestris is an annual herb which belongs to the Zygophyllaceae family. This plant has been used in traditional medicine for the treatment of various diseases for hundreds of decades. The main active phytoconstituents of this plant include flavonoids, alkaloids, saponins, lignin, amides, and glycosides. The plant parts have different pharmacological activities including aphrodisiac, antiinflammatory, antimicrobial and antioxidant potential. T. terrestris is most often used for infertility and loss of libido. It has potential application as immunomodulatory, hepatoprotective, hypolipidemic, anthelmintic and anticarcinogenic activities. The aim of the present article is to create a database for further investigation of the phytopharmacological properties of this plant to promote research. This study will definitely help to confirm its traditional use along with its value-added utility, eventually leading to higher revenues from the plant.

Isoprenylated flavonoids from the root bark of Morus alba and their hepatoprotective and neuroprotective activities.

PubMed

Jung, Jae-Woo; Ko, Won-Min; Park, Ji-Hae; Seo, Kyeong-Hwa; Oh, Eun-Ji; Lee, Dae-Young; Lee, Dong-Sung; Kim, Youn-Chul; Lim, Dong-Wook; Han, Daeseok; Baek, Nam-In

2015-11-01

A new isoprenylated flavonoid, 2S-5,7,2',4'-tetrahydroxy-3',5'-di-(γ,γ-dimethylallyl)flavanone, sanggenol Q (1), along with seven known isoprenylated flavonoids, sanggenol A (2), sanggenol L (3), kuwanon T (4), cyclomorusin (5), sanggenon F (6), sanggenol O (7), and sanggenon N (8), three known Diels-Alder type adducts, sanggenon G (9), mulberrofuran G (10), and mulberrofuran C (11), and a known benzofuran, moracin E (12), were isolated from the root bark of Morus alba using silica gel, ODS, and Sephadex LH-20 column chromatography. Chemical structures were determined based on spectroscopic data analyses including NMR, MS, CD, and IR. For the first time, compounds 1 and 7 were isolated from the root bark of M. alba. All compounds were evaluated for hepatoprotective activity on t-BHP-induced oxidative stress in HepG2 cells and neuroprotective activity on glutamate-induced cell death in HT22 cells. Compounds 1, 4, 8, 10, and 11 showed protective effects on t-BHP-induced oxidative stress with EC50 values of 6.94 ± 0.38, 30.32 ± 6.82, 23.45 ± 4.72, 15.31 ± 2.21, and 0.41 ± 0.48 μM, respectively, and compounds 1, 2, 10, 11, and 12 showed protective effects on glutamate-induced cell death with EC50 values of 5.54 ± 0.86, 34.03 ± 7.71, 19.71 ± 0.71, 16.50 ± 7.82, and 1.02 ± 0.13 μM, respectively.

Growth-hormone-induced signal transducer and activator of transcription 5 signaling causes gigantism, inflammation, and premature death but protects mice from aggressive liver cancer.

PubMed

Friedbichler, Katrin; Themanns, Madeleine; Mueller, Kristina M; Schlederer, Michaela; Kornfeld, Jan-Wilhelm; Terracciano, Luigi M; Kozlov, Andrey V; Haindl, Susanne; Kenner, Lukas; Kolbe, Thomas; Mueller, Mathias; Snibson, Kenneth J; Heim, Markus H; Moriggl, Richard

2012-03-01

Persistently high levels of growth hormone (GH) can cause liver cancer. GH activates multiple signal-transduction pathways, among them janus kinase (JAK) 2-signal transducer and activator of transcription (STAT) 5 (signal transducer and activator of transcription 5). Both hyperactivation and deletion of STAT5 in hepatocytes have been implicated in the development of hepatocellular carcinoma (HCC); nevertheless, the role of STAT5 in the development of HCC as a result of high GH levels remains enigmatic. Thus, we crossed a mouse model of gigantism and inflammatory liver cancer caused by hyperactivated GH signaling (GH(tg) ) to mice with hepatic deletion of STAT5 (STAT5(Δhep) ). Unlike GH(tg) mice, GH(tg) STAT5(Δhep) animals did not display gigantism. Moreover, the premature mortality, which was associated with chronic inflammation, as well as the pathologic alterations of hepatocytes observed in GH(tg) mice, were not observed in GH(tg) animals lacking STAT5. Strikingly, loss of hepatic STAT5 proteins led to enhanced HCC development in GH(tg) mice. Despite reduced chronic inflammation, GH(tg) STAT5(Δhep) mice displayed earlier and more advanced HCC than GH(tg) animals. This may be attributed to the combination of increased peripheral lipolysis, hepatic lipid synthesis, loss of hepatoprotective mediators accompanied by aberrant activation of tumor-promoting c-JUN and STAT3 signaling cascades, and accumulation of DNA damage secondary to loss of cell-cycle control. Thus, HCC was never observed in STAT5(Δhep) mice. As a result of their hepatoprotective functions, STAT5 proteins prevent progressive fatty liver disease and the formation of aggressive HCC in the setting of hyperactivated GH signaling. At the same time, they play a key role in controlling systemic inflammation and regulating organ and body size. Copyright © 2011 American Association for the Study of Liver Diseases.

Impact of edaphic factors and nutrient management on the hepatoprotective efficiency of Carlinoside purified from pigeon pea leaves: An evaluation of UGT1A1 activity in hepatitis induced organelles.

PubMed

Das, Subhasish; Teja, K Charan; Mukherjee, Sandip; Seal, Soma; Sah, Rajesh Kumar; Duary, Buddhadeb; Kim, Ki-Hyun; Bhattacharya, Satya Sundar

2018-02-01

Carlinoside is a unique compound well-known for its excellent curative potential in hepatitis. There is a substantial research gap regarding the medicinal use of carlinoside, as its concentrations are greatly variable (depending on locality). We cultivated Cajanus cajan using vermicompost as a major organic amendment at two locations (Sonitpur and Birbhum) with different soil types, but identical climate conditions. Sonitpur soils were richer in soil organic C (SOC), enzyme activation, and N/P content than Birbhum. However, vermi-treatment improved many soil properties (bulk density, water retention, pH, N/P/K, and enzyme activity) to narrow the locational gap in soil quality by 15-28%. We also recorded a many-fold increment in SOC storage capacities in both locations, which was significantly correlated with carlinoside, total phenol, and flavonoid contents in Cajanus leaves. This significantly up-regulated the carlinoside induced expression of the bilirubin-solubilizing UGT1A1enzyme in HepG2 cell and rat liver. Leaf extracts of vermicompost-aided plants could cure hepatitis in affected rat livers and in the HepG2 cell line. Accordingly, vermi-treatment is an effective route for the growth of Cajanus as a cash crop for biomedical applications and can produce a concurrent improvement in soil quality. Copyright © 2017 Elsevier Inc. All rights reserved.

Deoxyschizandrin, Isolated from Schisandra Berries, Induces Cell Cycle Arrest in Ovarian Cancer Cells and Inhibits the Protumoural Activation of Tumour-Associated Macrophages.

PubMed

Lee, Kijun; Ahn, Ji-Hye; Lee, Kyung-Tae; Jang, Dae Sik; Choi, Jung-Hye

2018-01-15

Deoxyschizandrin, a major lignan of Schisandra berries, has been demonstrated to have various biological activities such as antioxidant, hepatoprotective, and antidiabetic effects. However, the anti-cancer effects of deoxyschizandrin are poorly characterized. In the present study, we investigated the anti-cancer effect of deoxyschizandrin on human ovarian cancer cell lines and tumour-associated macrophages (TAMs). Deoxyschizandrin induced G₀/G₁ phase cell cycle arrest and inhibited cyclin E expression in human ovarian cancer cells. Overexpression of cyclin E significantly reversed the deoxyschizandrin-induced cell growth inhibition. Interestingly, increased production of reactive oxygen species and decreased activation of Akt were observed in A2780 cells treated with deoxyschizandrin, and the antioxidant compromised the deoxyschizandrin-induced cell growth inhibition and Akt inactivation. Moreover, deoxyschizandrin-induced cell growth inhibition was markedly suppressed by Akt overexpression. In addition, deoxyschizandrin was found to inhibit the expression of the M2 phenotype markers CD163 and CD209 in TAMs, macrophages stimulated by the ovarian cancer cells. Moreover, expression and production of the tumour-promoting factors MMP-9, RANTES, and VEGF, which are highly enhanced in TAMs, was significantly suppressed by deoxyschizandrin treatment. Taken together, these data suggest that deoxyschizandrin exerts anti-cancer effects by inducing G₀/G₁ cell cycle arrest in ovarian cancer cells and reducing the protumoural phenotype of TAMs.

GC-MS analysis and hepatoprotective activity of the n-hexane extract of Acrocarpus fraxinifolius leaves against paracetamol-induced hepatotoxicity in male albino rats.

PubMed

Abd El-Ghffar, Eman A; El-Nashar, Heba A S; Eldahshan, Omayma A; Singab, Abdel Nasser B

2017-12-01

In Egypt, the burden of liver diseases is exceptionally high. To investigate the components of the n-hexane extract of Acrocarpus fraxinifolius Arn. (Leguminosae) and its hepatoprotective activity against paracetamol (APAP)-induced hepatotoxicity in rats. TRACE GC ultra gas chromatogaphic spectrometry was used for extract analysis. Thirty albino rats were divided into six groups (five rats in each). Group 1 was the healthy control; Groups 2 and 3 were healthy treated groups (250 and 500 mg/kg b.w. of the extract, respectively) for seven days. Group 4 was hepatotoxicity control (APAP intoxicated group). Groups 5 and 6 received APAP + extract 250 and APAP + extract 500, respectively. Chromatographic analysis revealed the presence of 36 components. Major compounds were α-tocopherol (18.23%), labda-8 (20)-13-dien-15-oic acid (13.15%), lupeol (11.93%), phytol (10.95%) and squalene (7.19%). In the acute oral toxicity study, the mortality rates and behavioural signs of toxicity were zero in all groups (doses from 0 to 5 g/kg b.w. of A. fraxinifolius). LD 50 was found to be greater than 5 g/kg of the extract. Only the high dose (500 mg/kg b.w.) of extract significantly alleviated the liver relative weight (4.01 ± 0.06) and biomarkers, as serum aspartate aminotransferase (62.87 ± 1.41), alanine aminotransferase (46.74 ± 1.45), alkaline phosphatase (65.96 ± 0.74), lipid profiles (180.39 ± 3.51), bilirubin profiles (2.30 ± 0.06) and hepatic lipid peroxidation (114.20 ± 2.06), and increased body weight (11.58 ± 0.20), serum protein profile (11.09 ± 0.46) and hepatic total antioxidant capacity (23.78 ± 0.66) in APAP-induced hepatotoxicity in rats. Our study proves the antihepatotoxic/antioxidant efficacies of A. fraxinifolius hexane extract.

Dietary Supplementation of Calendula officinalis Counteracts the Oxidative Stress and Liver Damage Resulted from Aflatoxin

PubMed Central

Hamzawy, Mohamed A.; El-Denshary, Ezzeldein S. M.; Hassan, Nabila S.; Mannaa, Fathia A.; Abdel-Wahhab, Mosaad A.

