Gallic acid induces apoptosis in EGFR-mutant non-small cell lung cancers by accelerating EGFR turnover.

PubMed

Nam, Boas; Rho, Jin Kyung; Shin, Dong-Myung; Son, Jaekyoung

2016-10-01

Gallic acid is a common botanic phenolic compound, which is present in plants and foods worldwide. Gallic acid is implicated in various biological processes such as cell growth and apoptosis. Indeed, gallic acid has been shown to induce apoptosis in many cancer types. However, the molecular mechanisms of gallic acid-induced apoptosis in cancer, particularly lung cancer, are still unclear. Here, we report that gallic acid induces apoptosis in EGFR-mutant non-small cell lung cancer (NSCLC) cells, but not in EGFR-WT NSCLC cells. Treatment with gallic acid resulted in a significant reduction in proliferation and induction of apoptosis, only in EGFR-mutant NSCLC cells. Interestingly, treatment with gallic acid led to a robust decrease in EGFR levels, which is critical for NSCLC survival. Treatment with gallic acid had no significant effect on transcription, but induced EGFR turnover. Indeed, treatment with a proteasome inhibitor dramatically reversed gallic acid-induced EGFR downregulation. Moreover, treatment with gallic acid induced EGFR turnover leading to apoptosis in EGFR-TKI (tyrosine kinase inhibitor)-resistant cell lines, which are dependent on EGFR signaling for survival. Thus, these studies suggest that gallic acid can induce apoptosis in EGFR-dependent lung cancers that are dependent on EGFR for growth and survival via acceleration of EGFR turnover. Copyright © 2016 Elsevier Ltd. All rights reserved.

Protective effect of gallic acid against cisplatin-induced ototoxicity in rats.

PubMed

Kilic, Korhan; Sakat, Muhammed Sedat; Akdemir, Fazile Nur Ekinci; Yildirim, Serkan; Saglam, Yavuz Selim; Askin, Seda

2018-04-07

Cisplatin is an antineoplastic agent widely used in the treatment of a variety of cancers. Ototoxicity is one of the main side-effects restricting the use of cisplatin. The purpose of this study was to investigate the protective efficacy of gallic acid, in biochemical, functional and histopathological terms, against ototoxicity induced by cisplatin. Twenty-eight female Sprague Dawley rats were included. Rats were randomly assigned into four groups of seven animals each. Cisplatin group received a single intraperitoneal dose of 15mg/kg cisplatin. Gallic acid group received intraperitoneal gallic acid at 100mg/kg for five consecutive days. Cisplatin+Gallic acid group received intraperitoneal gallic acid at 100mg/kg for five consecutive days and a single intraperitoneal dose of 15mg/kg cisplatin at 3rd day. A control group received 1mL intraperitoneal saline solution for five consecutive days. Prior to drug administration, all rats were exposed to the distortion product otoacoustic emissions test. The test was repeated on the 6th day of the study. All rats were then sacrificed; the cochleas were removed and set aside for biochemical and histopathological analyses. In Cisplatin group, Day 6 signal noise ratio values were significantly lower than those of the other groups. Also, malondialdehyde levels in cochlear tissues were significantly higher, superoxide dismutase and glutathione peroxidase activities were significantly lower compared to the control group. Histopathologic evaluation revealed erosion in the stria vascularis, degeneration and edema in the connective tissue layer in endothelial cells, impairment of outer hair cells and a decrease in the number of these calls. In the Cisplatin+Gallic acid group, this biochemical, histopathological and functional changes were reversed. In the light of our findings, we think that gallic acid may have played a protective role against cisplatin-induced ototoxicity in rats, as indicated by the distortion product otoacoustic

Agdc1p - a Gallic Acid Decarboxylase Involved in the Degradation of Tannic Acid in the Yeast Blastobotrys (Arxula) adeninivorans.

PubMed

Meier, Anna K; Worch, Sebastian; Böer, Erik; Hartmann, Anja; Mascher, Martin; Marzec, Marek; Scholz, Uwe; Riechen, Jan; Baronian, Kim; Schauer, Frieder; Bode, Rüdiger; Kunze, Gotthard

2017-01-01

Tannins and hydroxylated aromatic acids, such as gallic acid (3,4,5-trihydroxybenzoic acid), are plant secondary metabolites which protect plants against herbivores and plant-associated microorganisms. Some microbes, such as the yeast Arxula adeninivorans are resistant to these antimicrobial substances and are able to use tannins and gallic acid as carbon sources. In this study, the Arxula gallic acid decarboxylase (Agdc1p) which degrades gallic acid to pyrogallol was characterized and its function in tannin catabolism analyzed. The enzyme has a higher affinity for gallic acid (K m -0.7 ± 0.2 mM, k cat -42.0 ± 8.2 s -1 ) than to protocatechuic acid (3,4-dihydroxybenzoic acid) (K m -3.2 ± 0.2 mM, k cat -44.0 ± 3.2 s -1 ). Other hydroxylated aromatic acids, such as 3-hydroxybenzoic acid, 4-hydroxybenzoic acid, 2,3-dihydroxybenzoic acid, 2,4-dihydroxybenzoic acid and 2,5-dihydroxybenzoic acid are not gallic acid decarboxylase substrates. A. adeninivorans G1212/YRC102-AYNI1-AGDC1, which expresses the AGDC1 gene under the control of the strong nitrate inducible AYNI1 promoter achieved a maximum gallic acid decarboxylase activity of 1064.4 U/l and 97.5 U/g of dry cell weight in yeast grown in minimal medium with nitrate as nitrogen source and glucose as carbon source. In the same medium, gallic acid decarboxylase activity was not detected for the control strain G1212/YRC102 with AGDC1 expression under the control of the endogenous promoter. Gene expression analysis showed that AGDC1 is induced by gallic acid and protocatechuic acid. In contrast to G1212/YRC102-AYNI1-AGDC1 and G1212/YRC102, A. adeninivorans G1234 [Δ agdc1 ] is not able to grow on medium with gallic acid as carbon source but can grow in presence of protocatechuic acid. This confirms that Agdc1p plays an essential role in the tannic acid catabolism and could be useful in the production of catechol and cis,cis -muconic acid. However, the protocatechuic acid catabolism via Agdc1p to catechol seems to be

Preparation and bactericide activity of gallic acid stabilized gold nanoparticles

NASA Astrophysics Data System (ADS)

Moreno-Álvarez, S. A.; Martínez-Castañón, G. A.; Niño-Martínez, N.; Reyes-Macías, J. F.; Patiño-Marín, N.; Loyola-Rodríguez, J. P.; Ruiz, Facundo

2010-10-01

In this work, gold nanoparticles with three different sizes (13.7, 39.4, and 76.7 nm) were prepared using a simple aqueous method with gallic acid as the reducing and stabilizing agent, the different sizes were obtained varying some experimental parameters as the pH of the reaction and the amount of the gallic acid. The prepared nanoparticles were characterized using X-ray diffraction, transmission electron microscopy, dynamic light scattering, and UV-Vis spectroscopy. Samples were identified as elemental gold and present spherical morphology, a narrow size distribution and good stabilization according to TEM and DLS results. The antibacterial activity of this gallic acid stabilized gold nanoparticles against S. mutans (the etiologic agent of dental caries) was assessed using a microdilution method obtaining a minimum inhibitory concentration of 12.31, 12.31, and 49.25 μg/mL for 13.7, 39.4, and 76.7 nm gold nanoparticles, respectively. The antibacterial assay showed that gold nanoparticles prepared in this work present a bactericide activity by a synergistic action with gallic acid. The MIC found for this nanoparticles are much lower than those reported for mixtures of gold nanoparticles and antibiotics.

Effect of gallic acid/chitosan coating on fresh pork quality in modified atmosphere packaging.

PubMed

Fang, Zhongxiang; Lin, Daniel; Warner, Robyn Dorothy; Ha, Minh

2018-09-15

Fresh meat safety and quality is a major concern of consumers in the current food market. The objective of this research was to investigate a newly developed gallic acid/chitosan edible coating on the preservation of fresh pork quality in modified atmosphere package (MAP) stored at 4 °C. The pork loins were coated with 2% chitosan (CHI), 0.2% gallic acid in 2% chitosan (CHI/0.2G), or 0.4% gallic acid in 2% chitosan (CHI/0.4G). Results showed that the antimicrobial activity of the chitosan coating was increased with the incorporation of gallic acid. The CHI/0.2G and CHI/0.4G pork loins also had lower lipid oxidation and myoglobin oxidation. However, the CHI/0.4G sample exhibited a pro-protein oxidation effect, suggesting an optimal concentration of gallic acid should be incorporated. This research provides a practical method in application of gallic acid/chitosan coatings on preservation of fresh pork to improve the safety and quality in MAP environment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Synthesis of molecular imprinting polymers for extraction of gallic acid from urine.

PubMed

Bhawani, Showkat Ahmad; Sen, Tham Soon; Ibrahim, Mohammad Nasir Mohammad

2018-02-21

The molecularly imprinted polymers for gallic acid were synthesized by precipitation polymerization. During the process of synthesis a non-covalent approach was used for the interaction of template and monomer. In the polymerization process, gallic acid was used as a template, acrylic acid as a functional monomer, ethylene glycol dimethacrylate as a cross-linker and 2,2'-azobisisobutyronitrile as an initiator and acetonitrile as a solvent. The synthesized imprinted and non-imprinted polymer particles were characterized by using Fourier-transform infrared spectroscopy and scanning electron microscopy. The rebinding efficiency of synthesized polymer particles was evaluated by batch binding assay. The highly selective imprinted polymer for gallic acid was MIPI1 with a composition (molar ratio) of 1:4:20, template: monomer: cross-linker, respectively. The MIPI1 showed highest binding efficiency (79.50%) as compared to other imprinted and non-imprinted polymers. The highly selective imprinted polymers have successfully extracted about 80% of gallic acid from spiked urine sample.

Gallic acid and p-coumaric acid attenuate type 2 diabetes-induced neurodegeneration in rats.

PubMed

Abdel-Moneim, Adel; Yousef, Ahmed I; Abd El-Twab, Sanaa M; Abdel Reheim, Eman S; Ashour, Mohamed B

2017-08-01

The brain of diabetics revealed deterioration in many regions, especially the hippocampus. Hence, the present study aimed to evaluate the effects of gallic acid and p-coumaric acid against the hippocampal neurodegeneration in type 2 diabetic rats. Adult male albino rats were randomly allocated into four groups: Group 1 served as control ones and others were induced with diabetes. Group 2 considered as diabetic, and groups 3 and 4 were further orally treated with gallic acid (20 mg/kg b.wt./day) and p-coumaric acid (40 mg/kg b.wt./day) for six weeks. Diabetic rats revealed significant elevation in the levels of serum glucose, blood glycosylated hemoglobin and serum tumor necrosis factor-α, while the level of serum insulin was significantly declined. Furthermore, the brain of diabetic rats showed a marked increase in oxidative stress and a decrease of antioxidant parameters as well as upregulation the protein expression of Bax and downregulation the protein expression of Bcl-2 in the hippocampus. Treatment of diabetic rats with gallic acid and p-coumaric acid significantly ameliorated glucose tolerance, diminished the brain oxidative stress and improved antioxidant status, declined inflammation and inhibited apoptosis in the hippocampus. The overall results suggested that gallic acid and p-coumaric acid may inhibit hippocampal neurodegeneration via their potent antioxidant, anti-inflammatory and anti-apoptotic properties. Therefore, both compounds can be recommended as hopeful adjuvant agents against brain neurodegeneration in diabetics.

Gallic Acid Protects 6-OHDA Induced Neurotoxicity by Attenuating Oxidative Stress in Human Dopaminergic Cell Line.

PubMed

Chandrasekhar, Y; Phani Kumar, G; Ramya, E M; Anilakumar, K R

2018-06-01

Gallic acid is one of the most important polyphenolic compounds, which is considered an excellent free radical scavenger. 6-Hydroxydopamine (6-OHDA) is a neurotoxin, which has been implicated in mainly Parkinson's disease (PD). In this study, we investigated the molecular mechanism of the neuroprotective effects of gallic acid on 6-OHDA induced apoptosis in human dopaminergic cells, SH-SY5Y. Our results showed that 6-OHDA induced cytotoxicity in SH-SY5Y cells was suppressed by pre-treatment with gallic acid. The percentage of live cells (90%) was high in the pre-treatment of gallic acid when compared with 6-OHDA alone treated cell line. Moreover, gallic acid was very effective in attenuating the disruption of mitochondrial membrane potential, elevated levels of intracellular ROS and apoptotic cell death induced by 6-OHDA. Gallic acid also lowered the ratio of the pro-apoptotic Bax protein and the anti-apoptotic Bcl-2 protein in SH-SY5Y cells. 6-OHDA exposure was up-regulated caspase-3 and Keap-1 and, down-regulated Nrf2, BDNF and p-CREB, which were sufficiently reverted by gallic acid pre-treatment. These findings indicate that gallic acid is able to protect the neuronal cells against 6-OHDA induced injury and proved that gallic acid might potentially serve as an agent for prevention of several human neurodegenerative diseases caused by oxidative stress and apoptosis.

Agdc1p – a Gallic Acid Decarboxylase Involved in the Degradation of Tannic Acid in the Yeast Blastobotrys (Arxula) adeninivorans

PubMed Central

Meier, Anna K.; Worch, Sebastian; Böer, Erik; Hartmann, Anja; Mascher, Martin; Marzec, Marek; Scholz, Uwe; Riechen, Jan; Baronian, Kim; Schauer, Frieder; Bode, Rüdiger; Kunze, Gotthard

2017-01-01

Tannins and hydroxylated aromatic acids, such as gallic acid (3,4,5-trihydroxybenzoic acid), are plant secondary metabolites which protect plants against herbivores and plant-associated microorganisms. Some microbes, such as the yeast Arxula adeninivorans are resistant to these antimicrobial substances and are able to use tannins and gallic acid as carbon sources. In this study, the Arxula gallic acid decarboxylase (Agdc1p) which degrades gallic acid to pyrogallol was characterized and its function in tannin catabolism analyzed. The enzyme has a higher affinity for gallic acid (Km −0.7 ± 0.2 mM, kcat −42.0 ± 8.2 s−1) than to protocatechuic acid (3,4-dihydroxybenzoic acid) (Km −3.2 ± 0.2 mM, kcat −44.0 ± 3.2 s−1). Other hydroxylated aromatic acids, such as 3-hydroxybenzoic acid, 4-hydroxybenzoic acid, 2,3-dihydroxybenzoic acid, 2,4-dihydroxybenzoic acid and 2,5-dihydroxybenzoic acid are not gallic acid decarboxylase substrates. A. adeninivorans G1212/YRC102-AYNI1-AGDC1, which expresses the AGDC1 gene under the control of the strong nitrate inducible AYNI1 promoter achieved a maximum gallic acid decarboxylase activity of 1064.4 U/l and 97.5 U/g of dry cell weight in yeast grown in minimal medium with nitrate as nitrogen source and glucose as carbon source. In the same medium, gallic acid decarboxylase activity was not detected for the control strain G1212/YRC102 with AGDC1 expression under the control of the endogenous promoter. Gene expression analysis showed that AGDC1 is induced by gallic acid and protocatechuic acid. In contrast to G1212/YRC102-AYNI1-AGDC1 and G1212/YRC102, A. adeninivorans G1234 [Δagdc1] is not able to grow on medium with gallic acid as carbon source but can grow in presence of protocatechuic acid. This confirms that Agdc1p plays an essential role in the tannic acid catabolism and could be useful in the production of catechol and cis,cis-muconic acid. However, the protocatechuic acid catabolism via Agdc1p to catechol seems to be

Interactive effects of gallic/ferulic/caffeic acids and anthocyanins on pigment thermal stabilities.

PubMed

Qian, Bing-Jun; Liu, Jian-Hua; Zhao, Shu-Juan; Cai, Jian-Xiong; Jing, Pu

2017-06-01

The data presented in this article are related to the research article entitled "The effects of gallic/ferulic/caffeic acids on colour intensification and anthocyanin stability" (Qian et al., 2017) [1]. This paper described preparation and isolation of anthocyanins from purple sweet potatoes (PSP) and the time-course of anthocyanin profiles treated with gallic, ferulic, or caffeic acids at 95 °C. The color appearance of PSPanthocyanins alone, or with gallic, ferulic, or caffeic acids was described after the 15 h of thermal treatment. The high resolution mass spectrographs of PSP anthocyanins were determined using UPLC-ESI-HRMS. The spatial interaction of peonidin 3-O-(2-O-β-D-glucopyranocyl-β-D-glucopyranoide)-5-O-β-D-glucopyranoside and gallic/ferulic/caffeic acids was illustrated by molecular dynamic simulation.

Gallic Acid Attenuates Postoperative Intra-Abdominal Adhesion by Inhibiting Inflammatory Reaction in a Rat Model

PubMed Central

Wei, Guangbing; Wu, Yunhua; Gao, Qi; Shen, Cong; Chen, Zilu; Wang, Kang; Yu, Junhui

2018-01-01

Background Intra-abdominal adhesion is one of the most common complications after abdominal surgery. The efficacy of current treatments for intra-abdominal adhesion is unsatisfactory. In this study, we investigated the effect of gallic acid on the prevention and treatment of intra-abdominal adhesions after abdominal surgery using an intra-abdominal adhesion rat model. Material/Methods The experimental rats were randomly divided into the sham operation group, the control group, the chitosan group, and 3 gallic acid groups of different concentrations. All rats except those in the sham operation group received cecal abrasion to induce adhesion. From the first postoperative day, the rats in the gallic acid groups were administered different concentrations of gallic acid in a 2-ml gavage daily. All rats were sacrificed on postoperative day 7, and the degree of intra-abdominal adhesion was evaluated by the naked eye. The amount of collagen deposited between the injured peritoneal tissues was assessed by Sirius red staining. Serum levels of interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and transforming growth factor-β (TGF-β) were measured by ELISA. Western blot was used to detect the level of NF-κB phosphorylation in the injured peritoneal or adhesion tissues of the rats. Results Compared with the control group, the scores of intra-abdominal adhesions in the rats treated with larger doses of gallic acid were significantly decreased, and the degree of inflammation and fibrosis was also significantly decreased. Gallic acid significantly reduced IL-6, TNF-α, and TGF-β1 serum levels. NF-κB phosphorylation in the higher gallic acid groups was significantly reduced. Conclusions Gallic acid inhibits the formation of postoperative intra-abdominal adhesions in rats by inhibiting the inflammatory reaction and fibrogenesis. Gallic acid is a promising drug for preventing intra-abdominal adhesions. PMID:29429982

Use of Gallic Acid to Enhance the Antioxidant and Mechanical Properties of Active Fish Gelatin Film.

PubMed

Limpisophon, Kanokrat; Schleining, Gerhard

2017-01-01

This study explores the potential roles of gallic acid in fish gelatin film for improving mechanical properties, UV barrier, and providing antioxidant activities. Glycerol, a common used plasticizer, also impacts on mechanical properties of the film. A factorial design was used to investigate the effects of gallic acid and glycerol concentrations on antioxidant activities and mechanical properties of fish gelatin film. Increasing the amount of gallic acid increased the antioxidant capacities of the film measured by radical scavenging assay and the ferric reducing ability of plasma assay. The released antioxidant power of gallic acid from the film was not reduced by glycerol. The presence of gallic acid not only increased the antioxidant capacity of the film, but also increased the tensile strength, elongation at break, and reduced UV absorption due to interaction between gallic acid and protein by hydrogen bonding. Glycerol did not affect the antioxidant capacities of the film, but increased the elasticity of the films. Overall, this study revealed that gallic acid entrapped in the fish gelatin film provided antioxidant activities and improved film characteristics, namely UV barrier, strength, and elasticity of the film. © 2016 Institute of Food Technologists®.

Gallic Acid Is an Antagonist of Semen Amyloid Fibrils That Enhance HIV-1 Infection.

PubMed

LoRicco, Josephine G; Xu, Changmingzi Sherry; Neidleman, Jason; Bergkvist, Magnus; Greene, Warner C; Roan, Nadia R; Makhatadze, George I

2016-07-01

Recent in vitro studies have demonstrated that amyloid fibrils found in semen from healthy and HIV-infected men, as well as semen itself, can markedly enhance HIV infection rates. Semen fibrils are made up of multiple naturally occurring peptide fragments derived from semen. The best characterized of these fibrils are SEVI (semen-derived enhancer of viral infection), made up of residues 248-286 of prostatic acidic phosphatase, and the SEM1 fibrils, made up of residues 86-107 of semenogelin 1. A small molecule screen for antagonists of semen fibrils identified four compounds that lowered semen-mediated enhancement of HIV-1 infectivity. One of the four, gallic acid, was previously reported to antagonize other amyloids and to exert anti-inflammatory effects. To better understand the mechanism by which gallic acid modifies the properties of semen amyloids, we performed biophysical measurements (atomic force microscopy, electron microscopy, confocal microscopy, thioflavin T and Congo Red fluorescence assays, zeta potential measurements) and quantitative assays on the effects of gallic acid on semen-mediated enhancement of HIV infection and inflammation. Our results demonstrate that gallic acid binds to both SEVI and SEM1 fibrils and modifies their surface electrostatics to render them less cationic. In addition, gallic acid decreased semen-mediated enhancement of HIV infection but did not decrease the inflammatory response induced by semen. Together, these observations identify gallic acid as a non-polyanionic compound that inhibits semen-mediated enhancement of HIV infection and suggest the potential utility of incorporating gallic acid into a multicomponent microbicide targeting both the HIV virus and host components that promote viral infection. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Gallic Acid Is an Antagonist of Semen Amyloid Fibrils That Enhance HIV-1 Infection*

PubMed Central

LoRicco, Josephine G.; Xu, Changmingzi Sherry; Neidleman, Jason; Bergkvist, Magnus; Greene, Warner C.; Roan, Nadia R.; Makhatadze, George I.

2016-01-01

Recent in vitro studies have demonstrated that amyloid fibrils found in semen from healthy and HIV-infected men, as well as semen itself, can markedly enhance HIV infection rates. Semen fibrils are made up of multiple naturally occurring peptide fragments derived from semen. The best characterized of these fibrils are SEVI (semen-derived enhancer of viral infection), made up of residues 248–286 of prostatic acidic phosphatase, and the SEM1 fibrils, made up of residues 86–107 of semenogelin 1. A small molecule screen for antagonists of semen fibrils identified four compounds that lowered semen-mediated enhancement of HIV-1 infectivity. One of the four, gallic acid, was previously reported to antagonize other amyloids and to exert anti-inflammatory effects. To better understand the mechanism by which gallic acid modifies the properties of semen amyloids, we performed biophysical measurements (atomic force microscopy, electron microscopy, confocal microscopy, thioflavin T and Congo Red fluorescence assays, zeta potential measurements) and quantitative assays on the effects of gallic acid on semen-mediated enhancement of HIV infection and inflammation. Our results demonstrate that gallic acid binds to both SEVI and SEM1 fibrils and modifies their surface electrostatics to render them less cationic. In addition, gallic acid decreased semen-mediated enhancement of HIV infection but did not decrease the inflammatory response induced by semen. Together, these observations identify gallic acid as a non-polyanionic compound that inhibits semen-mediated enhancement of HIV infection and suggest the potential utility of incorporating gallic acid into a multicomponent microbicide targeting both the HIV virus and host components that promote viral infection. PMID:27226574

Isolation of quercetin and mandelic acid from Aesculus indica fruit and their biological activities.

PubMed

Zahoor, Muhammad; Shafiq, Sadaf; Ullah, Habib; Sadiq, Abdul; Ullah, Farhat

2018-06-26

In this study Aesculus indica fruit was subjected to isolation of phytochemicals. Two antioxidants quercetin and Mandelic acid were isolated in pure state. The free radical scavenging and acetyl choline esterase inhibitory potential of the crude extract and sub fractions were also determined. The antioxidant capacity of crude extract, fractions and isolated compounds were determined by DPPH and ABTS methods. Folin-Ciocalteu reagent method was used to estimate the total phenolic contents and were found to be 78.34 ± 0.96, 44.16 ± 1.05, 65.45 ± 1.29, 37.85 ± 1.44 and 50.23 ± 2.431 (mg/g of gallic acid) in crude extract, ethyl acetate, chloroform, n-hexane and aqueous fractions respectively. The flavonoid concentration in crude extract, ethyl acetate, chloroform, n-hexane and aqueous fraction were; 85.30 ± 1.20, 53.80 ± 1.07, 77.50 ± 1.12, 26.30 ± 1.35 and 37.78 ± 1.25 (mg/g of quercetin) respectively. The chloroform fraction was more potent against enzymes, acetyl choline esterase and butyryl choline esterase (IC 50  = 85 and 160 μg/ml respectively). The phenolic compounds in the crude extract and fractions were determined using HPLC standard method. Chlorogenic acid, quercetin, phloroglucinol, rutin, mandelic acid and hydroxy benzoic acid were detected at retention times 6.005, 10.062, 22.623, 30.597, 35.490 and 36.211 in crude extract and different fractions. The ethyl acetate fraction was rich in the targeted compounds and was therefore subjected to column isolation. The HPLC chromatogram of isolated compounds showed single peak at specified retention times which confirms their isolation in pure state. The isolated compounds were then characterized by FTIR and NMR spectrophotometric techniques. The Aesculus indica fruit extracts showed antioxidant and anticholine esterase inhibitory potentials. Two bioactive compounds were isolated in the pure form ethyl acetate fraction. From results it was concluded that

Gallic acid attenuates pulmonary fibrosis in a mouse model of transverse aortic contraction-induced heart failure.

PubMed

Jin, Li; Piao, Zhe Hao; Sun, Simei; Liu, Bin; Ryu, Yuhee; Choi, Sin Young; Kim, Gwi Ran; Kim, Hyung-Seok; Kee, Hae Jin; Jeong, Myung Ho

2017-12-01

Gallic acid, a trihydroxybenzoic acid found in tea and other plants, attenuates cardiac hypertrophy, fibrosis, and hypertension in animal models. However, the role of gallic acid in heart failure remains unknown. In this study, we show that gallic acid administration prevents heart failure-induced pulmonary fibrosis. Heart failure induced in mice, 8weeks after transverse aortic constriction (TAC) surgery, was confirmed by echocardiography. Treatment for 2weeks with gallic acid but not furosemide prevented cardiac dysfunction in mice. Gallic acid significantly inhibited TAC-induced pathological changes in the lungs, such as increased lung mass, pulmonary fibrosis, and damaged alveolar morphology. It also decreased the expression of fibrosis-related genes, including collagen types I and III, fibronectin, connective tissue growth factor (CTGF), and phosphorylated Smad3. Further, it inhibited the expression of epithelial-mesenchymal transition (EMT)-related genes, such as N-cadherin, vimentin, E-cadherin, SNAI1, and TWIST1. We suggest that gallic acid has therapeutic potential for the treatment of heart failure-induced pulmonary fibrosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Anti-inflammatory potential of ellagic acid, gallic acid and punicalagin A&B isolated from Punica granatum.

PubMed

BenSaad, Lamees A; Kim, Kah Hwi; Quah, Chin Chew; Kim, Wee Ric; Shahimi, Mustafa

2017-01-14

Punica granatum (pomegranate), an edible fruit originating in the Middle East, has been used as a traditional medicine for treatment of pain and inflammatory conditions such as peptic ulcer. The numerous risks associated with nonsteroidal anti-inflammatory drugs (NSAIDs) for treatment of pain and inflammation give rise to using medicinal herbs as alternative therapies. This study aimed to evaluate the anti-inflammatory effect of isolated compounds from the ethyl acetate (EtOAc) fraction of P. granatum by determination of their inhibitory effects on lipopolysaccharide (LPS), stimulated nitric oxide (NO), prostaglandin E2 (PGE-2), interleukin-6 (IL-6) and cyclooxxgenase-2 (COX-2) release from RAW264.7 cells. The compounds ellagic acid, gallic acid and punicalagin A&B were isolated from EtOAc by high performance liquid chromatography (HPLC) and further identified by mass spectrometry (MS). The inhibitory effect of ellagic acid, gallic acid and punicalagin A&B were evaluated on the production of LPS-induced NO by Griess reagent, PGE-2 and IL-6 by immunoassay kit and prostaglandin E2 competitive ELISA kit, and COX-2 by Western blotting. Ellagic acid, gallic acid and punicalagin A&B potentially inhibited LPS-induced NO, PGE-2 and IL-6 production. The results indicate that ellagic acid, gallic acid and punicalagin may be the compounds responsible for the anti-inflammatory potential of P. granatum.

Determination of gallic acid with rhodanine by reverse flow injection analysis using simplex optimization.

PubMed

Phakthong, Wilaiwan; Liawruangrath, Boonsom; Liawruangrath, Saisunee

2014-12-01

A reversed flow injection (rFI) system was designed and constructed for gallic acid determination. Gallic acid was determined based on the formation of chromogen between gallic acid and rhodanine, resulting in a colored product with a λmax at 520 nm. The optimum conditions for determining gallic acid were also investigated. Optimizations of the experimental conditions were carried out based on the so-call univariate method. The conditions obtained were 0.6% (w/v) rhodanine, 70% (v/v) ethanol, 0.9 mol L(-1) NaOH, 2.0 mL min(-1) flow rate, 75 μL injection loop and 600 cm mixing tubing length, respectively. Comparative optimizations of the experimental conditions were also carried out by multivariate or simplex optimization method. The conditions obtained were 1.2% (w/v) rhodanine, 70% (v/v) ethanol, 1.2 mol L(-1) NaOH, flow rate 2.5 mL min(-1), 75 μL injection loop and 600 cm mixing tubing length, respectively. It was found that the optimum conditions obtained by the former optimization method were mostly similar to those obtained by the latter method. The linear relationship between peak height and the concentration of gallic acid was obtained over the range of 0.1-35.0 mg L(-1) with the detection limit 0.081 mg L(-1). The relative standard deviations were found to be in the ranges 0.46-1.96% for 1, 10, 30 mg L(-1) of gallic acid (n=11). The method has the advantages of simplicity extremely high selectivity and high precision. The proposed method was successfully applied to the determination of gallic acid in longan samples without interferent effects from other common phenolic compounds that might be present in the longan samples collected in northern Thailand. Copyright © 2014 Elsevier B.V. All rights reserved.

Investigation into structure and dehydration dynamic of gallic acid monohydrate: A Raman spectroscopic study.

PubMed

Cai, Qiang; Xue, Jiadan; Wang, Qiqi; Du, Yong

2018-05-02

The dehydration process of gallic acid monohydrate was carried out by heating method and characterized using Raman spectroscopic technique. Density functional theory calculation with B3LYP function is applied to simulate optimized structures and vibrational frequencies of anhydrous gallic acid and its corresponding monohydrated form. Different vibrational modes are assigned by comparison between experimental and theoretical Raman spectra of above two polymorphs. Raman spectra show that vibrational modes of the monohydrate are distinctively different from those of anhydrous one. Meanwhile, the dynamic information about dehydration process of gallic acid monohydrate could also be observed and monitored directly with the help of Raman spectral analysis. The decay rate of the characteristic band from gallic acid monohydrate and the growth rate of anhydrous one are pretty consistent with each other. It indicates that there is no intermediate present during the dehydration process of gallic acid monohydrate. The results could offer us benchmark works for identifying both anhydrous and hydrated pharmaceutical compounds, characterizing their corresponding molecular conformation within various crystalline forms, and also providing useful information about the process of dehydration dynamic at the microscopic molecular level. Copyright © 2018 Elsevier B.V. All rights reserved.

Gallic Acid Attenuates Platelet Activation and Platelet-Leukocyte Aggregation: Involving Pathways of Akt and GSK3β

PubMed Central

Chang, Shih-Sheng; Lee, Viola S. Y.; Tseng, Yu-Lun; Chang, Kuan-Cheng; Chen, Kuen-Bao; Chen, Yuh-Lien; Li, Chi-Yuan

2012-01-01

Platelet activation and its interaction with leukocytes play an important role in atherothrombosis. Cardiovascular diseases resulted from atherothrombosis remain the major causes of death worldwide. Gallic acid, a major constituent of red wine and tea, has been believed to have properties of cardiovascular protection, which is likely to be related to its antioxidant effects. Nonetheless, there were few and inconsistent data regarding the effects of gallic acid on platelet function. Therefore, we designed this in vitro study to determine whether gallic acid could inhibit platelet activation and the possible mechanisms. From our results, gallic acid could concentration-dependently inhibit platelet aggregation, P-selectin expression, and platelet-leukocyte aggregation. Gallic acid prevented the elevation of intracellular calcium and attenuated phosphorylation of PKCα/p38 MAPK and Akt/GSK3β on platelets stimulated by the stimulants ADP or U46619. This is the first mechanistic explanation for the inhibitory effects on platelets from gallic acid. PMID:22811749

One-Pot Procedure for Recovery of Gallic Acid from Wastewater and Encapsulation within Protein Particles.

PubMed

Nourbakhsh, Himan; Madadlou, Ashkan; Emam-Djomeh, Zahra; Wang, Yi-Cheng; Gunasekaran, Sundaram; Mousavi, Mohammad E

2016-02-24

A whey protein isolate solution was heat-denatured and treated with the enzyme transglutaminase, which cross-linked ≈26% of the amino groups and increased the magnitude of the ζ-potential value. The protein solution was microemulsified, and then the resulting water-in-oil microemulsion was dispersed within a gallic acid-rich model wastewater. Gallic acid extraction by the outlined microemulsion liquid membrane (MLM) from the exterior aqueous phase (wastewater) and accumulation within the internal aqueous nanodroplets induced protein cold-set gelation and resulted in the formation of gallic acid-enveloping nanoparticles. Measurements with a strain-controlled rheometer indicated a progressive increase in the MLM viscosity during gallic acid recovery corresponding to particle formation. The mean hydrodynamic size of the nanoparticles made from the heat-denatured and preheated enzymatically cross-linked proteins was 137 and 122 nm, respectively. The enzymatic cross-linking of whey proteins led to a higher gallic acid recovery yield and increased the glass transition enthalpy and temperature. A similar impact on glass transition indices was observed by the gallic acid-induced nanoparticulation of proteins. Scanning electron microscopy showed the existence of numerous jammed/fused nanoparticles. It was suggested on the basis of the results of Fourier transform infrared spectroscopy that the in situ nanoparticulation of proteins shifted the C-N stretching and C-H bending peaks to higher wavenumbers. X-ray diffraction results proposed a decreased β-sheet content for proteins because of the acid-induced particulation. The nanoparticles made from the enzymatically cross-linked protein were more stable against the in vitro gastrointestinal digestion and retained almost 19% of the entrapped gallic acid after 300 min sequential gastric and intestinal digestions.

Effect of gallic and protocatechuic acids on the metabolism of ethyl carbamate in Chinese yellow rice wine brewing.

PubMed

Zhou, Wanyi; Fang, Ruosi; Chen, Qihe

2017-10-15

It was studied that gallic and protocatechuic acids played important roles in ethyl carbamate (EC) forming. Gallic and protocatechuic acids can reduce the arginine consumption through inhibiting the arginine deiminase enzyme. Therefore, they are generally added to regulate EC catabolism in the course of yellow rice wine leavening at the third day. In this work, gallic and protocatechuic acids made little influence on the growth of Saccharomyces cerevisiae. Besides, the addition of 200mg/L gallic or protocatechuic acid could prevent the transformation from urea/citrulline to EC. Gallic acid showed better inhibiting effect that the content of EC could be reduced by 91.9% at most. Furthermore, the production of amino acids and volatile flavor compounds are not markedly affected by phenolic compounds. The discoveries reveal that EC can be reduced by supplying gallic acid or protocatechuic acid while yellow rice wine leavening. Copyright © 2017 Elsevier Ltd. All rights reserved.

Non-toxic agarose/gelatin-based microencapsulation system containing gallic acid for antifungal application.

PubMed

Lam, P-L; Gambari, R; Kok, S H-L; Lam, K-H; Tang, J C-O; Bian, Z-X; Lee, K K-H; Chui, C-H

2015-02-01

Aspergillus niger (A. niger) is a common species of Aspergillus molds. Cutaneous aspergillosis usually occurs in skin sites near intravenous injection and approximately 6% of cutaneous aspergillosis cases which do not involve burn or HIV-infected patients are caused by A. niger. Biomaterials and biopharmaceuticals produced from microparticle-based drug delivery systems have received much attention as microencapsulated drugs offer an improvement in therapeutic efficacy due to better human absorption. The frequently used crosslinker, glutaraldehyde, in gelatin-based microencapsulation systems is considered harmful to human beings. In order to tackle the potential risks, agarose has become an alternative polymer to be used with gelatin as wall matrix materials of microcapsules. In the present study, we report the eco-friendly use of an agarose/gelatin-based microencapsulation system to enhance the antifungal activity of gallic acid and reduce its potential cytotoxic effects towards human skin keratinocytes. We used optimal parameter combinations, such as an agarose/gelatin ratio of 1:1, a polymer/oil ratio of 1:60, a surfactant volume of 1% w/w and a stirring speed of 900 rpm. The minimum inhibitory concentration of microencapsulated gallic acid (62.5 µg/ml) was significantly improved when compared with that of the original drug (>750 µg/ml). The anti-A. niger activity of gallic acid -containing microcapsules was much stronger than that of the original drug. Following 48 h of treatment, skin cell survival was approximately 90% with agarose/gelatin microcapsules containing gallic acid, whereas cell viability was only 25-35% with free gallic acid. Our results demonstrate that agarose/gelatin-based microcapsules containing gallic acid may prove to be helpful in the treatment of A. niger-induced skin infections near intravenous injection sites.

Gallic Acid Inhibited Matrix Invasion and AP-1/ETS-1-Mediated MMP-1 Transcription in Human Nasopharyngeal Carcinoma Cells

PubMed Central

S. Pang, Jong-Hwei; Yen, Jia-Hau; Wu, Hsiao-Ting; Huang, Sheng-Teng

2017-01-01

Gallic acid is a trihydroxybenzoic acid found in natural herbal plants. Gallic acid has been reported to inhibit the migration and invasive capability of various cancers. Little is known about the underlying mechanisms of invasion responsible for cancer metastasis via gallic acid. The present study was intended to investigate the anti-invasive effect of gallic acid on human nasopharyngeal carcinoma cells (NPC-BM1) and its related mechanism. Gallic acid inhibited the invasion of NPC-BM1 cells dose- and time-dependently without significant cytotoxic effect. Affymetrix oligonucleotide microarray analysis revealed matrix metalloproteinase-1 (MMP-1) as the most down-regulated gene in NPC-BM1 cells by gallic acid. The cytosolic and secreted MMP-1 levels were both found to be inhibited by gallic acid as demonstrated by western blot analysis and ELISA respectively. The mRNA expression and transcription of MMP-1 gene was also down-regulated as determined by RT/real-time PCR and promoter activity assay. The expression of two major transcription binding factors in the MMP-1 promoter, AP-1 and ETS-1, were demonstrated to be reduced by gallic acid in NPC-BM1 cells. The effect of gallic acid was associated with the inhibition of p38 MAPK signaling pathway. In addition, gallic acid enhanced the gene expression of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) which further suppressed the MMP-1 activity. These findings may be useful to develop a novel chemotherapeutic agent to inhibit the metastasis of nasopharyngeal cancer. PMID:28672814

Gallic Acid Inhibited Matrix Invasion and AP-1/ETS-1-Mediated MMP-1 Transcription in Human Nasopharyngeal Carcinoma Cells.

PubMed

Pang, Jong-Hwei S; Yen, Jia-Hau; Wu, Hsiao-Ting; Huang, Sheng-Teng

2017-06-24

Gallic acid is a trihydroxybenzoic acid found in natural herbal plants. Gallic acid has been reported to inhibit the migration and invasive capability of various cancers. Little is known about the underlying mechanisms of invasion responsible for cancer metastasis via gallic acid. The present study was intended to investigate the anti-invasive effect of gallic acid on human nasopharyngeal carcinoma cells (NPC-BM1) and its related mechanism. Gallic acid inhibited the invasion of NPC-BM1 cells dose- and time-dependently without significant cytotoxic effect. Affymetrix oligonucleotide microarray analysis revealed matrix metalloproteinase-1 (MMP-1) as the most down-regulated gene in NPC-BM1 cells by gallic acid. The cytosolic and secreted MMP-1 levels were both found to be inhibited by gallic acid as demonstrated by western blot analysis and ELISA respectively. The mRNA expression and transcription of MMP-1 gene was also down-regulated as determined by RT/real-time PCR and promoter activity assay. The expression of two major transcription binding factors in the MMP-1 promoter, AP-1 and ETS-1, were demonstrated to be reduced by gallic acid in NPC-BM1 cells. The effect of gallic acid was associated with the inhibition of p38 MAPK signaling pathway. In addition, gallic acid enhanced the gene expression of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) which further suppressed the MMP-1 activity. These findings may be useful to develop a novel chemotherapeutic agent to inhibit the metastasis of nasopharyngeal cancer.

Gallic acid inhibits vascular calcification through the blockade of BMP2-Smad1/5/8 signaling pathway.