2013-01-01

This study was conducted to evaluate the total phenolic compounds, the antioxidant properties, and the hepatorenoprotective potential of Calendula officinalis extract against aflatoxins (AFs-) induced liver damage. Six groups of male Sprague-Dawley rats were treated for 6 weeks included the control; the group fed AFs-contaminated diet (2.5 mg/kg diet); the groups treated orally with Calendula extract at low (CA1) and high (CA2) doses (500 and 1000 mg/kg b.w); the groups treated orally with CA1 and CA2 one week before and during AFs treatment for other five weeks. The results showed that the ethanol extract contained higher phenolic compounds and posses higher 1,1-diphenyl 1-2-picryl hydrazyl (DPPH) radical scavenging activity than the aqueous extract. Animals fed AFs-contaminated diet showed significant disturbances in serum biochemical parameters, inflammatory cytokines, and the histological and histochemical pictures of the liver accompanied by a significant increase in malondialdehyde (MDA) and a significant decrease in superoxide dismutase (SOD) and glutathione peroxidase (GPx) in liver. Calendula extract succeeded to improve the biochemical parameters, inflammatory cytokines, decreased the oxidative stress, and improved the histological pictures in the liver of rats fed AFs-contaminated diet in a dose-dependent manner. It could be concluded that Calendula extract has potential hepatoprotective effects against AFs due to its antioxidant properties and radical scavenging activity. PMID:24959547

Effects of Low-Molecular-Weight Fucoidan and High Stability Fucoxanthin on Glucose Homeostasis, Lipid Metabolism, and Liver Function in a Mouse Model of Type II Diabetes.

PubMed

Lin, Hong-Ting Victor; Tsou, Yu-Chi; Chen, Yu-Ting; Lu, Wen-Jung; Hwang, Pai-An

2017-04-07

The combined effects of low-molecular-weight fucoidan (LMF) and fucoxanthin (Fx) in terms of antihyperglycemic, antihyperlipidemic, and hepatoprotective activities were investigated in a mouse model of type II diabetes. The intake of LMF, Fx, and LMF + Fx lowered the blood sugar and fasting blood sugar levels, and increased serum adiponectin levels. The significant decrease in urinary sugar was only observed in LMF + Fx supplementation. LMF and Fx had ameliorating effects on the hepatic tissue of db/db mice by increasing hepatic glycogen and antioxidative enzymes, and LMF was more effective than Fx at improving hepatic glucose metabolism. As for glucose and lipid metabolism in the adipose tissue, the expression of insulin receptor substrate (IRS)-1, glucose transporter (GLUT), peroxisome proliferator-activated receptor gamma (PPARγ), and uncoupling protein (UCP)-1 mRNAs in the adipose tissue of diabetic mice was significantly upregulated by Fx and LMF + Fx, and levels of inflammatory adipocytokines, such as adiponectin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6), were significantly modulated only by LMF + Fx supplementation. The efficacy of LMF + Fx supplementation on the decrease in urinary sugar and on glucose and lipid metabolism in the white adipose tissue of db/db mice was better than that of Fx or LMF alone, indicating the occurrence of a synergistic effect of LMF and Fx.

l-Theanine prevents ETEC-induced liver damage by reducing intrinsic apoptotic response and inhibiting ERK1/2 and JNK1/2 signaling pathways.

PubMed

Gong, Zhihua; Liu, Qiuling; Lin, Ling; Deng, Yanli; Cai, Shuxian; Liu, Zunying; Zhang, Sheng; Xiao, Wenjun; Xiong, Shuo; Chen, Dong

2018-01-05

l-Theanine (LTA; γ-glutamylethylamide), a peculiar non-protein-derived amino acid isolated from tea, is widely used as a functional ingredient and dietary supplement. l-Theanine has been confirmed to have hepatoprotective effects, but the underlying mechanism remains unknown. This study investigated the protective effect of l-Theanine-in vivo, using an enterotoxigenic Escherichia coli (ETEC)-infected mouse model. l-Theanine significantly decreased the elevated serum activities of both aspartate aminotransferase (AST) and alanine aminotransferase (ALT), two biomarkers of hepatic impairment. This was consistent with histopathological images from the microscopic observation of liver tissue. In addition, l-theanine significantly increased the mRNA and protein expression of Bcl-2 and decreased the expression of Bax, anti- and pro-apoptotic molecules, respectively, compared with levels in the ETEC control group. The expression of cleaved caspase-3 protein in the group pre-treated with l-theanine was significantly lower than that in the ETEC group. Additionally, decreases in extracellular signal-regulated kinase (ERK1/2) and c-Jun NH 2 -terminal kinase(JNK1/2) MAPK phosphorylation were observed in the l-theanine pre-treated group. Our study demonstrates that l-theanine possesses anti-apoptotic activity, which can be attributed to suppression of the intrinsic mitochondria-mediated apoptosis and MAPK phosphorylation signaling pathways. Copyright © 2017 Elsevier B.V. All rights reserved.

Bach1 gene ablation reduces steatohepatitis in mouse MCD diet model.

PubMed

Inoue, Motoki; Tazuma, Susumu; Kanno, Keishi; Hyogo, Hideyuki; Igarashi, Kazuhiko; Chayama, Kazuaki

2011-03-01

Bach1 is a transcriptional repressor of heme oxygenase-1 (HO-1, a.k.a. HSP-32), which is an inducible enzyme and has anti-oxidation/anti-inflammatory properties shown in various models of organ injuries. Since oxidative stress plays a pivotal role in the pathogenesis of nonalcoholic steatohepatitis (NASH), HO-1 induction would be expected to prevent the development of NASH. In this study, we investigated the influence of Bach1 ablation in mice on the progression of NASH in methionine-choline deficient (MCD) diet model. Bach1 ablation resulted in significant induction of HO-1 mRNA and its activity in the liver. When fed MCD diet, Bach1(-/-) mice exhibited negligible hepatic steatosis compared to pronounced steatohepatitis in wild type mice with 6-fold increase in hepatic triglyceride content. Whereas feeding of MCD diet decreased mRNA expressions of peroxisome proliferator-activated receptor (PPAR) α and microsomal triglyceride transfer protein (MTP) in wild type mice, there were no change in Bach1(-/-) mice. In addition, hepatic concentration of malondialdehyde (MDA), a biomarker for oxidative stress as well as plasma alanine aminotransferase (ALT) was significantly lower in Bach1(-/-) mice. These findings suggest that Bach1 ablation exerts hepatoprotective effect against steatohepatitis presumably via HO-1 induction and may be a potential therapeutic target.

Propolis Prevents Hepatorenal Injury Induced by Chronic Exposure to Carbon Tetrachloride

PubMed Central

Bhadauria, Monika

2012-01-01

Carbon tetrachloride (CCl4) is a well-known hepatotoxicant, and its exposure induces hepatorenal injury via oxidative stress and biochemical alterations. This study had been conducted to confirm the protective role of propolis extract on CCl4-induced hepatorenal oxidative stress and resultant injury. Propolis extracts collected from Gwalior district and 24 female Sprague Dawley rats were used for experiment. Animals were exposed to CCl4 (0.15 mL/kg, i.p.) for 12 weeks (5 days/week) followed by treatment with propolis extract (200 mg/kg, p.o.) for consecutive 2 weeks. CCl4 exposure significantly depleted blood sugar and hemoglobin level and raised the level of transaminases, alkaline phosphatase, lactate dehydrogenase, protein, urea, albumin, bilirubin, creatinine, triglycerides, and cholesterol in serum. Lipid peroxidation was enhanced, whereas GSH was decreased significantly in liver and kidney in CCl4-intoxicated group. Ethanolic extract of propolis successfully prevented these alterations in experimental animals. Activities of catalase, adenosine triphosphatase, glucose-6-phosphatase, acid, and alkaline phosphatase were also maintained towards normal with propolis therapy. Light microscopical studies showed considerable protection in liver and kidney with propolis treatment, thus, substantiated biochemical observations. This study confirmed hepatoprotective potential of propolis extract against chronic injury induced by CCl4 by regulating antioxidative defense activities. PMID:21837248

Effects of administration of the standardized Panax ginseng extract G115 on hepatic antioxidant function after exhaustive exercise.

PubMed

Voces, J; Alvarez, A I; Vila, L; Ferrando, A; Cabral de Oliveira, C; Prieto, J G

1999-06-01

The effect of prolonged treatment with the standardized Panax ginseng extract G115 on the antioxidant capacity of the liver was investigated. For this purpose, rats that had received G115 orally at different doses for 3 months and untreated control rats were subjected to exhaustive exercise on a treadmill. A bell-shaped dose response on running time was obtained. The results showed that the administration of G115 significantly increases the hepatic glutathione peroxidase activity (GPX) and the reduced glutathione (GSH) levels in the liver, with a dose-dependent reduction of the thiobarbituric acid reactant substances (TBARS). After the exercise, there is reduced hepatic lipid peroxidation, as evidenced by the TBARS levels in both the controls and the treated animals. The GPX (glutathione peroxidase) and SOD (superoxide dismutase) activity are also significantly increased in the groups receiving G115, compared with the controls. The hepatic transaminase levels, ALT (Alanine-amino-transferase) and AST (Aspartate-amino-transferase), in the recuperation phase 48 h after the exercise, indicate a clear hepatoprotective effect related to the administration of the standardized Panax ginseng extract G115. At hepatic level, G115 increases the antioxidant capacity, with a marked reduction of the effects of the oxidative stress induced by the exhaustive exercise.

Epigallocatechin-3-gallate (EGCG) attenuates concanavalin A-induced hepatic injury in mice.

PubMed

Liu, Dongmei; Zhang, Xiaoli; Jiang, Li; Guo, Yun; Zheng, Changqing

2014-05-01

(-)-Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenolic compound present in green tea and has been shown to possess anti-inflammatory and anti-oxidative properties. In this study, we investigated the protective effects of EGCG against concanavalin A (ConA)-induced liver injury and the underlying mechanisms. EGCG (5 mg/kg) was administered orally by gavage to mice twice daily for 10 days before an intravenous injection of ConA. We found that EGCG effectively rescued lethality, improved hepatic pathological damage, and decreased serum levels of alanine aminotransaminase (ALT) in ConA-challenged mice. Furthermore, EGCG also significantly prevented the release of tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-4, and IL-6 in serum, reduced malondialdehyde (MDA) levels, and restored glutathione (GSH) content and superoxide dismutase (SOD) activity in liver tissues from ConA-challenged mice. Finally, nuclear factor (NF)-κB activation and expression levels of Toll-like receptor (TLR) 2, TLR4 and TLR9 protein in liver tissues were significantly inhibited by EGCG pretreatment. Taken together, our data suggest that EGCG possesses hepatoprotective properties against ConA-induced liver injury through its anti-inflammatory and anti-oxidant actions. Copyright © 2013 Elsevier GmbH. All rights reserved.

Oral bioavailability of curcumin: problems and advancements.

PubMed

Liu, Weidong; Zhai, Yingjie; Heng, Xueyuan; Che, Feng Yuan; Chen, Wenjun; Sun, Dezhong; Zhai, Guangxi

2016-09-01

Curcumin is a natural compound of Curcuma longa L. and has shown many pharmacological activities such as anti-inflammatory, anti-oxidant in both preclinical and clinical studies. Moreover, curcumin has hepatoprotective, neuroprotective activities and protects against myocardial infarction. Particularly, curcumin has also demonstrated favorite anticancer efficacy. But limiting factors such as its extremely low oral bioavailability hampers its application as therapeutic agent. Therefore, many technologies have been developed and applied to overcome this limitation. This review described the main physicochemical properties of curcumin and summarized the recent studies in the design and development of oral delivery systems for curcumin to enhance the solubility and oral bioavailability, including liposomes, nanoparticles and polymeric micelles, phospholipid complexes, and microemulsions.

Ameliorative influence of Urtica dioica L against cisplatin-induced toxicity in mice bearing Ehrlich ascites carcinoma.

PubMed

Özkol, Halil; Musa, Davut; Tuluce, Yasin; Koyuncu, Ismail

2012-07-01

Cisplatin (CP) is a widely used cytotoxic agent against cancer, and high doses of CP have been known to cause nephrotoxicity and hepatotoxicity. Some reports claim that antioxidants can reduce CP-induced toxicity. This study investigated the hepatoprotective, nephroprotective, and antioxidant activity of Urtica dioica L methanolic extract (UDME) against CP toxicity in Erhlich ascites tumor (EAT)-bearing mice. Levels of serum hepatic enzymes, renal function markers, and oxidant/antioxidant parameters of liver tissue were measured. Mice were inoculated with EAT on day 0 and treated with nothing else for 24 hours. After a single dose of CP administration on day 1, the extract was given at the doses of 50, 100, 200, and 400 mg/kg body weight daily during 6 days. Almost all doses of UDME performed a significant (P < 0.05) preventive role against CP toxicity by decreasing aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, blood urea nitrogen, creatinine, lipid peroxidation, protein oxidation levels, and myeloperoxidase activity, as well as increasing reduced glutathione content, superoxide dismutase, catalase, glutathione S-transferase, and glutathione peroxidase activities. This suggests that UDME has a protective capacity and antioxidant activity against CP toxicity in EAT-bearing mice, probably by promoting antioxidative defense systems.

Chemical profile, radical scavenging and cytotoxic activity of yellow gentian leaves (Genitaneae luteaefolium) grown in northern regions of Montenegro.

PubMed

Balijagić, Jasmina; Janković, Teodora; Zdunić, Gordana; Bosković, Jelena; Savikin, Katarina; Godevac, Dejan; Stanojković, Tatjana; Jovancević, Miodrag; Menković, Nebojsa

2012-11-01

LC-ESI-MS and HPLC were used for the identification of the constituents from G. lutea leaves collected at different localities, as well as for quantification of the main compounds. Seven secoiridoids, five C-glucoflavones and three xanthones, were identified. Swertiamarin derivatives, namely eustomorusside (2), eustomoside (3) and septemfidoside (5), were detected in G. lutea for the first time. Concentrations of five constituents (swertiamarin, gentiopicrin, isovitexin, mangiferin and isogentisin) were determined. The relationship between concentrations of y-pyrones and altitude was observed with statistically significant correlation (r = 0.94). The extracts were also evaluated for their content of total phenolics, and antiradical and cytotoxic activities. The total phenolics content ranged from 7.7 to 12.7 mg GAE/g, and the IC50 values for DPPH radical scavenging activity varied between 0.45 to 2.02 mg/mL. The leaf extract exhibited moderate cytotoxic effects toward HeLa cells with an IC50 value of 41.1 microg/mL, while gentiopicrin, mangiferin and isogentisin exerted strong activity against HeLa cells, with IC50 values ranging from 5.7 to 8.8 microg/mL. The results confirm the traditional usage of G. lutea leaves and also suggest their possible utilization as hepatoprotective, hypoglycemic and anti-inflammatory agents.

Protective effect of human serum amyloid P on CCl4-induced acute liver injury in mice.

PubMed

Cong, Min; Zhao, Weihua; Liu, Tianhui; Wang, Ping; Fan, Xu; Zhai, Qingling; Bao, Xiaoli; Zhang, Dong; You, Hong; Kisseleva, Tatiana; Brenner, David A; Jia, Jidong; Zhuang, Hui

2017-08-01

Human serum amyloid P (hSAP), a member of the pentraxin family, inhibits the activation of fibrocytes in culture and inhibits experimental renal, lung, skin and cardiac fibrosis. As hepatic inflammation is one of the causes of liver fibrosis, in the present study, we investigated the hepatoprotective effects of hSAP against carbon tetrachloride (CCl4)-induced liver injury. Our data indicated that hSAP attenuated hepatic histopathological abnormalities and significantly decreased inflammatory cell infiltration and pro-inflammatory factor expression. Moreover, CCl4-induced apoptosis in the mouse liver was inhibited by hSAP, as measured by terminal-deoxynucleotidyl transferase mediated nick-end labeling (TUNEL) assay and cleaved caspase-3 expression. hSAP significantly restored the expression of B cell lymphoma/leukemia (Bcl)-2 and suppressed the expression of Bcl-2-associated X protein (Bax) in vivo. The number of hepatocytes in early apoptosis stained with Annexin V was significantly reduced by 28-30% in the hSAP treatment group compared with the CCl4 group, and the expression of Bcl-2 was increased, whereas the expression of Bax and cleaved caspase-3 were significantly inhibited in the hSAP pre-treatment group compared with the CCl4 group. hSAP administration also inhibited the migration and activation of hepatic stellate cells (HSCs) in CCl4-injured liver and suppressed the activation of isolated primary HSCs induced by transforming growth factor (TGF)-β1 in vitro. Collectively, these findings suggest that hSAP exerts a protective effect againts CCl4-induced hepatic injury by suppressing the inflammatory response and hepatocyte apoptosis, potentially by inhibiting HSC activation.

Protective effect of human serum amyloid P on CCl4-induced acute liver injury in mice

PubMed Central

Cong, Min; Zhao, Weihua; Liu, Tianhui; Wang, Ping; Fan, Xu; Zhai, Qingling; Bao, Xiaoli; Zhang, Dong; You, Hong; Kisseleva, Tatiana; Brenner, David A.; Jia, Jidong; Zhuang, Hui

2017-01-01

Human serum amyloid P (hSAP), a member of the pentraxin family, inhibits the activation of fibrocytes in culture and inhibits experimental renal, lung, skin and cardiac fibrosis. As hepatic inflammation is one of the causes of liver fibrosis, in the present study, we investigated the hepatoprotective effects of hSAP against carbon tetrachloride (CCl4)-induced liver injury. Our data indicated that hSAP attenuated hepatic histopathological abnormalities and significantly decreased inflammatory cell infiltration and pro-inflammatory factor expression. Moreover, CCl4-induced apoptosis in the mouse liver was inhibited by hSAP, as measured by terminal-deoxynucleotidyl transferase mediated nick-end labeling (TUNEL) assay and cleaved caspase-3 expression. hSAP significantly restored the expression of B cell lymphoma/leukemia (Bcl)-2 and suppressed the expression of Bcl-2-associated X protein (Bax) in vivo. The number of hepatocytes in early apoptosis stained with Annexin V was significantly reduced by 28–30% in the hSAP treatment group compared with the CCl4 group, and the expression of Bcl-2 was increased, whereas the expression of Bax and cleaved caspase-3 were significantly inhibited in the hSAP pre-treatment group compared with the CCl4 group. hSAP administration also inhibited the migration and activation of hepatic stellate cells (HSCs) in CCl4-injured liver and suppressed the activation of isolated primary HSCs induced by transforming growth factor (TGF)-β1 in vitro. Collectively, these findings suggest that hSAP exerts a protective effect againts CCl4-induced hepatic injury by suppressing the inflammatory response and hepatocyte apoptosis, potentially by inhibiting HSC activation. PMID:28627620

Effects of dietary milk thistle on blood parameters, liver pathology, and hepatobiliary scintigraphy in white carneaux pigeons (Columba livia) challenged with B1 aflatoxin.

PubMed

Grizzle, Judith; Hadley, Tarah L; Rotstein, David S; Perrin, Shannon L; Gerhardt, Lillian E; Beam, James D; Saxton, Arnold M; Jones, Michael P; Daniel, Gregory B

2009-06-01

Milk thistle (Silybum marianum) has been used in humans for the treatment of liver disease because of its antioxidant properties and its ability to stabilize cell membranes and regulate cell permeability. To investigate possible hepatoprotective effects in birds, standardized extracts (80%) of silymarin from milk thistle were tested in white Carneaux pigeons (Columba livia). Pigeons were separated into 3 groups and fed diets formulated to provide milk thistle at a level of 0, 10, or 100 mg/kg body weight per day. After acclimation, the birds were challenged with B1 aflatoxin (3 mg/kg body weight for 2 consecutive days) by oral gavage. Liver function then was assessed by hematologic testing and plasma biochemical analysis, liver histopathology, and hepatobiliary scintigraphy. Results of histopathology and hepatobiliary scintigraphy showed no protective effects from milk-thistle administration. Aflatoxin challenge resulted in hepatic inflammation and necrosis, biliary-duct hyperplasia, and lymphocyte infiltration. All hepatobiliary scintigraphy elements increased significantly after aflatoxin challenge. Bile acid levels and plasma enzyme concentrations of aspartate aminotransferase, lactate dehydrogenase, alanine aminotransferase, and creatine phosphokinase all increased after aflatoxin exposure and were mostly unchanged with consumption of milk thistle. Only birds fed 10 mg/kg body weight milk thistle showed significant reductions in lactate dehydrogenase, alanine aminotransferase, and creatine phosphokinase concentrations after aflatoxin exposure. Our results show that consumption of milk thistle is not associated with hepatoprotective effects against acute B1 aflatoxin exposure in pigeons.

Silibinin (Milk Thistle) potentiates ethanol-dependent hepatocellular carcinoma progression in male mice

PubMed Central

Brandon-Warner, Elizabeth; Eheim, Ashley L; Foureau, David M; Walling, Tracy L; Schrum, Laura W; McKillop, Iain H

2012-01-01

Hepatocellular carcinoma (HCC) is a global health burden with limited treatment options and poor prognosis. Silibinin, an antioxidant derived from the Milk Thistle plant (Silybum marianum), is reported to exert hepatoprotective and antitumorigenic effects in vitro and in vivo by suppressing oxidative stress and proliferation. Using a DEN-initiated mouse model of HCC, this study examined the effects of dietary silibinin supplementation alone, or in combination with chronic ethanol consumption on HCC progression. Our data demonstrate silibinin exerted marginal hepatoprotective effects in early stages of hepatocarcinogenesis but, when co-administered with ethanol, exacerbated the promotional effects of ethanol in HCC bearing mice, but only in males. PMID:22863537

Silibinin (Milk Thistle) potentiates ethanol-dependent hepatocellular carcinoma progression in male mice.

PubMed

Brandon-Warner, Elizabeth; Eheim, Ashley L; Foureau, David M; Walling, Tracy L; Schrum, Laura W; McKillop, Iain H

2012-12-29

Hepatocellular carcinoma (HCC) is a global health burden with limited treatment options and poor prognosis. Silibinin, an antioxidant derived from the Milk Thistle plant (Silybum marianum), is reported to exert hepatoprotective and antitumorigenic effects in vitro and in vivo by suppressing oxidative stress and proliferation. Using a DEN-initiated mouse model of HCC, this study examined the effects of dietary silibinin supplementation alone, or in combination with chronic ethanol consumption on HCC progression. Our data demonstrate silibinin exerted marginal hepatoprotective effects in early stages of hepatocarcinogenesis but, when co-administered with ethanol, exacerbated the promotional effects of ethanol in HCC bearing mice, but only in males. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Hepatoprotective Effect of Wedelolactone against Concanavalin A-Induced Liver Injury in Mice.