PubMed

Kee, Hae Jin; Cho, Soo-Na; Kim, Gwi Ran; Choi, Sin Young; Ryu, Yuhee; Kim, In Kyeom; Hong, Young Joon; Park, Hyung Wook; Ahn, Youngkeun; Cho, Jeong Gwan; Park, Jong Chun; Jeong, Myung Ho

2014-11-01

Vascular calcification is associated with increased risk of morbidity and mortality in patients with cardiovascular diseases, chronic kidney diseases, and diabetes. Gallic acid, a natural compound found in gallnut and green tea, is known to be antifungal, antioxidant, and anticancer. Here we investigated the effect of gallic acid on vascular smooth muscle cell (VSMC) calcification and the underlying mechanism. Gallic acid inhibited inorganic phosphate-induced osteoblast differentiation markers as well as calcification phenotypes (as determined by calcium deposition, Alizarin Red, and Von Kossa staining). Knockdown of BMP2 or Noggin blocked phosphate-induced calcification. Gallic acid suppressed phosphorylation of Smad1/5/8 protein induced by inorganic phosphate. Taken together, we suggest that gallic acid acts as a novel therapeutic agent of vascular calcification by mediating BMP2-Smad1/5/8 signaling pathway. Copyright © 2014 Elsevier Inc. All rights reserved.

Study on the interaction mechanism between aromatic amino acids and quercetin

NASA Astrophysics Data System (ADS)

Gou, Xingxing; Pu, Xiaohua; Li, Zongxiao

2017-11-01

In this paper, we selected quercetin and aromatic amino acids (tryptophan, tyrosine, phenylalanine) as the research objects to investigate the change rules in the reaction process. The thermodynamic functions (Ka, Δ G, and Δ S) of the interactions between quercetin and aromatic amino acids (tryptophan, tyrosine, phenylalanine) were measured by isothermal titration calorimetry. The values of binding constant (Ka) reached maximum at 25°C; the entropies and Gibbs free energies were both negative at different temperatures. The kinetic parameters of quercetin and amino acids in the interaction process was determined by microcalorimetry. The results inferred that the driving force of the reaction was hydrogen bond or van der Waals force.

Time-dependent inhibition of CYP3A4 by gallic acid in human liver microsomes and recombinant systems.

PubMed

Pu, Qiang-Hong; Shi, Liang; Yu, Chao

2015-03-01

1.Gallic acid is a main polyphenol in various fruits and plants. Inhibitory characteristics of gallic acid on CYP3A4 were still unclear. The objective of this work is hence to investigate inhibitory characteristics of gallic acid on CYP3A4 using testosterone as the probe substrate in human liver microsomes (HLMs) and recombinant CYP3A4 (rCYP3A4) systems. 2.Gallic acid caused concentration-dependent loss of CYP3A4 activity with IC50 values of 615.2 μM and 669.5 μM in HLM and rCYP3A4 systems, respectively. IC50-shift experiments showed that pre-incubation with gallic acid in the absence of NADPH contributed to 12- or 14-fold reduction of IC50 in HLM and rCYP3A4 systems, respectively, supporting a time-dependent inhibition. In HLM, time-dependent inactivation variables KI and Kinact were 485.8 μM and 0.05 min(-1), respectively. 3.Compared with the presence of NADPH, pre-incubation of gallic acid in the absence of NADPH markedly increased its inhibitory effects in HLM and rCYP3A4 systems. Those results indicate that CYP3A4 inactivation by gallic acid was independent on NADPH and was mainly mediated its oxidative products. 4.In conclusion, we showed that gallic acid weakly and time-dependently inactivated CYP3A4 via its oxidative products.

Enhanced oral bioavailability of metoprolol with gallic acid and ellagic acid in male Wistar rats: involvement of CYP2D6 inhibition.

PubMed

Athukuri, Bhargavi Latha; Neerati, Prasad

2016-12-01

Cytochrome P450-2D6 (CYP2D6), a member of the CYP450 mixed function oxidase system, is an important CYP isoform with regard to herbal-drug interactions and is responsible for the metabolism of nearly 25% of drugs. Until now, studies on the effects of various phytochemicals on CYP2D6 activity in vivo have been very rare. Gallic acid and ellagic acid are natural polyphenols which are widely distributed in fruits and medicinal plants. In the present study, the effects of gallic acid and ellagic acid pretreatment on intestinal transport and oral bioavailability of metoprolol were investigated. The intestinal transport of metoprolol was assessed by conducting an in situ single pass intestinal perfusion (SPIP) study. The bioavailability study was conducted to evaluate the pharmacokinetic parameters of orally administered metoprolol in rats. After pretreatment with gallic acid and ellagic acid, no significant change in effective permeability of metoprolol was observed at the ileum part of rat intestine. A significant improvement in the peak plasma concentration (Cmax) and area under the serum concentration-time profile (AUC) and decrease in clearance were observed in rats pretreated with gallic acid and ellagic acid. Gallic acid and ellagic acid significantly enhanced the oral bioavailability of metoprolol by inhibiting CYP2D6-mediated metabolism in the rat liver. Hence, adverse herbal-drug interactions may result with concomitant ingestion of gallic acid and ellagic acid supplements and drugs that are CYP2D6 substrates. The clinical assessment of these interactions should be further investigated in human volunteers.

Relative content of gallic acid over 5-galloylquinic acid as an index for the baking intensity of oolong teas.

PubMed

Wang, Miki Mei-Chi; Yeh, Yun; Shih, Yu-En; Tzen, Jason Tze-Cheng

2018-04-01

Phenolic compounds in a series of old oolong teas prepared by baking annually were monitored and compared. The results showed that the relative content of gallic acid over 5-galloylquinic acid was subsequently elevated during this preparatory process. To reveal the effect was mainly resulted from baking or aging, two sets of oolong teas were collected and examined; one set was generated from fresh oolong tea via continually daily baking and the other set was composed of aged oolong teas with no or light baking in the storage period. The relative content of gallic acid over 5-galloylquinic acid was observed to be subsequently elevated when oolong tea was continually baked at 90, 100, 110, and 120 °C for 8 h day after day. In contrast, the relative contents of gallic acid over 5-galloylquinic acid in aged oolong teas with no or light baking were found to be similar to or slightly higher than that in fresh oolong tea. The results suggest that the relative content of gallic acid over 5-galloylquinic acid seems to be a suitable index for the baking intensity of oolong tea in different preparations. Copyright © 2017. Published by Elsevier B.V.

Gallic Acid Decreases Inflammatory Cytokine Secretion Through Histone Acetyltransferase/Histone Deacetylase Regulation in High Glucose-Induced Human Monocytes.

PubMed

Lee, Wooje; Lee, Sang Yeol; Son, Young-Jin; Yun, Jung-Mi

2015-07-01

Hyperglycemia contributes to diabetes and several diabetes-related complications. Gallic acid is a polyhydroxy phenolic compound found in various natural products. In this study, we investigated the effects and mechanism of gallic acid on proinflammatory cytokine secretion in high glucose-induced human monocytes (THP-1 cells). THP-1 cells were cultured under normoglycemic or hyperglycemic conditions, in the absence or presence of gallic acid. Hyperglycemic conditions significantly induced histone acetylation, nuclear factor-κB (NF-κB) activation, and proinflammatory cytokine release from THP-1 cells, whereas gallic acid suppressed NF-κB activity and cytokine release. It also significantly reduced CREB-binding protein/p300 (CBP/p300, a NF-κB coactivator) gene expression, acetylation levels, and CBP/p300 histone acetyltransferase (HAT) activity. In addition, histone deacetylase 2 (HDAC2) expression was significantly induced. These results suggest that gallic acid inhibits hyperglycemic-induced cytokine production in monocytes through epigenetic changes involving NF-κB. Therefore, gallic acid may have potential for the treatment and prevention of diabetes and its complications.

Protective effect of gallic acid in experimental model of ketamine-induced psychosis: possible behaviour, biochemical, neurochemical and cellular alterations.

PubMed

Yadav, Monu; Jindal, Deepak Kumar; Dhingra, Mamta Sachdeva; Kumar, Anil; Parle, Milind; Dhingra, Sameer

2018-04-01

Gallic acid has been reported to possess a number of psychopharmacological activities. These activities are attributed to the antioxidant potential due to the presence of phenolic moeity. The present study was carried out to investigate the protective effects of gallic acid in an experimental model of ketamine-induced psychosis in mice. Ketamine (50 mg/kg, i.p.) was used to induce stereotyped psychotic behavioural symptoms in mice. Behavioural studies (locomotor activity, stereotype behaviour, immobility duration and memory retention) were carried out to investigate the protective of gallic acid on ketamine-induced psychotic symptoms, followed by biochemical and neurochemical changes and cellular alterations in the brain. Chronic treatment with gallic acid for 15 consecutive days significantly attenuated stereotyped behavioural symptoms in mice. Biochemical estimations revealed that gallic acid reduced the lipid peroxidation and restored the total brain proteins. Furthermore, gallic acid remarkably reduced the dopamine levels, AChE activity and inflammatory surge (serum TNF-α), and increased the levels of GABA and increased glutathione in mice. The study revealed that gallic acid could ameliorate psychotic symptoms and biochemical changes in mice, indicating protective effects in psychosis.

Simultaneous determination of gallic acid and gentisic acid in organic anion transporter expressing cells by liquid chromatography-tandem mass spectrometry.

PubMed

Wang, Li; Halquist, Matthew S; Sweet, Douglas H

2013-10-15

In order to elucidate the role of organic anion transporters (OATs) in the renal elimination of gallic acid and gentisic acid, a new, rapid, and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the simultaneous determination of gallic acid and gentisic acid in cell lysate, using Danshensu as the internal standard (IS). After a simple liquid-liquid extraction, the analytes were detected in negative ESI mode using selected reaction monitoring. The precursor-to-product ion transitions (m/z) were 169.0→125.0, 153.1→108.0, and 196.8→135.2 for gallic acid, gentisic acid, and the IS, respectively. Chromatographic separation was achieved on a C18 column using mobile phases consisting of water with 0.1% acetic acid (A) and acetonitrile with 0.05% formic acid. (B) The total run time was 3min and calibration curves were linear over the concentrations of 0.33-2400ng/mL for both compounds (r(2)>0.995). Good precision (between 3.11% and 14.1% RSD) and accuracy (between -12.7% and 11% bias) was observed for quality controls at concentrations of 0.33 (lower limit of quantification), 1, 50, and 2000ng/mL. The mean extraction recovery of gallic acid and gentisic acid was 80.7% and 83.5%, respectively. Results from post-column infusion and post-extraction methods indicated that the analytical method exhibited negligible matrix effects. Finally, this validated assay was successfully applied in a cellular uptake study to determine the intracellular concentrations of gallic acid and gentisic acid in OAT expressing cells. Copyright © 2013 Elsevier B.V. All rights reserved.

The Influence of Prefermentative Addition of Gallic Acid on the Phenolic Composition and Chromatic Characteristics of Cabernet Sauvignon Wines.

PubMed

Liu, Yue; Zhang, Bo; He, Fei; Duan, Chang-Qing; Shi, Ying

2016-07-01

In this study, the prefermentative addition of gallic acid in Cabernet Sauvignon red winemaking was performed. The influence of gallic acid addition on wine phenolic composition, the ratio of copigmentation, and the color parameters were monitored throughout the winemaking process. The results showed that the prefermentative addition of gallic acid enhanced the extraction of total anthocyanins and the copigmentation effect, producing wines with more darkness, redness, yellowness, and saturation. Moreover, the addition of gallic acid contributed to the concentration of total phenolic acids. However, it had a negative effect on the concentrations of flavonols and flavan-3-ols in the final wines. Thus, the prefermentative addition of gallic acid at appropriate levels might be a promising enological technology to obtain wines with high color quality and aging potential. © 2016 Institute of Food Technologists®

Preparation of Fe3O4 magnetic nanoparticles coated with gallic acid for drug delivery

PubMed Central

Dorniani, Dena; Hussein, Mohd Zobir Bin; Kura, Aminu Umar; Fakurazi, Sharida; Shaari, Abdul Halim; Ahmad, Zalinah

2012-01-01

Background and methods Magnetic iron oxide nanoparticles were prepared using a sonochemical method under atmospheric conditions at a Fe2+ to Fe3+ molar ratio of 1:2. The iron oxide nanoparticles were subsequently coated with chitosan and gallic acid to produce a core-shell structure. Results X-ray diffraction demonstrated that the magnetic nanoparticles were pure Fe3O4 with a cubic inverse spinel structure. Transmission electron microscopy showed that the Fe3O4 nanoparticles were of spherical shape with a mean diameter of 11 nm, compared with 13 nm for the iron oxide-chitosan-gallic acid (FCG) nanocarriers. Conclusion The magnetic nanocarrier enhanced the thermal stability of the drug, gallic acid. Release of the active drug from the FCG nanocarrier was found to occur in a controlled manner. The gallic acid and FCG nanoparticles were not toxic in a normal human fibroblast (3T3) line, and anticancer activity was higher in HT29 than MCF7 cell lines. PMID:23166439

Cardioprotective effects of gallic acid in diabetes-induced myocardial dysfunction in rats

PubMed Central

Patel, Snehal S.; Goyal, Ramesh K.

2011-01-01

Background: Normalization of hyperglycemia, hyperlipidemia, and oxidative stress is an important objective in preventing diabetes-induced cardiac dysfunction. Objective: This study was undertaken to examine the effects of gallic acid in myocardial dysfunctions associated with type-1 diabetes. Materials and Methods: Diabetes was induced by single intravenous injection of streptozotocin (STZ, 50 mg/kg i.v.). Gallic acid was administered daily at three different doses (100, 50, and 25 mg/kg p.o.) for 8 weeks at the end of which blood samples were collected and analyzed for various biochemical parameters. Results: Injection of STZ produced significant loss of body weight (BW), polyphagia, polydypsia, hyperglycemia, hypoinsulinemia, hyperlipidemia, hypertension, bradycardia, and myocardial functional alterations. Treatment with gallic acid significantly lowered fasting glucose, the AUCglucose level in a dose-dependent manner; however, the insulin level was not increased significantly at same the dose and prevented loss of BW, polyphagia, and polydypsia in diabetic rats. It also prevented STZ-induced hyperlipidemia, hypertension, bradycardia, structural alterations in cardiac tissue such as increase in force of contraction, left ventricular weight to body weight ratio, collagen content, protein content, serum lactate dehydrogenase, and creatinine kinase levels in a dose-dependent manner. Further, treatment also produced reduction in lipid peroxidation and increase in antioxidant parameters in heart of diabetic rats. Conclusion: The results of this study suggest that gallic acid to be beneficial for the treatment of myocardial damage associated with type-1 diabetes. PMID:22224046

[Simultaneous isolation and purification of gallic acid and brevifolincarboxylic acid from Polygonum capitatum by high-speed counter-current chromatography].

PubMed

Chen, Xinxia; Zhang, Liyan; Wan, Jinzhi; Liang, Bin; Xie, Yu

2010-08-01

To isolate and purify gallic acid and brevifolincarboxylic acid simultaneously by high-speed counter-current chromatography (HSCCC) from a crude extract of Polygonum capitatum. The biphasic solvent system composed of ethyl acetate-n-butanol-0.44% acetic acid (3:1:5) was used at a flow rate of 2.0 mL x min(-1), while the aqueous phase was selected as the mobile phase and the apparatus was rotated at 860 r x min(-1). The effluent was detected at 272 nm. 51.5 mg of gallic acid and 5.9 mg of brevifolincarboxylic acid were separated from 1.07 g of the crude extract with the purities of 99.7% and 97.5%, respectively, while brevifolincarboxylic acid was obtained firstly from the genus Polygonum. The structures of the compounds were identified by ultraviolet spectrometry (UV), infra-red spectrometry (IR), liquid chromatography/mass spectrometry (LC/MS), time-of-flight mass spectrometry( TOF-MS), 1H-nuclear magnetic resonance (NMR) and 13C-NMR. This method is feasible and rapid for isolation and purification of gallice acid and brevifolincarboxylil acid.

Statistical optimization of bioprocess parameters for enhanced gallic acid production from coffee pulp tannins by Penicillium verrucosum.

PubMed

Bhoite, Roopali N; Navya, P N; Murthy, Pushpa S

2013-01-01

Gallic acid (3,4,5-trihydroxybenzoic acid) was produced by microbial biotransformation of coffee pulp tannins by Penicillium verrucosum. Gallic acid production was optimized using response surface methodology (RSM) based on central composite rotatable design. Process parameters such as pH, moisture, and fermentation period were considered for optimization. Among the various fungi isolated from coffee by-products, Penicillium verrucosum produced 35.23 µg/g of gallic acid on coffee pulp as sole carbon source in solid-state fermentation. The optimum values of the parameters obtained from the RSM were pH 3.32, moisture 58.40%, and fermentation period of 96 hr. Gallic acid production with an increase of 4.6-fold was achieved upon optimization of the process parameters. The results optimized could be translated to 1-kg tray fermentation. High-performance liquid chromatography (HPLC) analysis and spectral studies such as mass spectroscopy (MS) and (1)H-nuclear magnetic resonance (NMR) confirmed that the bioactive compound isolated was gallic acid. Thus, coffee pulp, which is available in enormous quantity, could be used for the production of value-added products that can find avenues in food, pharmaceutical, and chemical industries.

Two shikimate dehydrogenases, VvSDH3 and VvSDH4, are involved in gallic acid biosynthesis in grapevine

PubMed Central

Bontpart, Thibaut; Marlin, Thérèse; Vialet, Sandrine; Guiraud, Jean-Luc; Pinasseau, Lucie; Meudec, Emmanuelle; Sommerer, Nicolas; Cheynier, Véronique; Terrier, Nancy

2016-01-01

In plants, the shikimate pathway provides aromatic amino acids that are used to generate numerous secondary metabolites, including phenolic compounds. In this pathway, shikimate dehydrogenases (SDH) ‘classically’ catalyse the reversible dehydrogenation of 3-dehydroshikimate to shikimate. The capacity of SDH to produce gallic acid from shikimate pathway metabolites has not been studied in depth. In grapevine berries, gallic acid mainly accumulates as galloylated flavan-3-ols. The four grapevine SDH proteins have been produced in Escherichia coli. In vitro, VvSDH1 exhibited the highest ‘classical’ SDH activity. Two genes, VvSDH3 and VvSDH4, mainly expressed in immature berry tissues in which galloylated flavan-3-ols are accumulated, encoded enzymes with lower ‘classical’ activity but were able to produce gallic acid in vitro. The over-expression of VvSDH3 in hairy-roots increased the content of aromatic amino acids and hydroxycinnamates, but had little or no effect on molecules more distant from the shikimate pathway (stilbenoids and flavan-3-ols). In parallel, the contents of gallic acid, β-glucogallin, and galloylated flavan-3-ols were increased, attesting to the influence of this gene on gallic acid metabolism. Phylogenetic analysis from dicotyledon SDHs opens the way for the examination of genes from other plants which accumulate gallic acid-based metabolites. PMID:27241494

Two shikimate dehydrogenases, VvSDH3 and VvSDH4, are involved in gallic acid biosynthesis in grapevine.

PubMed

Bontpart, Thibaut; Marlin, Thérèse; Vialet, Sandrine; Guiraud, Jean-Luc; Pinasseau, Lucie; Meudec, Emmanuelle; Sommerer, Nicolas; Cheynier, Véronique; Terrier, Nancy

2016-05-01

In plants, the shikimate pathway provides aromatic amino acids that are used to generate numerous secondary metabolites, including phenolic compounds. In this pathway, shikimate dehydrogenases (SDH) 'classically' catalyse the reversible dehydrogenation of 3-dehydroshikimate to shikimate. The capacity of SDH to produce gallic acid from shikimate pathway metabolites has not been studied in depth. In grapevine berries, gallic acid mainly accumulates as galloylated flavan-3-ols. The four grapevine SDH proteins have been produced in Escherichia coli In vitro, VvSDH1 exhibited the highest 'classical' SDH activity. Two genes, VvSDH3 and VvSDH4, mainly expressed in immature berry tissues in which galloylated flavan-3-ols are accumulated, encoded enzymes with lower 'classical' activity but were able to produce gallic acid in vitro The over-expression of VvSDH3 in hairy-roots increased the content of aromatic amino acids and hydroxycinnamates, but had little or no effect on molecules more distant from the shikimate pathway (stilbenoids and flavan-3-ols). In parallel, the contents of gallic acid, β-glucogallin, and galloylated flavan-3-ols were increased, attesting to the influence of this gene on gallic acid metabolism. Phylogenetic analysis from dicotyledon SDHs opens the way for the examination of genes from other plants which accumulate gallic acid-based metabolites. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Molecular mechanics and dynamics studies on the interaction of gallic acid with collagen-like peptides

NASA Astrophysics Data System (ADS)

Madhan, B.; Thanikaivelan, P.; Subramanian, V.; Raghava Rao, J.; Unni Nair, Balachandran; Ramasami, T.

2001-10-01

Molecular modelling approaches have been used to understand the interaction of collagen-like peptides with gallic acid, which mimic vegetable tanning processes involved in protein stabilization. Several interaction sites have been identified and the binding energies of the complexes have been calculated. The calculated binding energies for various geometries are in the range 6-13 kcal/mol. It is found that some complexes exhibit hydrogen bonding, and electrostatic interaction plays a dominant role in the stabilization of the peptide by gallic acid. The π-OH type of interaction is also observed in the peptide stabilization. Molecular dynamics (MD) simulation for 600 ps revealed the possibility of hydrogen bonding between the collagen-like peptide and gallic acid.

Effects of polyurethane matrices on fungal tannase and gallic acid production under solid state culture*

PubMed Central

Treviňo, Lucia; Contreras-Esquivel, Juan C.; Rodríguez-Herrera, Raul; Aguilar, Cristóbal Noé

2007-01-01

The influence of the physical structure of polyurethane matrix as a support in a solid state culture in tannase production and gallic acid accumulation by Aspergillus niger Aa-20 was evaluated. Three different polyurethane matrices were used as the support: continuous, semi-discontinuous and discontinuous. The highest tannase production at 2479.59 U/L during the first 12 h of culture was obtained using the discontinuous matrix. The gallic acid was accumulated at 7.64 g/L at the discontinuous matrix. The results show that the discontinuous matrix of polyurethane is better for tannase production and gallic acid accumulation in a solid state culture bioprocess than the continuous and semi-discontinuous matrices. PMID:17910122

Gallic acid, a phenolic compound isolated from Mimosa bimucronata (DC.) Kuntze leaves, induces diuresis and saluresis in rats.

PubMed

Schlickmann, Fabile; Boeing, Thaise; Mariano, Luisa Nathália Bolda; da Silva, Rita de Cássia Melo Vilhena de Andrade Fonseca; da Silva, Luisa Mota; de Andrade, Sérgio Faloni; de Souza, Priscila; Cechinel-Filho, Valdir

2018-06-01

Although present in the leaves of Mimosa bimucronata (DC.) and many other medicinal plants commonly used to augment urinary volume excretion, the effects of gallic acid as a diuretic agent remain to be studied. Wistar rats were orally treated with vehicle, hydrochlorothiazide, or gallic acid. The effects of gallic acid in the presence of hydrochlorothiazide, furosemide, amiloride, L-NAME, atropine, and indomethacin were also investigated. Diuretic index, pH, conductivity, and electrolyte excretion were evaluated at the end of the experiment (after 8 or 24 h). Gallic acid induced diuretic and saluretic (Na + and Cl - ) effects, without interfering with K + excretion, when orally given to female and male rats at a dose of 3 mg/kg. These effects were associated with increased creatinine and conductivity values while pH was unaffected by any of the treatments. Plasma Na + , K + , and Cl - levels were not affected by any of the acute treatments. The combination with hydrochlorothiazide or furosemide was unable to intensify the effects of gallic acid when compared with the response obtained with each drug alone. On the other hand, the treatment with amiloride plus gallic acid amplified both diuresis and saluresis, besides to a marked potassium-sparing effect. Its diuretic action was significantly prevented in the presence of indomethacin, a cyclooxygenase inhibitor, but not with the pretreatments with L-NAME or atropine. Although several biological activities have already been described for gallic acid, this is the first study demonstrating its potential as a diuretic agent.

Antiulcerogenic Effect of Gallic Acid in Rats and its Effect on Oxidant and Antioxidant Parameters in Stomach Tissue

PubMed Central

Sen, S.; Asokkumar, K.; Umamaheswari, M.; Sivashanmugam, A. T.; Subhadradevi, V.

2013-01-01

In the present study, we investigate the antiulcerogenic effect of gallic acid against aspirin plus pyrolus ligation-induced gastric ulcer in rats. Rats were treated with gallic acid (100 and 200 mg/kg) and famotidine (20 mg/kg) for 1 week, followed by induction of gastric ulcer using the aspirin plus pyrolus ligation model. At the end of 4 h after ligation, the rats were sacrificed and ulcer index, gastric juice volume, pH and other biochemical parameter of gastric juice were evaluated. Stomachs of rats were evaluated biochemically to determine oxidant and antioxidant parameters. Pretreatment with gallic acid significantly decreased ulcer index, gastric juice volume, free and total acidity, total protein, DNA content and increased pH and carbohydrates concentration. Gallic acid at a dose of 100 and 200 mg/kg exerted 69.7 and 78.9% ulcer inhibition, respectively. The levels of superoxide dismutase, catalase, reduced glutathione, glutathione reductase, glutathione peroxidise, glucose-6-phosphate dehydrogenase were increased while reduction in myeloperoxidase and lipid peroxidation were observed in the stomach tissues of the drug treated rats. The histopathological studies further confirmed the antiulcer activity of gallic acid. We conclude that the gallic acid possesses antiulcer effect and that these occur by a mechanism that involves attenuation of offensive factors, improvement of mucosal defensive with activation of antioxidant parameters and inhibition of some toxic oxidant parameters. PMID:24019562

Combined Efficacy of Gallic Acid and MiADMSA with Limited Beneficial Effects Over MiADMSA Against Arsenic-induced Oxidative Stress in Mouse.

PubMed

Pachauri, Vidhu; Flora, Sjs

2015-01-01

Gallic acid is an organic acid known for its antioxidant and anticancer properties. The present study is focused on evaluating the role of gallic acid in providing better therapeutic outcomes against arsenic-induced toxicity. Animals pre-exposed to arsenic were treated with monoisoamyl meso-2,3-dimercaptosuccinic acid (MiADMSA), a new chelating drug, alone and in combination with gallic acid, consecutively for 10 days. The study suggests that (1) gallic acid in presence of MiADMSA is only moderately beneficial against arsenic, (2) monotherapy with gallic acid is more effective than in combination with MiADMSA after arsenic exposure in reducing oxidative injury, and (3) MiADMSA monotherapy as reported previously provides significant therapeutic efficacy against arsenic. Thus, based on the present results, we conclude that gallic acid is effective against arsenic-induced oxidative stress but provides limited additional beneficial effects when administered in combination with MiADMSA. We still recommend that lower doses of gallic acid be evaluated both individually and in combination with MiADMSA, as it might not exhibit the shortcomings we observed with higher doses in this study.

The effects of gallic/ferulic/caffeic acids on colour intensification and anthocyanin stability.

PubMed

Qian, Bing-Jun; Liu, Jian-Hua; Zhao, Shu-Juan; Cai, Jian-Xiong; Jing, Pu

2017-08-01

The mechanism by which copigments stabilize colour, by protecting anthocyanin chromophores from nucleophilic attack, seems well accepted. This study was to determine effects of gallic/ferulic/caffeic acids on colour intensification and anthocyanin stability. Molecular dynamics simulations were applied to explore molecular interactions. Phenolic acids intensified the colour by 19%∼27%. Colour fading during heating followed first-order reactions with half-lives of 3.66, 9.64, 3.50, and 3.39h, whereas anthocyanin degradation, determined by the pH differential method (or HPLC-PDA), followed second-order reactions with half-lives of 3.29 (3.40), 3.43 (3.39), 2.29 (0.39), and 2.72 (0.32)h alone or with gallic/ferulic/caffeic acids, respectively, suggesting that anthocyanin degradation was faster than the colour fading. The strongest protection of gallic acids might be attributed to the shortest distance (4.37Å) of its aromatic ring to the anthocyanin (AC) panel. Hyperchromic effects induced by phenolic acids were pronounced and they obscured the accelerated anthocyanin degradation due to self-association interruption. Copyright © 2017 Elsevier Ltd. All rights reserved.

Gallic Acid Induces a Reactive Oxygen Species-Provoked c-Jun NH2-Terminal Kinase-Dependent Apoptosis in Lung Fibroblasts

PubMed Central

Chen, Chiu-Yuan; Chen, Kun-Chieh; Yang, Tsung-Ying; Liu, Hsiang-Chun; Hsu, Shih-Lan

2013-01-01

Idiopathic pulmonary fibrosis is a chronic lung disorder characterized by fibroblasts proliferation and extracellular matrix accumulation. Induction of fibroblast apoptosis therefore plays a crucial role in the resolution of this disease. Gallic acid (3,4,5-trihydroxybenzoic acid), a common botanic phenolic compound, has been reported to induce apoptosis in tumor cell lines and renal fibroblasts. The present study was undertaken to examine the role of mitogen-activated protein kinases (MAPKs) in lung fibroblasts apoptosis induced by gallic acid. We found that treatment with gallic acid resulted in activation of c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and protein kinase B (PKB, Akt), but not p38MAPK, in mouse lung fibroblasts. Inhibition of JNK using pharmacologic inhibitor (SP600125) and genetic knockdown (JNK specific siRNA) significantly inhibited p53 accumulation, reduced PUMA and Fas expression, and abolished apoptosis induced by gallic acid. Moreover, treatment with antioxidants (vitamin C, N-acetyl cysteine, and catalase) effectively diminished gallic acid-induced hydrogen peroxide production, JNK and p53 activation, and cell death. These observations imply that gallic acid-mediated hydrogen peroxide formation acts as an initiator of JNK signaling pathways, leading to p53 activation and apoptosis in mouse lung fibroblasts. PMID:23533505

Synthesis, structure, antitumor activity of novel pharmaceutical co-crystals based on bispyridyl-substituted α, β-unsaturated ketones with gallic acid

NASA Astrophysics Data System (ADS)

Liu, Lian-Dong; Liu, Shu-Lian; Liu, Zhi-Xian; Hou, Gui-Ge

2016-05-01

Three novel pharmaceutical co-crystals, (A)·(gallic acid) (1), (B)·(gallic acid) (2), and (C)·(gallic acid) (3) were generated based on 2,6-bis((pyridin-4-yl)methylene)cyclohexanone (A), N-methyl-3,5-bis((pyridin-3-yl)methylene)-4-piperidone (B), N-methyl-3,5-bis((pyridin-4-yl)methylene)-4-piperidone (C) with gallic acid, respectively. They are characterized by elemental analysis, FTIR spectroscopy, 1H NMR and single-crystal X-ray diffraction. Structural analysis reveals that two pharmaceutical ingredients link each other into H-bonding-driven 3D network in 1, 2, or 2D plane in 3. In addition, their antitumor activities against human neoplastic cell lines A549, SGC-7901, MCF-7, OVCA-433, HePG2 and cytotoxicity for HUVEC cell lines by CCK-8 method were evaluated primarily. Compared with gallic acid and free A, B and C, their antitumor activities have improved distinctly, while cytotoxicities have reduced markedly, especially for co-crystal 1. This is mainly because of the synergistic effect between pharmaceutical ingredients A, B, and C and gallic acid.

Antimicrobial activity of gallic acid against thermophilic Campylobacter is strain specific and associated with a loss of calcium ions.

PubMed

Sarjit, Amreeta; Wang, Yi; Dykes, Gary A

2015-04-01

Gallic acid has been suggested as a potential antimicrobial for the control of Campylobacter but its effectiveness is poorly studied. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of gallic acid against Campylobacter jejuni (n = 8) and Campylobacter coli (n = 4) strains was determined. Gallic acid inhibited the growth of five C. jejuni strains and three C. coli strains (MIC: 15.63-250 μg mL(-1)). Gallic acid was only bactericidal to two C. coli strains (MBC: 125 and 62.5 μg mL(-1)). The mechanism of the bactericidal effect against these two strains (and selected non-susceptible controls) was investigated by determining decimal reduction times and by monitoring the loss of cellular content and calcium ions, and changes in cell morphology. Gallic acid did not result in a loss of cellular content or morphological changes in the susceptible strains as compared to the controls. Gallic acid resulted in a loss of calcium ions (0.58-1.53 μg mL(-1) and 0.54-1.17 μg mL(-1), respectively, over a 180 min period) from the susceptible strains but not the controls. Gallic acid is unlikely to be an effective antimicrobial against Campylobacter in a practical sense unless further interventions to ensure an effective bactericidal mode of action against all strains are developed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Gallic acid against hepatocellular carcinoma: An integrated scheme of the potential mechanisms of action from in vivo study.

PubMed

Aglan, Hadeer A; Ahmed, Hanaa H; El-Toumy, Sayed A; Mahmoud, Nadia S

2017-06-01

The global burden of hepatocellular carcinoma is increasing; actually, it is estimated as 750,000 new cases annually. This study was initiated to emphasize the possibility that gallic acid could alleviate hepatocarcinogenesis in vivo. In this study, 40 rats were enrolled and distributed as follows; group 1 was set as negative control, while all of groups 2, 3, and 4 were orally received N-nitrosodiethylamine for hepatocellular carcinoma induction. Group 2 was left untreated, whereas groups 3 and 4 were orally treated with gallic acid and doxorubicin, respectively. The current data indicated that gallic acid administration in hepatocellular carcinoma bearing rats yielded significant decline in serum levels of alpha-fetoprotein, glypican-3, and signal transducer and activator of transcription 3 along with significant enhancement in serum suppressors of cytokine signaling 3 level. Also, gallic acid-treated group displayed significant downregulation in the gene expression levels of hepatic gamma glutamyl transferase and heat shock protein gp96. Intriguingly, treatment with gallic acid remarkably ameliorated the destabilization of liver tissue architecture caused by N-nitrosodiethylamine intoxication as evidenced by histopathological investigation. In conclusion, this study demonstrates that the hepatocarcinogenic effect of N-nitrosodiethylamine can be abrogated by gallic acid supplementation owing to its affinity to regulate signal transducer and activator of transcription 3 signaling pathway through its outstanding bioactivities including antioxidant, anti-inflammatory, apoptotic, and antitumor effects.

Exogenous application of rutin and gallic acid regulate antioxidants and alleviate reactive oxygen generation in Oryza sativa L.

PubMed

Singh, Akanksha; Gupta, Rupali; Pandey, Rakesh

2017-04-01

The effect of rutin and gallic acid on growth, phytochemical and defense gene activation of rice ( Oryza sativa L.) was investigated. The seeds of rice were primed with different concentrations of rutin and gallic acid (10-60 µg mL -1 ) to explicate the effect on germination on water agar plates. Further, to study the effect of most effective concentrations of gallic acid (60 µg mL -1 ) and rutin (50 µg mL -1 ), greenhouse pot experiment was set up to determine the changes in growth, antioxidant and defense parameters. The results revealed more pronounced effect of gallic acid on total chlorophyll and carotenoids as well as on total flavonoid content and free radical scavenging activities. Gene expression analysis of OsWRKY71, PAL, CHS and LOX genes involved in strengthening the plant defense further validated the results obtained from the biochemical analysis. Microscopic analysis also confirmed reduction in total reactive oxygen species, free radicals like H 2 O 2 and O 2 - by exogenous application of gallic acid and rutin. The data obtained thus suggest that both gallic acid and rutin can affect the growth and physiology of rice plants and therefore can be used to develop effective plant growth promoters and as substitute of biofertilizers for maximizing their use in field conditions.

Influence of phenolic compounds on the growth and arginine deiminase system in a wine lactic acid bacterium

PubMed Central

Alberto, María R.; de Nadra, María C. Manca; Arena, Mario E.

2012-01-01

The influence of seven phenolic compounds, normally present in wine, on the growth and arginine deiminase system (ADI) of Lactobacillus hilgardii X1B, a wine lactic acid bacterium, was established. This system provides energy for bacterial growth and produces citrulline that reacts with ethanol forming the carcinogen ethyl carbamate (EC), found in some wines. The influence of phenolic compounds on bacterial growth was compound dependent. Growth and final pH values increased in presence of arginine. Arginine consumption decreased in presence of protocatechuic and gallic acids (31 and 17%, respectively) and increased in presence of quercetin, rutin, catechin and the caffeic and vanillic phenolic acids (between 10 and 13%, respectively). ADI enzyme activities varied in presence of phenolic compounds. Rutin, quercetin and caffeic and vanillic acids stimulated the enzyme arginine deiminase about 37–40%. Amounts of 200 mg/L gallic and protocatechuic acids inhibited the arginine deiminase enzyme between 53 and 100%, respectively. Ornithine transcarbamylase activity was not modified at all concentrations of phenolic compounds. As gallic and protocatechuic acids inhibited the arginine deiminase enzyme that produces citrulline, precursor of EC, these results are important considering the formation of toxic compounds. PMID:24031815

Antistaphylococcal and biofilm inhibitory activities of gallic, caffeic, and chlorogenic acids.

PubMed

Luís, Ângelo; Silva, Filomena; Sousa, Sónia; Duarte, Ana Paula; Domingues, Fernanda

2014-01-01

Staphylococcus aureus is a Gram-positive pathogen which is able to form biofilms, exhibiting a more pronounced resistance to antibiotics and disinfectants. The hurdles posed in eradicating biofilms have driven the search for new compounds able to fight these structures. Phenolic compounds constitute one of the most numerous and ubiquitous group of plant secondary metabolites with many biological activities. The aim of the present work was to study the potential antimicrobial and antibiofilm properties of gallic, caffeic, and chlorogenic acids against S. aureus as well to elucidate its mechanism of action. It was concluded that the phenolic acids studied in this work have antistaphylococcal properties. For instance, gallic acid is able to influence the adhesion properties of S. aureus. The phenolic acids tested were also able to inhibit the production of α-hemolysin by this microorganism, with the exception of chlorogenic acid. Regarding its mechanism of action, caffeic acid interferes with the stability of the cell membrane and with the metabolic activity of the cells of S. aureus.

Natural flavonoids as antidiabetic agents. The binding of gallic and ellagic acids to glycogen phosphorylase b.

PubMed

Kyriakis, Efthimios; Stravodimos, George A; Kantsadi, Anastassia L; Chatzileontiadou, Demetra S M; Skamnaki, Vassiliki T; Leonidas, Demetres D

2015-07-08

We present a study on the binding of gallic acid and its dimer ellagic acid to glycogen phosphorylase (GP). Ellagic acid is a potent inhibitor with Kis of 13.4 and 7.5 μM, in contrast to gallic acid which displays Kis of 1.7 and 3.9 mM for GPb and GPa, respectively. Both compounds are competitive inhibitors with respect to the substrate, glucose-1-phoshate, and non-competitive to the allosteric activator, AMP. However, only ellagic acid functions with glucose in a strongly synergistic mode. The crystal structures of the GPb-gallic acid and GPb-ellagic acid complexes were determined at high resolution, revealing that both ligands bind to the inhibitor binding site of the enzyme and highlight the structural basis for the significant difference in their inhibitory potency. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

SERS spectrum of gallic acid obtained from a modified silver colloid

NASA Astrophysics Data System (ADS)

Garrido, C.; Diaz-Fleming, G.; Campos-Vallette, M. M.

2016-06-01

Two different crystals of the gallic acid were microscopically separated from a p.a. commercial product. The Raman spectra analysis allowed distinguishing monomeric and dimeric structures. The vibrational wave numbers were computed using DFT quantum chemical calculations. The data obtained from wave number calculations are used to assign vibrational bands obtained in the Raman spectrum. The dimer, characterized as ellagic acid, involves the carboxyl and hydroxyl moieties. The Raman spectrum in water solution of each species is dominated by the monomeric form. A low negatively charged Ag colloid allowed obtain to the best of our knowledge, the first surface enhanced Raman scattering (SERS) spectrum of the gallic acid. The possible electrophilic attacking sites of the title molecule are identified using MEP surface plot study and the orientation of the analyte on the metal surface is proposed tilted to the surface.

Combined Efficacy of Gallic Acid and MiADMSA with Limited Beneficial Effects Over MiADMSA Against Arsenic-induced Oxidative Stress in Mouse

PubMed Central

Pachauri, Vidhu; Flora, SJS

2015-01-01

Gallic acid is an organic acid known for its antioxidant and anticancer properties. The present study is focused on evaluating the role of gallic acid in providing better therapeutic outcomes against arsenic-induced toxicity. Animals pre-exposed to arsenic were treated with monoisoamyl meso-2,3-dimercaptosuccinic acid (MiADMSA), a new chelating drug, alone and in combination with gallic acid, consecutively for 10 days. The study suggests that (1) gallic acid in presence of MiADMSA is only moderately beneficial against arsenic, (2) monotherapy with gallic acid is more effective than in combination with MiADMSA after arsenic exposure in reducing oxidative injury, and (3) MiADMSA monotherapy as reported previously provides significant therapeutic efficacy against arsenic. Thus, based on the present results, we conclude that gallic acid is effective against arsenic-induced oxidative stress but provides limited additional beneficial effects when administered in combination with MiADMSA. We still recommend that lower doses of gallic acid be evaluated both individually and in combination with MiADMSA, as it might not exhibit the shortcomings we observed with higher doses in this study. PMID:26339189

Tuning stable and unstable aggregates of gallic acid capped gold nanoparticles using Mg2+ as coordinating agent.

PubMed

Kim, Dae-Young; Shinde, Surendra; Ghodake, Gajanan

2017-05-15

High reducibility of gallic acid allows synthesis of small sized monodisperse gold nanoparticles (GNPs) at ambient temperature (25°C). Mg 2+ rapidly interacts with the gallic acid ligands and suppresses the dispersion of GNPs therefore, causing a decrease in UV-vis absorbance intensity, and color change from red to blue. Thus, the colorimetric response of GNPs with Mg 2+ was investigated by observing temporal quenching of UV-vis absorbance and precise tuning of fractal growth of GNP aggregates. Moreover, Mg 2+ at concentrations as low as 200ppb can be detected using gallic acid ligand-mediated coordination chemistry which results quenching in UV-vis absorbance proportional to the exposure time. This gallic acid-based colorimetric sensor shown a great potential for the selective detection of pathologically important electrolyte Mg 2+ without any interference from other cations Ca 2+ and K + . Copyright © 2017 Elsevier Inc. All rights reserved.