PubMed

Luo, Qingqiong; Ding, Jieying; Zhu, Liping; Chen, Fuxiang; Xu, Lili

2018-05-08

Eclipta prostrata L. is a traditional Chinese herbal medicine that has been used in the treatment of liver diseases. However, its biological mechanisms remain elusive. The current study aimed to investigate the hepatoprotective effect of wedelolactone, a major coumarin ingredient of Eclipta prostrata L., on immune-mediated liver injury. Using the well-established animal model of Concanavalin A (ConA)-induced hepatitis (CIH), we found that pretreatment of mice with wedelolactone markedly reduced both the serum levels of transaminases and the severity of liver damage. We further investigated the mechanisms of the protective effect of wedelolactone. In mice treated with wedelolactone prior to the induction of CIH, increases of serum concentrations of tumor necrosis factor (TNF)-[Formula: see text], interferon (IFN)-[Formula: see text], and interleukin (IL)-6 were dramatically attenuated. Additionally, expressions of the interferon-inducible chemokine (C-X-C motif) ligand 10 gene CXCL10 and intercellular adhesion molecule 1 gene ICAM1 were lower in livers of the treated mice. Moreover, wedelolactone-treated CIH mice exhibited reduced leukocyte infiltration and T-cell activation in liver. Furthermore, wedelolactone suppressed the activity of nuclear factor-kappa B (NF-[Formula: see text]B), a critical transcriptional factor of the above-mentioned inflammatory cytokines by limiting the phosphorylation of I kappa B alpha (I[Formula: see text]B[Formula: see text] and p65. In conclusion, these findings demonstrate the inhibitory potential of wedelolactone in immune-mediated liver injury in vivo, and show that this protection is associated with modulation of the NF-[Formula: see text]B signaling pathway.

Betaine Treatment Attenuates Chronic Ethanol-Induced Hepatic Steatosis and Alterations to the Mitochondrial Respiratory Chain Proteome

PubMed Central

Kharbanda, Kusum K.; Todero, Sandra L.; King, Adrienne L.; Osna, Natalia A.; McVicker, Benita L.; Tuma, Dean J.; Wisecarver, James L.; Bailey, Shannon M.

2012-01-01

Introduction. Mitochondrial damage and disruption in oxidative phosphorylation contributes to the pathogenesis of alcoholic liver injury. Herein, we tested the hypothesis that the hepatoprotective actions of betaine against alcoholic liver injury occur at the level of the mitochondrial proteome. Methods. Male Wister rats were pair-fed control or ethanol-containing liquid diets supplemented with or without betaine (10 mg/mL) for 4-5 wks. Liver was examined for triglyceride accumulation, levels of methionine cycle metabolites, and alterations in mitochondrial proteins. Results. Chronic ethanol ingestion resulted in triglyceride accumulation which was attenuated in the ethanol plus betaine group. Blue native gel electrophoresis (BN-PAGE) revealed significant decreases in the content of the intact oxidative phosphorylation complexes in mitochondria from ethanol-fed animals. The alcohol-dependent loss in many of the low molecular weight oxidative phosphorylation proteins was prevented by betaine supplementation. This protection by betaine was associated with normalization of SAM : S-adenosylhomocysteine (SAH) ratios and the attenuation of the ethanol-induced increase in inducible nitric oxide synthase and nitric oxide generation in the liver. Discussion/Conclusion. In summary, betaine attenuates alcoholic steatosis and alterations to the oxidative phosphorylation system. Therefore, preservation of mitochondrial function may be another key molecular mechanism responsible for betaine hepatoprotection. PMID:22187660

Hepatoprotective effect of acetone semicarbazone on Ehrlich ascites carcinoma induced carcinogenesis in experimental mice

PubMed Central

Islam, Farhadul; Ali, Shaikh Mohummad Mohsin; Khanam, Jahan Ara

2013-01-01

Objective To determine the hepatoprotective effect of acetone semicarbazone (ASC) in vivo in normal and Ehrlich ascites carcinoma (EAC) bearing male Swiss albino mice. Methods Drug-induced changes in biochemical and behavioral parameters at dose of 2.0 mg/kg body weight for 14 d and nullifying the toxicity induced by EAC cells were studied. The histopathology studies of the protective effects of ASC on vital organs were also assessed. Results The administration of ASC made insignificant changes in body weight and behavioral (salivation, diarrhea, muscular numbness) changes during treatment period due to minor toxicity were minimized after the treatment in normal mice. The biochemical parameters, including serum glutamate pyruvate transaminase, glutamate oxaloactate transaminase, alkaline phosphatase, serum glucose, cholesterol, urea, triglyceride and billirubin changed modestly in normal mice receiving ASC. Though the treatment continued, these values gradually decreased to normal level after the treatment. In EAC bearing mice, the toxic effects due to EAC cells in all cases were nullified by treatment with the ASC. Significant abnormalities were not detected in histology of the various organs of the normal mice treated with ASC. Conclusions ASC can, therefore, be considered safe in formulating novel anticancer drug, as it exhibits strong protective effect against EAC cell bearing mice. PMID:23593588

Fibroblast Activation Protein Cleaves and Inactivates Fibroblast Growth Factor 21*

PubMed Central

Dunshee, Diana Ronai; Bainbridge, Travis W.; Kljavin, Noelyn M.; Zavala-Solorio, Jose; Schroeder, Amy C.; Chan, Ruby; Corpuz, Racquel; Wong, Manda; Zhou, Wei; Deshmukh, Gauri; Ly, Justin; Sutherlin, Daniel P.; Ernst, James A.; Sonoda, Junichiro

2016-01-01

FGF21 is a stress-induced hormone with potent anti-obesity, insulin-sensitizing, and hepatoprotective properties. Although proteolytic cleavage of recombinant human FGF21 in preclinical species has been observed previously, the regulation of endogenously produced FGF21 is not well understood. Here we identify fibroblast activation protein (FAP) as the enzyme that cleaves and inactivates human FGF21. A selective chemical inhibitor, immunodepletion, or genetic deletion of Fap stabilized recombinant human FGF21 in serum. In addition, administration of a selective FAP inhibitor acutely increased circulating intact FGF21 levels in cynomolgus monkeys. On the basis of our findings, we propose selective FAP inhibition as a potential therapeutic approach to increase endogenous FGF21 activity for the treatment of obesity, type 2 diabetes, non-alcoholic steatohepatitis, and related metabolic disorders. PMID:26797127

Polythiol-containing, recombinant mannosylated-albumin is a superior CD68+/CD206+ Kupffer cell-targeted nanoantioxidant for treatment of two acute hepatitis models.

PubMed

Maeda, Hitoshi; Hirata, Kenshiro; Watanabe, Hiroshi; Ishima, Yu; Chuang, Victor Tuan Giam; Taguchi, Kazuaki; Inatsu, Akihito; Kinoshita, Manabu; Tanaka, Motohiko; Sasaki, Yutaka; Otagiri, Masaki; Maruyama, Toru

2015-02-01

Since reactive oxygen species (ROS) derived from Kupffer cells (KC), especially CD68(+) KC, play a key role in the induction of hepatic oxidative stress and injuries, we developed a polythiolated- and mannosylated human serum albumin (SH-Man-HSA), which functions as a novel nanoantioxidant for delivering thiol to CD68(+) KC. In vitro electron paramagnetic resonance coupled with pharmacokinetics and immunohistochemical studies showed that SH-Man-HSA possessed powerful radical-scavenging activity and rapidly and selectively delivered thiols to the liver via mannose receptor (CD206) on CD68(+) cells. SH-Man-HSA significantly improved the survival rate of concanavalin-A (Con-A)-treated mice. Moreover, SH-Man-HSA exhibited excellent hepatoprotective functions, not by decreasing tumor necrosis factor or interferon-γ production that is closely associated with Con-A-induced hepatitis, but by suppressing ROS production. Interestingly, the protective effect of SH-Man-HSA was superior to N-acetyl cysteine (NAC). This could be attributed to the difference in the inhibition of hepatic oxidative stress between the two antioxidants depending on their potential for thiol delivery to the liver. Similar results were also observed for acetaminophen (APAP)-induced hepatopathy models. Flow cytometric data further confirmed that an increase in F4/80(+)/ROS(+) cells was dramatically decreased by SH-Man-HSA. The administration of SH-Man-HSA at 4 hours following a Con-A or APAP injection also exhibited a profound hepatoprotective action against these hepatitis models, whereas this was not observed for NAC. It can be concluded therefore that SH-Man-HSA has great potential for use in a rescue therapy for hepatopathy as a nanoantioxidant because of its ability to efficiently and rapidly deliver thiols to CD68(+)/CD206(+) KC. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

Protective Effects of Lemon Juice on Alcohol-Induced Liver Injury in Mice

PubMed Central

Zhang, Yu-Jie; Xu, Dong-Ping; Wang, Fang; Zhou, Yue; Zheng, Jie; Li, Ya; Zhang, Jiao-Jiao

2017-01-01

Chronic excessive alcohol consumption (more than 40–80 g/day for males and more than 20–40 g/day for females) could induce serious liver injury. In this study, effects of lemon juice on chronic alcohol-induced liver injury in mice were evaluated. The serum biochemical profiles and hepatic lipid peroxidation levels, triacylglycerol (TG) contents, antioxidant enzyme activities, and histopathological changes were examined for evaluating the hepatoprotective effects of lemon juice in mice. In addition, the in vitro antioxidant capacities of lemon juice were determined. The results showed that lemon juice significantly inhibited alcohol-induced increase of alanine transaminase (ALT), aspartate transaminase (AST), hepatic TG, and lipid peroxidation levels in a dose-dependent manner. Histopathological changes induced by alcohol were also remarkably improved by lemon juice treatment. These findings suggest that lemon juice has protective effects on alcohol-induced liver injury in mice. The protective effects might be related to the antioxidant capacity of lemon juice because lemon juice showed in vitro antioxidant capacity. PMID:28567423

Protective effect of Spirulina platensis enriched in phenolic compounds against hepatotoxicity induced by CCl4.

PubMed

Kepekçi, Remziye Aysun; Polat, Sait; Çelik, Ahmet; Bayat, Nuray; Saygideger, Saadet Demirörs

2013-12-01

Phenolic compounds make up the major secondary metabolites with high pharmaceutical potential. Microalgae were reported to contain low amounts of phenolic compounds. The present study aimed to investigate the hepatoprotective potential of biomass of Spirulina platensis enriched in phenolic compounds. The protective effects of the biomass of S. platensis with low amounts of phenolics (SP1) and with high amounts of phenolics (SP2) against CCl4-induced acute hepatotoxicity were evaluated in rats. The increased levels of ALT, AST and MDA along with decreased activities of SOD and CAT were significantly (p<0.01) ameliorated by SP2. Histological examinations revealed that SP2 was more potent than SP1 in protecting the liver from toxic injury of CCl4 and preserving the hepatocyte ultrastructure. The lesions including necrosis, lymphocyte infiltration, ballooning degeneration and hepatocyte injury as irregular lamellar organisation, dilations in endoplasmic reticulums and the presence of great number of cytoplasmic vacuolization were healed by SP2. Copyright © 2013 Elsevier Ltd. All rights reserved.

Protective Effects of Lemon Juice on Alcohol-Induced Liver Injury in Mice.