The fifth solvatomorph of gallic acid with a supramolecular channel structure: Structural complexity and phase transitions

NASA Astrophysics Data System (ADS)

Thomas, Sajesh P.; Kaur, Ramanpreet; Kaur, Jassjot; Sankolli, Ravish; Nayak, Susanta K.; Guru Row, Tayur N.

2013-01-01

A new solvatomorph of gallic acid was generated using chiral additive technique and characterized by single crystal and powder X-ray diffraction, C-13 NMR, IR spectroscopic techniques and thermal analysis. The supramolecular channels formed by hexameric motifs of gallic acid and solvent molecules contain highly disordered solvent molecules with fractional occupancies.

Propyl gallate synthesis using acidophilic tannase and simultaneous production of tannase and gallic acid by marine Aspergillus awamori BTMFW032.

PubMed

Beena, P S; Basheer, Soorej M; Bhat, Sarita G; Bahkali, Ali H; Chandrasekaran, M

2011-07-01

Marine Aspergillus awamori BTMFW032, recently reported by us, produce acidophilic tannase as extracellular enzyme. Here, we report the application of this enzyme for synthesis of propyl gallate by direct transesterification of tannic acid and in tea cream solubilisation besides the simultaneous production of gallic acid along with tannase under submerged fermentation by this fungus. This acidophilic tannase enabled synthesis of propyl gallate by direct transesterification of tannic acid using propanol as organic reaction media under low water conditions. The identity of the product was confirmed with thin layer chromatography and Fourier transform infrared spectroscopy. It was noted that 699 U/ml of enzyme could give 60% solubilisation of tea cream within 1 h. Enzyme production medium was optimized adopting Box-Behnken design for simultaneous synthesis of tannase and gallic acid. Process variables including tannic acid, sodium chloride, ferrous sulphate, dipotassium hydrogen phosphate, incubation period and agitation were recognized as the critical factors that influenced tannase and gallic acid production. The model obtained predicted 4,824.61 U/ml of tannase and 136.206 μg/ml gallic acid after 48 h of incubation, whereas optimized medium supported 5,085 U/ml tannase and 372.6 μg/ml of gallic acid production after 36 and 84 h of incubation, respectively, with a 15-fold increase in both enzyme and gallic acid production. Results indicated scope for utilization of this acidophilic tannase for transesterification of tannic acid into propyl gallate, tea cream solubilisation and simultaneous production of gallic acid along with tannase.

EPR spectral investigation of radiation-induced radicals of gallic acid.

PubMed

Tuner, Hasan

2017-11-01

In the present work, spectroscopic features of the radiation-induced radicals of gallic acid compounds were investigated using electron paramagnetic resonance (EPR) spectroscopy. While un-irradiated samples presented no EPR signal, irradiated samples exhibited an EPR spectrum consisting of an intense resonance line at the center and weak lines on both sides. Detailed microwave saturation investigations were carried out to determine the origin of the experimental EPR lines. It is concluded that the two side lines of the triplet satellite originate from forbidden "spin-flip" transitions. The spectroscopic and structural features of the radiation-induced radicals were determined using EPR spectrum fittings. The experimental EPR spectra of the two gallic acid compounds were consistent with the calculated EPR spectroscopic features of the proposed radicals. It is concluded that the most probable radicals are the cyclohexadienyl-type, [Formula: see text] radicals for both compounds.

Synergistic Effect of Quercetin and α-Lipoic Acid on Aluminium Chloride Induced Neurotoxicity in Rats.

PubMed

Al-Otaibi, Sooad Saud; Arafah, Maha Mohamad; Sharma, Bechan; Alhomida, Abdullah Salih; Siddiqi, Nikhat Jamal

2018-01-01

The present study was carried out to study the protective effects of quercetin and α -lipoic acid alone and in combination against aluminum chloride induced neurotoxicity in rats. The study consisted of eight groups, namely, Group 1: control rats, Group 2: rats receiving aluminium chloride 7 mg/kg body weight intraperitoneal route (i.p) for two weeks, Group 3: rats receiving quercetin 50 mg/kg body weight i.p. for two weeks, Group 4: rats receiving quercetin 50 mg/kg body weight followed by aluminium chloride 7 mg/kg body weight i.p. for two weeks, Group 5: rats receiving α -lipoic acid 20 mg/kg body weight i.p. for two weeks, Group 6: rats receiving lipoic acid 20 mg/kg body weight followed by aluminium chloride 7 mg/kg body weight i.p. for two weeks, Group 7: rats receiving α -lipoic acid 20 mg/kg body weight and quercetin 50 mg/kg body weight i.p. for two weeks, and Group 8: rats receiving α -lipoic acid 20 mg/kg body weight and quercetin 50 mg/kg body weight followed by aluminium chloride 7 mg/kg body weight i.p. for two weeks. The animals were killed after 24 hours of the last dose by cervical dislocation. Aluminium chloride treatment of rats resulted in significant increases in lipid peroxidation, protein carbonyl levels, and acetylcholine esterase activity in the brain. This was accompanied with significant decreases in reduced glutathione, activities of the glutathione reductase, and superoxide dismutase. Pretreatment of AlCl 3 exposed rats to either quercetin or α -lipoic acid also restored altered lipid peroxidation and superoxide dismutase to near normal levels. Quercetin or α -lipoic acid pretreatment of AlCl 3 exposed rats improved the protein carbonyl and reduced glutathione, glutathione reductase, and acetylcholine esterase activities in rat brains towards normal levels. Combined pretreatment of AlCl3 exposed rats with quercetin and α -lipoic acid resulted in a tendency towards normalization of most of the parameters

Synergistic Effect of Quercetin and α-Lipoic Acid on Aluminium Chloride Induced Neurotoxicity in Rats

PubMed Central

Al-Otaibi, Sooad Saud

2018-01-01

Objectives The present study was carried out to study the protective effects of quercetin and α-lipoic acid alone and in combination against aluminum chloride induced neurotoxicity in rats. Materials and Methods The study consisted of eight groups, namely, Group 1: control rats, Group 2: rats receiving aluminium chloride 7 mg/kg body weight intraperitoneal route (i.p) for two weeks, Group 3: rats receiving quercetin 50 mg/kg body weight i.p. for two weeks, Group 4: rats receiving quercetin 50 mg/kg body weight followed by aluminium chloride 7 mg/kg body weight i.p. for two weeks, Group 5: rats receiving α-lipoic acid 20 mg/kg body weight i.p. for two weeks, Group 6: rats receiving lipoic acid 20 mg/kg body weight followed by aluminium chloride 7 mg/kg body weight i.p. for two weeks, Group 7: rats receiving α-lipoic acid 20 mg/kg body weight and quercetin 50 mg/kg body weight i.p. for two weeks, and Group 8: rats receiving α-lipoic acid 20 mg/kg body weight and quercetin 50 mg/kg body weight followed by aluminium chloride 7 mg/kg body weight i.p. for two weeks. The animals were killed after 24 hours of the last dose by cervical dislocation. Results Aluminium chloride treatment of rats resulted in significant increases in lipid peroxidation, protein carbonyl levels, and acetylcholine esterase activity in the brain. This was accompanied with significant decreases in reduced glutathione, activities of the glutathione reductase, and superoxide dismutase. Pretreatment of AlCl3 exposed rats to either quercetin or α-lipoic acid also restored altered lipid peroxidation and superoxide dismutase to near normal levels. Quercetin or α-lipoic acid pretreatment of AlCl3 exposed rats improved the protein carbonyl and reduced glutathione, glutathione reductase, and acetylcholine esterase activities in rat brains towards normal levels. Combined pretreatment of AlCl3 exposed rats with quercetin and α-lipoic acid resulted in a tendency towards

Free radicals produced by the oxidation of gallic acid: An electron paramagnetic resonance study.

PubMed

Eslami, Angelique C; Pasanphan, Wanvimol; Wagner, Brett A; Buettner, Garry R

2010-08-05

Gallic acid (3,4,5-trihydroxybenzoic acid) is found in a wide variety of plants; it is extensively used in tanning, ink dyes, as well as in the manufacturing of paper. The gallate moiety is a key component of many functional phytochemicals. In this work electron paramagnetic spectroscopy (EPR) was used to detect the free radicals generated by the air-oxidation of gallic acid. We found that gallic acid produces two different radicals as a function of pH. In the pH range between 7-10, the spectrum of the gallate free radical is a doublet of triplets (aH = 1.00 G, aH = 0.23 G, aH = 0.28 G). This is consistent with three hydrogens providing hyperfine splitting. However, in a more alkaline environment, pH >10, the hyperfine splitting pattern transforms into a 1:2:1 pattern (aH (2) = 1.07 G). Using D2O as a solvent, we demonstrate that the third hydrogen (i.e. aH = 0.28 G) at lower pH is a slowly exchanging hydron, participating in hydrogen bonding with two oxygens in ortho position on the gallate ring. The pKa of this proton has been determined to be 10. This simple and novel approach permitted the understanding of the prototropic equilibrium of the semiquinone radicals generated by gallic acid, a ubiquitous compound, allowing new insights into its oxidation and subsequent reactions.

An Efficient Protocol for Preparation of Gallic Acid from Terminalia bellirica (Gaertn.) Roxb by Combination of Macroporous Resin and Preparative High-Performance Liquid Chromatography.

PubMed

Zou, Denglang; Chen, Tao; Chen, Chen; Li, Hongmei; Liu, Yongling; Li, Yulin

2016-08-01

In this article, macroporous resin column chromatography and preparative high-performance liquid chromatography were applied for preparation of gallic acid from Terminalia bellirica (Gaertn.) Roxb. In the first step, six kinds of resins were investigated by adsorption and desorption tests and AB-8 macroporous resin was selected for the enrichment of gallic acid. As a result, 20 g of gallic acid at a purity of 71% could be separated from 100 g of crude extract in which the content of gallic acid was 16.7% and the recovery of gallic acid reached 85.0%. In the second step, preparative high-performance liquid chromatography was selected to purify gallic acid. As a result, 640 mg of gallic acid at a purity of 99.1% was obtained from 1 g of sample in 35 min. The results demonstrated that macroporous resin coupled with preparative high-performance liquid chromatography was suitable for preparation of gallic acid from T. bellirica (Gaertn.) Roxb. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Gallic acid modulates phenotypic behavior and gene expression in oral squamous cell carcinoma cells by interfering with leptin pathway.

PubMed

Santos, Eliane Macedo Sobrinho; da Rocha, Rogério Gonçalves; Santos, Hércules Otacílio; Guimarães, Talita Antunes; de Carvalho Fraga, Carlos Alberto; da Silveira, Luiz Henrique; Batista, Paulo Ricardo; de Oliveira, Paulo Sérgio Lopes; Melo, Geraldo Aclécio; Santos, Sérgio Henrique; de Paula, Alfredo Maurício Batista; Guimarães, André Luiz Sena; Farias, Lucyana Conceição

2018-01-01

Gallic acid is a polyphenolic compost appointed to interfere with neoplastic cells behavior. Evidence suggests an important role of leptin in carcinogenesis pathways, inducing a proliferative phenotype. We investigated the potential of gallic acid to modulate leptin-induced cell proliferation and migration of oral squamous cell carcinoma cell lines. The gallic acid effect on leptin secretion by oral squamous cell carcinoma cells, as well as the underlying molecular mechanisms, was also assessed. For this, we performed proliferation, migration, immunocytochemical and qPCR assays. The expression levels of cell migration-related genes (MMP2, MMP9, Col1A1, and E-cadherin), angiogenesis (HIF-1α, mir210), leptin signaling (LepR, p44/42 MAPK), apoptosis (casp-3), and secreted leptin levels by oral squamous cell carcinoma cells were also measured. Gallic acid decreased proliferation and migration of leptin-treated oral squamous cell carcinoma cells, and reduced mRNA expression of MMP2, MMP9, Col1A1, mir210, but did not change HIF-1α. Gallic acid decreased levels of leptin secreted by oral squamous cell carcinoma cells, accordingly with downregulation of p44/42 MAPK expression. Thus, gallic acid appears to break down neoplastic phenotype of oral squamous cell carcinoma cells by interfering with leptin pathway. Copyright © 2017 Elsevier GmbH. All rights reserved.

The anti-inflammatory and anti-apoptotic effects of gallic acid against mucosal inflammation- and erosions-induced by gastric ischemia-reperfusion in rats

PubMed Central

Mard, Seyyed Ali; Mojadami, Shahnaz; Farbood, Yaghoob; Gharib Naseri, Mohammad Kazem

2015-01-01

The present study aimed to evaluate the protective effect of gallic acid on gastric mucosal lesions caused by ischemia-reperfusion (I/R) injury in rat. Forty male rats were randomly divided into sham, control (I/R injury) and three gallic acid-pretreated groups. To induce I/R lesions, the celiac artery was clamped for 30 min and then the clamp was removed to allow reperfusion for 6 hr. Pretreated rats received gallic acid (15, 30 or 60 mg kg-1, intraperitoneally) 30 min prior to the induction of I/R injury. Macroscopic and microscopic evaluations of the areas of ulceration were compared. Samples of gastric mucosa were collected to evaluate the protein expression of pro-apoptotic factor, caspase-3, and pro-inflammatory enzyme, inducible nitric oxide synthase (iNOS) using western blot. Pretreatment with gallic acid decreased the total area of gastric lesions. Gallic acid at 30 mg kg-1 decreased the levels of protein expression of caspase-3 and iNOS induced by I/R injury. Our findings showed the protective effect of gallic acid on gastric mucosa against ischemia-reperfusion injury. This effect of gallic acid was mainly mediated by reducing protein expression of iNOS and caspase-3. PMID:26973766

The anti-inflammatory and anti-apoptotic effects of gallic acid against mucosal inflammation- and erosions-induced by gastric ischemia-reperfusion in rats.

PubMed

Mard, Seyyed Ali; Mojadami, Shahnaz; Farbood, Yaghoob; Gharib Naseri, Mohammad Kazem

2015-01-01

The present study aimed to evaluate the protective effect of gallic acid on gastric mucosal lesions caused by ischemia-reperfusion (I/R) injury in rat. Forty male rats were randomly divided into sham, control (I/R injury) and three gallic acid-pretreated groups. To induce I/R lesions, the celiac artery was clamped for 30 min and then the clamp was removed to allow reperfusion for 6 hr. Pretreated rats received gallic acid (15, 30 or 60 mg kg(-1), intraperitoneally) 30 min prior to the induction of I/R injury. Macroscopic and microscopic evaluations of the areas of ulceration were compared. Samples of gastric mucosa were collected to evaluate the protein expression of pro-apoptotic factor, caspase-3, and pro-inflammatory enzyme, inducible nitric oxide synthase (iNOS) using western blot. Pretreatment with gallic acid decreased the total area of gastric lesions. Gallic acid at 30 mg kg(-1) decreased the levels of protein expression of caspase-3 and iNOS induced by I/R injury. Our findings showed the protective effect of gallic acid on gastric mucosa against ischemia-reperfusion injury. This effect of gallic acid was mainly mediated by reducing protein expression of iNOS and caspase-3.

Synergistic effect of the combination of gallic acid and famotidine in protection of rat gastric mucosa.

PubMed

Asokkumar, K; Sen, Saikat; Umamaheswari, M; Sivashanmugam, A T; Subhadradevi, V

2014-08-01

Antioxidant supplements with existing drugs may confer better therapeutic efficacy in oxidative stress related diseases. The purpose of the present work was to characterize the interaction and investigate the protective effect of H2 blocker famotidine and gallic acid in combination against experimentally induced peptic ulcer. Preventive effect of gallic acid and famotidine in different combinations was investigated against aspirin plus pyloric ligation induced ulcer in rat. Ulcer index, gastric juice volume, pH, other biochemical parameters of gastric juice and antioxidant activity using stomach tissue were estimated. Pretreatment with gallic acid and famotidine in combinations for 7 days, protected the gastric mucosa significantly (p<0.05, 0.01), which was evidenced by decrease in ulcer index, gastric juice volume, free and total acidity, total protein, pepsin and DNA content, and increase in pH, carbohydrates concentration in gastric juice. Combination treatment increases levels of superoxide dismutase, catalase, reduced glutathione, glutathione reductase and glucose-6-phosphate dehydrogenase, and decreases lipid peroxidation, myloperoxidase in stomach tissue. Along with higher dose combination, lower dose combinations like gallic acid (50mg/kg) plus famotidine (10mg/kg) also offered better antiulcer activity than their individual effect. Histopathological studies confirmed their antiulcer activity. Combination treatments confer synergistic protective effect against peptic ulcer in rats, which was related to the gastroprotective, antisecratory and antioxidant activity of combination treatment. Results proved that use of gallic acid with existing antiulcer drug will be more useful in the prevention/management of peptic ulcer. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Effect of the structure of gallic acid and its derivatives on their interaction with plant ferritin.

PubMed

Wang, Qunqun; Zhou, Kai; Ning, Yong; Zhao, Guanghua

2016-12-15

Gallic acid and its derivatives co-exist with protein components in foodstuffs, but there is few report on their interaction with proteins. On the other hand, plant ferritin represents not only a novel class of iron supplement, but also a new nanocarrier for encapsulation of bioactive nutrients. However, plant ferritin is easy to be degraded by pepsin in the stomach, thereby limiting its application. Herein, we investigated the interaction of gallic acid and its derivatives with recombinant soybean seed H-2 ferritin (rH-2). We found that these phenolic acids interacted with rH-2 in a structure-dependent manner; namely, gallic acid (GA), methyl gallate (MEGA) and propyl gallate (PG) having three HO groups can bind to rH-2, while their analogues with two HO groups cannot. Consequently, such binding largely inhibited ferritin degradation by pepsin. These findings advance our understanding of the relationship between the structure and function of phenolic acids. Copyright © 2016 Elsevier Ltd. All rights reserved.

Gallic acid-based indanone derivative interacts synergistically with tetracycline by inhibiting efflux pump in multidrug resistant E. coli.

PubMed

Dwivedi, Gaurav Raj; Tiwari, Nimisha; Singh, Aastha; Kumar, Akhil; Roy, Sudeep; Negi, Arvind Singh; Pal, Anirban; Chanda, Debabrata; Sharma, Ashok; Darokar, Mahendra P

2016-03-01

The purpose of the present study was to study the synergy potential of gallic acid-based derivatives in combination with conventional antibiotics using multidrug resistant cultures of Escherichia coli. Gallic acid-based derivatives significantly reduced the MIC of tetracycline against multidrug resistant clinical isolate of E. coli. The best representative, 3-(3',4,'5'-trimethoxyphenyl)-4,5,6-trimethoxyindanone-1, an indanone derivative of gallic acid, was observed to inhibit ethidium bromide efflux and ATPase which was also supported by in silico docking. This derivative extended the post-antibiotic effect and decreased the mutation prevention concentration of tetracycline. This derivative in combination with TET was able to reduce the concentration of TNFα up to 18-fold in Swiss albino mice. This derivative was nontoxic and well tolerated up to 300 mg/kg dose in subacute oral toxicity study in mice. This is the first report of gallic acid-based indanone derivative as drug resistance reversal agent acting through ATP-dependent efflux pump inhibition.

Acute toxicity and sublethal effects of gallic and pelargonic acids on the zebrafish Danio rerio.

PubMed

Techer, Didier; Milla, Sylvain; Fontaine, Pascal; Viot, Sandrine; Thomas, Marielle

2015-04-01

Gallic and pelargonic acids are naturally found in a variety of plants and food products. Despite their extensive use in man-made applications, little is known regarding their potential risks to aquatic vertebrates. The aim of this work was to assess the acute toxicity of these polyphenolic and fatty acid compounds to the zebrafish. In order to get insights into sublethal effects, the enzyme activity of usual biomarkers related to oxidative stress and biotransformation were also assessed in fish. These latter included total superoxide dismutase, catalase as well as total glutathione peroxidase for antioxidant defence mechanisms and glutathione S-transferase for biotransformation related enzyme. Gallic acid was practically non-toxic (96-h lethal concentration (LC50) > 100 mg/L) whereas pelargonic acid was slightly toxic (96-h LC50 of 81.2 mg/L). Moreover, biomarker analyses indicated enhanced superoxide dismutase activity in fish exposed to 20, 40 and 100 mg/L of gallic acid compared to control. A dose-dependent induction of glutathione peroxidase and glutathione S-transferase was reported following gallic acid exposure at the tested concentrations of 10, 20 and 40 mg/L, with the exception of 100 mg/L of substance where basal activity levels were reported. In the case of pelargonic acid, there was no change in antioxidant enzyme activity while an inhibition of glutathione S-transferase was observed from organisms exposed to 45, 58 and 76 mg/L of test solution. The results concerning sublethal effects on biological parameters of zebrafish highlighted thereby the need for further investigations following chronic exposure to both organic acids.

Effects of Gallic Acid and Cyclosporine A on Antioxidant Capacity and Cardiac Markers of Rat Isolated Heart After Ischemia/Reperfusion

PubMed Central

Badavi, Mohammad; Sadeghi, Najmeh; Dianat, Mahin; Samarbafzadeh, Alireza

2014-01-01

Background: Myocardial infarction is one of the important causes of death during old ages. Gallic acid as an antioxidant or cyclosporine A (CsA) as inhibitor of mitochondrial permeability transition pore (mPTP) alone could prevent these complications to some extent, but their combination effect has not been investigated. Objectives: The aim of this study was to determine the combined effect of gallic acid and CsA on antioxidant capacity of isolated heart tissues during ischemia reperfusion. Materials and Methods: Eighty male Wistar rats were randomly assigned to different groups: sham, control (Ca, received saline, 1 mL/kg); 3 groups were pretreated with gallic acid (G1a: 7.5, G2a: 15, G3a: 30 mg/kg) for 10 days, and the other 3 groups were pretreated with gallic acid and received CsA (0.2 µM) for 10 minutes before induction of ischemia and during the first 10 minutes of reperfusion (G1b, G2b and G3b) and the last group received CsA alone (Cb). After 10 days of pretreatment, the heart was isolated and transferred to the Langendorff apparatus and exposed to 30 minutes ischemia followed by 60 minutes of reperfusion. After that cardiac markers and antioxidant enzymes were assessed in cardiac tissues. Results: Lactate dehydrogenase (LDH), Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activity increased and malondialdehyde (MDA) decreased in animals pretreated with gallic acid significantly. However, pretreatment with gallic acid followed by CsA during reperfusion improved the antioxidant capacity and cardiac marker enzymes and restored the lipid peroxidation more effective than gallic acid or CsA alone. Nevertheless, CsA did not change the cardiac marker enzymes significantly. Conclusions: Gallic acid and CsA combination improved antioxidant capacity and cell membrane integrity more than each one alone. Therefore, it can be a therapeutic approach to reduce the I/R injury. PMID:25068044

Anti-Inflammatory Effect of Gallic Acid-Eluting Stent in a Porcine Coronary Restenosis Model

PubMed Central

Seob Lim, Kyung; Park, Jun-Kyu; Ho Jeong, Myung; Ho Bae, In; Sung Park, Dae; Won Shim, Jae; Ha Kim, Jung; Kuk Kim, Hyun; Soo Kim, Sung; Sun Sim, Doo; Joon Hong, Young; Han Kim, Ju; Ahn, Youngkeun

2018-01-01

Background Gallic acid (3,4,5-trihydroxybenzoic acid) is a natural polyphenol and strong natural antioxidant found abundantly in red wine and green tea. The aim of this study was to examine the anti-inflammatory effect of a novel gallic acid-eluting stent in a porcine coronary restenosis model. Methods Fifteen pigs were randomized into three groups; in which a total of 30 coronary arteries (10 in each group) were implanted with gallic acid-eluting stents (GESs, n = 10), gallic acid and sirolimus-eluting stents (GSESs, n = 10), or sirolimus-eluting stents (SESs, n = 10). Histopathologic analysis was performed 28 days after stenting. Results There were no significant differences in injury score and fibrin score among the groups, however there were significant differences in the internal elastic lamina (4.0 ± 0.83 mm2 in GES vs. 3.0 ± 0.53 mm2 in GSES vs. 4.6 ± 1.43 mm2 in SES, p < 0.0001), lumen area (2.3 ± 0.49 mm2 in GES vs. 1.9 ± 0.67 mm2 in GSES vs. 2.9 ± 0.56 mm2 in SES, p < 0.0001), neointimal area (1.7 ± 0.63 mm2 in GES vs. 1.1 ± 0.28 mm2 in GSES vs. 1.7 ± 1.17 mm2 in SES, p < 0.05), and percent area of stenosis (42.4% ± 9.22% in GES vs. 38.2% ± 12.77% in GSES vs. 33.9% ± 15.64% in SES, p < 0.05). The inflammation score was significantly lower in the GES and GSES groups compared to that in the SES group [1.0 (range: 1.0 to 2.0) in GES vs. 1.0 (range: 1.0 to 1.0) in GSES vs. 1.5 (range: 1.0 to 3.0) in SES, p < 0.05]. Conclusions The GES group had a greater percent area of stenosis than the SES group. Although gallic acid in the GES and GSES groups did not show a synergistic effect in suppressing neointimal hyperplasia, it resulted in greater inhibition of the inflammatory reaction in the porcine coronary restenosis model than in the SES group. PMID:29844643

Computational study of molecular electrostatic potential, docking and dynamics simulations of gallic acid derivatives as ABL inhibitors.

PubMed

Raghi, K R; Sherin, D R; Saumya, M J; Arun, P S; Sobha, V N; Manojkumar, T K

2018-04-05

Chronic myeloid leukemia (CML), a hematological malignancy arises due to the spontaneous fusion of the BCR and ABL gene, resulting in a constitutively active tyrosine kinase (BCR-ABL). Pharmacological activity of Gallic acid and 1,3,4-Oxadiazole as potential inhibitors of ABL kinase has already been reported. Objective of this study is to evaluate the ABL kinase inhibitory activity of derivatives of Gallic acid fused with 1,3,4-Oxadiazole moieties. Attempts have been made to identify the key structural features responsible for drug likeness of the Gallic acid and the 1,3,4-Oxadiazole ring using molecular electrostatic potential maps (MESP). To investigate the inhibitory activity of Gallic acid derivatives towards the ABL receptor, we have applied molecular docking and molecular dynamics (MD) simulation approaches. A comparative study was performed using Bosutinib as the standard which is an approved CML drug acting on the same receptor. Furthermore, the novel compounds designed and reported here in were evaluated for ADME properties and the results indicate that they show acceptable pharmacokinetic properties. Accordingly these compounds are predicted to be drug like with low toxicity potential. Copyright © 2018 Elsevier Ltd. All rights reserved.

EGFR-dependent signalling reduced and p38 dependent apoptosis required by Gallic acid in Malignant Mesothelioma cells.

PubMed

Demiroglu-Zergeroglu, Asuman; Candemir, Gulsife; Turhanlar, Ebru; Sagir, Fatma; Ayvali, Nurettin

2016-12-01

The unrestrained EGFR signalling contributes to malignant phenotype in a number of cancers including Malignant Mesotheliomas. Present study was designed to evaluate EGFR-dependent anti-proliferative and apoptotic effects of Gallic acid in transformed Mesothelial (MeT-5A) and Malignant Mesothelioma (SPC212) cells. Gallic acid reduced the viability of Malignant Mesothelioma cells in a concentration and time-dependent manner. However, viability of mesothelial cells reduced only at high concentration and longer time periods. Gallic acid restrained the activation of EGFR, ERK1/2 and AKT proteins and down regulated expression of Cyclin D and Bcl-2 genes, but upregulated the expression of p21 gene in EGF-induced SPC212 cells. GA-induced transitory G1 arrest and triggered mitochondrial and death receptor mediated apoptosis, which requires p38MAPK activation. The data provided here indicate that GA is able to inhibit EGFR dependent proliferation and survival signals and induces p38 pathway dependent apoptosis in Malignant Mesothelioma cells. On the basis of these experimental findings it is worthwhile to investigate further the biological activity of Gallic acid on other Mesothelioma cell lines harbouring aberrant EGFR signals. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Gallic acid as a protective antioxidant against anthocyanin degradation and color loss in vitamin-C fortified cranberry juice.

PubMed

Roidoung, Sunisa; Dolan, Kirk D; Siddiq, Muhammad

2016-11-01

The objective of this study was to evaluate different antioxidants for anthocyanin (ACY) retention in vitamin C fortified cranberry juice and assess its quality. Cranberry juice was fortified with 40-80mg/100mL vitamin C and added hesperidin, catechin, and gallic acid at different concentrations. Juice was pasteurized at 85°C for 1min and stored at 23°C for 16days. ACYs, vitamin C, color intensity, and browning index (BI) were evaluated at 2-day intervals. Gallic acid was found to be the most effective antioxidant against ACYs degradation and significantly (p<0.05) increased red color intensity by 37% and ACY concentration by 41%, compared to the control. After 16-day storage, the BI of gallic acid-added juice was significantly lower (0.80 vs 1.00) than the control juice. The outcome of this research provided a potential solution of using gallic acid to preserve a health-beneficial component (ACYs), and endogenous red color in cranberry juice. Copyright © 2016 Elsevier Ltd. All rights reserved.

Mitigation of diazinon-induced cardiovascular and renal dysfunction by gallic acid

PubMed Central

Ajibade, Temitayo Olabisi; Omobowale, Temidayo Olutayo; Asenuga, Ebunoluwa Racheal; Afolabi, Jeremiah Moyinoluwa; Adedapo, Adeolu Alex

2016-01-01

Studies of the link between environmental pollutants and cardiovascular dysfunction, neglected for decades, have recently provided new insights into the pathology and consequences of these killers. In this study, rats were divided into four groups, each containing 10 rats. The rats in group one served as controls and were administered normal saline, whereas the rats in group two were orally gavaged with 3 mg/kg of diazinon (DZN) alone for twenty one consecutive days. The rats in groups 3 and 4 were administered respective 60 mg/kg and 120 mg/kg gallic acid (GA) in addition to DZN for twenty one consecutive days. Exposure of rats to diazinon significantly (p<0.05) reduced the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) content. Malondialdehyde, hydrogen peroxide (H2O2) and nitric oxide (NO) contents were also significantly (p<0.05) elevated following DZN exposure. DZN further caused a significant (p<0.05) decrease of heart rate and QT interval prolongation. Hematologic analysis revealed significant reduction (p<0.05) in packed cell volume (PCV), hemoglobin concentration (Hb), red blood cell (RBC) count, and total white blood cell count of rats administered only DZN. Observations in this study suggest a modulatory role of gallic acid in diazinon-induced anemia and associated cardiovascular dysfunction in rats. Treatment with gallic acid reversed the oxidative stress markers studied, increased the antioxidant defence system and reduced deleterious effects on hematological parameters in rats. Pathologic findings of the heart and kidney were also found to be lessened. PMID:28652848

The effect of gallic acid on cytotoxicity, Ca(2+) homeostasis and ROS production in DBTRG-05MG human glioblastoma cells and CTX TNA2 rat astrocytes.

PubMed

Hsu, Shu-Shong; Chou, Chiang-Ting; Liao, Wei-Chuan; Shieh, Pochuen; Kuo, Daih-Huang; Kuo, Chun-Chi; Jan, Chung-Ren; Liang, Wei-Zhe

2016-05-25

Gallic acid, a polyhydroxylphenolic compound, is widely distributed in various plants, fruits and foods. It has been shown that gallic acid passes into blood brain barrier and reaches the brain tissue of middle cerebral artery occlusion rats. However, the effect of gallic acid on Ca(2+) signaling in glia cells is unknown. This study explored whether gallic acid affected Ca(2+) homeostasis and induced Ca(2+)-associated cytotoxicity in DBTRG-05MG human glioblastoma cells and CTX TNA2 rat astrocytes. Gallic acid (20-40 μM) concentration-dependently induced cytotoxicity and intracellular Ca(2+) level ([Ca(2+)]i) increases in DBTRG-05MG cells but not in CTX TNA2 cells. In DBTRG-05MG cells, the Ca(2+) response was decreased by half by removal of extracellular Ca(2+). In Ca(2+)-containing medium, gallic acid-induced Ca(2+) entry was inhibited by store-operated Ca(2+) channel inhibitors (2-APB, econazole and SKF96365). In Ca(2+)-free medium, pretreatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin abolished gallic acid-induced [Ca(2+)]i increases. Conversely, incubation with gallic acid also abolished thapsigargin-induced [Ca(2+)]i increases. Inhibition of phospholipase C with U73122 abolished gallic acid-induced [Ca(2+)]i increases. Gallic acid significantly caused cytotoxicity in DBTRG-05MG cells, which was partially prevented by prechelating cytosolic Ca(2+) with BAPTA-AM. Moreover, gallic acid activated mitochondrial apoptotic pathways that involved ROS production. Together, in DBTRG-05MG cells but not in CTX TNA2 cells, gallic acid induced [Ca(2+)]i increases by causing Ca(2+) entry via 2-APB, econazole and SKF96365-sensitive store-operated Ca(2+) entry, and phospholipase C-dependent release from the endoplasmic reticulum. This Ca(2+) signal subsequently evoked mitochondrial pathways of apoptosis that involved ROS production. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Polyphenols in red wine inhibit the proliferation and induce apoptosis of LNCaP cells.

PubMed

Romero, I; Páez, A; Ferruelo, A; Luján, M; Berenguer, A

2002-06-01

To assess the effect of five polyphenol constituents of red wine (quercetin, morin, rutin, gallic acid and tannic acid) on the proliferation of LNCaP cells, and to quantify the extent of apoptosis with each polyphenol. LNCaP cells (500) were cultured in microtitre plates and treated with gallic acid, tannic acid, quercetin (1, 5 and 10 micromol/L), rutin and morin (25, 50 and 75 micromol/L). A colorimetric immunoassay was then used to determine the extent of proliferation at 24, 48, 72 and 96 h, and a cell-death detection assay to assess apoptosis at 24, 48 and 72 h. Gallic and tannic acid (5 and 10 micromol/L), morin (50 and 75 micromol/L), quercetin (5 and 10 micromol/L) and rutin (50 and 75 micromol/L) all significantly inhibited (P<0.05) cell proliferation compared with the control. Apoptotic indexes were significantly greater (P<0.01) in the presence of gallic (5 and 10 micromol/L) and tannic acid (5 and 10 micromol/L), and rutin (75 micromol/L, P<0.05) than in the control. The apoptotic effect of morin (75 micromol/L), although significant (P<0.01), only appeared at 72 h. Conversely, while significant (P<0.05) quercetin (5 and 10 micromol/L) had a transient (first 48 h) apoptotic effect compared with the control. Quercetin, rutin, morin, gallic acid and tannic acid inhibited the growth of LNCaP cells at different concentrations, and induced apoptosis. The results provide a strong rationale for studying the in vivo effects of these compounds.

Effects of gallic acid on delta - aminolevulinic dehydratase activity and in the biochemical, histological and oxidative stress parameters in the liver and kidney of diabetic rats.

PubMed

de Oliveira, Lizielle Souza; Thomé, Gustavo Roberto; Lopes, Thauan Faccin; Reichert, Karine Paula; de Oliveira, Juliana Sorraila; da Silva Pereira, Aline; Baldissareli, Jucimara; da Costa Krewer, Cristina; Morsch, Vera Maria; Chitolina Schetinger, Maria Rosa; Spanevello, Roselia Maria

2016-12-01

Diabetes mellitus (DM) is characterised by hyperglycaemia associated with the increase of oxidative stress. Gallic acid has potent antioxidant properties. The aim of this study was to evaluate the effect of gallic acid on the biochemical, histological and oxidative stress parameters in the liver and kidney of diabetic rats. Male rats were divided in groups: control, gallic acid, diabetic and diabetic plus gallic acid. DM was induced in the animals by intraperitoneal injection of streptozotocin (65mg/kg). Gallic acid (30mg/kg) was administered orally for 21days. Our results showed an increase in reactive species levels and lipid peroxidation, and a decrease in activity of the enzymes superoxide dismutase and delta-aminolevulinic acid dehydratase in the liver and kidney of the diabetic animals (P<0.05). Gallic acid treatment showed protective effects in these parameters evaluated, and also prevented a decrease in the activity of catalase and glutathione S-transferase, and vitamin C levels in the liver of diabetic rats. In addition, gallic acid reduced the number of nuclei and increased the area of the core in hepatic tissue, and increased the glomerular area in renal tissue. These results indicate that gallic acid can protect against oxidative stress-induced damage in the diabetic state. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Anti-pandemic influenza A (H1N1) virus potential of catechin and gallic acid.

PubMed

You, Huey-Ling; Huang, Chao-Chun; Chen, Chung-Jen; Chang, Cheng-Chin; Liao, Pei-Lin; Huang, Sheng-Teng

2018-05-01

The pandemic influenza A (H1N1) virus has spread worldwide and infected a large proportion of the human population. Discovery of new and effective drugs for the treatment of influenza is a crucial issue for the global medical community. According to our previous study, TSL-1, a fraction of the aqueous extract from the tender leaf of Toonasinensis, has demonstrated antiviral activities against pandemic influenza A (H1N1) through the down-regulation of adhesion molecules and chemokine to prevent viral attachment. The aim of the present study was to identify the active compounds in TSL-1 which exert anti-influenza A (H1N1) virus effects. XTT assay was used to detect the cell viability. Meanwhile, the inhibitory effect on the pandemic influenza A (H1N1) virus was analyzed by observing plaque formation, qRT-PCR, neuraminidase activity, and immunofluorescence staining of influenza A-specific glycoprotein. Both catechin and gallic acid were found to be potent inhibitors in terms of influenza virus mRNA replication and MDCK plaque formation. Additionally, both compounds inhibited neuraminidase activities and viral glycoprotein. The 50% effective inhibition concentration (EC 50 ) of catechin and gallic acid for the influenza A (H1N1) virus were 18.4 μg/mL and 2.6 μg/mL, respectively; whereas the 50% cytotoxic concentrations (CC 50 ) of catechin and gallic acid were >100 μg/mL and 22.1 μg/mL, respectively. Thus, the selectivity indexes (SI) of catechin and gallic acid were >5.6 and 22.1, respectively. The present study demonstrates that catechin might be a safe reagent for long-term use to prevent influenza A (H1N1) virus infection; whereas gallic acid might be a sensitive reagent to inhibit influenza virus infection. We conclude that these two phyto-chemicals in TSL-1 are responsible for exerting anti-pandemic influenza A (H1N1) virus effects. Copyright © 2017. Published by Elsevier Taiwan LLC.

Inhibition of class IIa histone deacetylase activity by gallic acid, sulforaphane, TMP269, and panobinostat.

PubMed

Choi, Sin Young; Kee, Hae Jin; Jin, Li; Ryu, Yuhee; Sun, Simei; Kim, Gwi Ran; Jeong, Myung Ho

2018-05-01

Histone deacetylase (HDAC) inhibitors are gaining increasing attention as potential therapeutics for cardiovascular diseases as well as cancer. We recently reported that the class II HDAC inhibitor, MC1568, and the phytochemical, gallic acid, lowered high blood pressure in mouse models of hypertension. We hypothesized that class II HDACs may be involved in the regulation of hypertension. The aim of this study was to determine and compare the effects of well-known HDAC inhibitors (TMP269, panobinostat, and MC1568), phytochemicals (gallic acid, sulforaphane, and piceatannol), and anti-hypertensive drugs (losartan, carvedilol, and furosemide) on activities of class IIa HDACs (HDAC4, 5, 7, and 9). The selective class IIa HDAC inhibitor, TMP269, and the pan-HDAC inhibitor, panobinostat, but not MC1568, clearly inhibited class IIa HDAC activities. Among the three phytochemicals, gallic acid showed remarkable inhibition, whereas sulforaphane presented mild inhibition of class IIa HDACs. Piceatannol inhibited only HDAC7 activity. As expected, the anti-hypertensive drugs losartan, carvedilol, and furosemide did not affect the activity of any class IIa HDAC. In addition, we evaluated the inhibitory effect of several compounds on the activity of class l HDACs (HDAC1, 2, 3, and 8) and class IIb HDAC (HDAC6). MC1568 did not affect the activities of HDAC1, HDAC2, and HDAC3, but it reduced the activity of HDAC8 at concentrations of 1 and 10 μM. Gallic acid weakly inhibited HDAC1 and HDAC6 activities, but strongly inhibited HDAC8 activity with effectiveness comparable to that of trichostatin A. Inhibition of HDAC2 activity by sulforaphane was stronger than that by piceatnnaol. These results indicated that gallic acid is a powerful dietary inhibitor of HDAC8 and class IIa/b HDAC activities. Sulforaphane may also be used as a dietary inhibitor of HDAC2 and class IIa HDAC. Our findings suggest that the class II HDAC inhibitor, MC1568, does not inhibit class IIa HDAC, but inhibits

Phenolic compounds from the flowers of Nepalese medicinal plant Aconogonon molle and their DPPH free radical-scavenging activities.

PubMed

Joshi, Khem Raj; Devkota, Hari Prasad; Watanabe, Takashi; Yahara, Shoji

2014-01-01

Eleven phenolic compounds, quercetin (1), quercetin 3-O-β-d-galactopyranoside (2), quercetin 3-O-(6″-O-galloyl)-β-d-galactopyranoside (3), quercetin 3-O-(6″-O-caffeoyl)-β-d-galactopyranoside (4), quercetin 3-O-β-d-glucopyranoside (5), rutin (6) quercetin 3-O-α-l-arabinopyranoside (7), quercetin 3-O-α-l-arabinofuranoside (8), protocatechulic acid (9), gallic acid (10) and chlorogenic acid (11), were isolated from the flowers of Aconogonon molle, a Nepalese medicinal plant. Structures of these compounds were elucidated on the basis of spectroscopic methods. All these compounds were isolated for the first time from flowers, and five compounds (4, 5, 8, 9 and 11) were isolated for the first time from A. molle. All of these isolated compounds were evaluated for their in vitro antioxidant activity by using the 1,1-diphenyl-2-picrylhydrazyl radical-scavenging method. Quercetin (1), quercetin glycosides (2-8) and gallic acid (10) exhibited potent antioxidant activity.

Flavonoids uptake and their effect on cell cycle of human colon adenocarcinoma cells (Caco2)

PubMed Central

Salucci, M; Stivala, L A; Maiani, G; Bugianesi, R; Vannini, V

2002-01-01

Green tea, mainly through its constituents epigallocatechin gallate, epigallocatechin, epicatechin gallate and epicatechin, has demonstrated anticarcinogenic activity in several animal models, including those for skin, lung and gastro-intestinal tract cancer, although less is known about colorectal cancer. Quercetin, the major flavonoid present in vegetables and fruit, exerts potential anticarcinogenic effects in animal models and cell cultures, but less is known about quercetin glucosides. The objectives of this study were to investigate (i) the antioxidant activity of the phenolic compounds epicatechin, epigallocatechin gallate, gallic acid and quercetin-3-glucoside; (ii) the cytotoxicity of different concentrations of epicatechin, epigallocatechin gallate, and gallic acid; (iii) the cellular uptake of epicatechin, epigallocatechin gallate, gallic acid and quercetin-3-glucoside and (iv) their effect on the cell cycle. Human colon adenocarcinoma cells were used as experimental model. The results of this study indicate that all dietary flavonoids studied (epicatechin, epigallocatechin gallate, gallic acid and quercetin-3-glucoside) show a significant antioxidant effect in a chemical model system, but only epigallocatechin gallate or gallic acid are able to interfere with the cell cycle in Caco2 cell lines. These data suggest that the antioxidant activity of flavonoids is not related to the inhibition of cellular growth. From a structural point of view, the galloyl moiety appears to be required for both the antioxidant and the antiproliferative effects. British Journal of Cancer (2002) 86, 1645–1651. DOI: 10.1038/sj/bjc/6600295 www.bjcancer.com © 2002 Cancer Research UK PMID:12085217

Gallic acid prevents isoproterenol-induced cardiac hypertrophy and fibrosis through regulation of JNK2 signaling and Smad3 binding activity

PubMed Central

Ryu, Yuhee; Jin, Li; Kee, Hae Jin; Piao, Zhe Hao; Cho, Jae Yeong; Kim, Gwi Ran; Choi, Sin Young; Lin, Ming Quan; Jeong, Myung Ho

2016-01-01

Gallic acid, a type of phenolic acid, has been shown to have beneficial effects in inflammation, vascular calcification, and metabolic diseases. The present study was aimed at determining the effect and regulatory mechanism of gallic acid in cardiac hypertrophy and fibrosis. Cardiac hypertrophy was induced by isoproterenol (ISP) in mice and primary neonatal cardiomyocytes. Gallic acid pretreatment attenuated concentric cardiac hypertrophy. It downregulated the expression of atrial natriuretic peptide, brain natriuretic peptide, and beta-myosin heavy chain in vivo and in vitro. Moreover, it prevented interstitial collagen deposition and expression of fibrosis-associated genes. Upregulation of collagen type I by Smad3 overexpression was observed in cardiac myoblast H9c2 cells but not in cardiac fibroblasts. Gallic acid reduced the DNA binding activity of phosphorylated Smad3 in Smad binding sites of collagen type I promoter in rat cardiac fibroblasts. Furthermore, it decreased the ISP-induced phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal regulated kinase (ERK) protein in mice. JNK2 overexpression reduced collagen type I and Smad3 expression as well as GATA4 expression in H9c2 cells and cardiac fibroblasts. Gallic acid might be a novel therapeutic agent for the prevention of cardiac hypertrophy and fibrosis by regulating the JNK2 and Smad3 signaling pathway. PMID:27703224

Gallic acid abolishes the EGFR/Src/Akt/Erk-mediated expression of matrix metalloproteinase-9 in MCF-7 breast cancer cells.

PubMed

Chen, Ying-Jung; Lin, Ku-Nan; Jhang, Li-Mei; Huang, Chia-Hui; Lee, Yuan-Chin; Chang, Long-Sen

2016-05-25

Several studies have revealed that natural compounds are valuable resources to develop novel agents against dysregulation of the EGF/EGFR-mediated matrix metalloproteinase-9 (MMP-9) expression in cancer cells. In view of the findings that EGF/EGFR-mediated MMP-9 expression is closely related to invasion and metastasis of breast cancer. To determine the beneficial effects of gallic acid on the suppression of breast cancer metastasis, we explored the effect of gallic acid on MMP-9 expression in EGF-treated MCF-7 breast cancer cells. Treatment with EGF up-regulated MMP-9 mRNA and protein levels in MCF-7 cells. EGF treatment induced phosphorylation of EGFR and elicited Src activation, subsequently promoting Akt/NFκB (p65) and ERK/c-Jun phosphorylation in MCF-7 cells. Activation of Akt/p65 and ERK/c-Jun was responsible for the MMP-9 up-regulation in EGF-treated cells. Gallic acid repressed the EGF-induced activation of EGFR and Src; furthermore, inactivation of Akt/p65 and ERK/c-Jun was a result of the inhibitory effect of gallic acid on the EGF-induced MMP-9 up-regulation. Over-expression of constitutively active Akt and MEK1 or over-expression of constitutively active Src eradicated the inhibitory effect of gallic acid on the EGF-induced MMP-9 up-regulation. A chromosome conformation capture assay showed that EGF induced a chromosomal loop formation in the MMP-9 promoter via NFκB/p65 and AP-1/c-Jun activation. Treatment with gallic acid, EGFR inhibitor, or Src inhibitor reduced DNA looping. Taken together, our data suggest that gallic acid inhibits the activation of EGFR/Src-mediated Akt and ERK, leading to reduced levels of p65/c-Jun-mediated DNA looping and thus inhibiting MMP-9 expression in EGF-treated MCF-7 cells. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Luminescent behavior of cadmium sulfide quantum dots for gallic acid estimation

NASA Astrophysics Data System (ADS)

Singh, Suman; Garg, Sourav; Chahal, Jitender; Raheja, Khushboo; Singh, Deepak; Singla, M. L.

2013-03-01

Thioglycolic acid capped cadmium sulfide (CdS/T) quantum dots have been synthesized using wet chemistry and their optical behavior has been investigated using UV-visible absorption and fluorescence spectroscopy. The role of the capping agent, sulfide source concentration, pH and temperature has been studied and discussed. Studies showed that alkaline pH leads to a decrease in the size of quantum dots and reflux temperature above 70 °C resulted in red-shift of emission spectra which is due to narrowing of the bandgap. Further, to reduce the toxicity and photochemical instability of quantum dots, the quantum dots have been functionalized with polyethylene glycol (PEG), which resulted in a 20% enhancement of the fluorescence intensity. The application potential of CdS/T-PEG quantum dots was further studied using gallic acid as a model compound. The sensing is based on fluorescence quenching of quantum dots in the presence of gallic acid, and this study showed linearity in the range from 1.3 × 10-8 to 46.5 × 10-8 mM, with a detection limit of 3.6 × 10-8 mM.

Bioavailable Concentrations of Delphinidin and Its Metabolite, Gallic Acid, Induce Antioxidant Protection Associated with Increased Intracellular Glutathione in Cultured Endothelial Cells

PubMed Central

Goszcz, Katarzyna; Deakin, Sherine J.; Duthie, Garry G.; Stewart, Derek

2017-01-01

Despite limited bioavailability and rapid degradation, dietary anthocyanins are antioxidants with cardiovascular benefits. This study tested the hypothesis that the antioxidant protection conferred by the anthocyanin, delphinidin, is mediated by modulation of endogenous antioxidant defences, driven by its degradation product, gallic acid. Delphinidin was found to degrade rapidly (t1/2 ~ 30 min), generating gallic acid as a major degradation product. Both delphinidin and gallic acid generated oxygen-centred radicals at high (100 μM) concentrations in vitro. In a cultured human umbilical vein endothelial cell model of oxidative stress, the antioxidant protective effects of both delphinidin and gallic acid displayed a hormesic profile; 100 μM concentrations of both were cytotoxic, but relatively low concentrations (100 nM–1 μM) protected the cells and were associated with increased intracellular glutathione. We conclude that delphinidin is intrinsically unstable and unlikely to confer any direct antioxidant activity in vivo yet it offered antioxidant protection to cells at low concentrations. This paradox might be explained by the ability of the degradation product, gallic acid, to confer benefit. The findings are important in understanding the mode of protection conferred by anthocyanins and reinforce the necessity to conduct in vitro experiments at biologically relevant concentrations. PMID:29081896

Anti-inflammatory and ameliorative effects of gallic acid on fluoxetine-induced oxidative stress and liver damage in rats.

PubMed

Karimi-Khouzani, Omid; Heidarian, Esfandiar; Amini, Sayed Asadollah

2017-08-01

Fluoxetine-induced liver damage is a cause of chronic liver disease. In the present study the hepatoprotective effects of gallic acid against fluoxetine-induced liver damage were examined. Forty-eight male rats were divided into six groups as follow: group 1, the control group; group 2, rats receiving fluoxetine (24mg/kg bw daily, po) without treatment; group 3, rats receiving 24mg/kg bw fluoxetine, treated with 50mg/kg bw silymarin and groups 4, 5, and 6 in which gallic acid (50, 100, and 200mg/kg bw, po, respectively) was prescribed after the consumption of fluoxetine. The histopathological changes of hepatic tissues were checked out. Fluoxetine caused a significant increase in the levels of serum glutamate oxaloacetate transaminase (GOT), serum glutamate pyruvate transaminase (GPT), lipid profiles, urea, fasting blood sugar (FBS), creatinine (Cr), protein carbonyl (PC) content, malondialdehyde (MDA), and liver TNF-α as an inflammatory element. Also, the obtained results of group 2 revealed a significant decline in ferric reducing ability of plasma (FRAP), liver catalase (CAT), superoxide dismutase (SOD), and vitamin C levels. The treatment with gallic acid showed significant ameliorations in abnormalities of fluoxetine-induced liver injury as represented by the improvement of hepatic CAT, SOD activities, vitamin C levels, serum biochemical parameters, and histopathological changes, in addition to the recovery of antioxidant defense system status. Gallic acid has inhibitory effects on fluoxetine-induced liver damage. The effect of gallic acid is derived from free radical scavenging properties and the anti-inflammatory effect related to TNF-α. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

Antifungal Activity of Gallic Acid In Vitro and In Vivo.

PubMed

Li, Zhi-Jian; Liu, Meng; Dawuti, Gulina; Dou, Qin; Ma, Yu; Liu, Heng-Ge; Aibai, Silafu

2017-07-01

Gallic acid (GA) is a polyphenol natural compound found in many medicinal plant species, including pomegranate rind (Punica granatum L.), and has been shown to have antiinflammatory and antibacterial properties. Pomegranate rind is used to treat bacterial and fungal pathogens in Uyghur and other systems of traditional medicine, but, surprisingly, the effects of GA on antifungal activity have not yet been reported. In this study, we aimed to investigate the inhibitory effects of GA on fungal strains both in vitro and in vivo. The minimal inhibitory concentration (MIC) was determined by the NCCLS (M38-A and M27-A2) standard method in vitro, and GA was found to have a broad spectrum of antifungal activity, with MICs for all the tested dermatophyte strains between 43.75 and 83.33 μg/mL. Gallic acid was also active against three Candida strains, with MICs between 12.5 and 100.0 μg/mL. The most sensitive Candida species was Candida albicans (MIC = 12.5 μg/mL), and the most sensitive filamentous species was Trichophyton rubrum (MIC = 43.75 μg/mL), which was comparable in potency to the control, fluconazole. The mechanism of action was investigated for inhibition of ergosterol biosynthesis using an HPLC-based assay and an enzyme linked immunosorbent assay. Gallic acid reduced the activity of sterol 14α-demethylase P450 (CYP51) and squalene epoxidase in the T. rubrum membrane, respectively. In vivo model demonstrated that intraperitoneal injection administration of GA (80 mg/kg d) significantly enhanced the cure rate in a mice infection model of systemic fungal infection. Overall, our results confirm the antifungal effects of GA and suggest a mechanism of action, suggesting that GA has the potential to be developed further as a natural antifungal agent for clinical use. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Antioxidant activity of gallic acid and methyl gallate in triacylglycerols of Kilka fish oil and its oil-in-water emulsion.

PubMed

Asnaashari, Maryam; Farhoosh, Reza; Sharif, Ali

2014-09-15

The anti-DPPH radical effect as well as anti-peroxide activity of gallic acid, methyl gallate, and α-tocopherol in a bulk Kilka fish oil and its oil-in-water emulsion stabilized by soy protein isolate at 55°C were investigated. Gallic acid with the lowest hydrophobicity (log P=-0.28) was found to be the most active antiradical agent (IC50=29.5 μM), followed by methyl gallate (IC50=38.0 μM, log P=-0.23) and α-tocopherol (IC50=105.3 μM, log P=0.70). The anti-peroxide activity in the bulk oil system decreased in the order of methyl gallate>gallic acid>α-tocopherol. In the emulsion system, methyl gallate still behaved better than gallic acid, but the highest activity belonged to α-tocopherol. Based on the calculation of a number of kinetic parameters, the antioxidants, in general, showed better performances in the bulk oil system than in the emulsion system. Copyright © 2014 Elsevier Ltd. All rights reserved.

Gallic acid reduces cell growth by induction of apoptosis and reduction of IL-8 in HepG2 cells.

PubMed

Lima, Kelly Goulart; Krause, Gabriele Catyana; Schuster, Aline Daniele; Catarina, Anderson Velasque; Basso, Bruno Souza; De Mesquita, Fernanda Cristina; Pedrazza, Leonardo; Marczak, Elisa Simon; Martha, Bianca Andrade; Nunes, Fernanda Bordignon; Chiela, Eduardo Cremonese Filippi; Jaeger, Natália; Thomé, Marcos Paulo; Haute, Gabriela Viegas; Dias, Henrique Bregolin; Donadio, Márcio Vinícius Fagundes; De Oliveira, Jarbas Rodrigues

2016-12-01

Hepatocellular carcinoma is the most prevalent primary liver tumor and is among the top ten cancer that affect the world population. Its development is related, in most cases, to the existence of chronic liver injury, such as in cirrhosis. The knowledge about the correlation between chronic inflammation and cancer has driven new researches with anti-inflammatory agents that have potential for the development of antitumor drugs. Gallic acid is a phenolic acid found in many natural products and have shown anti-inflammatory, anti-tumor, anti-mutagenic and antioxidant actions. The purpose of this study was to investigate the effect of gallic acid on acute and chronic cell proliferation and inflammatory parameters of hepatocellular carcinoma cells (HepG2), as well as to investigate the mechanisms involved. Results showed that the gallic acid decreased the proliferation of HepG2 cells in a dose-dependent manner (Trypan blue exclusion assay), without causing necrosis (LDH assay). We observed a significant increase in the percentage of small and regular nuclei (Nuclear Morphometric Analysis assay), a significant induction of apoptosis by Annexin V-FITC and PI assay and no interference with the cell cycle using the FITC BrdU Flow Kit. We observed a significant reduction in the levels of IL-8 and increased levels of IL-10 and IL-12 (Cytometric Bead Array Human Inflammation Assay). Furthermore, gallic acid caused no cancer cells regrowth at a long term (Cumulative Population Doubling assay). According to these results, gallic acid showed a strong potential as an anti-tumor agent in hepatocellular carcinoma cells. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Synthesis and spectroscopic characterization of gallic acid and some of its azo complexes

NASA Astrophysics Data System (ADS)

Masoud, Mamdouh S.; Hagagg, Sawsan S.; Ali, Alaa E.; Nasr, Nessma M.

2012-04-01

A series of gallic acid and azo gallic acid complexes were prepared and characterized by elemental analysis, IR, electronic spectra and magnetic susceptibility. The complexes were of different geometries: Octahedral, Tetrahedral and Square Planar. ESR was studied for copper complexes. All of the prepared complexes were of isotropic nature. The thermal analyses of the complexes were studied by DTA and DSC techniques. The thermodynamic parameters and the thermal transitions, such as glass transitions, crystallization and melting temperatures for some ligands and their complexes were evaluated and discussed. The entropy change values, ΔS#, showed that the transition states are more ordered than the reacting complexes. The biological activities of some ligands and their complexes are tested against Gram positive and Gram negative bacteria. The results showed that some complexes have a well considerable activity against different organisms.

Antioxidant multi-walled carbon nanotubes by free radical grafting of gallic acid: new materials for biomedical applications.

PubMed

Cirillo, Giuseppe; Hampel, Silke; Klingeler, Rüdiger; Puoci, Francesco; Iemma, Francesca; Curcio, Manuela; Parisi, Ortensia Ilaria; Spizzirri, Umile Gianfranco; Picci, Nevio; Leonhardt, Albrecht; Ritschel, Manfred; Büchner, Bernd

2011-02-01

To prove the possibility of covalently functionalizing multi-walled carbon nanotubes (CNTs) by free radical grafting of gallic acid on their surface with the subsequent synthesis of materials with improved biological properties evaluated by specific in-vitro assays. Antioxidant CNTs were synthesized by radical grafting of gallic acid onto pristine CNTs. The synthesis of carbon nanotubes was carried out in a fixed-bed reactor and, after the removal of the amorphous carbon, the grafting process was performed. The obtained materials were characterized by fluorescence and Fourier transform infrared spectroscopy (FT-IR) analyses. After assessment of the biocompatibility and determination of the disposable phenolic group content, the antioxidant properties were evaluated in terms of total antioxidant activity and scavenger ability against 2,2'-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl and peroxyl radicals. Finally the inhibition activity on acetylcholinesterase was evaluated.   The covalent functionalization of CNTs with gallic acid was confirmed and the amount of gallic acid bound per g of CNTs was found to be 2.1±0.2 mg. Good antioxidant and scavenging properties were recorded in the functionalized CNTs, which were found to be able to inhibit the acetylcholinesterase with potential improved activity for biomedical and pharmaceutical applications. For the first time, a free radical grafting procedure was proposed as a synthetic approach for the covalent functionalization of CNTs with an antioxidant polyphenol. © 2010 The Authors. JPP © 2010 Royal Pharmaceutical Society.

Inhibition of Melanogenesis by Gallic Acid: Possible Involvement of the PI3K/Akt, MEK/ERK and Wnt/β-Catenin Signaling Pathways in B16F10 Cells

PubMed Central

Su, Tzu-Rong; Lin, Jen-Jie; Tsai, Chi-Chu; Huang, Tsu-Kei; Yang, Zih-Yan; Wu, Ming-O; Zheng, Yu-Qing; Su, Ching-Chyuan; Wu, Yu-Jen

2013-01-01

Gallic acid is one of the major flavonoids found in plants. It acts as an antioxidant, and seems to have anti-inflammatory, anti-viral, and anti-cancer properties. In this study, we investigated the effects of gallic acid on melanogenesis, including the activation of melanogenesis signaling pathways. Gallic acid significantly inhibited both melanin synthesis and tyrosinase activity in a dose- and time-dependent manner, and decreased the expression of melanogenesis-related proteins, such as microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP1), and dopachrome tautomerase (Dct). In addition, gallic acid also acts by phosphorylating and activating melanogenesis inhibitory proteins such as Akt and mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK). Using inhibitors against PI3K/Akt (LY294002) or MEK/ERK-specific (PD98059), the hypopigmentation effect was suppressed, and the gallic acid-initiated activation of MEK/ERK and PI3K/Akt was also revoked. Gallic acid also increased GSK3β and p-β-catenin expression but down-regulated p-GSK3β. Moreover, GSK3β-specific inhibitor (SB216763) restored gallic acid-induced melanin reduction. These results suggest that activation of the MEK/ERK, PI3K/Akt, and inhibition of Wnt/β-catenin signaling pathways is involved in the melanogenesis signaling cascade, and that activation by gallic acid reduces melanin synthesis via down-regulation of MITF and its downstream signaling pathway. In conclusion, gallic acid may be a potentially agent for the treatment of certain skin conditions. PMID:24129178

Synthesis of Gallic Acid Analogs as Histamine and Pro-Inflammatory Cytokine Inhibitors for Treatment of Mast Cell-Mediated Allergic Inflammation.

PubMed

Fei, Xiang; Je, In-Gyu; Shin, Tae-Yong; Kim, Sang-Hyun; Seo, Seung-Yong

2017-05-29

Gallic acid (3,4,5-trihydroxybenzoic acid), is a natural product found in various foods and herbs that are well known as powerful antioxidants. Our previous report demonstrated that it inhibits mast cell-derived inflammatory allergic reactions by blocking histamine release and pro-inflammatory cytokine expression. In this report, various amide analogs of gallic acid have been synthesized by introducing different amines through carbodiimide-mediated amide coupling and Pd/C-catalyzed hydrogenation. These compounds showed a modest to high inhibitory effect on histamine release and pro-inflammatory cytokine expression. Among them, the amide bearing ( S )-phenylglycine methyl ester 3d was found to be more active than natural gallic acid. Further optimization yielded several ( S )- and ( R )-phenylglycine analogs that inhibited histamine release in vitro. Our findings suggest that some gallamides could be used as a treatment for allergic inflammatory diseases.

Antidepressant-like effect of gallic acid in mice: Dual involvement of serotonergic and catecholaminergic systems.

PubMed

Can, Özgür Devrim; Turan, Nazlı; Demir Özkay, Ümide; Öztürk, Yusuf

2017-12-01

This study was planned to examine the antidepressant potency of gallic acid (30 and 60mg/kg), a phenolic acid widely distributed in nature, together with its possible underlying monoaminergic mechanisms. Antidepressant-like activity was assessed using the tail suspension (TST) and the modified forced swimming tests (MFST). Locomotor activity was evaluated in an activity cage. Administration of gallic acid at 60mg/kg reduced the immobility duration of mice in both the TST and MFST without any changes in the locomotor activity. The anti-immobility effect observed in the TST was abolished with pre-treatment of p-chlorophenylalanine methyl ester (an inhibitor of serotonin synthesis; 100mg/kg i.p. administered for 4-consecutive days), ketanserin (a 5-HT2A/2C antagonist; 1mg/kg i.p.), ondansetron (a 5-HT3 antagonist; 0.3mg/kg i.p.), α-methyl-para-tyrosine methyl ester (an inhibitor of catecholamine synthesis; 100mg/kg i.p.), phentolamine (non-selective alpha-adrenoceptor antagonist; 5mg/kg i.p.), SCH 23390 (a dopamine D1 antagonist; 0.05mg/kg s.c.), and sulpiride (a dopamine D2/D3 antagonist; 50mg/kg i.p.). However, NAN 190 (a 5-HT1A antagonist; 0.5mg/kg i.p.) and propranolol (a non-selective β-adrenoceptor antagonist; 5mg/kg i.p.) pre-treatments were ineffective at reversing the antidepressant-like effects of gallic acid. The results of the present study indicate that gallic acid seems to have a dual mechanism of action by increasing not only serotonin but also catecholamine levels in synaptic clefts of the central nervous system. Further alpha adrenergic, 5-HT2A/2C and 5-HT3 serotonergic, and D1, D2, and D3 dopaminergic receptors also seem to be involved in this antidepressant-like activity. Copyright © 2017 Elsevier Inc. All rights reserved.

Allelopathic potential and ecotoxicity evaluation of gallic and nonanoic acids to prevent cyanobacterial growth in lentic systems: A preliminary mesocosm study.

PubMed

Techer, Didier; Fontaine, Pascal; Personne, Aline; Viot, Sandrine; Thomas, Marielle

2016-03-15

The increase in anthropogenic nutrient loading affecting many freshwater ecosystems combined with global warming may lead to cyanobacterial blooms on an increasingly frequent basis. Among the various physicochemical and biological methods which have been proposed to rapidly control blue-green algae growth, the use of plant-derived substances such as allelochemicals has gained great interest as an environment-friendly approach. The primary aim of this work was to evaluate the efficiency of gallic and nonanoic acid application to preemptively inhibit cyanobacterial growth in lentic hydrosystems. In order to address the process feasibility under realistic exposure scenarios, thirteen outdoor freshwater mesocosms (unit volume: 3m(3)) were designed, each containing phytoplankton (including local blue-green algae species) and various non-target organisms from higher trophic levels (Physa, Lymnaea, Gammarus, and Scardinius erythrophthalmus). After an 8-week mesocosm stabilization period, a full factorial design based on the presence/absence of gallic acid (GA) and nonanoic acid (NA) (including a control group) was implemented into the exposure tanks. Regular monitoring of major phytoplankton taxa was conducted during a 28-day experiment using an on-line fluorometer. The main results suggested that gallic acid was more efficient than nonanoic acid at limiting cyanobacterial growth at concentrations as low as 1 mg L(-1). Successive gallic acid applications (at 1, 2 and 4 mg L(-1)) at the early stages of cyanobacterial growth did not allow the complete elimination of blue-green algae from the mesocosms. However, the specificity of the allelopathic effect of gallic acid towards cyanobacteria was compatible with the maintenance of a primary productivity in the treated tanks as indicated by the photoautotrophic growth of other algal taxa. Finally, no biomarker induction signal could be reported in non-target species. Further gallic acid application trials in lentic systems such

Enzymatic synthesis of novel quercetin sialyllactoside derivatives.

PubMed

Darsandhari, Sumangala; Bae, Jae Yoon; Shrestha, Biplav; Yamaguchi, Tokutaro; Jung, Hye Jin; Han, Jang Mi; Rha, Chan-Su; Pandey, Ramesh Prasad; Sohng, Jae Kyung

2018-06-06

Quercetin and its derivatives are important flavonols that show diverse biological activity, such as antioxidant, anticarcinogenic, anti-inflammatory, and antiviral activities. Adding different substituents to quercetin may change the biochemical activity and bioavailability of molecules, when compared to the aglycone. Here, we have synthesised two novel derivatives of quercetin, quercetin-3-O-β-d-glucopyranosyl, 4''-O-d-galactopyranosyl 3'''-O-α-N-acetyl neuraminic acid i.e. 3'-sialyllactosyl quercetin (3'SL-Q) and quercetin-3-O-β-d-glucopyranosyl, 4''-O-β-d-galactopyranosyl 6'''-O-α-N-acetyl neuraminic acid i.e. 6'-sialyllactosyl quercetin (6'SL-Q) with the use of glycosyltransferases and sialyltransferases enzymes. These derivatives of quercetin were characterised by high-resolution quadrupole-time-of-flight electrospray ionisation mass spectrometry (HR-QTOF-ESI/MS) and 1 H and 13 C nuclear magnetic resonance (NMR) analyses.

Rutin, quercetin, and free amino acid analysis in buckwheat (Fagopyrum) seeds from different locations.

PubMed

Bai, C Z; Feng, M L; Hao, X L; Zhong, Q M; Tong, L G; Wang, Z H

2015-12-29

In this study, five common buckwheats and nine tartary buckwheats grown at different locations were analyzed for the contents of rutin, quercetin, and amino acids by high-performance liquid chromatography and spectrophotometry. The rutin content was higher than quercetin in buckwheat seeds. Rutin content was in the range from 0.05 (0.05 g per 100 g dry seeds) to 1.35% of buckwheat seeds. Quercetin content varied from 0.01 to 0.17% and in some common buckwheats it was even difficult to detect. Comparatively, tartary buckwheat seeds contained more rutin and quercetin than common buckwheat seeds. Meanwhile, the bran has higher rutin content than the farina in tartary buckwheat seeds, with a respective content of 0.45 to 1.19% and 0.14 to 0.67%. It was found that amino acid contents were around 1.79 to 12.65% (farina) and 5.74 to 7.89% (bran) in common buckwheats, and 1.73 to 5.63% (farina) and 2.64 to 16.78% (bran) in tartary buckwheat seeds. The highest total rutin content was found to be 1.35% in tartary buckwheat seeds from Sichuan, China. The highest total amounts of amino acid were detected to be 20.13% in tartary buckwheat seeds from Changzhi, Shanxi Province (China). Our results suggested that food products made of whole-buckwheat flour are healthier than those made of fine white flour.

Quercetin-glutamic acid conjugate with a non-hydrolysable linker; a novel scaffold for multidrug resistance reversal agents through inhibition of P-glycoprotein.

PubMed

Kim, Mi Kyoung; Kim, Yunyoung; Choo, Hyunah; Chong, Youhoon

2017-02-01

Previously, we have reported remarkable effect of a quercetin-glutamic acid conjugate to reverse multidrug resistance (MDR) of cancer cells to a broad spectrum of anticancer agents through inhibition of P-glycoprotein (Pgp)-mediated drug efflux. Due to the hydrolysable nature, MDR-reversal activity of the quercetin conjugate was attributed to its hydrolysis product, quercetin. However, several lines of evidence demonstrated that the intact quercetin-glutamic acid conjugate has stronger MDR-reversal activity than quercetin. In order to evaluate this hypothesis and to identify a novel scaffold for MDR-reversal agents, we prepared quercetin conjugates with a glutamic acid attached at the 7-O position via a non-hydrolysable linker. Pgp inhibition assay, Pgp ATPase assay, and MDR-reversal activity assay were performed, and the non-hydrolysable quercetin conjugates showed significantly higher activities compared with those of quercetin. Unfortunately, the quercetin conjugates were not as effective as verapamil in Pgp-inhibition and thereby reversing MDR, but it is worth to note that the structurally modified quercetin conjugates with a non-cleavable linker showed significantly improved MDR-reversal activity compared with quercetin. Taken together, the quercetin conjugates with appropriate structural modifications were shown to have a potential to serve as a scaffold for the design of novel MDR-reversal agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

Enhanced Oral Bioavailability of Diltiazem by the Influence of Gallic Acid and Ellagic Acid in Male Wistar Rats: Involvement of CYP3A and P-gp Inhibition.

PubMed

Athukuri, Bhargavi Latha; Neerati, Prasad

2017-09-01

The oral bioavailability of diltiazem is very low due to rapid first pass metabolism in liver and intestine. The purpose of the study was to investigate the effect of gallic acid and ellagic acid on intestinal transport and oral bioavailability of diltiazem in rats. The intestinal transport and permeability of diltiazem was evaluated by in vitro non-everted sac method and in situ single pass intestinal perfusion study. The oral pharmacokinetics was evaluated by conducting oral bioavailability study. The intestinal transport and apparent permeability of diltiazem were significantly enhanced in duodenum, jejunum, and ileum of gallic and ellagic acid-treated groups. The effective permeability of diltiazem was significantly enhanced in ileum part of gallic and ellagic acid-treated groups. When compared with control group, the presence of these two phytochemicals significantly enhanced the area under plasma concentration-time curve and the peak plasma concentration of diltiazem (C max ). Gallic acid and ellagic acid significantly increased the bioavailability of diltiazem due to the inhibition of both CYP3A-mediated metabolism and P-glycoprotein-mediated efflux in the intestine and/or liver. Based on these results, the clinical experiments are warranted for the confirmation to reduce the dose of diltiazem when concomitantly administered with these phytochemicals. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Effect of fractionated extracts and isolated pure compounds of Spondias mombin (L. Anacardiaceae) leaves on novelty-induced rearing and grooming behaviours in mice.

PubMed

Ayoka, Abiodun O; Owolabi, Rotimi A; Bamitale, Samuel K; Akomolafe, Rufus O; Aladesanmi, Joseph A; Ukponmwan, Eghe O

2013-01-01

This study attempted to elucidate the neurotransmitter systems involved in the neurophysiological properties of ethanolic extract, fractions and pure isolates of Spondias mombin leaves in mice (n = 6) after intraperitoneal (i.p.) route of administration.The crude ethanolic extract of Spondian mombin leaves was fractionated using the partitioning method to obtain the ethylacetate, butanolic and aqueous fractions. Open column chromatographic fractionation of the ethylacetate fraction yielded seven sub-fractions, out of which the pure coumaroyl, quercetin and gallic acid derivatives were obtained after purification on Sephadex LH 20. The ethanolic extract, butanolic fraction, ethylacetate subfractions and pure isolates of the Spondian mombin leaves were tested on novelty-induced rearing and grooming behaviours in mice with standard pharmacological tools using the open field method. The extract and its fractions decreased novelty-induced rearing in a dose-dependent manner. While the Coumaroyl derivative had no effect on novelty-induced rearing, it significantly reversed the inhibitory effect of yohimbine, propranolol and haloperidol on novelty-induced rearing. Quercetin significantly potentiated the inhibitory effect of yohimbine on novelty-induced rearing. Naloxone significantly potentiated the quercetin-induced suppression of novelty-induced rearing. Gallic acid derivative significantly potentiated the inhibitory effect of yohimbine on novelty-induced rearing. Naloxone, atropine and haloperidol pretreatments significantly potentiated gallic acid derivative-induced suppression of novelty-induced rearing.The extract and its fractions had biphasic effect on novelty-induced grooming in mice. Coumaroyl derivative significantly increased novelty-induced grooming, while quercetin and gallic acid derivative decreased novelty-induced grooming significantly. The three pure isolates significantly reversed the effects of yohimbine and atropine on the novelty-induced grooming in

Improved Anticancer Effect of Magnetite Nanocomposite Formulation of GALLIC Acid (Fe₃O₄-PEG-GA) Against Lung, Breast and Colon Cancer Cells.

PubMed

Rosman, Raihana; Saifullah, Bullo; Maniam, Sandra; Dorniani, Dena; Hussein, Mohd Zobir; Fakurazi, Sharida

2018-02-02

Lung cancer, breast cancer and colorectal cancer are the most prevalent fatal types of cancers globally. Gallic acid (3,4,5-trihydroxybenzoic acid) is a bioactive compound found in plants and foods, such as white tea, witch hazel and it has been reported to possess anticancer, antioxidant and anti-inflammatory properties. In this study we have redesigned our previously reported anticancer nanocomposite formulation with improved drug loading based on iron oxide magnetite nanoparticles coated with polyethylene glycol and loaded with anticancer drug gallic acid (Fe₃O₄-PEG-GA). The in vitro release profile and percentage drug loading were found to be better than our previously reported formulation. The anticancer activity of pure gallic acid (GA), empty carrier (Fe₃O₄-PEG) nanocarrier and of anticancer nanocomposite (Fe₃O₄-PEG-GA) were screened against human lung cancer cells (A549), human breast cancer cells (MCF-7), human colon cancer cells (HT-29) and normal fibroblast cells (3T3) after incubation of 24, 48 and 72 h using (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay. The designed formulation (Fe₃O₄-PEG-GA) showed better anticancer activity than free gallic acid (GA). The results of the in vitro studies are highly encouraging to conduct the in vivo studies.

Polyphenols of Salix aegyptiaca modulate the activities of drug metabolizing and antioxidant enzymes, and level of lipid peroxidation.

PubMed

Nauman, Mohd; Kale, R K; Singh, Rana P

2018-03-07

Salix aegyptiaca is known for its medicinal properties mainly due to the presence of salicylate compounds. However, it also contains other beneficial phytochemicals such as gallic acid, quercetin, rutin and vanillin. The aim of the study was to examine the redox potential, antioxidant and anti-inflammatory activity of these phytochemicals along with acetylsalicylic acid. The redox potential and antioxidant activity of gallic acid, quercetin, rutin, vanillin and acetylsalicylic acid were determined by oxidation-reduction potential electrode method and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, respectively. In ex vivo studies, antioxidant activity of these phytochemicals was determined by lipid peroxidation and carbonyl content assay in the liver of mice. Anti-inflammatory activity was determined by protein denaturation method. Six-week old C57BL/6 mice treated with gallic acid (100 mg/kg body weight) and acetylsalicylic acid (25 and 50 mg/kg body weight) to investigate their in vivo modulatory effects on the specific activities of drug metabolizing phase I and phase II enzymes, antioxidant enzymes and level of lipid peroxidation in liver. The order of ability to donate electron and antioxidant activity was found to be: gallic acid > quercetin > rutin > vanillin > acetylsalicylic acid. In ex vivo studies, the similar pattern and magnitude of inhibitory effects of these phytochemicals against peroxidative damage in microsomes and protein carbonyl in cytosolic fraction were observed. In in vivo studies, gallic acid and acetylsalicylic acid alone or in combination, enhanced the specific activities of drug metabolizing phase I and phase II enzymes as well as antioxidant enzymes and also inhibited lipid peroxidation in liver. These findings show a close link between the electron donation and antioxidation potential of these phytochemicals, and in turn their biological activity. Gallic acid, quercetin, rutin and vanillin were found to be better electron donors and

Inhibitive Effects of Quercetin on Myeloperoxidase-Dependent Hypochlorous Acid Formation and Vascular Endothelial Injury.

PubMed

Lu, Naihao; Sui, Yinhua; Tian, Rong; Peng, Yi-Yuan

2018-05-16

Myeloperoxidase (MPO) from activated neutrophils plays important roles in multiple human inflammatory diseases by catalyzing the formation of powerful oxidant hypochlorous acid (HOCl). As a major flavonoid in the human diet, quercetin has been suggested to act as antioxidant and anti-inflammatory agent in vitro and in vivo. In this study, we showed that quercetin inhibited MPO-mediated HOCl formation (75.0 ± 6.2% for 10 μM quercetin versus 100 ± 5.2% for control group, P < 0.01) and cytotoxicity to endothelial cells in vitro, while this flavonoid was nontoxic to endothelial cell cultures ( P > 0.05, all cases). Moreover, quercetin inhibited HOCl generation by stimulated neutrophils (a rich source of MPO) and protected endothelial cells from neutrophils-induced injury. Furthermore, quercetin could inhibit HOCl-induced endothelial dysfunction such as loss of cell viability, and decrease of nitric oxide formation in endothelial cells ( P < 0.05, all cases). Consistent with these in vitro data, quercetin attenuated lipopolysaccharide-induced endothelial dysfunction and increase of MPO activity in mouse aortas, while this flavonoid could protect against HOCl-mediated endothelial dysfunction in isolated aortas ( P < 0.05). Therefore, it was proposed that quercetin attenuated endothelial injury in inflammatory vasculature via inhibition of vascular-bound MPO-mediated HOCl formation or scavenging of HOCl. These data indicate that quercetin is a nontoxic inhibitor of MPO activity and MPO/neutrophils-induced cytotoxicity in endothelial cells and may be useful for targeting MPO-dependent vascular disease and inflammation.

Caffeic acid and quercetin protect erythrocytes against the oxidative stress and the genotoxic effects of lambda-cyhalothrin in vitro.

PubMed

Abdallah, Fatma Ben; Fetoui, H; Fakhfakh, F; Keskes, L

2012-01-01

Lambda-cyhalothrin (LTC) is a synthetic pyrethroid with a broad spectrum of insecticidal and acaricidal activities used to control wide range of insect pests in a variety of applications. The aim of this study was to examine (i) the potency of LTC to induce oxidative stress response in rat erythrocytes in vitro and (ii) the role of caffeic acid (20 μM) and/or quercetin (10 μM) in preventing the cytotoxic effects. Erythrocytes were divided into four portions. The erythrocytes of the first portion were incubated for 4 h at 37°C with different concentrations (0, 50 and 100 μM) of LTC. The others portions were pretreated with caffeic acid and/or quercetin for 30 min prior to LTC incubation. Lipid peroxidation, protein oxidation, antioxidant enzyme activities and DNA damage were examined. LTC at different concentrations causes increased levels of lipid peroxidation, protein oxidation, DNA damage and decreased antioxidant enzyme activities. Combined caffeic acid and quercetin pretreatments significantly reduced the levels of lipid peroxidation markers, that is thiobarbituric acid reactive substance (TBARS), protein carbonyls (PCO) and decreased DNA damage in LTC portion. Further, combined caffeic acid and quercetin pretreatment maintain antioxidant enzyme activities and glutathione content near to normal values. These results suggest that LTC exerts its toxic effect by increasing lipid peroxidation, altering the antioxidant enzyme activities and DNA damage. Caffeic acid and quercetin pretreatments prevent the toxic effects of LTC, suggesting their role as a potential antioxidant.

Induction of Biofilm Formation in the Betaproteobacterium Burkholderia unamae CK43B Exposed to Exogenous Indole and Gallic Acid

PubMed Central

Kim, Dongyeop; Sitepu, Irnayuli R.