PubMed

Zhou, Tong; Zhang, Yu-Jie; Xu, Dong-Ping; Wang, Fang; Zhou, Yue; Zheng, Jie; Li, Ya; Zhang, Jiao-Jiao; Li, Hua-Bin

2017-01-01

Chronic excessive alcohol consumption (more than 40-80 g/day for males and more than 20-40 g/day for females) could induce serious liver injury. In this study, effects of lemon juice on chronic alcohol-induced liver injury in mice were evaluated. The serum biochemical profiles and hepatic lipid peroxidation levels, triacylglycerol (TG) contents, antioxidant enzyme activities, and histopathological changes were examined for evaluating the hepatoprotective effects of lemon juice in mice. In addition, the in vitro antioxidant capacities of lemon juice were determined. The results showed that lemon juice significantly inhibited alcohol-induced increase of alanine transaminase (ALT), aspartate transaminase (AST), hepatic TG, and lipid peroxidation levels in a dose-dependent manner. Histopathological changes induced by alcohol were also remarkably improved by lemon juice treatment. These findings suggest that lemon juice has protective effects on alcohol-induced liver injury in mice. The protective effects might be related to the antioxidant capacity of lemon juice because lemon juice showed in vitro antioxidant capacity.

Recent Advances in Momordica charantia: Functional Components and Biological Activities.

PubMed

Jia, Shuo; Shen, Mingyue; Zhang, Fan; Xie, Jianhua

2017-11-28

Momordica charantia L. ( M. charantia ), a member of the Cucurbitaceae family, is widely distributed in tropical and subtropical regions of the world. It has been used in folk medicine for the treatment of diabetes mellitus, and its fruit has been used as a vegetable for thousands of years. Phytochemicals including proteins, polysaccharides, flavonoids, triterpenes, saponins, ascorbic acid and steroids have been found in this plant. Various biological activities of M. charantia have been reported, such as antihyperglycemic, antibacterial, antiviral, antitumor, immunomodulation, antioxidant, antidiabetic, anthelmintic, antimutagenic, antiulcer, antilipolytic, antifertility, hepatoprotective, anticancer and anti-inflammatory activities. However, both in vitro and in vivo studies have also demonstrated that M. charantia may also exert toxic or adverse effects under different conditions. This review addresses the chemical constituents of M. charantia and discusses their pharmacological activities as well as their adverse effects, aimed at providing a comprehensive overview of the phytochemistry and biological activities of M. charantia .

Recent Advances in Momordica charantia: Functional Components and Biological Activities

PubMed Central

Jia, Shuo; Shen, Mingyue; Zhang, Fan; Xie, Jianhua

2017-01-01

Momordica charantia L. (M. charantia), a member of the Cucurbitaceae family, is widely distributed in tropical and subtropical regions of the world. It has been used in folk medicine for the treatment of diabetes mellitus, and its fruit has been used as a vegetable for thousands of years. Phytochemicals including proteins, polysaccharides, flavonoids, triterpenes, saponins, ascorbic acid and steroids have been found in this plant. Various biological activities of M. charantia have been reported, such as antihyperglycemic, antibacterial, antiviral, antitumor, immunomodulation, antioxidant, antidiabetic, anthelmintic, antimutagenic, antiulcer, antilipolytic, antifertility, hepatoprotective, anticancer and anti-inflammatory activities. However, both in vitro and in vivo studies have also demonstrated that M. charantia may also exert toxic or adverse effects under different conditions. This review addresses the chemical constituents of M. charantia and discusses their pharmacological activities as well as their adverse effects, aimed at providing a comprehensive overview of the phytochemistry and biological activities of M. charantia. PMID:29182587

Maca polysaccharides: A review of compositions, isolation, therapeutics and prospects.

PubMed

Li, Yujuan; Xu, Fangxue; Zheng, Mengmeng; Xi, Xiaozhi; Cui, Xiaowei; Han, Chunchao

2018-05-01

Maca polysaccharides, some of the major bioactive substances in Lepidium meyenii (Walp.) (Maca), have various biological properties, including anti-oxidant, anti-fatigue, anti-tumor, and immunomodulatory effects, as well as hepatoprotective activity and regulation function. Although many therapeutics depend on multiple structures of maca polysaccharides in addition to providing sufficient foundations for maca polysaccharide products in industrial applications, the relationships between the pharmacological effects and structures have not been established. Therefore, this article summarizes the extraction and purification methods, compositions, pharmacological effects, prospects and industrial applications of maca polysaccharides. Copyright © 2018 Elsevier B.V. All rights reserved.

Decursin attenuates hepatic fibrogenesis through interrupting TGF-beta-mediated NAD(P)H oxidase activation and Smad signaling in vivo and in vitro.

PubMed

Choi, Young Ji; Kim, Da Hye; Kim, Sang Jun; Kim, Ju; Jeong, Seung-Il; Chung, Chang Ho; Yu, Kang-Yeol; Kim, Seon-Young

2014-07-17

We studied that a potent antifibrotic effect of decursin on in vivo liver damage model and the mechanism in inhibiting which transforming growth factor (TGF)-β1-induced human hepatic stellate cells (HSCs) activation. Liver injury was induced in vivo by intraperitoneal injection of carbon tetrachloride (CCl4) with or without decursin for 4weeks in mice. Human hepatic stellate cell line, an immortalized human HSC line, was used in in vitro assay system. The effects of decursin on HSC activation were measured by analyzing the expression of α-smooth muscle actin (α-SMA) and collagen I in liver tissue and human HSCs. Decursin treatment significantly reduced the ratio of liver/body weight, α-SMA activation, and type I collagen overexpression in CCl4 treated mice liver. The elevated serum levels, including ALT, AST, and ALP, were also decreased by decursin treatment. Treatment of decursin markedly proved the generation of reactive oxygen species, NAD(P)H oxidase (NOX) protein (1, 2, and 4) upregulation, NOX activity, and superoxide anion production in HSCs by TGF-β1. It also significantly reduced TGF-β1-induced Smad 2/3 phosphorylation, nuclear translocation of Smad 4, and association of Smad 2/3-Smad 4 complex. Consistent with in vitro results, decursin treatment effectively blocked the levels of NOX protein, and Smad 2/3 phosphorylation in injured mice liver. Decursin blocked CCl4-induced liver fibrosis and inhibited TGF-β1-mediated HSC activation in vitro. These data demonstrated that decursin exhibited hepatoprotective effects on experimental fibrosis, potentially by inhibiting the TGF-β1 induced NOX activation and Smad signaling. Copyright © 2014 Elsevier Inc. All rights reserved.

Heme oxygenase-1 upregulated by Ginkgo biloba extract: potential protection against ethanol-induced oxidative liver damage.

PubMed

Yao, Ping; Li, Ke; Song, Fangfang; Zhou, Shaoliang; Sun, Xiufa; Zhang, Xiping; Nüssler, Andreas K; Liu, Liegang

2007-08-01

Oxidative stress plays a pivotal role in the pathogenesis and progression of alcoholic liver disease (ALD) and HO-1 induction is suggested to protect hepatocytes from ethanol hepatotoxicity. Here, we present the data to explore the hepatoprotective effect and underlying mechanism(s) of Ginkgo biloba extract (EGB), a naturally occurring HO-1 inducer, against ethanol-induced oxidative damage. Ethanol-fed (2.4 g/kg) male rats were pretreated by EGB (48 or 96 mg/kg) for 90 days. Liver damage was evaluated by histopathology and serum aminotransferase assay. Hepatic redox parameters were measured by spectrophotometry. Heme oxygenase-1 (HO-1) expression was determined by RT-PCR and flow cytometry on mRNA and protein level, respectively. Our results showed that EGB, especially at high dose, ameliorated ethanol-induced macrovesicular steatosis and parenchymatous degeneration in hepatocytes, and decreased serum aminotransferases level. Furthermore, EGB reduced ethanol-derived glutathione depletion and lipid peroxidation, and inhibited the inactivation of superoxide dismutase, glutathione peroxidase and catalase, although EGB itself had no influence on such parameters. Importantly, EGB induced hepatic microsomal HO-1 on mRNA, protein expression and enzymatic activity, which is paralleled to the EGB-derived hepatoprotective effect. Hence, HO-1 upregulation by EGB may enhance the antioxidative capacity against the ethanol-induced oxidative stress and maintain the cellular redox balance.

Effects of parsley (Petroselinum crispum) on the liver of diabetic rats: a morphological and biochemical study.

PubMed

Bolkent, S; Yanardag, R; Ozsoy-Sacan, O; Karabulut-Bulan, O

2004-12-01

Parsley is used by diabetics in Turkey to reduce blood glucose. The present study aims to investigate both the morphological and biochemical effects of parsley on liver tissue. Rat hepatocytes were examined by light and electron microscopy. Degenerative changes were observed in the hepatocytes of diabetic rats. These degenerative changes were significantly reduced or absent in the hepatocytes of diabetic rats treated with parsley. Blood glucose levels, alanine transaminase and alkaline phosphatase were observed to be raised in diabetic rats. Diabetic rats treated with parsley demonstrated significantly lower levels of blood glucose, alanine transaminase and alkaline phosphatase. The present study suggests that parsley demonstrates a significant hepatoprotective effect in diabetic rats. 2004 John Wiley & Sons, Ltd.

Pharmacological potentials of betalains.

PubMed

Kaur, Ginpreet; Thawkar, Baban; Dubey, Shivangi; Jadhav, Priyanka

2018-06-06

Betalains are water soluble plant pigments in plants of the order Caryophyllales, which are widely used as colorants. Several preclinical studies reported that betanin reveals antioxidants, anti-inflammatory, hepatoprotective, anticancer, anti-diabetes, anti-lipid emic, antimicrobial activity, radio protective and anti-proliferative activity. They are isolated from sources such as red beetroot, amaranth, prickly pear, red pitahaya, etc. Betalains are divided into two groups based on the colour and confer either the betacyanins (purple reddish) or betaxanthins (yellowish orange). Betalain is one of the promising nutraceuticals which can provide beneficial effects for prevention and cure of various diseases. The purpose of this review is to focus on nutraceutical facts of betalains by focusing on the ongoing treatment using betalains and to address its future nutraceuticals implications.

Maize Bioactive Peptides against Cancer

NASA Astrophysics Data System (ADS)

Díaz-Gómez, Jorge L.; Castorena-Torres, Fabiola; Preciado-Ortiz, Ricardo E.; García-Lara, Silverio

2017-06-01

Cancer is one of the main chronic degenerative diseases worldwide. In recent years, consumption of whole-grain cereals and their derived food products has been associated with reduction risks of various types of cancer. Cereals main biomolecules includes proteins, peptides, and amino acids present in different quantities within the grain. The nutraceutical properties associated with peptides exerts biological functions that promote health and prevent this disease. In this review, we report the current status and advances on maize peptides regarding bioactive properties that have been reported such as antioxidant, antihypertensive, hepatoprotective, and anti-tumour activities. We also highlighted its biological potential through which maize bioactive peptides exert anti-cancer activity. Finally, we analyse and emphasize the possible areas of application for maize peptides.

Role of Curcumin in Disease Prevention and Treatment.

PubMed

Rahmani, Arshad Husain; Alsahli, Mohammed A; Aly, Salah M; Khan, Masood A; Aldebasi, Yousef H

2018-01-01

Treatment based on traditional medicine is very popular in developing world due to inexpensive properties. Nowadays, several types of preparations based on medicinal plants at different dose have been extensively recognized in the diseases prevention and treatment. In this vista, latest findings support the effect of Curcuma longa and its chief constituents curcumin in a broad range of diseases cure via modulation of physiological and biochemical process. In addition, various studies based on animal mode and clinical trials showed that curcumin does not cause any adverse complications on liver and kidney function and it is safe at high dose. This review article aims at gathering information predominantly on pharmacological activities such as anti-diabetic, anti-microbial, hepato-protective activity, anti-inflammatory, and neurodegenerative diseases.

Role of Curcumin in Disease Prevention and Treatment

PubMed Central

Rahmani, Arshad Husain; Alsahli, Mohammed A.; Aly, Salah M.; Khan, Masood A.; Aldebasi, Yousef H.

2018-01-01

Treatment based on traditional medicine is very popular in developing world due to inexpensive properties. Nowadays, several types of preparations based on medicinal plants at different dose have been extensively recognized in the diseases prevention and treatment. In this vista, latest findings support the effect of Curcuma longa and its chief constituents curcumin in a broad range of diseases cure via modulation of physiological and biochemical process. In addition, various studies based on animal mode and clinical trials showed that curcumin does not cause any adverse complications on liver and kidney function and it is safe at high dose. This review article aims at gathering information predominantly on pharmacological activities such as anti-diabetic, anti-microbial, hepato-protective activity, anti-inflammatory, and neurodegenerative diseases. PMID:29629341

A Review on Ethnopharmacological Applications, Pharmacological Activities, and Bioactive Compounds of Mangifera indica (Mango)

PubMed Central

2017-01-01

Mangifera indica (family Anacardiaceae), commonly known as mango, is a pharmacologically, ethnomedically, and phytochemically diverse plant. Various parts of M. indica tree have been used in traditional medicine for the treatment of different ailments, and a number of bioactive phytochemical constituents of M. indica have been reported, namely, polyphenols, terpenes, sterols, carotenoids, vitamins, and amino acids, and so forth. Several studies have proven the pharmacological potential of different parts of mango trees such as leaves, bark, fruit peel and flesh, roots, and flowers as anticancer, anti-inflammatory, antidiabetic, antioxidant, antibacterial, antifungal, anthelmintic, gastroprotective, hepatoprotective, immunomodulatory, antiplasmodial, and antihyperlipemic. In the present review, a comprehensive study on ethnopharmacological applications, pharmacological activities, and bioactive compounds of M. indica has been described. PMID:29456572

Structures, biological activities, and industrial applications of the polysaccharides from Hericium erinaceus (Lion's Mane) mushroom: A review.

PubMed

He, Xirui; Wang, Xiaoxiao; Fang, Jiacheng; Chang, Yu; Ning, Ning; Guo, Hao; Huang, Linhong; Huang, Xiaoqiang; Zhao, Zefeng

2017-04-01

Hericium erinaceus (Bull.) Pers., also known as Yamabushitake, Houtou and Lion's Mane, is capable of fortifying the spleen and nourishing the stomach, tranquilizing the mind, and fighting cancer. Over the past decade, it has been demonstrated that H. erinaceus polysaccharides possess various promising bioactivities, including antitumor and immunomodulation, anti-gastric ulcer, neuroprotection and neuroregeneration, anti-oxidation and hepatoprotection, anti-hyperlipidemia, anti-hyperglycemia, anti-fatigue and anti-aging. The purpose of the present review is to provide systematically reorganized information on extraction and purification, structure characteristics, biological activities, and industrial applications of H. erinaceus polysaccharides to support their therapeutic potentials and sanitarian functions. Copyright © 2017 Elsevier B.V. All rights reserved.

Chrysin abrogates early hepatocarcinogenesis and induces apoptosis in N-nitrosodiethylamine-induced preneoplastic nodules in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khan, Mahaboob S.; Department of Biochemistry, Govt. Home Science College, Panjab University, Chandigarh; Devaraj, Halagowder

Flavonoids possess strong anti-oxidant and cancer chemopreventive activities. Chrysin (5,7-dihydroxyflavone) occurs naturally in many plants, honey, and propolis. In vitro, chrysin acts as a general anti-oxidant, causes cell cycle arrest and promotes cell death. However, the mechanism by which chrysin inhibits cancer cell growth and the subcellular pathways activated remains poorly understood. Effect of dietary supplementation with chrysin on proliferation and apoptosis during diethylnitrosamine (DEN)-induced early hepatocarcinogenesis was investigated in male Wistar rats. To induce hepatocarcinogenesis, rats were given DEN injections (i.p., 200 mg/kg) three times at a 15 day interval. An oral dose of chrysin (250 mg/kg bodyweight) wasmore » given three times weekly for 3 weeks, commencing 1 week after the last dose of DEN. Changes in the mRNA expression of COX-2, NFkB p65, p53, Bcl-xL and {beta}-arrestin-2 were assessed by quantitative real-time PCR. Changes in the protein levels were measured by western blotting. Chrysin administration significantly (P < 0.001) reduced the number and size of nodules formed. Also, a significant (P < 0.01) reduction in serum activities of AST, ALT, ALP, LDH and {gamma}GT was noticed. Expression of COX-2 and NFkB p65 was significantly reduced whereas that of p53, Bax and caspase 3 increased at the mRNA and protein levels. Likewise, a decrease in levels of {beta}-arrestin and the anti-apoptotic marker Bcl-xL was also noted. These findings suggest that chrysin exerts global hepato-protective effect and its chemopreventive activity is associated with p53-mediated apoptosis during early hepatocarcinogenesis.« less

Enhanced oral bioavailability and anticancer activity of novel curcumin loaded mixed micelles in human lung cancer cells.

PubMed

Patil, Sharvil; Choudhary, Bhavana; Rathore, Atul; Roy, Krishtey; Mahadik, Kakasaheb

2015-11-15

Curcumin has a wide range of pharmacological activities including antioxidant, anti-inflammatory, antidiabetic, antibacterial, wound healing, antiatherosclerotic, hepatoprotective and anti-carcinogenic. However, its clinical applications are limited owing to its poor aqueous solubility, multidrug pump P-gp efflux, extensive in vivo metabolism and rapid elimination due to glucuronidation/sulfation. The objective of the current work was to prepare novel curcumin loaded mixed micelles (CUR-MM) of Pluronic F-127 (PF127) and Gelucire® 44/14 (GL44) in order to enhance its oral bioavailability and cytotoxicity in human lung cancer cell line A549. 3(2) Factorial design was used to assess the effect of formulation variables for optimization of mixed micelle batch. CUR-MM was prepared by a solvent evaporation method. The optimized CUR-MM was evaluated for size, entrapment efficiency (EE), in vitro curcumin release, cytotoxicity and oral bioavailability in rats. The average size of CUR-MM was found to be around 188 ± 3 nm with an EE of about 76.45 ± 1.18% w/w. In vitro dissolution profile of CUR-MM revealed controlled release of curcumin. Additionally, CUR-MM showed significant improvement in cytotoxic activity (3-folds) and oral bioavailability (around 55-folds) of curcumin as compared to curcumin alone. Such significant improvement in cytotoxic activity and oral bioavailability of curcumin when formulated into mixed micelles could be attributed to solubilization of hydrophobic curcumin into micelle core along with P-gp inhibition effect of both, PF127 and GL44. Thus the present work propose the formulation of mixed micelles of PF127 and GL44 which can act as promising carrier systems for hydrophobic drugs such as curcumin with significant improvement in their oral bioavailability. Copyright © 2015 Elsevier GmbH. All rights reserved.

Bacoside A downregulates matrix metalloproteinases 2 and 9 in DEN-induced hepatocellular carcinoma.

PubMed

Janani, Panneerselvam; Sivakumari, Kanakarajan; Geetha, Arumugam; Yuvaraj, Sambandam; Parthasarathy, Chandrakesan

2010-03-01

Cancer metastasis is a complex multi-step process, responsible for a majority of cancer-related deaths by affecting the critical organs and causing complications in therapies. Hepatocellular carcinoma is a multi-factorial disease and is the third most common cause of cancer related mortality worldwide. Clinical and experimental studies have shown that MMP-2 and MMP-9 are involved in tumor invasion and metastases and their elevated expression has been associated with poor prognosis. Our recent studies showed a strong anti-oxidant and hepatoprotective effects of bacoside A (BA) against carcinogen. Nevertheless the effect of BA on the activities and expression of MMP-2 and MMP-9 during hepatocellular carcinoma is not yet recognized. Therefore, the present study was designed to assess the same. Results of gelatin zymography study showed that BA co-treatment significantly decreased the activities of MMP-2 and MMP-9, which is increased during hepatocellular carcinoma. Further immunoblot analysis showed decreased expression of MMP-2 and MMP-9 in rats co-treated with BA compared to DEN-induced hepatocellular carcinoma. Our results reveal that BA exerts its anti-metastatic effect against DEN-induced hepatocellular carcinoma by inhibiting the activities and expressions of MMP-2 and MMP-9. 2010 John Wiley & Sons, Ltd.

Berberine nanoparticles with enhanced in vitro bioavailability: characterization and antimicrobial activity

PubMed Central

Faidah, Hani S; Khurram, Muhammad; Amin, Muhammad Usman; Haseeb, Abdul; Kakar, Maria

2018-01-01

Background Berberine is an isoquinoline alkaloid widely used in Ayurveda and traditional Chinese medicine to treat illnesses such as hypertension and inflammatory conditions, and as an anticancer and hepato-protective agent. Berberine has low oral bioavailability due to poor aqueous solubility and insufficient dissolution rate, which can reduce the efficacy of drugs taken orally. In this study, evaporative precipitation of nanosuspension (EPN) and anti-solvent precipitation with a syringe pump (APSP) were used to address the problems of solubility, dissolution rate and bioavailability of berberine. Methods Semi-crystalline nanoparticles (NPs) of 90–110 nm diameter for APSP and 65–75 nm diameter for EPN were prepared and then characterized using differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRD). Thereafter, drug content solubility and dissolution studies were undertaken. Berberine and its NPs were evaluated for their antibacterial activity. Results The results indicate that the NPs have significantly increased solubility and dissolution rate due to conversion of the crystalline structure to a semi-crystalline form. Conclusion Berberine NPs produced by both APSP and EPN methods have shown promising activities against Gram-positive and Gram-negative bacteria, and yeasts, with NPs prepared through the EPN method showing superior results compared to those made with the APSP method and the unprocessed drug. PMID:29491706

Protective Effect of Baccharis trimera Extract on Acute Hepatic Injury in a Model of Inflammation Induced by Acetaminophen

PubMed Central

Pádua, Bruno da Cruz; Rossoni Júnior, Joamyr Victor; de Brito Magalhães, Cíntia Lopes; Chaves, Míriam Martins; Silva, Marcelo Eustáquio; Pedrosa, Maria Lucia; de Souza, Gustavo Henrique Bianco; Brandão, Geraldo Célio; Rodrigues, Ivanildes Vasconcelos; Lima, Wanderson Geraldo; Costa, Daniela Caldeira

2014-01-01

Background. Acetaminophen (APAP) is a commonly used analgesic and antipyretic. When administered in high doses, APAP is a clinical problem in the US and Europe, often resulting in severe liver injury and potentially acute liver failure. Studies have demonstrated that antioxidants and anti-inflammatory agents effectively protect against the acute hepatotoxicity induced by APAP overdose. Methods. The present study attempted to investigate the protective effect of B. trimera against APAP-induced hepatic damage in rats. The liver-function markers ALT and AST, biomarkers of oxidative stress, antioxidant parameters, and histopathological changes were examined. Results. The pretreatment with B. trimera attenuated serum activities of ALT and AST that were enhanced by administration of APAP. Furthermore, pretreatment with the extract decreases the activity of the enzyme SOD and increases the activity of catalase and the concentration of total glutathione. Histopathological analysis confirmed the alleviation of liver damage and reduced lesions caused by APAP. Conclusions. The hepatoprotective action of B. trimera extract may rely on its effect on reducing the oxidative stress caused by APAP-induced hepatic damage in a rat model. General Significance. These results make the extract of B. trimera a potential candidate drug capable of protecting the liver against damage caused by APAP overdose. PMID:25435714

Hederagenin Supplementation Alleviates the Pro-Inflammatory and Apoptotic Response to Alcohol in Rats.