2013-01-01

Burkholderia unamae CK43B, a member of the Betaproteobacteria that was isolated from the rhizosphere of a Shorea balangeran sapling in a tropical peat swamp forest, produces neither indole nor extracellular polymeric substances associated with biofilm formation. When cultured in a modified Winogradsky's medium supplemented with up to 1.7 mM indole, B. unamae CK43B maintains its planktonic state by cell swelling and effectively degrades exogenous indole. However, in medium supplemented with 1.7 mM exogenous indole and 1.0 mM gallic acid, B. unamae CK43B produced extracellular polymeric substances and formed a biofilm. The concentration indicated above of gallic acid alone had no effect on either the growth or the differentiation of B. unamae CK43B cells above a certain concentration threshold, whereas it inhibited indole degradation by B. unamae CK43B to 3-hydroxyindoxyl. In addition, coculture of B. unamae CK43B with indole-producing Escherichia coli in nutrient-rich Luria-Bertani medium supplemented with 1.0 mM gallic acid led to the formation of mixed cell aggregates. The viability and active growth of B. unamae CK43B cells in a coculture system with Escherichia coli were evidenced by fluorescence in situ hybridization. Our data thus suggest that indole facilitates intergenus communication between indole-producing gammaproteobacteria and some indole-degrading bacteria, particularly in gallic acid-rich environments. PMID:23747701

Thermally and vibrationally induced conformational isomerizations, infrared spectra, and photochemistry of gallic acid in low-temperature matrices

NASA Astrophysics Data System (ADS)

Justino, Licínia L. G.; Reva, Igor; Fausto, Rui

2016-07-01

Near-infrared (near-IR) narrowband selective vibrational excitation and annealing of gallic acid (3,4,5-trihydroxybenzoic acid) isolated in cryogenic matrices were used to induce interconversions between its most stable conformers. The isomerizations were probed by infrared spectroscopy. An extensive set of quantum chemical calculations, carried out at the DFT(B3LYP)/6-311++G(d,p) level of approximation, was used to undertake a detailed analysis of the ground state potential energy surface of the molecule. This investigation of the molecule conformational space allowed extracting mechanistic insights into the observed annealing- or near-IR-induced isomerization processes. The infrared spectra of the two most stable conformers of gallic acid in N2, Xe, and Ar matrices were fully assigned. Finally, the UV-induced photochemistry of the matrix isolated compound was investigated.

Highly selective and efficient imprinted polymers based on carboxyl-functionalized magnetic nanoparticles for the extraction of gallic acid from pomegranate rind.

PubMed

Zhang, Junjie; Li, Benqiang; Yue, Huijuan; Wang, Jing; Zheng, Yuansuo

2018-01-01

With the combined surface imprinting technique and immobilized template strategy, molecularly imprinted magnetic nanoparticles were successfully prepared and coupled with high-performance liquid chromatography to selectively separate and determine gallic acid from the pomegranate rind. On the surface of carboxyl-functionalized magnetic nanospheres, thin imprinting shells were formed using dopamine as monomer and crosslinker. The characteristics, polymerization conditions, and adsorption performances of the resultant nanomaterials were investigated in detail. In addition of good crystallinity, satisfactory magnetism, and uniform morphology of the obtained polymers, they had rapid binding kinetics, high adsorption capacity, and favorable reusability. In the mixed solution of four hydroxybenzoic acids, the prepared nanomaterials have an excellent selectivity to gallic acid with an imprinting factor of as high as 17.5. Therefore, the polymers have great potentials in specific extraction and enrichment of gallic acid from the complex natural resources. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Influence of waterborne gallic and pelargonic acid exposures on biochemical and reproductive parameters in the zebrafish (Danio rerio).

PubMed

Techer, Didier; Milla, Sylvain; Fontaine, Pascal; Viot, Sandrine; Thomas, Marielle

2017-01-01

Gallic and pelargonic acids are biologically derived substances receiving a growing interest as eco-friendly biocides with potential applications in freshwater system management. However, some data gaps remain to address their chronic ecotoxicity issue, particularly for fish. This work aimed at investigating the sublethal effects of a long-term waterborne exposure of zebrafish to these compounds. Mature fish were exposed to gallic or pelargonic acid at the concentrations of 0, 0.05, 0.5 and 5 mg/L during one month under semi-static conditions. Fecundity, hatching rate and median hatching time were regularly evaluated. Circulating sex hormone levels (11 ketotestosterone -11 KT, 17 βestradiol -E2-), plasma vitellogenin (Vtg), and gonad histology were monitored in males and females after exposure. Lactate dehydrogenase (LDH), total glutathione peroxydase (GPx) and glutathione-S transferase (GST) activities were assessed as enzymatic biomarkers of exposure in fish liver. Significant increases of GPx activity were reported in females exposed to both type of chemicals regardless the contamination level. Moreover, 5 mg/L gallic acid induced a decrease in 11-KT levels for males. For fish exposed to pelargonic acid, decreases in circulating hormone levels were reported respectively at 0.05 and 5 mg/L for 11-KT in males, and at 0.5 mg/L for E2 in females. However, no histological alteration in gonads neither significant variation in reproductive performances were detected following zebrafish exposure to gallic or pelargonic acid. Additional investigations concerning the mode of application and the environmental fate of these substances may warrant their further use in freshwater systems at concentrations compatible with biocidal/allelochemical effects. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 227-240, 2017. © 2015 Wiley Periodicals, Inc.

[Gallic acid inhibits inflammatory response of RAW264.7 macrophages by blocking the activation of TLR4/NF-κB induced by LPS].

PubMed

Huang, Lihua; Hou, Lin; Xue, Hainan; Wang, Chunjie

2016-12-01

Objective To observe the influence of gallic acid on Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) pathway in the RAW264.7 macrophages stimulated by lipopolysaccharide (LPS). Methods RAW264.7 macrophages were divided into the following groups: control group, LPS group, LPS combined with gallic acid group, LPS combined with pyrrolidine dithiocarbamate (PDTC) group and LPS combined with dexamethasone (DM) group. RAW264.7 cells were cultured for 24 hours after corresponding treatments. The levels of tumor necrosis factor α (TNF-α), interleukin-1 (IL-1) and IL-6 were detected by ELISA. The levels of TLR4 and NF-κB mRNAs were tested by real-time PCR. The levels of p-IκBα, p65, p-p65 and TLR4 proteins were examined by Western blotting. Results The expression levels of TNF-α, IL-1 and IL-6 were up-regulated in the RAW264.7 macrophages after stimulated by LPS. Gallic acid could reduce the elevated expression levels of TNF-α, IL-1 and IL-6 induced by LPS. The expression of TLR4 significantly increased after stimulated by LPS and NF-κB was activated. Gallic acid could reverse the above changes and prevent the activation of NF-κB. Conclusion Gallic acid could inhibit LPS-induced inflammatory response in RAW264.7 macrophages via TLR4/NF-κB pathway.

In Vitro Antioxidant-Activity Evaluation of Gallic-Acid-Grafted Chitosan Conjugate Synthesized by Free-Radical-Induced Grafting Method.

PubMed

Hu, Qiaobin; Wang, Taoran; Zhou, Mingyong; Xue, Jingyi; Luo, Yangchao

2016-07-27

The major objective of this work was to develop a green and facile process to prepare gallic acid-chitosan conjugate and comprehensively evaluate the physicochemical properties and biological activities of an as-prepared water-soluble chitosan derivative. A free-radical-induced grafting approach using an ascorbic acid-hydrogen peroxide redox pair was adopted. The obtained conjugate was characterized by Fourier transform infrared spectroscopy, UV-vis, X-ray diffraction, and pKa analysis. The antioxidant activities were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6)-sulphonic acid (ABTS), reducing power, and oxygen-radical antioxidant-capacity assays. The results showed that the mass ratio of gallic acid to chitosan played a vital role in determining the grafting degree and ζ potential of the conjugates, with the ratio of 0.5:1 being the optimal ratio that resulted in the highest grafting degree. The antioxidant assays demonstrated that conjugation significantly improved the antioxidant activities, being dramatically higher than that of free chitosan. It was notable that the DPPH- and ABTS-scavenging activities of conjugate at 0.4 mg/mL reached the same level as the free gallic acid at the equivalent concentration. Our study demonstrated a green and facile synthesis approach to preparing a novel water-soluble chitosan derivative that may have promising potentials in the food industry.

In Vitro Sustained Release Study of Gallic Acid Coated with Magnetite-PEG and Magnetite-PVA for Drug Delivery System

PubMed Central

Kura, Aminu Umar; Hussein-Al-Ali, Samer Hasan; Bin Hussein, Mohd Zobir; Fakurazi, Sharida; Shaari, Abdul Halim; Ahmad, Zalinah

2014-01-01

The efficacy of two nanocarriers polyethylene glycol and polyvinyl alcohol magnetic nanoparticles coated with gallic acid (GA) was accomplished via X-ray diffraction, infrared spectroscopy, magnetic measurements, thermal analysis, and TEM. X-ray diffraction and TEM results showed that Fe3O4 nanoparticles were pure iron oxide having spherical shape with the average diameter of 9 nm, compared with 31 nm and 35 nm after coating with polyethylene glycol-GA (FPEGG) and polyvinyl alcohol-GA (FPVAG), respectively. Thermogravimetric analyses proved that after coating the thermal stability was markedly enhanced. Magnetic measurements and Fourier transform infrared (FTIR) revealed that superparamagnetic iron oxide nanoparticles could be successfully coated with two polymers (PEG and PVA) and gallic acid as an active drug. Release behavior of gallic acid from two nanocomposites showed that FPEGG and FPVAG nanocomposites were found to be sustained and governed by pseudo-second-order kinetics. Anticancer activity of the two nanocomposites shows that the FPEGG demonstrated higher anticancer effect on the breast cancer cell lines in almost all concentrations tested compared to FPVAG. PMID:24737969

Thermally and vibrationally induced conformational isomerizations, infrared spectra, and photochemistry of gallic acid in low-temperature matrices

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

Justino, Licínia L. G., E-mail: liciniaj@ci.uc.pt; Reva, Igor; Fausto, Rui

2016-07-07

Near-infrared (near-IR) narrowband selective vibrational excitation and annealing of gallic acid (3,4,5-trihydroxybenzoic acid) isolated in cryogenic matrices were used to induce interconversions between its most stable conformers. The isomerizations were probed by infrared spectroscopy. An extensive set of quantum chemical calculations, carried out at the DFT(B3LYP)/6-311++G(d,p) level of approximation, was used to undertake a detailed analysis of the ground state potential energy surface of the molecule. This investigation of the molecule conformational space allowed extracting mechanistic insights into the observed annealing- or near-IR-induced isomerization processes. The infrared spectra of the two most stable conformers of gallic acid in N{sub 2},more » Xe, and Ar matrices were fully assigned. Finally, the UV-induced photochemistry of the matrix isolated compound was investigated.« less

Gallic acid-capped gold nanoparticles inhibit EGF-induced MMP-9 expression through suppression of p300 stabilization and NFκB/c-Jun activation in breast cancer MDA-MB-231 cells

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

Chen, Ying-Jung; Lee, Yuan-Chin; Huang, Chia-Hui

Triple-negative breast cancers (TNBCs) are highly invasive and have a higher rate of distant metastasis. Matrix metalloproteinase-9 (MMP-9) plays a crucial role in EGF/EGFR-mediated malignant progression and metastasis of TNBCs. Various studies have revealed that treatment with gallic acid down-regulates MMP-9 expression in cancer cells, and that conjugation of phytochemical compounds with gold nanoparticles (AuNPs) increases the anti-tumor activity of the phytochemical compounds. Thus, the effect of gallic acid-capped AuNPs (GA-AuNPs) on MMP-9 expression in EGF-treated TNBC MDA-MB-231 cells was analyzed in the present study. The so-called green synthesis of AuNPs by means of gallic acid was performed at pHmore » 10, and the resulting GA-AuNPs had spherical shape with an average diameter of approximately 50 nm. GA-AuNPs notably suppressed migration and invasion of EGF-treated cells, and inhibited EGF-induced MMP-9 up-regulation. GA-AuNPs abrogated EGF-induced Akt/p65 and ERK/c-Jun phosphorylation, leading to down-regulation of MMP-9 mRNA and protein expression in EGF-treated cells. Meanwhile, EGF-induced p300 stabilization was found to be involved in MMP-9 expression, whereas GA-AuNPs inhibited the EGF-promoted stability of the p300 protein. Although GA-AuNPs and gallic acid suppressed EGF-induced MMP-9 up-regulation via the same signaling pathway, the effective concentration of gallic acid was approximately 100-fold higher than that of GA-AuNPs for inhibition of MMP-9 expression in EGF-treated cells to a similar extent. Collectively, our data indicate that, in comparison with gallic acid, GA-AuNPs have a superior ability to inhibit EGF/EGFR-mediated MMP-9 expression in TNBC MDA-MB-231 cells. Our findings also point to a way to improve the anti-tumor activity of gallic acid. - Highlights: • Gallic acid-capped gold nanoparticles inhibit EGF-induced MMP-9 expression. • EGF-induced MMP-9 expression via p300 stabilization and NFκB/c-Jun activation. • Gallic

Synthesis and application of in-situ molecularly imprinted silica monolithic in pipette-tip solid-phase microextraction for the separation and determination of gallic acid in orange juice samples.

PubMed

Arabi, Maryam; Ghaedi, Mehrorang; Ostovan, Abbas

2017-03-24

A novel strategy was presented for the synthesis and application of functionalized silica monolithic as artificial receptor of gallic acid at micro-pipette tip. A sol-gel process was used to prepare the sorbent. In this in-situ polymerization reaction, tetraethyl orthosilicate (TEOS), 3-aminopropyl trimethoxysilane (APTMS), gallic acid and thiourea were used, respectively, as cross-linker, functionalized monomer, template and precursor to make crack-free and non-fragile structure. Such durable and inexpensive in-situ monolithic was successfully employed as useful tool for highly efficient extraction of gallic acid from orange juice samples. The effective parameters in extraction recovery were investigated and optimum conditions were obtained using experimental design methodology. Applying HPLC-UV for separation quantification at optimal conditions, the gallic acid was efficiently extracted without significant matrix interference. Good linearity for gallic acid in the range of 0.02-5.0mgL -1 with correlation coefficients of R 2 >0.999 revealed well applicability of the method for trace analysis. Copyright © 2017. Published by Elsevier B.V.

Gallic acid indanone and mangiferin xanthone are strong determinants of immunosuppressive anti-tumour effects of Mangifera indica L. bark in MDA-MB231 breast cancer cells.

PubMed

García-Rivera, Dagmar; Delgado, René; Bougarne, Nadia; Haegeman, Guy; Berghe, Wim Vanden

2011-06-01

Vimang is a standardized extract derived from Mango bark (Mangifera Indica L.), commonly used as anti-inflammatory phytomedicine, which has recently been used to complement cancer therapies in cancer patients. We have further investigated potential anti-tumour effects of glucosylxanthone mangiferin and indanone gallic acid, which are both present in Vimang extract. We observed significant anti-tumour effects of both Vimang constituents in the highly aggressive and metastatic breast cancer cell type MDA-MB231. At the molecular level, mangiferin and gallic acid both inhibit classical NFκB activation by IKKα/β kinases, which results in impaired IκB degradation, NFκB translocation and NFκB/DNA binding. In contrast to the xanthone mangiferin, gallic acid further inhibits additional NFκB pathways involved in cancer cell survival and therapy resistance, such as MEK1, JNK1/2, MSK1, and p90RSK. This results in combinatorial inhibition of NFκB activity by gallic acid, which results in potent inhibition of NFκB target genes involved in inflammation, metastasis, anti-apoptosis and angiogenesis, such as IL-6, IL-8, COX2, CXCR4, XIAP, bcl2, VEGF. The cumulative NFκB inhibition by gallic acid, but not mangiferin, is also reflected at the level of cell survival, which reveals significant tumour cytotoxic effects in MDA-MB231 cells. Altogether, we identify gallic acid, besides mangiferin, as an essential anti-cancer component in Vimang extract, which demonstrates multifocal inhibition of NFκB activity in the cancer-inflammation network. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Plant Natural Products Calycosin and Gallic Acid Synergistically Attenuate Neutrophil Infiltration and Subsequent Injury in Isoproterenol-Induced Myocardial Infarction: A Possible Role for Leukotriene B4 12-Hydroxydehydrogenase?

PubMed Central

Cheng, Yuanyuan; Tse, Hung Fat; Le, X. Chris; Rong, Jianhui

2015-01-01

Leukotriene B4 12-hydroxydehydrogenase (LTB4DH) catalyzes the oxidation of proinflammatory LTB4 into less bioactive 12-oxo-LTB4. We recently discovered that LTB4DH was induced by two different natural products in combination. We previously isolated gallic acid from Radix Paeoniae through a bioactivity-guided fractionation procedure. The purpose of this study is to test the hypothesis that LTB4DH inducers may suppress neutrophil-mediated inflammation in myocardial infarction. We first isolated the active compound(s) from another plant, Radix Astragali, by the similar strategy. By evaluating LTB4DH induction, we identified calycosin and formononetin from Radix Astragali by HPLC-ESI-MS technique. We confirmed that gallic acid and commercial calycosin or formononetin could synergistically induce LTB4DH expression in HepG2 cells and human neutrophils. Moreover, calycosin and gallic acid attenuated the effects of LTB4 on the survival and chemotaxis of neutrophil cell culture. We further demonstrated that calycosin and gallic acid synergistically suppressed neutrophil infiltration and protected cardiac integrity in the isoproterenol-induced mice model of myocardial infarction. Calycosin and gallic acid dramatically suppressed isoproterenol-induced increase in myeloperoxidase (MPO) activity and malondialdehyde (MDA) level. Collectively, our results suggest that LTB4DH inducers (i.e., calycosin and gallic acid) may be a novel combined therapy for the treatment of neutrophil-mediated myocardial injury. PMID:26265982

Quercetin, kaempferol, myricetin, and fatty acid content among several Hibiscus sabdariffa accession calyces based on maturity in a greenhouse

USDA-ARS?s Scientific Manuscript database

Flavonols including quercetin, kaempferol, myricetin, and fatty acids in plants have many useful health attributes including antioxidants, cholesterol lowering, and cancer prevention. Six accessions of roselle, Hibiscus sabdariffa calyces were evaluated for quercetin, kaempferol, and myricetin conte...

Bifunctional viscous nanovesicles co-loaded with resveratrol and gallic acid for skin protection against microbial and oxidative injuries.

PubMed

Vitonyte, Justina; Manca, Maria Letizia; Caddeo, Carla; Valenti, Donatella; Peris, Josè Esteban; Usach, Iris; Nacher, Amparo; Matos, Maria; Gutiérrez, Gemma; Orrù, Germano; Fernàndez-Busquets, Xavier; Fadda, Anna Maria; Manconi, Maria

2017-05-01

Resveratrol and gallic acid were co-loaded in phospholipid vesicles aiming at protecting the skin from external injuries, such as oxidative stress and microbial infections. Liposomes were prepared using biocompatible phospholipids dispersed in water. To improve vesicle stability and applicability, the phospholipids and the phenols were dispersed in water/propylene glycol or water/glycerol, thus obtaining PEVs and glycerosomes, respectively. The vesicles were characterized by size, morphology, physical stability, and their therapeutic efficacy was investigated in vitro. The vesicles were spherical, unilamellar and small in size: liposomes and glycerosomes were around 70nm in diameter, while PEVs were larger (∼170nm). The presence of propylene glycol or glycerol increased the viscosity of the vesicle systems, positively affecting their stability. The ability of the vesicles to promote the accumulation of the phenols (especially gallic acid) in the skin was demonstrated, as well as their low toxicity and great ability to protect keratinocytes and fibroblasts from oxidative damage. Additionally, an improvement of the antimicrobial activity of the phenols was shown against different skin pathogens. The co-loading of resveratrol and gallic acid in modified phospholipid vesicles represents an innovative, bifunctional tool for preventing and treating skin affections. Copyright © 2017 Elsevier B.V. All rights reserved.

Gallic acid attenuates hypertension, cardiac remodeling, and fibrosis in mice with NG-nitro-L-arginine methyl ester-induced hypertension via regulation of histone deacetylase 1 or histone deacetylase 2.

PubMed

Jin, Li; Lin, Ming Quan; Piao, Zhe Hao; Cho, Jae Yeong; Kim, Gwi Ran; Choi, Sin Young; Ryu, Yuhee; Sun, Simei; Kee, Hae Jin; Jeong, Myung Ho

2017-07-01

Gallic acid, a natural chemical found in plants, has been reported to show antioxidant, anticancer, and anti-inflammatory effects. We investigated the efficacy of a short-term or long-term treatment with gallic acid in N-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive mice and the underlying regulatory mechanism. Hypertension was sufficiently induced after 2 weeks of L-NAME administration. Cardiac remodeling was assessed by echocardiography. Hypertrophic markers, transcription factors, and fibrosis-related gene expression were evaluated by quantitative real-time polymerase chain reaction and western blotting. Gallic acid effectively lowered SBP, regardless of the administration route (intraperitoneal or oral). L-NAME increased the left ventricular (LV) thickness without an increase in the total heart weight. Weekly echocardiography demonstrated that gallic acid significantly reduced LV posterior wall and septum thickness in chronic L-NAME mice from 3 to 7 weeks. The administration of gallic acid to mice showed a dual preventive and therapeutic effect on the L-NAME-induced LV remodeling. The effect was associated with the suppression of the gene expression of hypertrophy markers and the GATA-binding factor 6 (GATA6) transcription factor. Short-term or long-term treatment with gallic acid attenuated cardiac fibrosis and reduced the expression of histone deacetylase 1 and 2 in H9c2 cells and in rat primary cardiac fibroblasts, as well as in vivo. Small interfering RNA knockdown confirmed the association of these enzymes with L-NAME-induced cardiac remodeling and fibrosis. These results suggested that gallic acid may be a potential therapeutic agent for the treatment of cardiovascular diseases with hypertension and cardiac fibrosis.

Gallic Acid Content in Taiwanese Teas at Different Degrees of Fermentation and Its Antioxidant Activity by Inhibiting PKCδ Activation: In Vitro and in Silico Studies.

PubMed

Kongpichitchoke, Teeradate; Chiu, Ming-Tzu; Huang, Tzou-Chi; Hsu, Jue-Liang

2016-10-12

Teas can be classified according to their degree of fermentation, which has been reported to affect both the bioactive components in the teas and their antioxidative activity. In this study, four kinds of commercial Taiwanese tea at different degrees of fermentation, which include green (non-fermented), oolong (semi-fermented), black (fully fermented), and Pu-erh (post-fermented) tea, were profiled for catechin levels by using high performance liquid chromatography (HPLC). The result indicated that the gallic acid content in tea was directly proportional to the degree of fermentation in which the lowest and highest gallic acid content were 1.67 and 21.98 mg/g from green and Pu-erh tea, respectively. The antioxidative mechanism of the gallic acid was further determined by in vitro and in silico analyses. In vitro assays included the use of phorbol ester-induced macrophage RAW264.7 cell model for determining the inhibition of reactive oxygen species (ROS) production, and PKCδ and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit (p47) activations. The results showed that only at a concentration of 5.00 μM could gallic acid significantly ( p < 0.05) reduce ROS levels in phorbol ester-activated macrophages. Moreover, protein immunoblotting expressed similar results in which activations of PKCδ and p47 were only significantly ( p < 0.05) attenuated by 5.00 μM treatment. Lastly, in silico experiments further revealed that gallic acid could block PKCδ activation by occupying the phorbol ester binding sites of the protein.

Simultaneous analysis of tea catechins, caffeine, gallic acid, theanine and ascorbic acid by micellar electrokinetic capillary chromatography.

PubMed

Aucamp, J P; Hara, Y; Apostolides, Z

2000-04-21

A micellar electrokinetic capillary chromatography (MEKC) method for the simultaneous analysis of five tea catechins, theanine, caffeine, gallic acid and ascorbic acid has been developed. The catechins are (-)-epicatechin, (+)-catechin, (-)-epigallocatechin, (-)-epicatechin gallate and (-)-epigallocatechin gallate. p-Nitrophenol serves as both reference and internal standard. All the components are separated within 13 min with a 57 cm uncoated fused-silica column. On-column detection was carried out at 200 nm. This method has been used to measure these compounds in fresh tea leaves and tea liquor. The limit of detection for all analytes ranged from 1 to 20 microg/ml.

Gallic acid ameliorates hyperglycemia and improves hepatic carbohydrate metabolism in rats fed a high-fructose diet.

PubMed

Huang, Da-Wei; Chang, Wen-Chang; Wu, James Swi-Bea; Shih, Rui-Wen; Shen, Szu-Chuan

2016-02-01

Herein, we investigated the hypoglycemic effect of plant gallic acid (GA) on glucose uptake in an insulin-resistant cell culture model and on hepatic carbohydrate metabolism in rats with a high-fructose diet (HFD)-induced diabetes. Our hypothesis is that GA ameliorates hyperglycemia via alleviating hepatic insulin resistance by suppressing hepatic inflammation and improves abnormal hepatic carbohydrate metabolism by suppressing hepatic gluconeogenesis and enhancing the hepatic glycogenesis and glycolysis pathways in HFD-induced diabetic rats. Gallic acid increased glucose uptake activity by 19.2% at a concentration of 6.25 μg/mL in insulin-resistant FL83B mouse hepatocytes. In HFD-induced diabetic rats, GA significantly alleviated hyperglycemia, reduced the values of the area under the curve for glucose in an oral glucose tolerance test, and reduced the scores of the homeostasis model assessment of insulin resistance index. The levels of serum C-peptide and fructosamine and cardiovascular risk index scores were also significantly decreased in HFD rats treated with GA. Moreover, GA up-regulated the expression of hepatic insulin signal transduction-related proteins, including insulin receptor, insulin receptor substrate 1, phosphatidylinositol-3 kinase, Akt/protein kinase B, and glucose transporter 2, in HFD rats. Gallic acid also down-regulated the expression of hepatic gluconeogenesis-related proteins, such as fructose-1,6-bisphosphatase, and up-regulated expression of hepatic glycogen synthase and glycolysis-related proteins, including hexokinase, phosphofructokinase, and aldolase, in HFD rats. Our findings indicate that GA has potential as a health food ingredient to prevent diabetes mellitus. Copyright © 2016 Elsevier Inc. All rights reserved.

Two choices for the functionalization of silica nanoparticles with gallic acid: characterization of the nanomaterials and their antimicrobial activity against Paenibacillus larvae

NASA Astrophysics Data System (ADS)

Vico, Tamara A.; Arce, Valeria B.; Fangio, María F.; Gende, Liesel B.; Bertran, Celso A.; Mártire, Daniel O.; Churio, María S.

2016-11-01

Silica nanoparticles attached to gallic acid were synthesized from 7-nm diameter fumed silica particles by different functionalization methods involving the condensation of hydroxyl or carboxyl groups. The particles were characterized by thermal analyses and UV-vis, FTIR, NMR, and EPR spectroscopies. In comparison to free gallic acid, enhanced stability and increased antimicrobial activity against Paenibacillus larvae were found for the functionalized nanoparticles. Thus, both derivatization strategies result in improved properties of the natural polyphenol as antimicrobial agent for the treatment of honeybee pathologies.

Evaluation of gallic acid loaded zein sub-micron electrospun fibre mats as novel active packaging materials.

PubMed

Neo, Yun Ping; Swift, Simon; Ray, Sudip; Gizdavic-Nikolaidis, Marija; Jin, Jianyong; Perera, Conrad O

2013-12-01

The applicability of gallic acid loaded zein (Ze-GA) electrospun fibre mats towards potential active food packaging material was evaluated. The surface chemistry of the electrospun fibre mats was determined using X-ray photon spectroscopy (XPS). The electrospun fibre mats showed low water activity and whitish colour. Thermogravimetric analysis (TGA) and Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy revealed the stability of the fibre mats over time. The Ze-GA fibre mats displayed similar rapid release profiles, with Ze-GA 20% exhibiting the fastest release rate in water as compared to the others. Gallic acid diffuses from the electrospun fibres in a Fickian diffusion manner and the data obtained exhibited a better fit to Higuchi model. L929 fibroblast cells were cultured on the electrospun fibres to demonstrate the absence of cytotoxicity. Overall, the Ze-GA fibre mats demonstrated antibacterial activity and properties consistent with those considered desirable for active packaging material in the food industry. Copyright © 2013 Elsevier Ltd. All rights reserved.

Relationship between the lipophilicity of gallic acid n-alquil esters' derivatives and both myeloperoxidase activity and HOCl scavenging.

PubMed

Rosso, Rober; Vieira, Tiago O; Leal, Paulo C; Nunes, Ricardo J; Yunes, Rosendo A; Creczynski-Pasa, Tânia B

2006-09-15

The gallic acid and several n-alkyl gallates, with the same number of hydroxyl substituents, varying only in the side carbonic chain length, with respective lipophilicity defined through the C log P, were studied. It evidenced the structure-activity relationship of the myeloperoxidase activity inhibition and the hypochlorous acid scavenger property, as well as its low toxicity in rat hepatic tissue. The gallates with C log P below 3.0 (compounds 2-7) were more active against the enzyme activity, what means that the addition of 1-6 carbons (C log P between 0.92 and 2.92) at the side chain increased approximately 50% the gallic acid effect. However, a relationship between the HOCl scavenging capability and the lipophilicity was not observed. With these results it is possible to suggest that the gallates protect the HOCl targets through two mechanisms: inhibiting its production by the enzyme and scavenging the reactive specie.

Strecker Aldehyde Formation in Wine: New Insights into the Role of Gallic Acid, Glucose, and Metals in Phenylacetaldehyde Formation.

PubMed

Monforte, Ana Rita; Martins, Sara I F S; Silva Ferreira, Antonio C

2018-03-14

Strecker degradation (SD) leading to the formation of phenylacetaldehyde (PA) was studied in wine systems. New insights were gained by using two full factorial designs focusing on the effects of (1) pH and (2) temperature. In each design of experiments (DoE) three factors, glucose, gallic acid, and metals at two levels (present or absence), were varied while phenylalanine was kept constant. The obtained results gave a clear indication, with statistical significance, that in wine conditions, the SD occurs in the presence of metals preferentially via the phenolic oxidation independent of the temperature (40 or 80 °C). The reaction of the amino acid with the o-quinone formed by the oxidation of the gallic acid seems to be favored when compared with the SD promoted by the reaction with α-dicarbonyls formed by MR between glucose and phenylalanine. In fact, kinetics results showed that the presence of glucose had an inhibitory effect on PA rate of formation. PA formation was 4 times higher in the control wine when compared to the same wine with 10 g/L glucose added. By gallic acid quinone quantitation it is shown that glucose affects directly the concentration of the quinone. decreasing the rate of quinone formation. This highlights the role of sugar in o-quinone concentration and consequently in the impact on Strecker aldehyde formation, a promising new perspective regarding wine shelf-life understanding.

Computational screen and experimental validation of anti-influenza effects of quercetin and chlorogenic acid from traditional Chinese medicine

PubMed Central

Liu, Zekun; Zhao, Junpeng; Li, Weichen; Shen, Li; Huang, Shengbo; Tang, Jingjing; Duan, Jie; Fang, Fang; Huang, Yuelong; Chang, Haiyan; Chen, Ze; Zhang, Ran

2016-01-01

The Influenza A virus is a great threat for human health, while various subtypes of the virus made it difficult to develop drugs. With the development of state-of-art computational chemistry, computational molecular docking could serve as a virtual screen of potential leading compound. In this study, we performed molecular docking for influenza A H1N1 (A/PR/8/34) with small molecules such as quercetin and chlorogenic acid, which were derived from traditional Chinese medicine. The results showed that these small molecules have strong binding abilities with neuraminidase from H1N1 (A/PR/8/34). Further details showed that the structural features of the molecules might be helpful for further drug design and development. The experiments in vitro, in vivo have validated the anti-influenza effect of quercetin and chlorogenic acid, which indicating comparable protection effects as zanamivir. Taken together, it was proposed that chlorogenic acid and quercetin could be employed as the effective lead compounds for anti-influenza A H1N1. PMID:26754609

Computational screen and experimental validation of anti-influenza effects of quercetin and chlorogenic acid from traditional Chinese medicine

NASA Astrophysics Data System (ADS)

Liu, Zekun; Zhao, Junpeng; Li, Weichen; Shen, Li; Huang, Shengbo; Tang, Jingjing; Duan, Jie; Fang, Fang; Huang, Yuelong; Chang, Haiyan; Chen, Ze; Zhang, Ran

2016-01-01

The Influenza A virus is a great threat for human health, while various subtypes of the virus made it difficult to develop drugs. With the development of state-of-art computational chemistry, computational molecular docking could serve as a virtual screen of potential leading compound. In this study, we performed molecular docking for influenza A H1N1 (A/PR/8/34) with small molecules such as quercetin and chlorogenic acid, which were derived from traditional Chinese medicine. The results showed that these small molecules have strong binding abilities with neuraminidase from H1N1 (A/PR/8/34). Further details showed that the structural features of the molecules might be helpful for further drug design and development. The experiments in vitro, in vivo have validated the anti-influenza effect of quercetin and chlorogenic acid, which indicating comparable protection effects as zanamivir. Taken together, it was proposed that chlorogenic acid and quercetin could be employed as the effective lead compounds for anti-influenza A H1N1.

Crystal water as the mol-ecular glue for obtaining different co-crystal ratios: the case of gallic acid tris-caffeine hexa-hydrate.

PubMed

Vella-Zarb, L; Baisch, U

2018-04-01

The crystal structure of the hexa-hydrate co-crystal of gallic acid and caffeine, C 7 H 6 O 5 ·3C 8 H 10 N 4 O 2 ·6H 2 O or GAL3CAF·6H 2 O , is a remarkable example of the importance of hydrate water acting as structural glue to facilitate the crystallization of two components of different stoichiometries and thus to compensate an imbalance of hydrogen-bond donors and acceptors. The water mol-ecules provide the additional hydrogen bonds required to form a crystalline solid. Whereas the majority of hydrogen bonds forming the inter-molecular network between gallic acid and caffeine are formed by crystal water, only one direct classical hydrogen bond between two mol-ecules is formed between the carb-oxy-lic oxygen of gallic acid and the carbonyl oxygen of caffeine with d ( D ⋯ A ) = 2.672 (2) Å. All other hydrogen bonds either involve crystal water or utilize protonated carbon atoms as donors.

Gallic Acid Grafted Chitosan Has Enhanced Oxidative Stability in Bulk Oils.

PubMed

Gim, Seo Yeong; Hong, Seungmi; Kim, Mi-Ja; Lee, JaeHwan

2017-07-01

Gallic acid (GA) was grafted in chitosan and the effects of GA grafted chitosan (GA-g-CS) on the oxidative stability in bulk oil was tested at 60 and 140 °C. To text oxidative stability in oils, headspace oxygen content, conjugated dienoic acid (CDA) value, p-anisidine value (p-AV), and acid value were determined. Chitosan itself did not show antioxidative or prooxidative effects in oils at 60 °C. However, GA-g-CS and GA acted as antioxidants at 60 °C. At 140 °C heating with moisture supplied condition, different results were observed. GA-g-CS acted as antioxidants based on the results of CDA and p-AV. However, chitosan showed the highest oxidative stability based on results of acid value and brown color formation at 140 °C. This could be due to reduction of moisture content by chitosan. GA was continuously released from GA-g-CS in bulk oil. This might have provided extra antioxidant activities to oils. © 2017 Institute of Food Technologists®.

Prescription Proportion of Pomegranate Extract Gallic Acid Gel by Orthogonal Design

NASA Astrophysics Data System (ADS)

Fan, Gaofu; Liu, Xiushu; Tang, Jie; Gong, Jumei; Fu, Entao; Cai, Yuhua; Xu, Zhenguo

2018-05-01

The aim of the present work was to optimize the formulation of pomegranate extract gallic acid gel by orthogonal design. Using orthogonal design, propylene glycol, carbomer-940 and gel pH level as influencing factors, the evaluation key index was external apearance malleability, uniformity, and eccentric for gel, and the optimum formula was selected. The present findings suggest that 10% propylene glycol, 1.5% Carbopol-940, and gel pH in the range of 4.5∼5.5, and the indexes of the optimal. The inclusion complexes showed that after the orthogonal design, the preparation process was simple, stable and controllable quality, with production feasibility.

Radioprotective Effects of Gallic Acid in Mice

PubMed Central

Nair, Gopakumar Gopinathan

2013-01-01

Radioprotecting ability of the natural polyphenol, gallic acid (3,4,5-trihydroxybenzoic acid, GA), was investigated in Swiss albino mice. Oral administration of GA (100 mg/kg body weight), one hour prior to whole body gamma radiation exposure (2–8 Gy; 6 animals/group), reduced the radiation-induced cellular DNA damage in mouse peripheral blood leukocytes, bone marrow cells, and spleenocytes as revealed by comet assay. The GA administration also prevented the radiation-induced decrease in the levels of the antioxidant enzyme, glutathione peroxidise (GPx), and nonprotein thiol glutathione (GSH) and inhibited the peroxidation of membrane lipids in these animals. Exposure of mice to whole body gamma radiation also caused the formation of micronuclei in blood reticulocytes and chromosomal aberrations in bone marrow cells, and the administration of GA resulted in the inhibition of micronucleus formation and chromosomal aberrations. In irradiated animals, administration of GA elicited an enhancement in the rate of DNA repair process and a significant increase in endogenous spleen colony formation. The administration of GA also prevented the radiation-induced weight loss and mortality in animals (10 animals/group) exposed to lethal dose (10 Gy) of gamma radiation. (For every experiment unirradiated animals without GA administration were taken as normal control; specific dose (Gy) irradiated animals without GA administration serve as radiation control; and unirradiated GA treated animals were taken as drug alone control). PMID:24069607

Gallic acid-capped gold nanoparticles inhibit EGF-induced MMP-9 expression through suppression of p300 stabilization and NFκB/c-Jun activation in breast cancer MDA-MB-231 cells.

PubMed

Chen, Ying-Jung; Lee, Yuan-Chin; Huang, Chia-Hui; Chang, Long-Sen

2016-11-01

Triple-negative breast cancers (TNBCs) are highly invasive and have a higher rate of distant metastasis. Matrix metalloproteinase-9 (MMP-9) plays a crucial role in EGF/EGFR-mediated malignant progression and metastasis of TNBCs. Various studies have revealed that treatment with gallic acid down-regulates MMP-9 expression in cancer cells, and that conjugation of phytochemical compounds with gold nanoparticles (AuNPs) increases the anti-tumor activity of the phytochemical compounds. Thus, the effect of gallic acid-capped AuNPs (GA-AuNPs) on MMP-9 expression in EGF-treated TNBC MDA-MB-231 cells was analyzed in the present study. The so-called green synthesis of AuNPs by means of gallic acid was performed at pH10, and the resulting GA-AuNPs had spherical shape with an average diameter of approximately 50nm. GA-AuNPs notably suppressed migration and invasion of EGF-treated cells, and inhibited EGF-induced MMP-9 up-regulation. GA-AuNPs abrogated EGF-induced Akt/p65 and ERK/c-Jun phosphorylation, leading to down-regulation of MMP-9 mRNA and protein expression in EGF-treated cells. Meanwhile, EGF-induced p300 stabilization was found to be involved in MMP-9 expression, whereas GA-AuNPs inhibited the EGF-promoted stability of the p300 protein. Although GA-AuNPs and gallic acid suppressed EGF-induced MMP-9 up-regulation via the same signaling pathway, the effective concentration of gallic acid was approximately 100-fold higher than that of GA-AuNPs for inhibition of MMP-9 expression in EGF-treated cells to a similar extent. Collectively, our data indicate that, in comparison with gallic acid, GA-AuNPs have a superior ability to inhibit EGF/EGFR-mediated MMP-9 expression in TNBC MDA-MB-231 cells. Our findings also point to a way to improve the anti-tumor activity of gallic acid. Copyright © 2016 Elsevier Inc. All rights reserved.

Quantum chemical density functional theory studies on the molecular structure and vibrational spectra of Gallic acid imprinted polymers

NASA Astrophysics Data System (ADS)

Pardeshi, Sushma; Dhodapkar, Rita; Kumar, Anupama

2013-12-01

Gallic acid (GA) is known by its antioxidant, anticarcinogenic properties and scavenger activity against several types of harmful free radicals. Molecularly imprinted polymers (MIPs) are used in separation of a pure compound from complex matrices. A stable template-monomer complex generates the MIPs with the highest affinity and selectivity for the template. The quantum chemical computations based on density functional theory (DFT) was used on the template Gallic acid (GA), monomer acrylic acid (AA) and GA-AA complex to study the nature of interactions involved in the GA-AA complex. B3LYP/6-31+G(2d,2p) model chemistry was used to optimize their structures and frequency calculations. The effect of porogen acetonitrile (ACN) on complex formation was included by using polarizable continuum model (PCM). The results demonstrated the formation of a stable GA-AA complex through the intermolecular hydrogen bonding between carboxylic acid groups of GA and AA. The Mulliken atomic charge analysis and simulated vibrational spectra also supported the stable hydrogen bonding interaction between the carboxylic acid groups of GA and AA with minimal interference of porogen ACN. Further, simulations on GA-AA mole ratio revealed that 1:4 GA-AA was optimum for synthesis of MIP for GA.

Anti-Inflammatory Activities of Pentaherbs Formula, Berberine, Gallic Acid and Chlorogenic Acid in Atopic Dermatitis-Like Skin Inflammation.