PubMed

Kim, Gyeong-Ji; Song, Da Hye; Yoo, Han Seok; Chung, Kang-Hyun; Lee, Kwon Jai; An, Jeung Hee

2017-01-06

In this study, we determined the effects of hederagenin isolated from Akebia quinata fruit on alcohol-induced hepatotoxicity in rats. Specifically, we investigated the hepatoprotective, anti-inflammatory, and anti-apoptotic effects of hederagenin, as well as the role of AKT and mitogen-activated protein kinase (MAPK) signaling pathways in ethanol-induced liver injury. Experimental animals were randomly divided into three groups: normal (sham), 25% ethanol, and 25% ethanol + hederagenin (50 mg/kg/day). Each group was orally administered the respective treatments once per day for 21 days. Acetaldehyde dehydrogenase-2 mRNA expression was higher and alcohol dehydrogenase mRNA expression was lower in the ethanol + hederagenin group than those in the ethanol group. Pro-inflammatory cytokines, including TNF-α, IL-6, and cyclooxygenase-2, significantly increased in the ethanol group, but these increases were attenuated by hederagenin. Moreover, Western blot analysis showed increased expression of the apoptosis-associated protein, Bcl-2, and decreased expression of Bax and p53 after treatment with hederagenin. Hederagenin treatment attenuated ethanol-induced increases in activated p38 MAPK and increased the levels of phosphorylated AKT and ERK. Hederagenin alleviated ethanol-induced liver damage through anti-inflammatory and anti-apoptotic activities. These results suggest that hederagenin is a potential candidate for preventing alcoholic liver injury.

Berberine nanoparticles with enhanced in vitro bioavailability: characterization and antimicrobial activity.

PubMed

Sahibzada, Muhammad Umar Khayam; Sadiq, Abdul; Faidah, Hani S; Khurram, Muhammad; Amin, Muhammad Usman; Haseeb, Abdul; Kakar, Maria

2018-01-01

Berberine is an isoquinoline alkaloid widely used in Ayurveda and traditional Chinese medicine to treat illnesses such as hypertension and inflammatory conditions, and as an anticancer and hepato-protective agent. Berberine has low oral bioavailability due to poor aqueous solubility and insufficient dissolution rate, which can reduce the efficacy of drugs taken orally. In this study, evaporative precipitation of nanosuspension (EPN) and anti-solvent precipitation with a syringe pump (APSP) were used to address the problems of solubility, dissolution rate and bioavailability of berberine. Semi-crystalline nanoparticles (NPs) of 90-110 nm diameter for APSP and 65-75 nm diameter for EPN were prepared and then characterized using differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRD). Thereafter, drug content solubility and dissolution studies were undertaken. Berberine and its NPs were evaluated for their antibacterial activity. The results indicate that the NPs have significantly increased solubility and dissolution rate due to conversion of the crystalline structure to a semi-crystalline form. Berberine NPs produced by both APSP and EPN methods have shown promising activities against Gram-positive and Gram-negative bacteria, and yeasts, with NPs prepared through the EPN method showing superior results compared to those made with the APSP method and the unprocessed drug.

Purification and in vitro antioxidant activities of tellurium-containing phycobiliproteins from tellurium-enriched Spirulina platensis.

PubMed

Yang, Fang; Wong, Ka-Hing; Yang, Yufeng; Li, Xiaoling; Jiang, Jie; Zheng, Wenjie; Wu, Hualian; Chen, Tianfeng

2014-01-01

Tellurium-containing phycocyanin (Te-PC) and allophycocyanin (Te-APC), two organic tellurium (Te) species, were purified from tellurium-enriched Spirulina platensis by a fast protein liquid chromatographic method. It was found that the incorporation of Te into the peptides enhanced the antioxidant activities of both phycobiliproteins. With fractionation by ammonium sulfate precipitation and hydroxylapatite chromatography, Te-PC and Te-APC could be effectively separated with high purity, and Te concentrations were 611.1 and 625.3 μg g(-1) protein in Te-PC and Te-APC, respectively. The subunits in the proteins were identified by using MALDI-TOF-TOF mass spectrometry. Te incorporation enhanced the antioxidant activities of both phycobiliproteins, as examined by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid assay. Moreover, Te-PC and Te-APC showed dose-dependent protection on erythrocytes against the water-soluble free radical initiator 2,2'-azo(2-asmidinopropane)dihydrochloride-induced hemolysis. In the hepatoprotective model, apoptotic cell death and nuclear condensation induced by tert-butyl hydroperoxide in HepG2 cells was significantly attenuated by Te-PC and Te-APC. Taken together, these results suggest that Te-PC and Te-APC are promising Te-containing proteins with application potential for treatment of diseases related to oxidative stress.

Purification and in vitro antioxidant activities of tellurium-containing phycobiliproteins from tellurium-enriched Spirulina platensis

PubMed Central

Yang, Fang; Wong, Ka-Hing; Yang, Yufeng; Li, Xiaoling; Jiang, Jie; Zheng, Wenjie; Wu, Hualian; Chen, Tianfeng

2014-01-01

Tellurium-containing phycocyanin (Te-PC) and allophycocyanin (Te-APC), two organic tellurium (Te) species, were purified from tellurium-enriched Spirulina platensis by a fast protein liquid chromatographic method. It was found that the incorporation of Te into the peptides enhanced the antioxidant activities of both phycobiliproteins. With fractionation by ammonium sulfate precipitation and hydroxylapatite chromatography, Te-PC and Te-APC could be effectively separated with high purity, and Te concentrations were 611.1 and 625.3 μg g−1 protein in Te-PC and Te-APC, respectively. The subunits in the proteins were identified by using MALDI-TOF-TOF mass spectrometry. Te incorporation enhanced the antioxidant activities of both phycobiliproteins, as examined by 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid assay. Moreover, Te-PC and Te-APC showed dose-dependent protection on erythrocytes against the water-soluble free radical initiator 2,2′-azo(2-asmidinopropane)dihydrochloride-induced hemolysis. In the hepatoprotective model, apoptotic cell death and nuclear condensation induced by tert-butyl hydroperoxide in HepG2 cells was significantly attenuated by Te-PC and Te-APC. Taken together, these results suggest that Te-PC and Te-APC are promising Te-containing proteins with application potential for treatment of diseases related to oxidative stress. PMID:25336922

Quercus dilatata Lindl. ex Royle ameliorates BPA induced hepatotoxicity in Sprague Dawley rats.

PubMed

Kazmi, Syeda Tayyaba Batool; Majid, Muhammad; Maryam, Sonia; Rahat, Aymen; Ahmed, Madiha; Khan, Muhammad Rashid; Haq, Ihsan Ul

2018-06-01

Quercus dilatata Lindl. ex Royle was evaluated for in vitro polyphenol content and antioxidant potential as well as in vivo protective role against bisphenol A (BPA) induced hepatotoxicity. The distilled water-acetone (QDDAE) and methanol-ethyl acetate (QDMEtE) extracts were standardized and administered in high (300 mg/kg body weight (BW) and low (150 mg/kg BW) doses to Sprague Dawley rats, injected with BPA (25 mg/kg BW). Silymarin (50 mg/kg BW) was used as positive control. Subsequently, blood and liver homogenates were collected after four weeks of treatment, and the defensive effects of both extracts against oxidative damage and genotoxicity were assessed via hematological and biochemical investigations, determination of endogenous expression of enzymes as well as levels of free radicals and comet assay. Between the two extracts, maximum phenolics (213 ± 0.15 μg gallic acid equivalent/mg dry extract (DE) and flavonoids (55.6 ± 0.16 μg quercetin equivalent/mg DE) content, DPPH scavenging activity (IC 50 : 8.1 ± 0.5 μg/ml), antioxidant capacity (53.7 ± 0.98 μg ascorbic acid equivalent (AAE)/mg DE) and reducing potential (228.4 ± 2.4 μg AAE/mg DE) were observed in QDMEtE. In in vivo analysis, a dose dependent hepatoprotective activity was exhibited by both the extracts. QDDAE demonstrated maximum reduction in levels of alanine transaminase (49.77 ± 3.83 U/l), thiobarbituric acid reactant substances (33.46 ± 0.70 nM/min/mg protein), hydrogen peroxide (18.08 ± 0.01 ng/mg tissue) and nitrite (55.64 ± 1.79 μM/ml), along with decline in erythrocyte sedimentation rate (4.13 ± 0.072 mm/h), histopathological injuries and DNA damage in BPA intoxicated rats as compared with QDMEtE. Likewise, QDDAE also significantly restored activity levels of endogenous antioxidants, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (POD) and GSH with values of 6.46 ± 0.15 U/mg protein, 6.87 ± 0.1 U/min, 11.94 ± 0.17 U/min and 16.86 ± 1.56 nM/min/mg protein, respectively. Comparative results were obtained for QDMEtE. In conclusion, the present study endorses the significant hepatoprotective potential of standardized extracts of Q. dilatata with known polyphenolics content and validates the traditional use of this plant in natural medicine to manage disorders like hepatotoxicity. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Beneficial effects of apple peel polyphenols on vascular endothelial dysfunction and liver injury in high choline-fed mice.

PubMed

Jia, Mengfan; Ren, Daoyuan; Nie, Yan; Yang, Xingbin

2017-03-22

This study was designed to investigate the preventive effects of Red Fuji apple peel polyphenolic extract (APP) on vascular endothelial dysfunction and liver injury in mice fed a high choline diet. The mice were fed 3% dietary choline in drinking water for 8 weeks and displayed vascular dysfunction and liver damage (p < 0.01). The administration of APP at 600 and 900 mg per kg bw significantly elevated serum NO, HDL and 6-Keto-PGF1a levels and lowered serum TC, TG, LDL, ET-1 and TXB2 levels in the HC-fed mice. Besides, APP also caused the reduction of AST, ALT activities and MDA, CRP, TNF-α levels, and increased the hepatic GSH-Px and SOD activities of the HC-fed mice. Furthermore, the histopathology of the liver by conventional H&E and oil red O staining confirmed the liver steatosis induced by a choline diet and the hepatoprotective effect of APP. The experiment results indicated that the polyphenolic extract from apple peel might be regarded as a preventive and therapeutic product for the amelioration of HC diet-induced vascular dysfunction and hepatic injury.

Rhus chinensis and Galla Chinensis--folklore to modern evidence: review.

PubMed

Djakpo, Odilon; Yao, Weirong

2010-12-01

The species Rhus chinensis Mill. (Anacardiaceae) is an important representative of the genus Rhus, which contains over 250 individual species found in temperate and tropical regions worldwide. Rhus chinensis has long been used by folk medicine practitioners in Asia. Leaves, roots, stem, bark, fruit and particularly the galls on Rhus chinensis leaves, Galla chinensis, are recognized to have preventative and therapeutic effects on different ailments (such as diarrhea, dysentery, rectal and intestinal cancer, diabetes mellitus, sepsis, oral diseases and inflammation). However, it is critical to separate evidence from anecdote. Fortunately, recent scientific research has revealed that Rhus chinensis compounds possess strong antiviral, antibacterial, anticancer, hepatoprotective, antidiarrheal and antioxidant activities. Moreover, compounds isolated from the stem of Rhus chinensis significantly suppressed HIV-1 activity in vitro. Compounds from this plant were also found to inhibit enamel demineralization in vitro and enhance remineralization of dental enamel with fluoride. This review highlights claims from traditional and tribal medicinal lore and makes a contemporary summary of phytochemical, biological and pharmacological findings on this plant material. It aims to show that the pharmaceutical potential of this plant deserves closer attention. Copyright © 2010 John Wiley & Sons, Ltd.