PubMed

Tsang, Miranda S M; Jiao, Delong; Chan, Ben C L; Hon, Kam-Lun; Leung, Ping C; Lau, Clara B S; Wong, Eric C W; Cheng, Ling; Chan, Carmen K M; Lam, Christopher W K; Wong, Chun K

2016-04-20

Atopic dermatitis (AD) is a common allergic skin disease, characterized by dryness, itchiness, thickening and inflammation of the skin. Infiltration of eosinophils into the dermal layer and presence of edema are typical characteristics in the skin biopsy of AD patients. Previous in vitro and clinical studies showed that the Pentaherbs formula (PHF) consisting of five traditional Chinese herbal medicines, Flos Lonicerae, Herba Menthae, Cortex Phellodendri, Cortex Moutan and Rhizoma Atractylodis at w/w ratio of 2:1:2:2:2 exhibited therapeutic potential in treating AD. In this study, an in vivo murine model with oxazolone (OXA)-mediated dermatitis was used to elucidate the efficacy of PHF. Active ingredients of PHF water extract were also identified and quantified, and their in vitro anti-inflammatory activities on pruritogenic cytokine IL-31- and alarmin IL-33-activated human eosinophils and dermal fibroblasts were evaluated. Ear swelling, epidermis thickening and eosinophils infiltration in epidermal and dermal layers, and the release of serum IL-12 of the murine OXA-mediated dermatitis were significantly reduced upon oral or topical treatment with PHF (all p < 0.05). Gallic acid, chlorogenic acid and berberine contents (w/w) in PHF were found to be 0.479%, 1.201% and 0.022%, respectively. Gallic acid and chlorogenic acid could suppress the release of pro-inflammatory cytokine IL-6 and chemokine CCL7 and CXCL8, respectively, in IL-31- and IL-33-treated eosinophils-dermal fibroblasts co-culture; while berberine could suppress the release of IL-6, CXCL8, CCL2 and CCL7 in the eosinophil culture and eosinophils-dermal fibroblasts co-culture (all p < 0.05). These findings suggest that PHF can ameliorate allergic inflammation and attenuate the activation of eosinophils.

Gastroprotective Effect of Ginger Rhizome (Zingiber officinale) Extract: Role of Gallic Acid and Cinnamic Acid in H+, K+-ATPase/H. pylori Inhibition and Anti-Oxidative Mechanism

PubMed Central

Nanjundaiah, Siddaraju M.; Annaiah, Harish Nayaka Mysore; Dharmesh, Shylaja M.

2011-01-01

Zinger officinale has been used as a traditional source against gastric disturbances from time immemorial. The ulcer-preventive properties of aqueous extract of ginger rhizome (GRAE) belonging to the family Zingiberaceae is reported in the present study. GRAE at 200 mg kg−1 b.w. protected up to 86% and 77% for the swim stress-/ethanol stress-induced ulcers with an ulcer index (UI) of 50 ± 4.0/46 ± 4.0, respectively, similar to that of lansoprazole (80%) at 30 mg kg−1 b.w. Increased H+, K+-ATPase activity and thiobarbituric acid reactive substances (TBARS) were observed in ulcer-induced rats, while GRAE fed rats showed normalized levels and GRAE also normalized depleted/amplified anti-oxidant enzymes in swim stress and ethanol stress-induced animals. Gastric mucin damage was recovered up to 77% and 74% in swim stress and ethanol stress, respectively after GRAE treatment. GRAE also inhibited the growth of H. pylori with MIC of 300 ± 38 μg and also possessed reducing power, free radical scavenging ability with an IC50 of 6.8 ± 0.4 μg mL−1 gallic acid equivalent (GAE). DNA protection up to 90% at 0.4 μg was also observed. Toxicity studies indicated no lethal effects in rats fed up to 5 g kg−1 b.w. Compositional analysis favored by determination of the efficacy of individual phenolic acids towards their potential ulcer-preventive ability revealed that between cinnamic (50%) and gallic (46%) phenolic acids, cinnamic acid appear to contribute to better H+, K+-ATPase and Helicobacter pylori inhibitory activity, while gallic acid contributes significantly to anti-oxidant activity. PMID:19570992

Graphene Oxide-Gallic Acid Nanodelivery System for Cancer Therapy

NASA Astrophysics Data System (ADS)

Dorniani, Dena; Saifullah, Bullo; Barahuie, Farahnaz; Arulselvan, Palanisamy; Hussein, Mohd Zobir Bin; Fakurazi, Sharida; Twyman, Lance J.

2016-11-01

Despite the technological advancement in the biomedical science, cancer remains a life-threatening disease. In this study, we designed an anticancer nanodelivery system using graphene oxide (GO) as nanocarrier for an active anticancer agent gallic acid (GA). The successful formation nanocomposite (GOGA) was characterized using XRD, FTIR, HRTEM, Raman, and UV/Vis spectroscopy. The release study shows that the release of GA from the designed anticancer nanocomposite (GOGA) occurs in a sustained manner in phosphate-buffered saline (PBS) solution at pH 7.4. In in vitro biological studies, normal fibroblast (3T3) and liver cancer cells (HepG2) were treated with different concentrations of GO, GOGA, and GA for 72 h. The GOGA nanocomposite showed the inhibitory effect to cancer cell growth without affecting normal cell growth. The results of this research are highly encouraging to go further for in vivo studies.

Synthesis and structure identification of 2-amino-4, 6- dimethyl pyrimidine with gallic acid and pimelic acid

NASA Astrophysics Data System (ADS)

Mekala, R.; Jagdish, P.; Mathammal, R.

2018-07-01

Reaction of 2-amino-4, 6- dimethyl pyrimidine with carboxylic acid such as gallic acid and pimelic acid, yielded a salt and co-crystal, respectively. The new crystal forms were obtained from slow evaporation technique. The crystal structure and hydrogen bond interaction of the two crystals were determined by single X-ray diffraction analysis. Inter molecular interactions of the compounds were investigated using the 3D Hirshfeld surfaces and the associated 2D fingerprint plots. The functional groups were identified by the FTIR, FT-Raman spectral studies. The presence of carbon and hydrogen in the two samples were identified by the 1H and 13C NMR analysis. The excited energy was observed using UV-Visible spectral analysis. The fluorescence spectra revealed the emission state of the two samples. The thermal behaviour and stability of the two compounds were evaluated by the TGA-DSC analysis.

Synthesis of Quercetin-imprinted Polymer Spherical Particles with Improved Ability to Capture Quercetin Analogues.

PubMed

Pardo, Antonelle; Josse, Thomas; Mespouille, Laetitia; Blankert, Bertrand; Dubois, Philippe; Duez, Pierre

2017-07-01

Molecularly imprinted polymers (MIPs) are composed of specific cavities able to selectively recognise a template molecule. Used as chromatographic sorbents, MIPs may not trap related structures due to the high rigidity of their cross-linking. To improve the capture of quercetin analogues by modulating the synthesis strategy for a quercetin-imprinted polymer (Qu MIP). An additional comonomer bearing a short oligoethylene glycol (OEG) unit was used to prepare a Qu MIP that was compared to a traditional one formulated in a similar fashion, but without the OEG-comonomer. The Qu MIPs were prepared in bead form through fluorocarbon suspension polymerisation. After solid phase extraction (SPE) assessment of their imprinted cavities, the MIPs were evaluated by HPLC for their recognition properties towards quercetin and other polyphenols, including flavonoids, phenolic acids and curcumin. The Qu MIPs were finally SPE-tested on a white onion extract. The incorporation of OEG units modulated the selectivity of the Qu MIP by improving the recognition of quercetin related structures (12-61% increase in the imprinting effect for distant analogues). It also allowed limiting or suppressing non-specific hydrophobic interactions (decrease of about 10% in the rate of quercetin retention on the non-imprinted polymer). The SPE application of the MIP to a white onion extract indicates its interest for the selective extraction of quercetin and its analogues. The OEG-modified Qu MIP appears to be an attractive tool to discover new drug candidates from natural sources by extracting, amongst interfering compounds, structural analogues of quercetin. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Rise in the pH of an unfrozen solution in ice due to the presence of NaCl and promotion of decomposition of gallic acids owing to a change in the pH.

PubMed

Takenaka, Norimichi; Tanaka, Masayuki; Okitsu, Kenji; Bandow, Hiroshi

2006-09-14

Oxidative decomposition of gallic acid occurs in alkaline solutions but hardly arises in acidic solutions. We have found that the addition of sodium chloride promotes the decomposition of gallic acid caused by freezing even under neutral and acidic conditions. Even at pH 4.5, gallic acid was decomposed by freezing in the presence of NaCl; however, in the absence of NaCl, it was hardly decomposed by freezing at pH lower than 7. Chloride ions are more easily incorporated in ice than sodium ions when the NaCl solution is frozen. The unfrozen solution in ice becomes positively charged, and as a result, protons transfer from the unfrozen solution to the ice. We measured the pH in the unfrozen solution which coexists with single-crystal ice formed from a 5 mmol dm(-3) NaCl solution and determined the pH to be 8.6 at equilibrium with CO(2) of 380 ppm or 11.3 in the absence of CO(2) compared to pH 5.6 in the original solution. From the model calculation performed for gallic acid solution in the presence of 5 mmol dm(-3) NaCl, it can be estimated that the amount of OH(-) transferred from the ice to the solution corresponds to 1.26 x 10(-5) mol dm(-3). The amount of OH(-) transferred is concentrated into the unfrozen solution and affects the pH of the unfrozen solution. Therefore, the pH in an unfrozen gallic acid solution in ice becomes alkaline, and the decomposition of gallic acid proceeds. It is expected that other base-catalyzed reactions in weakly acidic solutions also proceed by freezing in the presence of NaCl without the need for any alkaline reagents.

Effects and interactions of gallic acid, eugenol and temperature on thermal inactivation of Salmonella spp. in ground chicken

USDA-ARS?s Scientific Manuscript database

The combined effects of heating temperature (55 to 65C), gallic acid (0 to 2.0%), and eugenol (0 to 2.0%) on thermal inactivation of Salmonella in ground chicken were assessed. Thermal death times were determined in bags submerged in a heated water bath maintained at various set temperatures, follo...

Terahertz spectroscopic investigation of gallic acid and its monohydrate

NASA Astrophysics Data System (ADS)

Zhang, Bo; Li, Shaoping; Wang, Chenyang; Zou, Tao; Pan, Tingting; Zhang, Jianbing; Xu, Zhou; Ren, Guanhua; Zhao, Hongwei

2018-02-01

The low-frequency spectra of gallic acid (GA) and its monohydrate were investigated by terahertz time-domain spectroscopy (THz-TDS) in the range of 0.5 to 4.5 THz. The dehydration process of GA monohydrate was monitored on-line. The kinetic mechanism of the dehydration process was analyzed depending on the THz spectral change at different temperatures. The results indicate that the diffusion of water molecule dominates the speed of the entire dehydration process. Solid-state density functional theory (DFT) calculations of the vibrational modes of both GA and its monohydrate were performed based on their crystalline structures for better interpreting the experimental THz spectra. The results demonstrate that the characterized features of GA mainly originate from the collective vibrations of molecules. And the interactions between GA and water molecules are responsible for THz fingerprint of GA monohydrate. Multi-techniques including differential scanning calorimetry and thermogravimetry (DSC-TG) and powder X-ray diffraction (PXRD) were also carried out to further investigate GA and its monohydrate.

HPLC determination of phenolic acids, flavonoids and juglone in walnut leaves.

PubMed

Nour, Violeta; Trandafir, Ion; Cosmulescu, Sina

2013-10-01

A high-performance liquid chromatographic method with gradient elution and diode-array detection was developed to quantify free phenolic acids (gallic, vanillic, chlorogenic, caffeic, syringic, p-coumaric, ferulic, sinapic, salycilic, elagic and trans-cinnamic), flavonoids (catechin, epicatechin, rutin, myricetin and quercetin) and juglone in walnut leaves. Chromatographic separation was performed on a Hypersil Gold C18 column (5 µm particle size, 250 × 4.6 mm) and detection was conducted at three different wavelengths (254, 278 and 300 nm) according to the absorption maxima of the analyzed compounds. Validation procedures were conducted and the method was proven to be precise, accurate and sensitive. The developed method has been applied to analyze walnut leaves samples from nine different cultivars, with the same agricultural, geographical and climatic conditions. The experimental results revealed high concentrations of myricetin, catechin hydrate and rutin, and low concentrations of quercetin and epicatechin aglycones. Ellagic acid was established as the dominating phenolic acid of walnut leaves, followed by trans-cinnamic, chlorogenic and caffeic acids. Juglone content varied between 44.55 and 205.12 mg/100 g fresh weight. Significant differences were detected among cultivars for the concentration levels of phenolics.

Meta-Analysis of Global Transcriptomics Suggests that Conserved Genetic Pathways are Responsible for Quercetin and Tannic Acid Mediated Longevity in C. elegans

PubMed Central

Pietsch, Kerstin; Saul, Nadine; Swain, Suresh C.; Menzel, Ralph; Steinberg, Christian E. W.; Stürzenbaum, Stephen R.

2012-01-01

Recent research has highlighted that the polyphenols Quercetin and Tannic acid are capable of extending the lifespan of Caenorhabditis elegans. To gain a deep understanding of the underlying molecular genetics, we analyzed the global transcriptional patterns of nematodes exposed to three concentrations of Quercetin or Tannic acid, respectively. By means of an intricate meta-analysis it was possible to compare the transcriptomes of polyphenol exposure to recently published datasets derived from (i) longevity mutants or (ii) infection. This detailed comparative in silico analysis facilitated the identification of compound specific and overlapping transcriptional profiles and allowed the prediction of putative mechanistic models of Quercetin and Tannic acid mediated longevity. Lifespan extension due to Quercetin was predominantly driven by the metabolome, TGF-beta signaling, Insulin-like signaling, and the p38 MAPK pathway and Tannic acid’s impact involved, in part, the amino acid metabolism and was modulated by the TGF-beta and the p38 MAPK pathways. DAF-12, which integrates TGF-beta and Insulin-like downstream signaling, and genetic players of the p38 MAPK pathway therefore seem to be crucial regulators for both polyphenols. Taken together, this study underlines how meta-analyses can provide an insight of molecular events that go beyond the traditional categorization into gene ontology-terms and Kyoto encyclopedia of genes and genomes-pathways. It also supports the call to expand the generation of comparative and integrative databases, an effort that is currently still in its infancy. PMID:22493606

Dynamic calibration approach for determining catechins and gallic acid in green tea using LC-ESI/MS.

PubMed

Bedner, Mary; Duewer, David L

2011-08-15

Catechins and gallic acid are antioxidant constituents of Camellia sinensis, or green tea. Liquid chromatography with both ultraviolet (UV) absorbance and electrospray ionization mass spectrometric (ESI/MS) detection was used to determine catechins and gallic acid in three green tea matrix materials that are commonly used as dietary supplements. The results from both detection modes were evaluated with 14 quantitation models, all of which were based on the analyte response relative to an internal standard. Half of the models were static, where quantitation was achieved with calibration factors that were constant over an analysis set. The other half were dynamic, with calibration factors calculated from interpolated response factor data at each time a sample was injected to correct for potential variations in analyte response over time. For all analytes, the relatively nonselective UV responses were found to be very stable over time and independent of the calibrant concentration; comparable results with low variability were obtained regardless of the quantitation model used. Conversely, the highly selective MS responses were found to vary both with time and as a function of the calibrant concentration. A dynamic quantitation model based on polynomial data-fitting was used to reduce the variability in the quantitative results using the MS data.

Antioxidant and antimicrobial potentials of Serbian red wines produced from international Vitis vinifera grape varieties.

PubMed

Radovanović, Aleksandra N; Jovančićević, Branimir S; Radovanović, Blaga C; Mihajilov-Krstev, Tatjana; Zvezdanović, Jelena B

2012-08-15

Antioxidant and antimicrobial potentials of Serbian red wines produced from different international Vitis vinifera grape varieties and their correlation with contents of phenolic compounds were studied by spectrophotometric and chromatographic methods. The antioxidant activity of red wines was estimated through their ability to scavenge 2,2'-diphenyl-1-picrylhydrazyl free radical (DPPH(•) ). The red wines, gallic acid, (+)-catechin and quercetin were screened in vitro for antimicrobial activity against Gram-positive and Gram-negative strains using microdilution and disc diffusion techniques. Excellent correlations between the contents of quercetin-3-glucoside (R(2) = 0.9463) and quercetin (R(2) = 0.9337) and DPPH(•) -scavenging ability of the red wines were found. Serbian red wines exhibited significant activity against Staphylococcus aureus, Listeria inocua, Micrococcus flavus, Sarcina lutea, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Salmonella enteritidis and Shigella sonnei strains, which was in correlation with their phenolic composition and antioxidant activity. The compounds gallic acid, quercetin and (+)-catechin showed high activity against B. subtilis, S. aureus, S. lutea and M. flavus Gram-positive and S. enteritidis and P. aeruginosa Gram-negative strains. The results show that quercetin-3-glucoside and quercetin concentrations can be used as markers for the determination of antioxidant and antimicrobial potentials of red wines. Copyright © 2012 Society of Chemical Industry.

A C8-Modified Graphene@mSiO2 Composites Based Method for Quantification of Gallic Acid in Rat Plasma after Oral Administration of Changtai Granule and Its Application to Pharmacokinetics.

PubMed

Xu, Chen; Yu, Yingjia; Ling, Li; Wang, Yang; Zhang, Jundong; Li, Yan; Duan, Gengli

2017-01-01

A rapid, effective extraction technique has been established for measuring the gallic acid in rat plasma by using sandwich-structured graphene/mesoporous silica composites with C 8 -modified interior pore-walls as adsorbent. The unique characteristics of the graphene-silica composites excluded large molecules, like proteins, from the mesopore channels as a result of size exclusion effect, leading to a direct extraction of drug molecules from protein-rich biological samples such as plasma without any other pretreatment procedure. Followed by elution and centrifugation, the gallic acid-absorbed composites were rapidly isolated before LC-MS/MS. Serving as a reliable tool for analysis of Traditional Chinese Medicine: Changtai Granule, the newly developed method was fully validated and successfully applied in the pharmacokinetic study of gallic acid in rat plasma. Extraction recovery, matrix effect and stability were satisfactory in rat plasma. According to the results of pharmacokinetic studies, Changtai Granule exhibited greater adsorption, distribution and clearance properties of gallic acid in the treatment of ulcerative colitis. Hence, this study may offer a valuable alternative to simplify and speed up sample preparation, and be useful for clinical studies of related preparations.

[Polyphenol compounds from Hamamelis virginiana L].

PubMed

Kostálová, D; Misíková, E; Gáborová, G

2001-01-01

Two phenolic acids and two flavone aglycones were isolated from the aboveground part of Hamamelis virginiana L. and identified with the use of thin-layer chromatography, melting points, and spectroscopic methods as gallic acid, ethyl gallate, quercetin, and kaempferol.

Docking analysis of gallic acid derivatives as HIV-1 protease inhibitors.

PubMed

Singh, Anjali; Pal, Tapan Kumar

2015-01-01

HIV-1 Protease (HIV-1 PR) enzymes are essential for accurate assembly and maturation of infectious HIV retroviruses. The significant role of HIV-1 protease in viral replication has made it a potential drug target. In the recent past, phytochemical Gallic Acid (GA) derivatives have been screened for protease inhibitor activity. The present work aims to design and evaluate potential GA-based HIV-1 PR phytoinhibitors by docking approach. The ligands were prepared by ChemDraw and docking was performed in HEX software. In this present study, one of the GA analogues (GA4) emerged as a potent drug candidate for HIV-1 PR inhibition, and docking results showed it to be comparable with anti-HIV drugs, darunavir and amprenavir. The GA4 derivative provided a lead for designing more effective HIV-1 PR inhibitors.

Intestinal Permeability and Cellular Antioxidant Activity of Phenolic Compounds from Mango (Mangifera indica cv. Ataulfo) Peels.

PubMed

Pacheco-Ordaz, Ramón; Antunes-Ricardo, Marilena; Gutiérrez-Uribe, Janet A; González-Aguilar, Gustavo A

2018-02-08

Mango ( Mangifera indica cv. Ataulfo) peel contains bound phenolics that may be released by alkaline or acid hydrolysis and may be converted into less complex molecules. Free phenolics from mango cv. Ataulfo peel were obtained using a methanolic extraction, and their cellular antioxidant activity (CAA) and permeability were compared to those obtained for bound phenolics released by alkaline or acid hydrolysis. Gallic acid was found as a simple phenolic acid after alkaline hydrolysis along with mangiferin isomers and quercetin as aglycone and glycosides. Only gallic acid, ethyl gallate, mangiferin, and quercetin were identified in the acid fraction. The acid and alkaline fractions showed the highest CAA (60.5% and 51.5%) when tested at 125 µg/mL. The value of the apparent permeability coefficient (Papp) across the Caco-2/HT-29 monolayer of gallic acid from the alkaline fraction was higher (2.61 × 10 -6 cm/s) than in the other fractions and similar to that obtained when tested pure (2.48 × 10 -6 cm/s). In conclusion, mango peels contain bound phenolic compounds that, after their release, have permeability similar to pure compounds and exert an important CAA. This finding can be applied in the development of nutraceuticals using this important by-product from the mango processing industry.

Gallic acid grafting effect on delivery performance and antiglaucoma efficacy of antioxidant-functionalized intracameral pilocarpine carriers.

PubMed

Chou, Shih-Feng; Luo, Li-Jyuan; Lai, Jui-Yang

2016-07-01

Functionalization of therapeutic carrier biomaterials can potentially provide additional benefits in drug delivery for disease treatment. Given that this modification determines final therapeutic efficacy of drug carriers, here, we investigate systematically the role of grafting amount of antioxidant gallic acid (GA) onto GN in situ gelling copolymers made of biodegradable gelatin and thermo-responsive poly(N-isopropylacrylamide) for intracameral delivery of pilocarpine in antiglaucoma treatment. As expected, increasing redox reaction time increased total antioxidant activities and free radical scavenging abilities of synthesized carrier biomaterials. The hydrophilic nature of antioxidant molecules strongly affected physicochemical properties of carrier materials with varying GA grafting amounts, thereby dictating in vitro release behaviors and mechanisms of pilocarpine. In vitro oxidative stress challenges revealed that biocompatible carriers with high GA content alleviated lens epithelial cell damage and reduced reactive oxygen species. Intraocular pressure and pupil diameter in glaucomatous rabbits showed correlations with GA-mediated release of pilocarpine. Additionally, enhanced pharmacological treatment effects prevented corneal endothelial cell loss during disease progression. Increasing GA content increased total antioxidant level and decreased nitrite level in the aqueous humor, suggesting a much improved antioxidant status in glaucomatous eyes. This work significantly highlights the dependence of physicochemical properties, drug release behaviors, and bioactivities on intrinsic antioxidant capacities of therapeutic carrier biomaterials for glaucoma treatment. Development of injectable biodegradable polymer depots and functionalization of carrier biomaterials with antioxidant can potentially provide benefits such as improved bioavailability, controlled release pattern, and increased therapeutic effect in intracameral pilocarpine administration for glaucoma

Combination of quercetin and tannic acid in inhibiting 26S proteasome affects S5a and 20S expression, and accumulation of ubiquitin resulted in apoptosis in cancer chemoprevention.

PubMed

Chang, Tsui-Ling; Wang, Chi-Hsien

2013-04-01

To look for oral proteasome inhibitors, daily injested food is the best source for cancer chemoprevention. A combination of active components from vegetables, coffee, tea, and fruit could be more efficient to inhibit 26S proteasome activities for preventing cancer diseases. Tannic acid and quercetin have been shown to strongly inhibit 26S proteasome activity, but the molecular target involved remains unknown. Overlay assay, peptide assay, Western blot, and 2-D gels were used to assess the combination of quercetin and tannic acid as a potential inhibitor. Here, we demonstrated that the combination of quercetin and tannic acid (1) synergistically suppresses chymotrypsin-, caspase-, and trypsin-like proteolytic activities, (2) are tightly binding substrates, (3) do not perturb the proteasome structure, (4) inhibit the 26S proteasome affected by ubiquitin, ATP, or β-casein, and (5) inhibit β-casein degradation by the 26S proteasome in vitro. Finally, the inhibition of the proteasome by a combination of quercetin plus tannic acid in Hep-2 cells resulted in the induction of S5a at low dose, accumulation of ubiquitin, and the cleavage of pro-caspase-3, followed by the induction of apoptotic cell death. Evaluating the combination of quercetin and tannic acid as an oral drug to prevent cancer may provide a pharmacological rationale to pursue preclinical trials of this combination.

Gallic Acid Promotes Wound Healing in Normal and Hyperglucidic Conditions.

PubMed

Yang, Dong Joo; Moh, Sang Hyun; Son, Dong Hwee; You, Seunghoon; Kinyua, Ann W; Ko, Chang Mann; Song, Miyoung; Yeo, Jinhee; Choi, Yun-Hee; Kim, Ki Woo

2016-07-08

Skin is the outermost layer of the human body that is constantly exposed to environmental stressors, such as UV radiation and toxic chemicals, and is susceptible to mechanical wounding and injury. The ability of the skin to repair injuries is paramount for survival and it is disrupted in a spectrum of disorders leading to skin pathologies. Diabetic patients often suffer from chronic, impaired wound healing, which facilitate bacterial infections and necessitate amputation. Here, we studied the effects of gallic acid (GA, 3,4,5-trihydroxybenzoic acid; a plant-derived polyphenolic compound) on would healing in normal and hyperglucidic conditions, to mimic diabetes, in human keratinocytes and fibroblasts. Our study reveals that GA is a potential antioxidant that directly upregulates the expression of antioxidant genes. In addition, GA accelerated cell migration of keratinocytes and fibroblasts in both normal and hyperglucidic conditions. Further, GA treatment activated factors known to be hallmarks of wound healing, such as focal adhesion kinases (FAK), c-Jun N-terminal kinases (JNK), and extracellular signal-regulated kinases (Erk), underpinning the beneficial role of GA in wound repair. Therefore, our results demonstrate that GA might be a viable wound healing agent and a potential intervention to treat wounds resulting from metabolic complications.

Gallic acid is an active component for the anticarcinogenic action of grape seed procyanidins in pancreatic cancer cells.

PubMed

Cedó, Lídia; Castell-Auví, Anna; Pallarès, Victor; Macià, Alba; Blay, Mayte; Ardévol, Anna; Motilva, Maria-José; Pinent, Montserrat

2014-01-01

The aim of the present work was to evaluate the effects of a grape seed procyanidin extract (GSPE) on proliferation and apoptosis in the pancreatic adenocarcinoma cell line MIA PaCa-2 and identify the components of the extract with higher activity. The effects of the extract were analyzed on the proliferation and apoptosis processes in MIA PaCa-2 cells, as well as in the levels of the apoptosis markers Bcl-2 and Bax, the mitochondrial membrane potential, and reactive oxygen species levels. Finally, the components of the extract with higher effects were elucidated using enriched fractions of the extract and pure compounds. The results showed that GSPE inhibits cell proliferation and increases apoptosis in MIA PaCa-2 cells, which is primarily mediated by the downregulation of the antiapoptotic protein Bcl-2 and the depolarization of the mitochondrial membrane. GSPE also reduced the formation of reactive oxygen species. The component of the extract that possesses the highest antiproliferative and proapoptotic activity was gallic acid. In conclusion, GSPE acts as anticarcinogenic in MIA PaCa-2 cells, with gallic acid as the major single active constituent of the extract.

Quercetin as colorimetric reagent for determination of zirconium

USGS Publications Warehouse

Grimaldi, F.S.; White, C.E.

1953-01-01

Methods described in the literature for the determination of zirconium are generally designed for relatively large amounts of this element. A good procedure using colorimetric reagent for the determination of trace amounts is desirable. Quercetin has been found to yield a sensitive color reaction with zirconium suitable for the determination of from 0.1 to 50?? of zirconium dioxide. The procedure developed involves the separation of zirconium from interfering elements by precipitation with p-dimethylaminoazophenylarsonic acid prior to its estimation with quercetin. The quercetin reaction is carried out in 0.5N hydrochloric acid solution. Under the operating conditions it is indicated that quercetin forms a 2 to 1 complex with zirconium; however, a 2 to 1 and a 1 to 1 complex can coexist under special conditions. Approximate values for the equilibrium constants of the complexes are K1 = 0.33 ?? 10-5 and K2 = 1.3 ?? 10-9. Seven Bureau of Standards samples of glass sands and refractories were analyzed with excellent results. The method described should find considerable application in the analysis of minerals and other materials for macro as well as micro amounts of zirconium.

Metabolomics Reveals that Dietary Ferulic Acid and Quercetin Modulate Metabolic Homeostasis in Rats.

PubMed

Zhang, Limin; Dong, Manyuan; Guangyong Xu; Yuan Tian; Tang, Huiru; Wang, Yulan

2018-02-21

Phenolic compounds ingestion has been shown to have potential preventive and therapeutic effects against various metabolic diseases such as obesity and cancer. To provide a better understanding of these potential benefit effects, we investigated the metabolic alterations in urine and feces of rat ingested ferulic acid (FA) and quercetin (Qu) using NMR-based metabolomics approach. Our results suggested that dietary FA and/or Qu significantly decreased short chain fatty acids and elevated oligosaccharides in the feces, implying that dietary FA and Qu may modulate gut microbial community with inhibition of bacterial fermentation of dietary fibers. We also found that dietary FA and/or Qu regulated several host metabolic pathways including TCA cycle and energy metabolism, bile acid, amino acid, and nucleic acid metabolism. These biological effects suggest that FA and Qu display outstanding bioavailability and bioactivity and could be used for treatment of some metabolic syndromes, such as inflammatory bowel diseases and obesity.

Biomedical applications of SPION@APTES@PEG-folic acid@carboxylated quercetin nanodrug on various cancer cells

NASA Astrophysics Data System (ADS)

Akal, Z. Ü.; Alpsoy, L.; Baykal, A.

2016-08-01

In this study, carboxylated quercetin (CQ) was conjugated to superparamagnetic iron oxide nanoparticles (SPIONs) which were modified by (3-aminopropyl) triethoxysilane (APTES), Folic acid (FA) and carboxylated Polyethylene glycol (PEG); (SPION@APTES@FA-PEG@CQ), nanodrug has been synthesized via polyol and accompanying by various chemical synthesis routes. The characterization of the final product was done via X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Thermal gravimetric analysis (TGA), Transmission electron spectroscopy (TEM) and Vibrating sample magnetometer (VSM). Its cytotoxic and apoptotic activities on over expressed folic acid receptor (FR +) (MCF-7, HeLa) and none expressed folic acid receptor (FR-) (A549) cancer cell lines were determined by using MTT assay, Real-Time Cell Analysis, TUNEL assay, Annexin assay and RT-PCR analysis for Caspase3/7 respectively. SPION@APTES@FA-PEG@CQ nanodrug showed higher cytotoxicity against HeLa and MCF-7 cell lines as compared with A549 cell line. Moreover, SPION@APTES@FA-PEG@CQ nanodrug also caused higher apoptotic and necrotic effects in 100 μg/mL HeLa and MCF-7 cells than A549 cells. The findings showed that SPION@APTES@FA-PEG@CQ nanodrug has cytotoxic, apoptotic and necrotic effects on HeLa and MCF-7 which are FR over expressed cell lines and can be potentially used for the delivery of quercetin to cervical and breast cancer cells.

Quercetin inhibits hexose transport in a human diploid fibroblast

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

Salter, D.W.; Custead-Jones, S.; Cook, J.S.

1978-01-01

The flavonol quercetin, a phloretin analog, inhibits transport of 2-deoxyglucose and 3-O-methylglucose in a cultured human diploid fibroblast. This inhibition is related to transport itself and not to the reported effects of flavonoids on membrane-bound ATPases. From concentration-inhibition curves at several pH's we conclude that uncharged (acid) quercetin (pH = 7.65) is the inhibitory form of the molecule (K/sub I/ = 10 ..mu..m). Quercetin, unlike phloretin, is rapidly degraded in 0.1 N NaOH; the degradation products are weakly inhibitory to hexose transport.

Biomimetic growth of gallic acid-ZnO hybrid assemblies and their applications

NASA Astrophysics Data System (ADS)

Sarker, Nazmul H.; Barnaby, Stacey N.; Fath, Karl R.; Frayne, Stephen H.; Nakatsuka, Nako; Banerjee, Ipsita A.

2012-03-01

In this study, we probed the biomimetic formation of gallic acid (GA)-ZnO nanoparticle hybrids. It was found that the morphologies formed were dependent upon pH values, resulting in GA-ZnO hybrids of varying shapes such as micro or nanoplates or fibers. The formed supramolecular GA-ZnO hybrids were found to be luminescent as indicated by confocal microscopy and were utilized for the photocatalytic degradation of the organic dye methylene blue. We also explored the bactericidal effects of the hybrids on Staphylococcus aureus ( S. aureus) as well as Escherichia Coli ( E. Coli). Thus, we have developed a new class of shape-controlled nanohybrid assemblies via mild, green synthetic methods that may be utilized for photocatalytic degradation for environmental remediation as well as for antibacterial applications.

Phytic acid enhances the oral absorption of isorhamnetin, quercetin, and kaempferol in total flavones of Hippophae rhamnoides L.

PubMed

Xie, Yan; Luo, Huilin; Duan, Jingze; Hong, Chao; Ma, Ping; Li, Guowen; Zhang, Tong; Wu, Tao; Ji, Guang

2014-03-01

Total flavones of Hippophae rhamnoides L. (TFH) have a clinical use in the treatment of cardiac disease. The pharmacological effects of TFH are attributed to its major flavonoid components, isorhamnetin, kaempferol, and quercetin. However, poor oral bioavailability of these flavonoids limits the clinical applications of TFH. This study explores phytic acid (IP6) enhancement of the oral absorption in rats of isorhamnetin, kaempferol, and quercetin in TFH. In vitro Caco-2 cell experiments and in vivo pharmacokinetic studies were performed to investigate the effects of IP6. The aqueous solubility and lipophilicity of isorhamnetin, quercetin, and kaempferol were determined with and without IP6, and mucosal epithelial damage resulting from IP6 addition was evaluated by MTT assays and morphology observations. The Papp of isorhamnetin, kaempferol, and quercetin was improved 2.03-, 1.69-, and 2.11-fold in the presence of 333 μg/mL of IP6, respectively. Water solubility was increased 22.75-, 15.15-, and 12.86-fold for isorhamnetin, kaempferol, and quercetin, respectively, in the presence of 20mg/mL IP6. The lipophilicity of the three flavonoids was slightly decreased, but their hydrophilicity was increased after the addition of IP6 in the water phase as the logP values of isorhamnetin, kaempferol, and quercetin decreased from 2.38±0.12 to 1.64±0.02, from 2.57±0.20 to 2.01±0.04, and from 2.39±0.12 to 1.15±0.01, respectively. The absorption enhancement ratios were 3.21 for isorhamnetin, 2.98 for kaempferol, and 1.64 for quercetin with co-administration of IP6 (200 mg/kg) in rats. In addition, IP6 (200 mg/kg, oral) caused neither significant irritation to the rat intestines nor cytotoxicity (400 μg/mL) in Caco-2 cells. The oral bioavailability of isorhamnetin, kaempferol, and quercetin in TFH was enhanced by the co-administration of IP6. The main mechanisms are related to their enhanced aqueous solubility and permeability in the presence of IP6. In summary, IP6 is a

Novel approach for extraction of quercetin using molecular imprinted membranes

NASA Astrophysics Data System (ADS)

Kamarudin, Siti Fatimah; Ahmad, Mohd Noor; Dzahir, Irfan Hatim Mohamed; Nasir, Azalina Mohamed; Ishak, Noorhidayah; Halim, Nurul Farhanah

2017-12-01

Quercetin imprinted membrane (QIM) was synthesized and applied for the extraction of quercetin. The quercetin imprinted membranes (QIM) were fabricated through a non-covalent approach via surface thermal polymerization. Polyvinylidene fluoride (PVDF) microfiltration membrane was used as a support to improve mechanical stability of the membrane. The thin imprinted layer was formed by copolymerization of acrylamide (AA) as functional monomer and ethylene glycol dimethacrylate (EGDMA) as crosslinker in the presence of quercetin as template in tetrahydrofuran (THF) solution. The Atomic Force Microscopy (AFM) and Field Emission Scanning Electron Microscope (FESEM) were used to visualize the surface of membrane. Batch rebinding and binding kinetic experiments proved that the binding properties of the QIM are higher than non-imprinted membranes (NIM). QIM also have higher selectivity towards quercetin compared to sinensetin and rosmarinic acid.

Characterization of cyanidin- and quercetin-derived flavonoids and other phenolics in mature saskatoon fruits (Amelanchier alnifolia Nutt.).

PubMed

Ozga, Jocelyn A; Saeed, Asma; Wismer, Wendy; Reinecke, Dennis M

2007-12-12

In order to further characterize the anthocyanins, flavonols, and other phenolics present in mature saskatoon ( Amelanchier alnifolia Nutt.) fruit, extracts were characterized using high-performance liquid chromatography, gas chromatography, and liquid chromatography-mass spectrometry. Cyanidin 3-O-galactoside, cyanidin 3-O-glucoside, cyanidin 3-O-arabinoside, and cyanidin 3-O-xyloside were identified as the four major anthocyanins in the mature fruit. The quercetin-derived flavonols, quercetin 3-O-glucoside, quercetin 3-O-galactoside, quercetin 3-O-arabinoside, quercetin 3-O-xyloside, quercetin 3-O-arabinoglucoside, quercetin 3-O-robinobioside, and quercetin 3-O-rutinoside were also identified in mature fruit extracts. In addition, two chlorogenic acid isomers (hydroxycinnamates), 3-O-caffeoylquinic acid and 5-O-caffeoylquinic acid were detected. The total content of the anthocyanin-, flavonol-, and hydroxycinnamate-type phenolics detected in mature 'Smoky' saskatoon fruit was 140, 25, and 96 mg/100 g fresh weight, respectively. These data further our knowledge of the phenolic composition of mature saskatoon fruit, and as anthocyanins, flavonols, and hydroxycinnamates exhibit antioxidant activities, the presence and levels of these classes of phenolics will aid in the understanding of the potential health-beneficial effects of saskatoon fruits in the human diet.

Intestinal Permeability and Cellular Antioxidant Activity of Phenolic Compounds from Mango (Mangifera indica cv. Ataulfo) Peels

PubMed Central

Pacheco-Ordaz, Ramón; González-Aguilar, Gustavo A.

2018-01-01

Mango (Mangifera indica cv. Ataulfo) peel contains bound phenolics that may be released by alkaline or acid hydrolysis and may be converted into less complex molecules. Free phenolics from mango cv. Ataulfo peel were obtained using a methanolic extraction, and their cellular antioxidant activity (CAA) and permeability were compared to those obtained for bound phenolics released by alkaline or acid hydrolysis. Gallic acid was found as a simple phenolic acid after alkaline hydrolysis along with mangiferin isomers and quercetin as aglycone and glycosides. Only gallic acid, ethyl gallate, mangiferin, and quercetin were identified in the acid fraction. The acid and alkaline fractions showed the highest CAA (60.5% and 51.5%) when tested at 125 µg/mL. The value of the apparent permeability coefficient (Papp) across the Caco-2/HT-29 monolayer of gallic acid from the alkaline fraction was higher (2.61 × 10−6 cm/s) than in the other fractions and similar to that obtained when tested pure (2.48 × 10−6 cm/s). In conclusion, mango peels contain bound phenolic compounds that, after their release, have permeability similar to pure compounds and exert an important CAA. This finding can be applied in the development of nutraceuticals using this important by-product from the mango processing industry. PMID:29419800

Simultaneous Determination of Gallic Acid, Ellagic Acid, and Eugenol in Syzygium aromaticum and Verification of Chemical Antagonistic Effect by the Combination with Curcuma aromatica Using Regression Analysis

PubMed Central

Seo, Chang-Seob; Kim, Seong-Sil; Ha, Hyekyung

2013-01-01

This study was designed to perform simultaneous determination of three reference compounds in Syzygium aromaticum (SA), gallic acid, ellagic acid, and eugenol, and to investigate the chemical antagonistic effect when combining Curcuma aromatica (CA) with SA, based on chromatographic analysis. The values of LODs and LOQs were 0.01–0.11 μg/mL and 0.03–0.36 μg/mL, respectively. The intraday and interday precisions were <3.0 of RSD values, and the recovery was in the range of 92.19–103.24%, with RSD values <3.0%. Repeatability and stability were 0.38–0.73% and 0.49–2.24%, respectively. Compared with the content of reference and relative peaks in SA and SA combined with CA (SAC), the amounts of gallic acid and eugenol were increased, while that of ellagic acid was decreased in SAC (compared with SA), and most of peak areas in SA were reduced in SAC. Regression analysis of the relative peak areas between SA and SAC showed r 2 values >0.87, indicating a linear relationship between SA and SAC. These results demonstrate that the components contained in CA could affect the extraction of components of SA mainly in a decreasing manner. The antagonistic effect of CA on SA was verified by chemical analysis. PMID:23878761

Gallic acid attenuates high-fat diet fed-streptozotocin-induced insulin resistance via partial agonism of PPARγ in experimental type 2 diabetic rats and enhances glucose uptake through translocation and activation of GLUT4 in PI3K/p-Akt signaling pathway.

PubMed

Gandhi, Gopalsamy Rajiv; Jothi, Gnanasekaran; Antony, Poovathumkal James; Balakrishna, Kedike; Paulraj, Michael Gabriel; Ignacimuthu, Savarimuthu; Stalin, Antony; Al-Dhabi, Naif Abdullah

2014-12-15

In this study, the therapeutic efficacy of gallic acid from Cyamopsis tetragonoloba (L.) Taub. (Fabaceae) beans was examined against high-fat diet fed-streptozotocin-induced experimental type 2 diabetic rats. Molecular-dockings were done to determine the putative binding modes of gallic acid into the active sites of key insulin-signaling markers. Gallic acid (20 mg/kg) given to high-fat diet fed-streptozotocin-induced rats lowered body weight gain, fasting blood glucose and plasma insulin in diabetic rats. It further restored the alterations of biochemical parameters to near normal levels in diabetic treated rats along with cytoprotective action on pancreatic β-cell. Histology of liver and adipose tissues supported the biochemical findings. Gallic acid significantly enhanced the level of peroxisome proliferator-activated receptor γ (PPARγ) expression in the adipose tissue of treated rat compared to untreated diabetic rat; it also slightly activated PPARγ expressions in the liver and skeletal muscle. Consequently, it improved insulin-dependent glucose transport in adipose tissue through translocation and activation of glucose transporter protein 4 (GLUT4) in phosphatidylinositol 3-kinase (PI3K)/phosphorylated protein kinase B (p-Akt) dependent pathway. Gallic acid docked with PPARγ; it exhibited promising interactions with the GLUT4, glucose transporter protein 1 (GLUT1), PI3K and p-Akt. These findings provided evidence to show that gallic acid could improve adipose tissue insulin sensitivity, modulate adipogenesis, increase adipose glucose uptake and protect β-cells from impairment. Hence it can be used in the management of obesity-associated type 2 diabetes mellitus. Copyright © 2014 Elsevier B.V. All rights reserved.

Antibacterial Potential of Northeastern Portugal Wild Plant Extracts and Respective Phenolic Compounds

PubMed Central

Ferreira, Isabel C. F. R.; Barros, Lillian; Carvalho, Ana Maria; Soares, Graça; Henriques, Mariana

2014-01-01

The present work aims to assess the antibacterial potential of phenolic extracts, recovered from plants obtained on the North East of Portugal, and of their phenolic compounds (ellagic, caffeic, and gallic acids, quercetin, kaempferol, and rutin), against bacteria commonly found on skin infections. The disk diffusion and the susceptibility assays were used to identify the most active extracts and phenolic compounds. The effect of selected phenolic compounds on animal cells was assessed by determination of cellular metabolic activity. Gallic acid had a higher activity, against gram-positive (S. epidermidis and S. aureus) and gram-negative bacteria (K. pneumoniae) at lower concentrations, than the other compounds. The caffeic acid, also, showed good antibacterial activity against the 3 bacteria used. The gallic acid was effective against the 3 bacteria without causing harm to the animal cells. Gallic and caffeic acid showed a promising applicability as antibacterial agents for the treatment of infected wounds. PMID:24804249

Quercetin, a Natural Flavonoid Interacts with DNA, Arrests Cell Cycle and Causes Tumor Regression by Activating Mitochondrial Pathway of Apoptosis

PubMed Central

Srivastava, Shikha; Somasagara, Ranganatha R.; Hegde, Mahesh; Nishana, Mayilaadumveettil; Tadi, Satish Kumar; Srivastava, Mrinal; Choudhary, Bibha; Raghavan, Sathees C.

2016-01-01

Naturally occurring compounds are considered as attractive candidates for cancer treatment and prevention. Quercetin and ellagic acid are naturally occurring flavonoids abundantly seen in several fruits and vegetables. In the present study, we evaluate and compare antitumor efficacies of quercetin and ellagic acid in animal models and cancer cell lines in a comprehensive manner. We found that quercetin induced cytotoxicity in leukemic cells in a dose-dependent manner, while ellagic acid showed only limited toxicity. Besides leukemic cells, quercetin also induced cytotoxicity in breast cancer cells, however, its effect on normal cells was limited or none. Further, quercetin caused S phase arrest during cell cycle progression in tested cancer cells. Quercetin induced tumor regression in mice at a concentration 3-fold lower than ellagic acid. Importantly, administration of quercetin lead to ~5 fold increase in the life span in tumor bearing mice compared to that of untreated controls. Further, we found that quercetin interacts with DNA directly, and could be one of the mechanisms for inducing apoptosis in both, cancer cell lines and tumor tissues by activating the intrinsic pathway. Thus, our data suggests that quercetin can be further explored for its potential to be used in cancer therapeutics and combination therapy. PMID:27068577

Antioxidant and antimicrobial properties of phenolic rich fraction of Seabuckthorn (Hippophae rhamnoides L.) leaves in vitro.

PubMed

Yogendra Kumar, M S; Tirpude, R J; Maheshwari, D T; Bansal, Anju; Misra, Ksipra

2013-12-15

Phenolic rich fraction (PRF) from Seabuckthorn leaves was prepared by sequential fractionation. Total phenolic content of PRF estimated as gallic acid equivalent was found to be 319.33±7.02 mg/g of PRF. Its major constituents gallic acid, rutin, quercetin-3-galactoside, quercetin-3-glucoside, myricetin, quercetin, kaempferol and isorhamnetin, were found in the range of 1.551-196.89 mg/g of PRF as determined by RP-HPLC. Antioxidant activity of PRF evaluated using 2,2-diphenyl-2-picrylhydrazyl, superoxide and nitric oxide scavenging assays. Reducing power of PRF increased with increasing amount of PRF; the equation of reducing power (y) and amount of PRF (x) was y=8.004x (r(2)=0.99), indicating that reducing ability correlated well with amount of PRF. Antibacterial activity of PRF, tested against certain medically important bacterial species showed growth inhibiting effect against Escherichia coli, Salmonella typhi, Shigella dysenteriae, Streptococcus pneumoniae and Staphylococcus aureus. In conclusion, PRF has potent antioxidant and broad spectrum antibacterial properties. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effect of quercetin on apoptosis of PANC-1 cells.

PubMed

Lee, Joo Hyun; Lee, Han-Beom; Jung, Gum O; Oh, Jung Taek; Park, Dong Eun; Chae, Kwon Mook

2013-12-01

To investigate the chemotherapeutic effect of quercetin against cancer cells, signaling pathway of apoptosis was explored in human pancreatic cells. Various anticancer drugs including adriamycin, cisplatin, 5-fluorouracil (5-FU) and gemcitabine were used. Cell viability was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphe-nyltetra zolium bromide assay. Apoptosis was determined by 4'-6-diamidino-2-phenylindole nuclei staining and flow cytometry in PANC-1 cells treated with 50 µg/mL quercetin for 24 hours. Expression of endoplas mic reticulum (ER) stress mediators including, Grp78/Bip, p-PERK, PERK, ATF4, ATF6 and GADD153/CHOP proteins were measured by Western blot analysis. Mitochondrial membrane potential was measured by fluorescence staining with JC-1, rhodamine 123. Quercetin induced the apoptosis of PANC-1, which was characterized as nucleic acid and genomic DNA fragmentation, chromatin condensation, and sub-G0/G1 fraction of cell cycle increase. But not adriamycin, cisplatin, gemcitabine, and 5-FU. PANC-1 cells were markedly sensitive to quercetin. Treatment with quercetin resulted in the increased accumulation of intracellular Ca(2+) ion. Treatment with quercetin also increased the expression of Grp78/Bip and GADD153/CHOP protein and induced mitochondrial dysfunction. Quercetin exerted cytotoxicity against human pancreatic cancer cells via ER stress-mediated apoptotic signaling including reactive oxygen species production and mitochondrial dysfunction. These data suggest that quercetin may be an important modulator of chemosensitivity of cancer cells against anticancer chemotherapeutic agents.

Alterations in blood pressure, antioxidant status and caspase 8 expression in cobalt chloride-induced cardio-renal dysfunction are reversed by Ocimum gratissimum and gallic acid in Wistar rats.

PubMed

Akinrinde, A S; Oyagbemi, A A; Omobowale, T O; Asenuga, E R; Ajibade, T O

2016-07-01

The protective abilities of the chloroform extract of Ocimum gratissimum (COG) and gallic acid against cobalt chloride (CoCl2) - induced cardiac and renal toxicity were evaluated. Rats were exposed to CoCl2 (350ppm) for 7 days, either alone, or in combination with COG (100 and 200mg/kg) or gallic acid (120mg/kg). CoCl2 given alone, caused significant increases (p<0.05) in oxidative stress parameters (hydrogen peroxide, H2O2 and malondialdehyde, MDA) and increased expression of the apoptotic initiator caspase 8 in the heart and kidneys. There was significant reduction (p<0.05) in reduced glutathione (GSH) in cardiac and renal tissues; reduction in superoxide dismutase (SOD) activity in the kidneys and adaptive increases in Glutathione S-transferase (GST) and catalase (CAT). CoCl2 also produced significant reduction (p<0.05) in systolic (SBP), diastolic (DBP) and mean arterial (MAP) blood pressures. Oral COG and gallic acid treatment significantly reduced (p<0.05) the levels of H2O2 and MDA; with reduced expression of caspase 8 and restoration of GSH levels, GPx, SOD and CAT activities, howbeit, to varying degrees in the heart and kidneys. COG (200mg/kg) was most effective in restoring the blood pressures in the rats to near control levels. CoCl2-induced histopathological lesions including myocardial infarction and inflammation and renal tubular necrosis and inflammation were effectively ameliorated by the treatments administered. This study provides evidence for the protective roles of O. gratissimum and gallic acid by modulation of CoCl2-induced alterations in blood pressure, antioxidant status and pro-apoptotic caspase 8 in Wistar rats. Copyright © 2016 Elsevier GmbH. All rights reserved.

Evaluation of ozonation technique for pesticide residue removal and its effect on ascorbic acid, cyanidin-3-glucoside, and polyphenols in apple (Malus domesticus) fruits.

PubMed

Swami, Saurabh; Muzammil, Raunaq; Saha, Supradip; Shabeer, Ahammed; Oulkar, Dasharath; Banerjee, Kaushik; Singh, Shashi Bala

2016-05-01

Ozonated water dip technique was evaluated for the detoxification of six pesticides, i.e., chlorpyrifos, cypermethrin, azoxystrobin, hexaconazole, methyl parathion, and chlorothalonil from apple fruits. Results revealed that ozonation was better than washing alone. Ozonation for 15 min decreased residues of the test pesticides in the range of from 26.91 to 73.58%, while ozonation for 30 min could remove the pesticide residues by 39.39-95.14 % compared to 19.05-72.80 % by washing. Cypermethrin was the least removed pesticide by washing as well as by ozonation. Chlorothalonil, chlorpyrifos, and azoxystrobin were removed up to 71.45-95.14 % in a 30-min ozonation period. In case of methyl parathion removal, no extra advantage could be obtained by ozonation. The HPLC analysis indicated that ozonation also affected adversely the ascorbic acid and cyanidin-3-glucoside content of apples. However, 11 polyphenols studied showed a mixed trend. Gallic acid, 3,4-dihydroxybenzoic acid, catechin, epicatechin, p-coumaric acid, quercetin-3-O-glucoside, quercetin, and kaempferol were found to decrease while syringic acid, rutin, and resveratrol were found to increase in 30-min ozonation.

Preparation of starch nanoparticles loaded with quercetin using nanoprecipitation technique.

PubMed

Farrag, Yousof; Ide, Walther; Montero, Belén; Rico, Maite; Rodríguez-Llamazares, Saddys; Barral, Luis; Bouza, Rebeca

2018-07-15

Nanoparticles of starches from different botanical origin were prepared by nanoprecipitation using 0.1M hydrochloric acid as non-solvent. The morphology and the particle size were analyzed using field emission scanning electron microscopy and dynamic light scattering. The nanoparticles were spherical and their sizes vary depending on the origin and the concentration of the starch solution. Starch nanoparticles loaded with quercetin were prepared. In-vitro release studies of the quercetin from the starch nanoparticles were performed in 35% ethanol as a release medium. The starch origin affects the quercetin loading percentage, the release kinetics and the antioxidant activity of the produced nanoparticles. The starch-quercetin nanoparticles from cereal origin showed the lowest loading percentage and the lowest fraction released of quercetin in comparison with nanoparticles from tuber and legume origin. The release kinetics seem to be controlled mainly by Fickian diffusion which have been revealed fitting the release data to the Peppas-Sahlin model. Copyright © 2018 Elsevier B.V. All rights reserved.

Bacillus sphaericus: the highest bacterial tannase producer with potential for gallic acid synthesis.

PubMed

Raghuwanshi, Shailendra; Dutt, Kakoli; Gupta, Pritesh; Misra, Swati; Saxena, Rajendra Kumar

2011-06-01

An indigenously isolated strain of Bacillus sphaericus was found to produce 1.21 IU/ml of tannase under unoptimized conditions. Optimizing the process one variable at a time resulted in the production of 7.6 IU/ml of tannase in 48 h in the presence of 1.5% tannic acid. A 9.26-fold increase in tannase production was achieved upon further optimization using response surface methodology (RSM), a statistical approach. This increase led to a production level of 11.2I U/ml in medium containing 2.0% tannic acid, 2.5% galactose, 0.25% ammonium chloride, and 0.1% MgSO(4) pH 6.0 incubated at 37°C and 100 rpm for 48 h with a 2.0% inoculum level. Scaling up tannase production in a 30-l bioreactor resulted in the production of 16.54 IU/ml after 36 h. Thus far, this tannase production is the highest reported in this bacterial strain. Partially purified tannase exhibited an optimum pH of 5.0 with activity in the pH range of 3 to 8; 50°C was the optimal temperature for activity. Efficient conversion of tannic acid to purified gallic acid (90.80%) was achieved through crystallization. Copyright © 2011 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Radiation induced chemical changes of phenolic compounds in strawberries

NASA Astrophysics Data System (ADS)

Breitfellner, F.; Solar, S.; Sontag, G.

2003-06-01

In unirradiated strawberries four phenolic acids (gallic acid, p-coumaric acid, caffeic acid and 4-hydroxybenzoic acid), the flavonoids (+)-catechin, (-)-epicatechin and glycosides from kaempferol and quercetin were determined by reversed phase chromatography with diode array detection. Characteristic linear dose/concentration relationships were found for 4-hydroxybenzoic acid and two unidentified compounds. One of them may be usable as marker to prove an irradiation treatment.

A phytochemical study of the Cuphea glutinosa from Southern Brazil: Na+,K+-ATPase activity inhibition and antioxidant properties.

PubMed

Zago, Adriana M; Carvalho, Fabiano B; Gutierres, Jessié Martins; Bohnert, Crystiani; Fernandes, Marilda da Cruz; Morandini, Liziane M; Coelho, Helena S; Fogaça, Aline O; Andrade, Cinthia M; Mostardeiro, Marco A; Dalcol, Ionara I; Morel, Ademir F

2018-05-21

This study investigated the antioxidant activity of Cuphea glutinosa (CG) and its effect on Na + , K + -ATPase from cardiac muscle. The ethanolic extract showed higher antioxidant capacity compared to aqueous and ethyl acetate fraction. Ethyl acetate fraction showed β-sitosterol-3-O-β-glucoside, kaempferol, quercetin, isoquercetin, gallic acid methyl ester, and gallic acid. The ethanolic extract also reduced the Na + ,K + -ATPase activity. CG presented a promising antioxidant activity and inhibitory effect on the Na + , K + -ATPase activity, supporting biochemical evidences the popular use of this plant in the treatment of heart failure.

A cellular uptake and cytotoxicity properties study of gallic acid-loaded mesoporous silica nanoparticles on Caco-2 cells

NASA Astrophysics Data System (ADS)

Rashidi, Ladan; Vasheghani-Farahani, Ebrahim; Soleimani, Masoud; Atashi, Amir; Rostami, Khosrow; Gangi, Fariba; Fallahpour, Masoud; Tahouri, Mohammad Taher

2014-03-01

In this study, the effects of intracellular delivery of various concentrations of gallic acid (GA) as a semistable antioxidant, gallic acid-loaded mesoporous silica nanoparticles (MSNs-GA), and cellular uptake of nanoparticles into Caco-2 cells were investigated. MSNs were synthesized and loaded with GA, then characterized using transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, N2 adsorption isotherms, X-ray diffraction, and thermal gravimetric analysis. The cytotoxicity of MSNs and MSNs-GA at low and high concentrations were studied by means of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) test and flow cytometry. MSNs did not show significant toxicity in various concentrations (0-500 μg/ml) on Caco-2 cells. For MSNs-GA, cell viability was reduced as a function of incubation time and different concentrations of nanoparticles. The in vitro GA release from MSNs-GA exhibited the same antitumor properties as free GA on Caco-2 cells. Flow cytometry results confirmed those obtained using MTT assay. TEM and fluorescent microscopy confirmed the internalization of MSNs by Caco-2 cells through nonspecific cellular uptake. MSNs can easily internalize into Caco-2 cells without deleterious effects on cell viability. The cell viability of Caco-2 cells was affected during MSNs-GA uptake. MSNs could be designed as suitable nanocarriers for antioxidants delivery.

Effects of quercetin and quercetin 3-glucuronide on the expression of bone sialoprotein gene.

PubMed

Kim, Dong-Soon; Takai, Hideki; Arai, Masato; Araki, Shouta; Mezawa, Masaru; Kawai, Yoshichika; Murota, Kaeko; Terao, Junji; Ogata, Yorimasa

2007-06-01

Quercetin is a typical flavonol-type flavonoid and is present in a variety of vegetables, and their antioxidant effect implies their possible role in the prevention of oxidative stress related chronic diseases. Bone sialoprotein (BSP) is a noncollagenous protein of the extracellular matrix in the mineralized connective tissues that has been implicated in the nucleation of hydroxyapatite crystals. Previously, we reported that isoflavone (genistein) activated BSP gene transcription is mediated through an inverted CCAAT box in the proximal BSP gene promoter. The present study investigates the regulation of BSP transcription in a rat osteoblast-like cell line, ROS 17/2.8 cells, by quercetin and its conjugated metabolite quercetin 3-glucuronide. Quercetin and quercetin 3-glucuronide (5 microM) increased the BSP mRNA levels at 12 h and quercetin upregulated the Cbfa1/Runx2 mRNA expression at 12 h. From transient transfection assays using various sized BSP promoter-luciferase constructs, quercetin increased the luciferase activity of the construct (pLUC3), including the promoter sequence nucleotides -116 to -43. Transcriptional stimulations by quercetin were almost completely abrogated in the constructs that included 2 bp mutations in the inverted CCAAT and FRE elements whereas the CCAAT-protein complex did not change after stimulation by quercetin according to gel shift assays. Quercetin increased the nuclear protein binding to the FRE and 3'-FRE. These data suggest that quercetin and quercetin 3-glucuronide increased the BSP mRNA expression, and that the inverted CCAAT and FRE elements in the promoter of the BSP gene are required for quercetin induced BSP transcription.

Effect of quercetin on apoptosis of PANC-1 cells

PubMed Central

Lee, Joo Hyun; Lee, Han-Beom; Jung, Gum O; Oh, Jung Taek; Park, Dong Eun

2013-01-01

Purpose To investigate the chemotherapeutic effect of quercetin against cancer cells, signaling pathway of apoptosis was explored in human pancreatic cells. Methods Various anticancer drugs including adriamycin, cisplatin, 5-fluorouracil (5-FU) and gemcitabine were used. Cell viability was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphe-nyltetra zolium bromide assay. Apoptosis was determined by 4'-6-diamidino-2-phenylindole nuclei staining and flow cytometry in PANC-1 cells treated with 50 µg/mL quercetin for 24 hours. Expression of endoplas mic reticulum (ER) stress mediators including, Grp78/Bip, p-PERK, PERK, ATF4, ATF6 and GADD153/CHOP proteins were measured by Western blot analysis. Mitochondrial membrane potential was measured by fluorescence staining with JC-1, rhodamine 123. Quercetin induced the apoptosis of PANC-1, which was characterized as nucleic acid and genomic DNA fragmentation, chromatin condensation, and sub-G0/G1 fraction of cell cycle increase. But not adriamycin, cisplatin, gemcitabine, and 5-FU. PANC-1 cells were markedly sensitive to quercetin. Results Treatment with quercetin resulted in the increased accumulation of intracellular Ca2+ ion. Treatment with quercetin also increased the expression of Grp78/Bip and GADD153/CHOP protein and induced mitochondrial dysfunction. Quercetin exerted cytotoxicity against human pancreatic cancer cells via ER stress-mediated apoptotic signaling including reactive oxygen species production and mitochondrial dysfunction. Conclusion These data suggest that quercetin may be an important modulator of chemosensitivity of cancer cells against anticancer chemotherapeutic agents. PMID:24368982

Antimicrobial and enhancement of the antibiotic activity by phenolic compounds: Gallic acid, caffeic acid and pyrogallol.

PubMed

Lima, Valéria N; Oliveira-Tintino, Cícera D M; Santos, Enaide S; Morais, Luís P; Tintino, Saulo R; Freitas, Thiago S; Geraldo, Yuri S; Pereira, Raimundo L S; Cruz, Rafael P; Menezes, Irwin R A; Coutinho, Henrique D M

2016-10-01

The indiscriminate use of antimicrobial drugs has increased the spectrum of exposure of these organisms. In our studies, these phenolic compounds were evaluated: gallic acid, caffeic acid and pyrogallol. The antibacterial, antifungal and modulatory of antibiotic activities of these compounds were assayed using microdilution method of Minimum Inhibitory Concentration (MIC) to bacteria and Minimum Fungicide Concentration (MFC) to fungi. The modulation was made by comparisons of the MIC and MFC of the compounds alone and combined with drugs against bacteria and fungi respectively, using a sub-inhibitory concentration of 128 μg/mL of substances (MIC/8). All substances not demonstrated clinically relevant antibacterial activity with a MIC above ≥1024 μg/mL. As a result, we observed that the caffeic acid presented a potentiating antibacterial effect over the 3 groups of bacteria studied. Pyrogallol showed a synergistic effect with two of the antibiotics tested, but only against Staphylococcus aureus. In general, caffeic acid was the substance that presented with the greatest number of antibiotics and with the greatest number of bacteria. In relation to the antifungal activity of all the compounds, the verified results were ≥1024 μg/mL, not demonstrating significant activity. Regarding potentiation of the effect of fluconazole, was observed synergistic effect only when assayed against Candida tropicalis, with all substances. Therefore, as can be seen, the compounds presented as substances that can be promising potentiating agents of antimicrobial drugs, even though they do not have direct antibacterial and antifungal action. Copyright © 2016 Elsevier Ltd. All rights reserved.

Intracellular ROS protection efficiency and free radical-scavenging activity of quercetin and quercetin-encapsulated liposomes.

PubMed

Rezaei-Sadabady, Rogaie; Eidi, Akram; Zarghami, Nosratollah; Barzegar, Abolfazl

2016-01-01

Quercetin (3,5,7,3',4'-pentahydroxyflavone) is a natural bio-flavonoid originating from fruits, vegetables, seeds, berries, and tea. The antioxidant activity of quercetin and its protective effects against cardiovascular disorders, anti-cancer, anti-inflammatory, and anti-viral activities have been extensively documented; however, the clinical request of quercetin in cancer treatment is significantly limited due to its very poor delivery features. In order to increase the hydrophilicity and drug delivery capability, we encapsulated quercetin into liposomes. Our data indicated that liposomal quercetin can significantly improve the solubility and bioavailability of quercetin and can be used as an effective antioxidant for ROS protection within the polar cytoplasm, and the nano-sized quercetin encapsulated by liposomes enhanced the cellular uptake (cancer cell human MCF_7). Quercetin has many pharmaceutical applications, many of which arise from its potent antioxidant properties. The present research examined the antioxidant activities of quercetin in polar solvents by a comparative study using reduction of ferric iron in aqueous medium, intracellular ROS/toxicity assays, and reducing DPPH assays. Cell viability and ROS assays demonstrated that quercetin was able to penetrate into the polar medium inside the cells and to protect them against the highly toxic and deadly belongings of cumene hydroperoxide. The purpose of this study was to determine whether a liposomal formulation of quercetin can suggestively improve its solubility and bioavailability and can be a possible request in the treatment of tumor. The authors encapsulated quercetin in a liposomal delivery system. They studied the in vitro effects of this compound on proliferation using human MCF-7 carcinoma cells. The activity of liposomal quercetin was equal to or better than that of free quercetin at equimolar concentrations. Our data indicated that liposomal quercetin can significantly improve the

Anti-tumour potential of a gallic acid-containing phenolic fraction from Oenothera biennis.

PubMed

Pellegrina, Chiara Dalla; Padovani, Giorgia; Mainente, Federica; Zoccatelli, Gianni; Bissoli, Gaetano; Mosconi, Silvia; Veneri, Gianluca; Peruffo, Angelo; Andrighetto, Giancarlo; Rizzi, Corrado; Chignola, Roberto

2005-08-08

A phenolic fraction purified form defatted seeds of Oenothera biennis promoted selective apoptosis of human and mouse bone marrow-derived cell lines following first-order kinetics through a caspase-dependent pathway. In non-leukemia tumour cell lines, such as human colon carcinoma CaCo(2) cells and mouse fibrosarcoma WEHI164 cells, this fraction inhibited (3)H-thymidine incorporation but not cell death or cell cycle arrest. Human peripheral blood mononuclear cells showed low sensitivity to treatment. Single bolus injection of the phenolic fraction could delay the growth of established myeloma tumours in syngeneic animals. HPLC and mass spectrometry analysis revealed that the fraction contains gallic acid. However, the biological activity of the fraction differs from the activity of this phenol and hence it should be attributed to other co-purified molecules which remain still unidentified.

Cocrystals of a 1,2,4-thiadiazole-based potent neuroprotector with gallic acid: solubility, thermodynamic stability relationships and formation pathways.

PubMed

Surov, Artem O; Churakov, Andrei V; Proshin, Alexey N; Dai, Xia-Lin; Lu, Tongbu; Perlovich, German L

2018-05-30

Three distinct solid forms, namely anhydrous cocrystals with 2 : 1 and 1 : 1 drug/acid ratios ([TDZ : GA] (2 : 1), [TDZ : GA] (1 : 1)), and a hydrated one having 1 : 1 : 1 drug/acid/water stoichiometry ([TDZ : GA : H2O] (1 : 1 : 1)), have been formed by cocrystallization of the biologically active 1,2,4-thiadiazole derivative (TDZ) with gallic acid (GA). The thermodynamic stability relationships between the cocrystals were rationalized in terms of Gibbs energies of the formation reactions and further verified by performing a set of competitive and exchange mechanochemical reactions. Interestingly, competitive grinding in the presence of the structurally related vanillic acid led to the formation of a new polymorphic form of the [TDZ : Vanillic acid] (1 : 1) cocrystal, which was promoted by gallic acid. The mechanochemical method was also applied to elucidate the alternative pathways of the [TDZ : GA : H2O] (1 : 1 : 1) cocrystal formation. Direct cocrystallization of TDZ with GA monohydrate was found to proceed much faster than the reaction of TDZ and anhydrous GA in the presence of an acetonitrile/water mixture, which may indicate the presence of a transitional stage. According to dissolution studies, the [TDZ : GA : H2O] (1 : 1 : 1) cocrystal was ca. 6.6 times more soluble than the parent 1,2,4-thiadiazole at pH 2.0 and 25.0 °C. The apparent two-step dehydration behavior of the [TDZ : GA : H2O] (1 : 1 : 1) cocrystal monohydrate was clarified by analyzing the intermolecular interactions of water molecules with the crystalline environment derived from solid state DFT calculations.

Effect of different exposed lights on quercetin and quercetin glucoside content in onion (Allium cepa L.)

PubMed Central

Ko, Eun Young; Nile, Shivraj Hariram; Sharma, Kavita; Li, Guan Hao; Park, Se Won

2014-01-01

Quercetin and quercetin glucosides are the major flavonols present in onion (Allium cepa L.) and are predominantly present as quercetin, quercetin-3,4′-diglucoside and quercetin-4′-glucoside. Effect of different light wavelengths on onion after harvest and storage, with fluorescent, blue, red and ultra violet light influenced the quercetin and quercetin glucosides profile. In a peeled onion, all the light treatments elevated quercetin content in bulb. Among them, particularly fluorescent light effect was more eminent which stimulates the maximum synthesis of quercetin in onion. In case of whole onion bulb, skin and pulp showed different responses to light treatment, respectively. The pulp had the highest quercetin glucosides under blue light, whereas the lowest under fluorescent light. Onion skin showed nearly opposite pattern as compared to the pulp. In particular, light treatment proved to be a better way to increase the level of quercetin content in onions which might be utilized for industrial production of bioactive compounds from onion and onion waste products. PMID:26150744

Effect of different exposed lights on quercetin and quercetin glucoside content in onion (Allium cepa L.).

PubMed

Ko, Eun Young; Nile, Shivraj Hariram; Sharma, Kavita; Li, Guan Hao; Park, Se Won

2015-07-01

Quercetin and quercetin glucosides are the major flavonols present in onion (Allium cepa L.) and are predominantly present as quercetin, quercetin-3,4'-diglucoside and quercetin-4'-glucoside. Effect of different light wavelengths on onion after harvest and storage, with fluorescent, blue, red and ultra violet light influenced the quercetin and quercetin glucosides profile. In a peeled onion, all the light treatments elevated quercetin content in bulb. Among them, particularly fluorescent light effect was more eminent which stimulates the maximum synthesis of quercetin in onion. In case of whole onion bulb, skin and pulp showed different responses to light treatment, respectively. The pulp had the highest quercetin glucosides under blue light, whereas the lowest under fluorescent light. Onion skin showed nearly opposite pattern as compared to the pulp. In particular, light treatment proved to be a better way to increase the level of quercetin content in onions which might be utilized for industrial production of bioactive compounds from onion and onion waste products.

Glucuronidated Quercetin Lowers Blood Pressure in Spontaneously Hypertensive Rats via Deconjugation

PubMed Central

Galindo, Pilar; Rodriguez-Gómez, Isabel; González-Manzano, Susana; Dueñas, Montserrat; Jiménez, Rosario; Menéndez, Carmen; Vargas, Félix; Tamargo, Juan; Santos-Buelga, Celestino; Pérez-Vizcaíno, Francisco; Duarte, Juan

2012-01-01

Background Chronic oral quercetin reduces blood pressure and restores endothelial dysfunction in hypertensive animals. However, quercetin (aglycone) is usually not present in plasma, because it is rapidly metabolized into conjugated, mostly inactive, metabolites. The aim of the study is to analyze whether deconjugation of these metabolites is involved in the blood pressure lowering effect of quercetin. Methodology/Principal Findings We have analyzed the effects on blood pressure and vascular function in vitro of the conjugated metabolites of quercetin (quercetin-3-glucuronide, Q3GA; isorhamnetin-3-glucuronide, I3GA; and quercetin-3′-sulfate, Q3'S) in spontaneously hypertensive rats (SHR). Q3GA and I3GA (1 mg/kg i.v.), but not Q3'S, progressively reduced mean blood pressure (MBP), measured in conscious SHR. The hypotensive effect of Q3GA was abolished in SHR treated with the specific inhibitor of β-glucuronidase, saccharic acid 1,4-lactone (SAL, 10 mg/ml). In mesenteric arteries, unlike quercetin, Q3GA had no inhibitory effect in the contractile response to phenylephrine after 30 min of incubation. However, after 1 hour of incubation Q3GA strongly reduced this contractile response and this effect was prevented by SAL. Oral administration of quercetin (10 mg/Kg) induced a progressive decrease in MBP, which was also suppressed by SAL. Conclusions Conjugated metabolites are involved in the in vivo antihypertensive effect of quercetin, acting as molecules for the plasmatic transport of quercetin to the target tissues. Quercetin released from its glucuronidated metabolites could be responsible for its vasorelaxant and hypotensive effect. PMID:22427863

Functional Characterization of Epitheaflagallin 3-O-Gallate Generated in Laccase-Treated Green Tea Extracts in the Presence of Gallic Acid.

PubMed

Itoh, Nobuya; Kurokawa, Junji; Isogai, Yasuhiro; Ogasawara, Masaru; Matsunaga, Takayuki; Okubo, Tsutomu; Katsube, Yuji

2017-12-06

Epitheaflagallin (ETFG) and epitheaflagallin 3-O-gallate (ETFGg) are minor polyphenols in black tea extract that are enzymatically synthesized from epigallocatechin (EGC) and epigallocatechin gallate (EGCg), respectively, in green tea extract via laccase oxidation in the presence of gallic acid. The constituents of laccase-treated green tea extract in the presence of gallic acid are thus quite different from those of nonlaccase-treated green tea extract: EGC and EGCg are present in lower concentrations, and ETFG and ETFGg are present in higher concentrations. Additionally, laccase-treated green tea extract contains further polymerized catechin derivatives, comparable with naturally fermented teas such as oolong tea and black tea. We found that ETFGg and laccase-treated green tea extracts exhibit versatile physiological functions in vivo and in vitro, including antioxidative activity, pancreatic lipase inhibition, Streptococcus sorbinus glycosyltransferase inhibition, and an inhibiting effect on the activity of matrix metalloprotease-1 and -3 and their synthesis by human gingival fibroblasts. We confirmed that these inhibitory effects of ETFGg in vitro match well with the results obtained by docking simulations of the compounds with their target enzymes or noncatalytic protein. Thus, ETFGg and laccase-treated green tea extracts containing ETFGg are promising functional food materials with potential antiobesity and antiperiodontal disease activities.

Quercetin, Inflammation and Immunity

PubMed Central

Li, Yao; Yao, Jiaying; Han, Chunyan; Yang, Jiaxin; Chaudhry, Maria Tabassum; Wang, Shengnan; Liu, Hongnan; Yin, Yulong

2016-01-01

In vitro and some animal models have shown that quercetin, a polyphenol derived from plants, has a wide range of biological actions including anti-carcinogenic, anti-inflammatory and antiviral activities; as well as attenuating lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the physicochemical properties, dietary sources, absorption, bioavailability and metabolism of quercetin, especially main effects of quercetin on inflammation and immune function. According to the results obtained both in vitro and in vivo, good perspectives have been opened for quercetin. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of quercetin on inflammation and immunity. PMID:26999194

Flexible graphene/carbon nanotube hybrid papers chemical-reduction-tailored by gallic acid for high-performance electrochemical capacitive energy storages

NASA Astrophysics Data System (ADS)

Yao, Lu; Zhou, Chao; Hu, Nantao; Hu, Jing; Hong, Min; Zhang, Liying; Zhang, Yafei

2018-03-01

Mechanically robust graphene papers with both high gravimetric and volumetric capacitances are desired for high-performance energy storages. However, it's still a challenge to tailor the structure of graphene papers in order to meet this requirement. In this work, a kind of chemical-reduction-tailored mechanically-robust reduced graphene oxide/carbon nanotube hybrid paper has been reported for high-performance electrochemical capacitive energy storages. Gallic acid (GA), as an excellent reducing agent, was used to reduce graphene oxide. Through vacuum filtration of gallic acid reduced graphene oxide (GA-rGO) and carboxylic multiwalled carbon nanotubes (MWCNTs) aqueous suspensions, mechanically robust GA-rGO/MWCNTs hybrid papers were obtained. The resultant hybrid papers showed high gravimetric capacitance of 337.6 F g-1 (0.5 A g-1) and volumetric capacitance of 151.2 F cm-3 (0.25 A cm-3). In addition, the assembled symmetric device based on the hybrid papers exhibited high gravimetric capacitance of 291.6 F g-1 (0.5 A g-1) and volumetric capacitance of 136.6 F cm-3 (0.25 A cm-3). Meanwhile, it exhibited excellent rate capability and cycling stability. Above all, this chemical reduction tailoring technique and the resultant high-performance GA-rGO/MWCNTs hybrid papers give an insight for designing high-performance electrodes and hold a great potential in the field of energy storages.

Improved Quantification of Free and Ester-Bound Gallic Acid in Foods and Beverages by UHPLC-MS/MS.

PubMed

Newsome, Andrew G; Li, Yongchao; van Breemen, Richard B

2016-02-17

Hydrolyzable tannins are measured routinely during the characterization of food and beverage samples. Most methods for the determination of hydrolyzable tannins use hydrolysis or methanolysis to convert complex tannins to small molecules (gallic acid, methyl gallate, and ellagic acid) for quantification by HPLC-UV. Often unrecognized, analytical limitations and variability inherent in these approaches for the measurement of hydrolyzable tannins include the variable mass fraction (0-0.90) that is released as analyte, contributions of sources other than tannins to hydrolyzable gallate (can exceed >10 wt %/wt), the measurement of both free and total analyte, and lack of controls to account for degradation. An accurate, specific, sensitive, and higher-throughput approach for the determination of hydrolyzable gallate based on ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) that overcomes these limitations was developed.

The effects of biodegradable poly(lactic-co-glycolic acid)-based microspheres loaded with quercetin on stemness, viability and osteogenic differentiation potential of stem cell spheroids.

PubMed

Lee, H; Nguyen, T T; Kim, M; Jeong, J-H; Park, J-B

2018-05-31

Quercetin has been reported to exert many beneficial effects on the protection against various diseases, such as diabetes, cancer, and inflammation. The aim of this study is to evaluate the potential osteogenic differentiation ability of mesenchymal stem cells in the presence of quercetin. Quercetin-loaded poly(lactic-co-glycolic acid) microspheres were prepared using an electrospraying technique. Characterization of the microspheres was evaluated with a scanning electron microscope and release profile. Three-dimensional cell spheroids were fabricated using silicon elastomer-based concave microwells. Qualitative results of cellular viability were seen under a confocal microscope, and quantitative cellular viability was evaluated using the Cell Counting Kit-8 assay. The alkaline phosphatase activity and Alizarin Red S staining were performed. A quantitative real-time polymerase chain reaction and a western blot analysis were performed. Spheroids were well formed irrespective of quercetin concentration. Most of the cells in spheroids emitted green fluorescence, and the morphology was round without significant changes. The application of quercetin-loaded microspheres produced a significant increase in the alkaline phosphatase activity. The real-time polymerase chain reaction results showed a significant increase in Runx2, and western blot results showed higher expression of Runx2 protein expression. Biodegradable microspheres loaded with quercetin produced prolonged release profiles with increased mineralization. Microspheres loaded with quercetin can be used for the enhancement of osteoblastic differentiation in cell therapy. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of Parsley (Petroselinum crispum) and its Flavonol Constituents, Kaempferol and Quercetin, on Serum Uric Acid Levels, Biomarkers of Oxidative Stress and Liver Xanthine Oxidoreductase Aactivity inOxonate-Induced Hyperuricemic Rats.

PubMed

Haidari, Fatemeh; Keshavarz, Seid Ali; Mohammad Shahi, Majid; Mahboob, Soltan-Ali; Rashidi, Mohammad-Reza

2011-01-01

Increased serum uric acid is known to be a major risk related to the development of several oxidative stress diseases. The aim of this study was to investigate the effect of parsley, quercetin and kaempferol on serum uric acid levels, liver xanthine oxidoreductase activity and two non-invasive biomarkers of oxidative stress (total antioxidant capacity and malondialdehyde concentration) in normal and oxonate-induced hyperuricemic rats. A total of 60 male Wistar rats were randomly divided into ten equal groups; including 5 normal groups (vehicle, parsley, quercetin, kaempferol and allopurinol) and 5 hyperuricemic groups (vehicle, parsley, quercetin, kaempferol and allopurinol). Parsley (5 g/Kg), quercetin (5 mg/Kg), kaempferol (5 mg/Kg) and allopurinol (5 mg/Kg) were administrated to the corresponding groups by oral gavage once a day for 2 weeks. The results showed that parsley and its flavonol did not cause any significant reduction in the serum uric acid levels in normal rats, but significantly reduced the serum uric acid levels of hyperuricemic rats in a time-dependent manner. All treatments significantly inhibited liver xanthine oxidoreductase activity. Parsley, kaempferol and quercetin treatment led also to a significant increase in total antioxidant capacity and decrease in malondialdehyde concentration in hyperuricemic rats. Although the hypouricemic effect of allopurinol was much higher than that of parsley and its flavonol constituents, it could not significantly change oxidative stress biomarkers. These features of parsley and its flavonols make them as a possible alternative for allopurinol, or at least in combination therapy to minimize the side effects of allopurinol to treat hyperuricemia and oxidative stress diseases.

Effects of Parsley (Petroselinum crispum) and its Flavonol Constituents, Kaempferol and Quercetin, on Serum Uric Acid Levels, Biomarkers of Oxidative Stress and Liver Xanthine Oxidoreductase Aactivity inOxonate-Induced Hyperuricemic Rats

PubMed Central

Haidari, Fatemeh; Keshavarz, Seid Ali; Mohammad Shahi, Majid; Mahboob, Soltan-Ali; Rashidi, Mohammad-Reza

2011-01-01

Increased serum uric acid is known to be a major risk related to the development of several oxidative stress diseases. The aim of this study was to investigate the effect of parsley, quercetin and kaempferol on serum uric acid levels, liver xanthine oxidoreductase activity and two non-invasive biomarkers of oxidative stress (total antioxidant capacity and malondialdehyde concentration) in normal and oxonate-induced hyperuricemic rats. A total of 60 male Wistar rats were randomly divided into ten equal groups; including 5 normal groups (vehicle, parsley, quercetin, kaempferol and allopurinol) and 5 hyperuricemic groups (vehicle, parsley, quercetin, kaempferol and allopurinol). Parsley (5 g/Kg), quercetin (5 mg/Kg), kaempferol (5 mg/Kg) and allopurinol (5 mg/Kg) were administrated to the corresponding groups by oral gavage once a day for 2 weeks. The results showed that parsley and its flavonol did not cause any significant reduction in the serum uric acid levels in normal rats, but significantly reduced the serum uric acid levels of hyperuricemic rats in a time-dependent manner. All treatments significantly inhibited liver xanthine oxidoreductase activity. Parsley, kaempferol and quercetin treatment led also to a significant increase in total antioxidant capacity and decrease in malondialdehyde concentration in hyperuricemic rats. Although the hypouricemic effect of allopurinol was much higher than that of parsley and its flavonol constituents, it could not significantly change oxidative stress biomarkers. These features of parsley and its flavonols make them as a possible alternative for allopurinol, or at least in combination therapy to minimize the side effects of allopurinol to treat hyperuricemia and oxidative stress diseases. PMID:24250417

Molecular Targets Underlying the Anticancer Effects of Quercetin: An Update

PubMed Central

Khan, Fazlullah; Niaz, Kamal; Maqbool, Faheem; Ismail Hassan, Fatima; Abdollahi, Mohammad; Nagulapalli Venkata, Kalyan C.; Nabavi, Seyed Mohammad; Bishayee, Anupam

2016-01-01

Quercetin, a medicinally important member of the flavonoid family, is one of the most prominent dietary antioxidants. It is present in a variety of foods—including fruits, vegetables, tea, wine, as well as other dietary supplements—and is responsible for various health benefits. Numerous pharmacological effects of quercetin include protection against diseases, such as osteoporosis, certain forms of malignant tumors, and pulmonary and cardiovascular disorders. Quercetin has the special ability of scavenging highly reactive species, such as hydrogen peroxide, superoxide anion, and hydroxyl radicals. These oxygen radicals are called reactive oxygen species, which can cause oxidative damage to cellular components, such as proteins, lipids, and deoxyribonucleic acid. Various oxygen radicals play important roles in pathophysiological and degenerative processes, such as aging. Subsequently, several studies have been performed to evaluate possible advantageous health effects of quercetin and to collect scientific evidence for these beneficial health claims. These studies also gather data in order to evaluate the exact mechanism(s) of action and toxicological effects of quercetin. The purpose of this review is to present and critically analyze molecular pathways underlying the anticancer effects of quercetin. Current limitations and future directions of research on this bioactive dietary polyphenol are also critically discussed. PMID:27589790

Effect of quercitrin gallate on zymosan A-induced peroxynitrite production in macrophages.