Assessment of hepatoprotective and nephroprotective potential of withaferin A on bromobenzene-induced injury in Swiss albino mice: possible involvement of mitochondrial dysfunction and inflammation.

PubMed

Vedi, Mahima; Sabina, Evan Prince

2016-10-01

Bromobenzene is a well-known environmental toxin which causes liver and kidney damage through CYP450-mediated bio-activation to generate reactive metabolites and, consequently, oxidative stress. The present study aimed to evaluate the possible protective role of withaferin A against bromobenzene-induced liver and kidney damage in mice. Withaferin A (10 mg/kg) was administered orally to the mice for 8 days before intragastric intubation of bromobenzene (10 mmol/kg). As results of this experiment, the levels of liver and kidney functional markers, lipid peroxidation, and cytokines (TNF-α and IL-1β) presented an increase and there was a decrease in anti-oxidant activity in the bromobenzene-treated group of mice. Pre-treatment with withaferin A not only significantly decreased the levels of liver and kidney functional markers and cytokines but also reduced oxidative stress, as evidenced by improved anti-oxidant status. In addition, the mitochondrial dysfunction shown through the decrease in the activities of mitochondrial enzymes and imbalance in the Bax/Bcl-2 expression in the livers and kidneys of bromobenzene-treated mice was effectively prevented by pre-administration of withaferin A. These results validated our conviction that bromobenzene caused liver and kidney damage via mitochondrial pathway and withaferin A provided significant protection against it. Thus, withaferin A may have possible usage in clinical liver and kidney diseases in which oxidative stress and mitochondrial dysfunction may be existent.

Protective effect of wedelolactone against CCl4-induced acute liver injury in mice.

PubMed

Lu, Yang; Hu, DongMei; Ma, ShanBo; Zhao, Xian; Wang, Shan; Wei, Guo; Wang, XiFang; Wen, AiDong; Wang, JingWen

2016-05-01

Eclipta, a traditional Chinese medicine, has been used to treat liver disease for centuries. However, the chemical basis and biological mechanisms of Eclipta remain elusive. The current study aims to investigate the hepatoprotective effect of wedelolactone (WEL), a major coumarin in Eclipta, using C57BL/6 mice with carbon tetrachloride CCl4-induced acute liver injury (ALI). Our data showed that WEL markedly decreased the CCl4-induced elevation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, and improved hepatic histopathology changes. WEL also significantly decreased the content of MDA in liver tissues, meanwhile increased the activities of antioxidant enzymes SOD and GSH-Px. In addition, WEL reduced the protein expression of TNF-α, IL-1β and IL-6, as well as mRNA expression. Western blot results revealed that WEL repressed phosphorylation of extracellular signal-regulated kinase (ERK) and translocation of NF-κB p65 from cytoplasm to nucleus and enhanced the phosphorylation of c-Jun. N-terminal kinase (JNK). Moreover, results showed that WEL significantly inhibited CCl4-induced hepatocytes apoptosis, markedly suppressed the down-regulation of Bax and active Caspase-3 expression and accelerated the expression of Bcl-2. Overall, the findings indicate that WEL exhibits a protective effect against CCl4-induced ALI in mice by enhancing the antioxidative defense system, suppressing the inflammatory response and cell apoptosis of liver. Copyright © 2016 Elsevier B.V. All rights reserved.

Eleusine indica L. possesses antioxidant activity and precludes carbon tetrachloride (CCl₄)-mediated oxidative hepatic damage in rats.

PubMed

Iqbal, Mohammad; Gnanaraj, Charles

2012-07-01

The purpose of this study was to evaluate the ability of aqueous extract of Eleusine indica to protect against carbon tetrachloride (CCl₄)-induced hepatic injury in rats. The antioxidant activity of E. indica was evaluated using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging assay. The total phenolic content of E. indica was also determined. Biochemical parameters [e.g. alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), glutathione (GSH), catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase and quinone reductase] were used to evaluate hepatic damage in animals pretreated with E. indica and intoxicated with CCl₄. CCl₄-mediated hepatic damage was also evaluated by histopathologically. E. indica extract was able to reduce the stable DPPH level in a dose-dependent manner. The half maximal inhibitory concentration (IC₅₀) value was 2350 μg/ml. Total phenolic content was found to be 14.9 ± 0.002 mg/g total phenolic expressed as gallic acid equivalent per gram of extract. Groups pretreated with E. indica showed significantly increased activity of antioxidant enzymes compared to the CCl₄-intoxicated group (p < 0.05). The increased levels of serum ALT and AST were significantly prevented by E. indica pretreatment (p < 0.05). The extent of MDA formation due to lipid peroxidation was significantly reduced (p < 0.05), and reduced GSH was significantly increased in a dose-dependently manner (p < 0.05) in the E. indica-pretreated groups as compared to the CCl₄-intoxicated group. The protective effect of E. indica was further evident through decreased histopathological alterations in the liver. The results of our study indicate that the hepatoprotective effects of E. indica might be ascribable to its antioxidant and free radical scavenging property.

A standardized extract from Paeonia lactiflora and Astragalus membranaceus attenuates liver fibrosis induced by porcine serum in rats.

PubMed

Sun, Wu-Yi; Wang, Ling; Liu, Hao; Li, Xiang; Wei, Wei

2012-03-01

Paeonia lactiflora and Astragalus membranaceus are two popular traditional Chinese medicines, commonly used in Chinese herb prescription to treat liver disease. The extract prepared from the roots of Paeonia lactiflora and Astragalus membranaceus (PAE) demonstrated better hepatoprotective activity than the herbs used individually as shown in our previous studies. This study was carried out to investigate the effects of PAE on liver fibrosis induced by porcine serum (PS) in rats and to explore its possible mechanisms. Liver fibrosis was induced in male Wistar rats by injection with PS intraperitoneally. The rats were randomly divided into a normal control group, a liver fibrosis model group and a PAE (40, 80, 160 mg•kg-1) treated group. After a 16-week treatment, PAE-treated rats showed significantly reduced liver damage and symptoms of liver fibrosis upon pathological examination. Administration of PAE significantly decreased serum HA, PC III levels, and content of hydroxyproline in the liver tissue of fibrotic rats. It also restored the decrease in SOD and GSH-Px activities and inhibited the formation of lipid peroxidative products during PS treatment. In vitro, PAE also significantly decreased [3H]-thymidine incorporation in hepatic stellate cells (HSCs) stimulated with platelet-derived growth factor-B subunit homodimer (PDGF-BB). Moreover, PAE significantly decreased the expression of PDGF receptor beta (PDGFR-β) and p-ERK1/2, p-p38, p-JNK. The results showed that PAE displays antifibrotic effects in rats induced by PS, the mechanism by which might be associated with its ability to scavenge free radicals, decreasing the expression of PDGFR-β, inhibition of HSC proliferation and MAPK activation. These findings indicate that PAE is a potential agent for the prevention of liver fibrosis.

Glycogen-gold nanohybrid escalates the potency of silymarin.

PubMed

Kandimalla, Raghuram; Dash, Suvakanta; Bhowal, Ashim Chandra; Kalita, Sanjeeb; Talukdar, Narayan Chandra; Kundu, Sarathi; Kotoky, Jibon

2017-01-01

In this study, a glycogen-gold nanohybrid was fabricated to enhance the potency of a promising hepatoprotective agent silymarin (Sly) by improving its solubility and gut permeation. By utilizing a facile green chemistry approach, biogenic gold nanoparticles were synthesized from Annona reticulata leaf phytoconstituents in combination with Sly (SGNPs). Further, the SGNPs were aggregated in glycogen biopolymer to yield the therapeutic nanohybrids (GSGNPs). Transmission electron microscopy, UV-Vis spectroscopy, X-ray diffraction, and Fourier transform infrared spectroscopy analysis confirmed the successful formation and conjugation of both SGNPs and GSGNPs. The fabricated nanohybrids showed significant protection against CCl 4 -induced hepatic injury in Wistar rats and maintained natural antioxidant (superoxide dismutase and catalase) levels. Animals treated with GSGNPs (10 mg/kg) and SGNPs (20 mg/kg) retained usual hepatic functions with routine levels of hepatobiliary enzymes (aspartate transferase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase) and inflammatory markers (interleukin-1β and tumor necrosis factor-α) with minimal lipid peroxidation, whereas those treated with 100 mg/kg of Sly showed the similar effect. These results were also supported by histopathology of the livers where pronounced hepatoprotection with normal hepatic physiology and negligible inflammatory infiltrate were observed. Significant higher plasma C max supported the enhanced bioavailability of Sly upon GSGNPs treatment compared to SGNPs and free Sly. Graphite furnace atomic absorption spectrophotometry analysis also substantiated the efficient delivery of GSGNPs over SGNPs. The fabricated therapeutic nanohybrids were also found to be biocompatible toward human erythrocytes and L929 mouse fibroblast cells. Overall, due to increased solubility, bioavailability and profuse gut absorption; GSGNPs demonstrated tenfold enhanced potency compared to free Sly.

Improved Hepatoprotective Effect of Liposome-Encapsulated Astaxanthin in Lipopolysaccharide-Induced Acute Hepatotoxicity

PubMed Central

Chiu, Chun-Hung; Chang, Chun-Chao; Lin, Shiang-Ting; Chyau, Charng-Cherng; Peng, Robert Y.

2016-01-01

Lipopolysaccharide (LPS)-induced acute hepatotoxicity is significantly associated with oxidative stress. Astaxanthin (AST), a xanthophyll carotenoid, is well known for its potent antioxidant capacity. However, its drawbacks of poor aqueous solubility and low bioavailability have limited its utility. Liposome encapsulation is considered as an effective alternative use for the improvement of bioavailability of the hydrophobic compound. We hypothesized that AST encapsulated within liposomes (LA) apparently shows improved stability and transportability compared to that of free AST. To investigate whether LA administration can efficiently prevent the LPS-induced acute hepatotoxicity, male Sprague-Dawley rats (n = six per group) were orally administered liposome-encapsulated AST at 2, 5 or 10 mg/kg-day (LA-2, LA-5, and LA-10) for seven days and then were LPS-challenged (i.p., 5 mg/kg). The LA-10 administered group, but not the other groups, exhibited a significant amelioration of serum glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), blood urea nitrogen (BUN), creatinine (CRE), hepatic malondialdehyde (MDA) and glutathione peroxidase (GSH-Px), IL-6, and hepatic nuclear NF-κB and inducible nitric oxide synthase (iNOS), suggesting that LA at a 10 mg/kg-day dosage renders hepatoprotective effects. Moreover, the protective effects were even superior to that of positive control N-acetylcysteine (NAC, 200 mg/kg-day). Histopathologically, NAC, free AST, LA-2 and LA-5 partially, but LA-10 completely, alleviated the acute inflammatory status. These results indicate that hydrophobic AST after being properly encapsulated by liposomes improves bioavailability and can also function as potential drug delivery system in treating hepatotoxicity. PMID:27428953