PubMed

Kim, Byung Hak; Cho, Sung-Min; Chang, Yoon Sook; Han, Sang Bae; Kim, Youngsoo

2007-06-01

We previously isolated quercetin 3-O-beta-(2"-galloyl)-rhamnopyranoside (QGR), a quercitrin gallate, from aerial parts of Persicaria lapathifolia (Polygonaceae) to prevent superoxide produc tion in monocytes from venous blood of healthy human donors. In this study, effects of QGR and its building moieties (quercitrin, quercetin and gallic acid) on the production of peroxyni trite, a coupling oxidant between superoxide and nitric oxide (NO) radicals, were investigated in zymosan A-stimulated macrophages RAW 264.7. The QGR, quercitrin and quercetin inhib ited peroxynitrite production in dose-dependent manners with IC50 values of 2.1 microM, 24.5 microM and 5.1 microM, respectively, but gallic acid even at 100 microM was inactive. QGR also inhibited both zymosan A- and phorbol 12-myristate 13-acetate-induced superoxide productions with IC50 values of 3.2 microM and 4.7 microM, respectively. However, QGR affected neither zymosan A-induced NO production nor inducible NO synthase synthesis. Taken together, QGR could inhibit peroxynitrite production by blocking superoxide production without affecting NO production. Finally, this study could provide a pharmacological potential of QGR in the oxidative stress-implicated disorders.

Onion skin waste as a valorization resource for the by-products quercetin and biosugar.

PubMed

Choi, In Seong; Cho, Eun Jin; Moon, Jae-Hak; Bae, Hyeun-Jong

2015-12-01

Onion skin waste (OSW), which is produced from processed onions, is a major industrial waste. We evaluated the use of OSW for biosugar and quercetin production. The carbohydrate content of OSW was analyzed, and the optimal conversion conditions were evaluated by varying enzyme mixtures and loading volumes for biosugar production and quercetin extraction. The enzymatic conversion rate of OSW to biosugar was 98.5% at 0.72 mg of cellulase, 0.16 mg of pectinase, and 1.0mg of xylanase per gram of dry OSW. Quercetin extraction also increased by 1.61-fold after complete enzymatic hydrolysis. In addition, the newly developed nano-matrix (terpyridine-immobilized silica-coated magnetic nanoparticles-zinc (TSMNP-Zn matrix) was utilized to separate quercetin from OSW extracts. The nano-matrix facilitated easy separation and purification of quercetin. Using the TSMNP-Zn matrix the quercetin was approximately 90% absorbed. In addition, the recovery yield of quercetin was approximately 75% after treatment with ethylenediaminetetraacetic acid. Copyright © 2015 Elsevier Ltd. All rights reserved.

A computational investigation on the structure, global parameters and antioxidant capacity of a polyphenol, Gallic acid.

PubMed

Rajan, Vijisha K; Muraleedharan, K

2017-04-01

A computational DFT-B3LYP structural analysis of a poly phenol, Gallic acid (GA) has been performed by using 6-311++ G (df, p) basis set. The GA is a relatively stable molecule with considerable radical scavenging capacity. It is a well known antioxidant. The NBO analysis shows that the aromatic system is delocalized. The results reveal that the most stable radical is formed at O 3 -atom upon scavenging the free radicals. Global descriptive parameters show that GA acts as an acceptor center in charge transfer complex formation which is supported by ESP and contour diagrams and also by Q max value. The GA is a good antioxidant and it can be better understood by HAT and TMC mechanisms as it has low BDE, ΔH acidity and ΔG acidity values. The ΔBDE and ΔAIP values also confirm that the antioxidant capacity of GA can be explained through HAT rather than the SET-PT mechanism. Copyright © 2016 Elsevier Ltd. All rights reserved.

Skin delivery of antioxidant surfactants based on gallic acid and hydroxytyrosol.

PubMed

Alonso, Cristina; Lucas, Ricardo; Barba, Clara; Marti, Meritxell; Rubio, Laia; Comelles, Francesc; Morales, Juan Carlos; Coderch, Luisa; Parra, José Luís

2015-07-01

The aim of this study has been to investigate the dermal absorption profile of the antioxidant compounds gallic acid and hydroxytyrosol as well as their derivatives, hexanoate (hexyl gallate and hydroxytyrosol hexanoate) and octanoate (octyl gallate and octanoate derivative) alkyl esters (antioxidant surfactants). Previously, the scavenging capacity of these compounds, expressed as efficient dose ED50, has also determined. The percutaneous absorption of these compounds was obtained by an in vitro methodology using porcine skin biopsies on Franz static diffusion cells. The antiradical activity of compounds was determined using the 1,1-diphenyl-2-picrylhydrazyl free radical method. The percutaneous penetration results show the presence of antioxidants in all layers of the skin. The content of the cutaneously absorbed compound is higher for the antioxidant surfactants (ester derivatives). This particular behaviour could be due to the higher hydrophobicity of these compounds and the presence of surface activity in the antioxidant surfactants. These new antioxidant surfactants display optimum properties, which may be useful in the preparation of emulsified systems in cosmetic and pharmaceutical formulations because of their suitable surface activity and because they can protect the skin from oxidative damage. © 2015 Royal Pharmaceutical Society.

Analysis of Antibacterial Activity and Bioactive Compounds of the Giant Mushroom, Macrocybe gigantea (Agaricomycetes), from India.

PubMed

Gaur, Tanvi; Rao, P B

2017-01-01

The antibacterial activity, phenolic profile, and bioactive compounds of fruiting bodies from 2 strains (MA1 and MA2) of the giant mushroom Macrocybe gigantea were evaluated to access their nutraceutical efficacy. The antibacterial activity was higher in MA2 against all selected pathogenic bacteria. Selected phenolics were analyzed by high-performance liquid chromatography coupled with ultraviolet-visible detection. Gallic acid, ferulic acid, quercetin, p-hydroxy benzoic acid, cinnamic acid, and rutin contents (micrograms per gram dry weight) were quantified. Quercetin and rutin were absent in both strains of M. gigantea. M. gigantea MA2 showed relatively higher phenolic content (915.8 μg/g dry weight) than M. gigantea MA1 (854.4 μg/g dry weight). Among the phenolics, gallic acid is found in the largest amount; in M. gigantea MA2, it was 847.9 ± 2.67 μg/g dry weight. Gas chromatography-mass spectrometry analysis showed the presence of bioactive compounds in both strains; most compounds were antibacterial. Thus, the selected strains of M. gigantea can combat oxidative damage and can be used in foods, pharmaceuticals, and cosmetics because of their antioxidant potential.

Simulated Gastrointestinal Digestion, Bioaccessibility and Antioxidant Capacity of Polyphenols from Red Chiltepin (Capsicum annuum L. Var. glabriusculum) Grown in Northwest Mexico.

PubMed

Ovando-Martínez, Maribel; Gámez-Meza, Nohemí; Molina-Domínguez, Claudia Celeste; Hayano-Kanashiro, Corina; Medina-Juárez, Luis Angel

2018-06-01

Chiltepin, a wild chili mostly used in different traditional foods and traditional medicine in Northwest Mexico, represents a source of polyphenols. However, studies about the bioaccessibility of polyphenols as a parameter to measure the nutritional quality and bioefficacy of them in the fruit after consumption are scarce. Chiltepin showed phenolic acids and flavonoids contents between 387 and 65 μg/g, respectively. Nevertheless, these values decreased after the digestion process. Before digestion, gallic acid, 4-hydroxibenzoinc acid, chlorogenic acid, caffeic acid, p-coumaric acid, quercetin and luteolin were the main polyphenols found in chiltepin by HPLC-DAD and confirmed by FIA-ESI-IT-MS/MS. Gallic and chlorogenic acids were non-detected in the gastric phase, while only p-coumaric acid (5.35 ± 3.89 μg/g), quercetin (5.91 ± 0.92 μg/g) and luteolin (2.86 ± 0.62 μg/g) were found in the intestinal phase. The bioaccessibility of phenolic acids, flavonoids, and total polyphenols after the intestinal phase was around 24, 17 and 23%, respectively. Overall, results indicated that release of polyphenols from chiltepin fruit might be affected by the food matrix and gastrointestinal conditions due to the low bioaccessibility values observed.

Intermolecular interactions in aqueous solutions of gallic acid at 296-306 K according to spectrofluorimetry and densimetry data

NASA Astrophysics Data System (ADS)

Grigoryan, K. R.; Sargsyan, L. S.

2015-12-01

Features of intermolecular interactions in aqueous solutions of gallic acid (GA) are studied by means of densimetry and fluorescence spectroscopy (intrinsic fluorescence, 2D spectra, and excitation/ emission matrix fluorescence spectra, 3D) at 296.15, 301.15, and 306.15 K in the concentration range of 5.88 × 10-4-5.88 × 10-2 mol L-1. It is shown by analyzing the concentration and temperature dependences of the apparent molar volumes and fluorescence parameters of GA that the equilibrium between nonassociated and associated species in the solution and the hydration of these species undergo changes.

Lymphatic metabolites of quercetin after intestinal administration of quercetin-3-glucoside and its aglycone in rats.

PubMed

Nakamura, Toshiyuki; Kinjo, Chinatsu; Nakamura, Yoshimasa; Kato, Yoji; Nishikawa, Miyu; Hamada, Masahiro; Nakajima, Noriyuki; Ikushiro, Shinichi; Murota, Kaeko

2018-05-01

Quercetin is a major flavonoid, present as its glycosidic forms in plant foods. In this study, quercetin-3-glucoside (Q3G) was administered intraduodenally to thoracic lymph-cannulated rats, and its lymphatic transport was investigated. The resulting lymphatic and plasma metabolites were identified with LC-MS/MS and compared with those after administration of quercetin aglycone. The total concentration of quercetin metabolites in the lymph was about four times lower than that in the plasma, and quercetin and its methylated form isorhamnetin were detected as their glucuronides, sulfates and diglucuronides both in the lymph and the plasma after Q3G and quercetin administrations. The lymph levels of the glucuronides after Q3G administration were lower than those after quercetin administration, whereas those in the plasma showed the opposite pattern. Both the lymph and plasma levels of the sulfates after Q3G administration were lower than those after quercetin administration. Some of the intestinal metabolites like quercetin monoglucuronides were transported directly into the lymph and the hepatic metabolites like the diglucuronides were eventually transferred from the plasma into the lymph. These results indicate that the absorbed Q3G is partly transported into the intestinal lymph as quercetin metabolites. Deglycosylation in the enterocyte is also suggested to affect the subsequent metabolic pathways. Copyright © 2018 Elsevier Inc. All rights reserved.

Prediction of oxidation parameters of purified Kilka fish oil including gallic acid and methyl gallate by adaptive neuro-fuzzy inference system (ANFIS) and artificial neural network.

PubMed

Asnaashari, Maryam; Farhoosh, Reza; Farahmandfar, Reza

2016-10-01

As a result of concerns regarding possible health hazards of synthetic antioxidants, gallic acid and methyl gallate may be introduced as natural antioxidants to improve oxidative stability of marine oil. Since conventional modelling could not predict the oxidative parameters precisely, artificial neural network (ANN) and neuro-fuzzy inference system (ANFIS) modelling with three inputs, including type of antioxidant (gallic acid and methyl gallate), temperature (35, 45 and 55 °C) and concentration (0, 200, 400, 800 and 1600 mg L(-1) ) and four outputs containing induction period (IP), slope of initial stage of oxidation curve (k1 ) and slope of propagation stage of oxidation curve (k2 ) and peroxide value at the IP (PVIP ) were performed to predict the oxidation parameters of Kilka oil triacylglycerols and were compared to multiple linear regression (MLR). The results showed ANFIS was the best model with high coefficient of determination (R(2)  = 0.99, 0.99, 0.92 and 0.77 for IP, k1 , k2 and PVIP , respectively). So, the RMSE and MAE values for IP were 7.49 and 4.92 in ANFIS model. However, they were to be 15.95 and 10.88 and 34.14 and 3.60 for the best MLP structure and MLR, respectively. So, MLR showed the minimum accuracy among the constructed models. Sensitivity analysis based on the ANFIS model suggested a high sensitivity of oxidation parameters, particularly the induction period on concentrations of gallic acid and methyl gallate due to their high antioxidant activity to retard oil oxidation and enhanced Kilka oil shelf life. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Higher plasma quercetin levels following oral administration of an onion skin extract compared with pure quercetin dihydrate in humans.

PubMed

Burak, Constanze; Brüll, Verena; Langguth, Peter; Zimmermann, Benno F; Stoffel-Wagner, Birgit; Sausen, Udo; Stehle, Peter; Wolffram, Siegfried; Egert, Sarah

2017-02-01

To investigate the plasma kinetics of quercetin derived from hard capsules filled with onion skin extract powder or quercetin dihydrate in humans. In a randomized, single-blind, diet-controlled crossover study, 12 healthy subjects (six men and six women) aged 21-33 years were administered a single oral supra-nutritional dose of approximately 163 mg quercetin derived from onion skin extract powder (containing 95.3 % of total flavonoids as quercetin aglycone) or quercetin dihydrate (134 mg quercetin aglycone equivalent). Blood samples were collected before and during a 24-h period after quercetin administration. The concentrations of quercetin and its two monomethylated derivatives, isorhamnetin (3'-O-methyl quercetin), and tamarixetin (4'-O-methyl quercetin), were measured using HPLC with fluorescence detection after plasma enzymatic treatment. The systemic availability, determined by comparing the plasma concentration-time curves of quercetin, was 4.8 times higher, and the maximum plasma concentration (C max ) was 5.4 times higher after ingestion of the onion skin extract than after ingestion of pure quercetin dihydrate. By contrast, t max did not differ significantly between the two formulations. The C max values for isorhamnetin and tamarixetin were 3.8 and 4.4 times higher, respectively, after administration of onion skin extract than after pure quercetin dihydrate. The plasma kinetics of quercetin were not significantly different in men and women. Quercetin aglycone derived from onion skin extract powder is significantly more bioavailable than that from quercetin dihydrate powder filled hard capsules.

Polyphenolic profile and bioactivity study of Oenothera speciosa Nutt. aerial parts.

PubMed

Marzouk, Mohamed S; Moharram, Fatma A; El Dib, Rabab A; El-Shenawy, Siham M; Tawfike, Ahmed F

2009-04-07

Two new flavonol glycosides, myricetin 4'-O-alpha-L-rhamnopyranoside (1) and quercetin 3'-O-alpha-L-rhamnopyranoside (2), together with a novel biflavonol compound, speciin (3), as well as eleven phenolic metabolites, namely myricitrin (4), europetin 3-O-alpha-L-(1)C(4)-rhamnopyranoside (5), quercitrin (6), hyperin (7), rhamnetin 3-O-beta-galacto-pyranoside (8), caffeic acid (9), caffeic acid methyl ester (10), chlorogenic acid (11), chlorogenic acid methyl ester (12), gallic acid (13) and gallic acid methyl ester (14), were identified from the 80 % methanol extract of the aerial parts (leaves and stems) of Oenothera speciosa Nutt. (Onagraceae). In addition myricetin (15), quercetin (16) and ellagic acid (17) were identified from the chloroform extract. The structures were established depending on their chemical and physical analyses (UV, HR-ESIMS, 1D and 2D NMR). It was found that 80 % aqueous methanol extract of O. speciosa is non-toxic to mice up to 5 g kg(-1)b wt. The investigated extract exhibited significant antihyperglycaemic and anti-inflammatory activities in a dose dependant manner. Also, the 80 % methanol extract, myricitrin(4) and hyperin(7) showed potent antioxidant activity in vitro using 1,1-diphenyl 2-picryl hydrazyl (DPPH) radical assay.

Enhancement of periodate-hydrogen peroxide chemiluminescence by nitrogen doped carbon dots and its application for the determination of pyrogallol and gallic acid.

PubMed

Shah, Syed Niaz Ali; Li, Haifang; Lin, Jin-Ming

2016-06-01

A new sensitized chemiluminescence (CL) was developed to broaden the analytical application of KIO4-H2O2 system. The nitrogen doped carbon dots (N-CDs) dramatically boosted the CL intensity of KIO4-H2O2 system which was further enriched by basic medium. In light of EPR analysis, free radical scavenging studies and CL spectra the detail mechanism for the enhancement was conferred in the presence of N-CDs and NaOH. The results suggested that CL of KIO4-H2O2 system in the presence and absence of N-CDs and NaOH proceeds via radical pathway. The enhanced CL was used for the determination of pyrogallol and gallic acid in range of 1.0×10(-4)-1.0×10(-7)M with 4.6×10(-8) and 6.1×10(-8)M limit of detection respectively. The relative standard deviation (RSD) at a concentration of 10(-5) for gallic acid and pyrogallol was 1.4% and 2.3% respectively (n=11). The attained results unveil that the present method is sensitive, faster, simpler and less costly compared to other methods and could be applied to determine polyphenols in real samples. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparison of the contents of various antioxidants of sea buckthorn berries using CE.

PubMed

Gorbatsova, Jelena; Lõugas, Tiina; Vokk, Raivo; Kaljurand, Mihkel

2007-11-01

The increased interest in sea buckthorn (Hippophae rhamnoides L.) made it possible to investigate the antioxidant content in it. To address this issue, the presence of following antioxidant compounds were analyzed: trans-resveratrol, catechin, myricetin, quercetin, p-coumaric acid, caffeic acid, L-ascorbic acid (AA), and gallic acid (linear range of 50-150 micromol/L) in six different varieties of sea buckthorn berries extracts (sea buckthorn varieties: "Trofimovskaja (TR)," "Podarok Sadu (PS)," and "Avgustinka (AV),") received from two local Estonian companies. Trans-Resveratrol, catechin, AA, myricetin, and quercetin were found in extracts of sea buckthorn. Moreover, AA, myricetin, and quercetin contents were quantified. The biggest average AA content was found in TR (740 mg/100 g of dried berries, respectively). Furthermore, the same varieties gave the biggest quercetin content 116 mg/100 g of dried berries, respectively. For analysis, CZE was used and the results were partly validated by HPLC. Statistically no big differences in levels of antioxidants were consistently found in different varieties of sea buckthorn extracts investigated in this work.

Regioselective formation of quercetin 5-O-glucoside from orally administered quercetin in the silkworm, Bombyx mori.

PubMed

Hirayama, Chikara; Ono, Hiroshi; Tamura, Yasumori; Konno, Kotaro; Nakamura, Masatoshi

2008-03-01

The cocoons of some races of the silkworm, Bombyx mori, have been shown to contain 5-O-glucosylated flavonoids, which do not occur naturally in the leaves of their host plant, mulberry (Morus alba). Thus, dietary flavonoids could be biotransformed in this insect. In this study, we found that after feeding silkworms a diet rich in the flavonol quercetin, quercetin 5-O-glucoside was the predominant metabolite in the midgut tissue, while quercetin 5,4'-di-O-glucoside was the major constituent in the hemolymph and silk glands. UDP-glucosyltransferase (UGT) in the midgut could transfer glucose to each of the hydroxyl groups of quercetin, with a preference for formation of 5-O-glucoside, while quercetin 5,4'-di-O-glucoside was predominantly produced if the enzyme extracts of either the fat body or silk glands were incubated with quercetin 5-O-glucoside and UDP-glucose. These results suggest that dietary quercetin was glucosylated at the 5-O position in the midgut as the first-pass metabolite of quercetin after oral absorption, then glucosylated at the 4'-O position in the fat body or silk glands. The 5-O-glucosylated flavonoids retained biological activity in the insect, since the total free radical scavenging capacity of several tissues increased after oral administration of quercetin.

Insulin-secretagogue, antihyperlipidemic and other protective effects of gallic acid isolated from Terminalia bellerica Roxb. in streptozotocin-induced diabetic rats.

PubMed

Latha, R Cecily Rosemary; Daisy, P

2011-01-15

Diabetes mellitus causes derangement of carbohydrate, protein and lipid metabolism which eventually leads to a number of secondary complications. Terminalia bellerica is widely used in Indian medicine to treat various diseases including diabetes. The present study was carried out to isolate and identify the putative antidiabetic compound from the fruit rind of T. bellerica and assess its chemico-biological interaction in experimental diabetic rat models. Bioassay guided fractionation was followed to isolate the active compound, structure was elucidated using (1)H and (13)C NMR, IR, UV and mass spectrometry and the compound was identified as gallic acid (GA). GA isolated from T. bellerica and synthetic GA was administered to streptozotocin (STZ)-induced diabetic male Wistar rats at different doses for 28 days. Plasma glucose level was significantly (p<0.05) reduced in a dose-dependent manner when compared to the control.Histopathological examination of the pancreatic sections showed regeneration of β-cells of islets of GA-treated rats when compared to untreated diabetic rats. In addition, oral administration of GA (20mg/kg bw) significantly decreased serum total cholesterol, triglyceride, LDL-cholesterol, urea, uric acid, creatinine and at the same time markedly increased plasma insulin, C-peptide and glucose tolerance level. Also GA restored the total protein, albumin and body weight of diabetic rats to near normal. Thus our findings indicate that gallic acid present in fruit rind of T. bellerica is the active principle responsible for the regeneration of β-cells and normalizing all the biochemical parameters related to the patho-biochemistry of diabetes mellitus and hence it could be used as a potent antidiabetic agent. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Singlet Oxygen Detection Using Red Wine Extracts as Photosensitizers.

PubMed

Lagunes, Irene; Vázquez-Ortega, Fernanda; Trigos, Ángel

2017-09-01

Moderate consumption of red wine provides beneficial effects to health. This is attributed to polyphenol compounds present in wine such as resveratrol, quercetin, gallic acid, rutin, and vanillic acid. The amount of these antioxidants is variable; nevertheless, the main beneficial effects of red wine are attributed to resveratrol. However, it has been found that resveratrol and quercetin are able to photosensitize singlet oxygen generation and conversely, gallic acid acts as quencher. Therefore, and since resveratrol and quercetin are some of the most important antioxidants reported in red wines, the aim of this research was to evaluate the photosensitizing ability of 12 red wine extracts through photo-oxidation of ergosterol. The presence of 1 O 2 was detected by ergosterol conversion into peroxide of ergosterol through 1 H NMR analysis. Our results showed that 10 wine extracts were able to act as photosensitizers in the generation of singlet oxygen. The presence of 1 O 2 can damage other compounds of red wine and cause possible organoleptic alterations. Finally, although the reaction conditions employed in this research do not resemble the inherent conditions in wine making processing or storing, or even during its consumption, this knowledge could be useful to prevent possible pro-oxidant effects and avoid detrimental effects in red wines. © 2017 Institute of Food Technologists®.

Comparison of Antioxidant Evaluation Assays for Investigating Antioxidative Activity of Gallic Acid and Its Alkyl Esters in Different Food Matrices.

PubMed

Phonsatta, Natthaporn; Deetae, Pawinee; Luangpituksa, Pairoj; Grajeda-Iglesias, Claudia; Figueroa-Espinoza, Maria Cruz; Le Comte, Jérôme; Villeneuve, Pierre; Decker, Eric A; Visessanguan, Wonnop; Panya, Atikorn

2017-08-30

The addition of antioxidants is one of the strategies to inhibit lipid oxidation, a major cause of lipid deterioration in foods leading to rancidity development and nutritional losses. However, several studies have been reported that conventional antioxidant assays, e.g., TPC, ABTS, FRAP, and ORAC could not predict antioxidant performance in several foods. This study aimed to investigate the performance of two recently developed assays, e.g., the conjugated autoxidizable triene (CAT) and the apolar radical-initiated conjugated autoxidizable triene (ApoCAT) assays to predict the antioxidant effectiveness of gallic acid and its esters in selected food models in comparison with the conventional antioxidant assays. The results indicated that the polarities of the antioxidants have a strong impact on antioxidant activities. In addition, different oxidant locations demonstrated by the CAT and ApoCAT assays influenced the overall antioxidant performances of the antioxidants with different polarities. To validate the predictability of the assays, the antioxidative performance of gallic acid and its alkyl esters was investigated in oil-in-water (O/W) emulsions, bulk soybean oils, and roasted peanuts as the lipid food models. The results showed that only the ApoCAT assay could be able to predict the antioxidative performances in O/W emulsions regardless of the antioxidant polarities. This study demonstrated that the relevance of antioxidant assays to food models was strongly dependent on physical similarities between the tested assays and the food structure matrices.

Quercetin Protects against Okadaic Acid-Induced Injury via MAPK and PI3K/Akt/GSK3β Signaling Pathways in HT22 Hippocampal Neurons.

PubMed

Jiang, Wei; Luo, Tao; Li, Sheng; Zhou, Yue; Shen, Xiu-Yin; He, Feng; Xu, Jie; Wang, Hua-Qiao

2016-01-01

Increasing evidence shows that oxidative stress and the hyperphosphorylation of tau protein play essential roles in the progression of Alzheimer's disease (AD). Quercetin is a major flavonoid that has anti-oxidant, anti-cancer and anti-inflammatory properties. We investigated the neuroprotective effects of quercetin to HT22 cells (a cell line from mouse hippocampal neurons). We found that Okadaic acid (OA) induced the hyperphosphorylation of tau protein at Ser199, Ser396, Thr205, and Thr231 and produced oxidative stress to the HT22 cells. The oxidative stress suppressed the cell viability and decreased the levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), mitochondria membrane potential (MMP) and Glutathione peroxidase (GSH-Px). It up-regulated malondialdehyde (MDA) production and intracellular reactive oxygen species (ROS). In addition, phosphoinositide 3 kinase/protein kinase B/Glycogen synthase kinase3β (PI3K/Akt/GSK3β) and mitogen activated protein kinase (MAPK) were also involved in this process. We found that pre-treatment with quercetin can inhibited OA-induced the hyperphosphorylation of tau protein and oxidative stress. Moreover, pre-treatment with quercetin not only inhibited OA-induced apoptosis via the reduction of Bax, and up-regulation of cleaved caspase 3, but also via the inhibition of PI3K/Akt/GSK3β, MAPKs and activation of NF-κB p65. Our findings suggest the therapeutic potential of quercetin to treat AD.

Quercetin Protects against Okadaic Acid-Induced Injury via MAPK and PI3K/Akt/GSK3β Signaling Pathways in HT22 Hippocampal Neurons

PubMed Central

Li, Sheng; Zhou, Yue; Shen, Xiu-Yin; He, Feng; Xu, Jie; Wang, Hua-Qiao

2016-01-01

Increasing evidence shows that oxidative stress and the hyperphosphorylation of tau protein play essential roles in the progression of Alzheimer’s disease (AD). Quercetin is a major flavonoid that has anti-oxidant, anti-cancer and anti-inflammatory properties. We investigated the neuroprotective effects of quercetin to HT22 cells (a cell line from mouse hippocampal neurons). We found that Okadaic acid (OA) induced the hyperphosphorylation of tau protein at Ser199, Ser396, Thr205, and Thr231 and produced oxidative stress to the HT22 cells. The oxidative stress suppressed the cell viability and decreased the levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD), mitochondria membrane potential (MMP) and Glutathione peroxidase (GSH-Px). It up-regulated malondialdehyde (MDA) production and intracellular reactive oxygen species (ROS). In addition, phosphoinositide 3 kinase/protein kinase B/Glycogen synthase kinase3β (PI3K/Akt/GSK3β) and mitogen activated protein kinase (MAPK) were also involved in this process. We found that pre-treatment with quercetin can inhibited OA-induced the hyperphosphorylation of tau protein and oxidative stress. Moreover, pre-treatment with quercetin not only inhibited OA-induced apoptosis via the reduction of Bax, and up-regulation of cleaved caspase 3, but also via the inhibition of PI3K/Akt/GSK3β, MAPKs and activation of NF-κB p65. Our findings suggest the therapeutic potential of quercetin to treat AD. PMID:27050422

Long Chain Fatty Acid Acylated Derivatives of Quercetin-3-O-Glucoside as Antioxidants to Prevent Lipid Oxidation

PubMed Central

Warnakulasuriya, Sumudu N.; Ziaullah; Rupasinghe, H.P. Vasantha

2014-01-01

Flavonoids have shown promise as natural plant-based antioxidants for protecting lipids from oxidation. It was hypothesized that their applications in lipophilic food systems can be further enhanced by esterification of flavonoids with fatty acids. Quercetin-3-O-glucoside (Q3G) was esterified individually with six selected long chain fatty acids: stearic acid (STA), oleic acid (OLA), linoleic acid (LNA), α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and decosahexaenoic acid (DHA), using Candida antarctica B lipase as the biocatalyst. The antioxidant activity of esterified flavonoids was evaluated using lipid oxidation model systems of poly-unsaturated fatty acids-rich fish oil and human low density lipoprotein (LDL), in vitro. In the oil-in-water emulsion, Q3G esters exhibited 50% to 100% inhibition in primary oxidation and 30% to 75% inhibition in secondary oxidation. In bulk oil, Q3G esters did not provide considerable protection from lipid oxidation; however, Q3G demonstrated more than 50% inhibition in primary oxidation. EPA, DHA and ALA esters of Q3G showed significantly higher inhibition in Cu2+- and peroxyl radical-induced LDL oxidation in comparison to Q3G. PMID:25384198

Long chain fatty acid acylated derivatives of quercetin-3-o-glucoside as antioxidants to prevent lipid oxidation.

PubMed

Warnakulasuriya, Sumudu N; Ziaullah; Rupasinghe, H P Vasantha

2014-11-06

Flavonoids have shown promise as natural plant-based antioxidants for protecting lipids from oxidation. It was hypothesized that their applications in lipophilic food systems can be further enhanced by esterification of flavonoids with fatty acids. Quercetin-3-O-glucoside (Q3G) was esterified individually with six selected long chain fatty acids: stearic acid (STA), oleic acid (OLA), linoleic acid (LNA), α-linolenic acid (ALA), eicosapentaenoic acid (EPA) and decosahexaenoic acid (DHA), using Candida antarctica B lipase as the biocatalyst. The antioxidant activity of esterified flavonoids was evaluated using lipid oxidation model systems of poly-unsaturated fatty acids-rich fish oil and human low density lipoprotein (LDL), in vitro. In the oil-in-water emulsion, Q3G esters exhibited 50% to 100% inhibition in primary oxidation and 30% to 75% inhibition in secondary oxidation. In bulk oil, Q3G esters did not provide considerable protection from lipid oxidation; however, Q3G demonstrated more than 50% inhibition in primary oxidation. EPA, DHA and ALA esters of Q3G showed significantly higher inhibition in Cu2+- and peroxyl radical-induced LDL oxidation in comparison to Q3G.

Frataxin-Mediated PINK1-Parkin-Dependent Mitophagy in Hepatic Steatosis: The Protective Effects of Quercetin.

PubMed

Liu, Peiyi; Lin, Hongkun; Xu, Yanyan; Zhou, Feng; Wang, Jing; Liu, Jingjing; Zhu, Xinhong; Guo, Xiaoping; Tang, Yuhan; Yao, Ping

2018-06-23

Naturally occurring quercetin has been found to induce mitophagy and prevent non-alcoholic fatty liver disease (NAFLD). However, it still remains elusive whether frataxin upregulation by quercetin contributes to the beneficial effect through mitophagy or not. Adult male C57BL/J mice were fed a high fat diet (HFD, 60% of energy from fat) with quercetin (100 mg/kg.bw) or not for 10 weeks. Quercetin alleviated HFD-induced histopathological changes, disorders of lipid metabolism, mitochondrial damage. Moreover, quercetin blocked mitophagy suppression by HFD based on the increased LC3II, PINK1 and Beclin1 expressions, as well as decreased p62 levels. Quercetin also improved the Parkin translocation to mitochondria confirmed by immunofluorescence. Specifically, frataxin was lowered in the liver of HFD-fed mice or HepG2 cell incubated with oleate/palmitate but restored by quercetin. And quercetin's regulation of frataxin may depend on p53. Furthermore, lentivirus-mediated stable knockdown of frataxin in HepG2 inhibited PINK1- Parkin-associated mitophagy and resulted in lipid accumulation. Frataxin was further decreased by free fatty acids in knockdown cells concomitantly with depressed PINK1-Parkin-associated mitophagy, which was partially normalized by quercetin. Quercetin alleviated hepatic steatosis by enhancing frataxin-mediated PINK1/Parkin-dependent mitophagy, highlighting a promising preventive strategy and mechanism for NAFLD by quercetin. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Radiation sensitivity and EPR dosimetric potential of gallic acid and its esters

NASA Astrophysics Data System (ADS)

Tuner, Hasan; Oktay Bal, M.; Polat, Mustafa

2015-02-01

In the preset work the radiation sensitivities of Gallic Acid anhydrous and monohydrate, Octyl, Lauryl, and Ethyl Gallate (GA, GAm, OG, LG, and EG) were investigated in the intermediate (0.5-20 kGy) and low radiation (<10 Gy) dose range using Electron Paramagnetic Resonance (EPR) spectroscopy. While OG, LG, and EG are presented a singlet EPR spectra, their radiation sensitivity found to be very different in the intermediate dose range. At low radiation dose range (<10 Gy) only LG is found to be present a signal that easily distinguished from the noise signals. The intermediate and low dose range radiation sensitivities are compared using well known EPR dosimeter alanine. The radiation yields (G) of the interested material were found to be 1.34×10-2, 1.48×10-2, 4.14×10-2, and 6.03×10-2, 9.44×10-2 for EG, GA, GAm, OG, and LG, respectively at the intermediate dose range. It is found that the simple EPR spectra and the noticeable EPR signal of LG make it a promising dosimetric material to be used below 10 Gy of radiation dose.

Protection of ascorbic acid from copper(II)-catalyzed oxidative degradation in the presence of flavonoids: quercetin, catechin and morin.

PubMed

Beker, Bilge Yildoğan; Sönmezoğlu, Inci; Imer, Filiz; Apak, Reşat

2011-08-01

Protection of ascorbic acid (AA) (vitamin C) from Cu(II)-catalyzed autoxidation is an important aspect of antioxidant chemistry. The autoxidation of AA in the absence and presence of Cu(II) ions was investigated in aerated solution at room temperature and I = 0.1 ionic strength (KNO(3)); the effects of three different flavonoids of similar structure (quercetin, morin and catechin) and their mixtures on the AA system were studied. The concentration of unoxidized AA remaining in solution was measured with the modified cupric ion reducing antioxidant capacity spectrophotometric method. The Cu(II)-catalyzed oxidation at pH 4.5 followed first-order kinetics with respect to AA concentration. Catalytic autoxidation of AA was inhibited to a greater extent by stable quercetin and morin complexes of Cu(II) than by catechin complex. The inhibitive effectiveness order of mixtures gives information about possible synergistic or antagonistic combinations of flavonoid antioxidants, which should be further confirmed with other antioxidant tests.

Identification of Phenolic Compounds in Red and Green Pistachio (Pistacia vera L.) Hulls (Exo- and Mesocarp) by HPLC-DAD-ESI-(HR)-MS(n).

PubMed

Erşan, Sevcan; Güçlü Üstündağ, Özlem; Carle, Reinhold; Schweiggert, Ralf M

2016-07-06

Phenolic constituents of the nonlignified red and green pistachio hulls (exo- and mesocarp) were assessed by HPLC-DAD-ESI-MS(n) as well as by HR-MS. A total of 66 compounds was identified in the respective aqueous methanolic extracts. Among them, gallic acid, monogalloyl glucoside, monogalloyl quinic acid, penta-O-galloyl-β-d-glucose, hexagalloyl hexose, quercetin 3-O-galactoside, quercetin 3-O-glucoside, quercetin 3-O-glucuronide, and (17:1)-, (13:0)-, and (13:1)-anacardic acids were detected at highest signal intensity. The main difference between red and green hulls was the presence of anthocyanins in the former ones. Differently galloylated hydrolyzable tannins, anthocyanins, and minor anacardic acids were identified for the first time. Pistachio hulls were thus shown to be a source of structurally diverse and potentially bioactive phenolic compounds. They therefore represent a valuable byproduct of pistachio processing having potential for further utilization as raw material for the recovery of pharmaceutical, nutraceutical, and chemical products.

Quercetin improves postpartum hypogalactia in milk-deficient mice via stimulating prolactin production in pituitary gland.

PubMed

Lin, Man; Wang, Na; Yao, Bei; Zhong, Yao; Lin, Yan; You, Tianhui

2018-04-19

Postpartum dysgalactia is a common clinical problem for lactating women. Seeking out the safe and efficient phytoestrogens will be a promising strategy for postpartum dysgalactia therapy. In this study, the postpartum mice within four groups, including control group, the model group, and the treatment groups intragastrically administrated with normal saline, bromocriptine, bromocriptine plus 17α-ethinyl estradiol, and bromocriptine plus quercetin, respectively, were used. The results showed that quercetin, a kind of natural phytoestrogen, could efficiently promote lactation yield and mammary gland development in the agalactosis mice produced by bromocriptine administration. Mechanically, quercetin, such as 17α-ethinyl estradiol, significantly stimulated prolactin (PRL) production and deposition in the mammary gland in the agalactosis mice determined by western blotting, quantitative polymerase chain reaction, and enzyme-linked immunosorbent assay, respectively. Furthermore, quercetin could increase the expression of β-casein, stearoyl-CoA desaturase, fatty acid synthase, and α-lactalbumin in the breast tissues that are responsible for the production of fatty acid, lactose, and galactose in the milk at the transcriptional level determined by quantitative polymerase chain reaction. Specifically, quercetin promoted primary mammary epithelial cell proliferation and stimulated prolactin receptor (PRLR) expression probably via AKT activation in vitro. In conclusion, this study indicates that estrogen-like quercetin promotes mammary gland development and lactation yield in milk-deficient mice, probably via stimulating PRL expression and release from the pituitary gland, as well as induces PRLR expression in primary mammary epithelial cells. Copyright © 2018 John Wiley & Sons, Ltd.

Effects of Quercetin in a Mouse Model of Experimental Dry Eye.

PubMed

Oh, Ha Na; Kim, Chae Eun; Lee, Ji Hyun; Yang, Jae Wook

2015-09-01

To evaluate the effect of treatment with quercetin in a mouse model of dry eye. 0.5% quercetin eye drops were prepared and an experimental dry eye model was induced in NOD.B10.H2(b) mice through desiccation stress. The mice were divided into 3 groups according to the treatment regimen: the DS 10D group (desiccation stress for 10 days), the phosphate buffered saline (PBS) group, and the quercetin group. Tear volumes and corneal irregularity scores were measured at 3, 5, 7, and 10 days after treatment. Hematoxylin and eosin staining, periodic acid-Schiff staining, and immunohistochemistry were performed at the end of the experiment. The quercetin group had increased tear volumes (0.2 ± 0.03 μm, P < 0.05) and decreased corneal irregularity scores (0.7 ± 0.6, P < 0.05) compared with those of the PBS group. On histological examination, the quercetin group exhibited restored smooth corneal surfaces without detaching corneal epithelial cells and had significantly increased goblet cell density (13.8 ± 0.8 cells/0.1 mm², P < 0.05) compared with the PBS group. The quercetin group also exhibited significant declines of MMP-2 (5.1-fold of control, P < 0.01), MMP-9 (2.5-fold of control, P < 0.01), ICAM-1 (2.2-fold of control, P < 0.01), and VCAM-1 (2.3-fold of control, P < 0.01) levels in the lacrimal gland than did the PBS group. Topical application of quercetin can help to improve ocular surface disorders of dry eye not only by decreasing the corneal surface irregularity but also by increasing the tear volume and goblet cell density. Moreover, quercetin has the potential for use in eye drops as a treatment for dry eye disease with antiinflammatory effects on the lacrimal functional unit.

Mechanistic insights into the inhibition of quercetin on xanthine oxidase.

PubMed

Zhang, Cen; Wang, Rui; Zhang, Guowen; Gong, Deming

2018-06-01

Quercetin, one of the most abundant flavonoid in the daily diet, was found to reversibly inhibit the generation of uric acid and superoxide radicals (O 2 - )catalyzed by xanthine oxidase (XOD) in a mixed-type manner with IC 50 values of (2.74±0.04)×10 -6 and (2.90±0.03)×10 -6 molL -1 , respectively, and the inhibition of quercetin on O 2 - generation may be ascribed to the reduced form of XOD by a ping-pong mechanism. XOD had one high affinity binding site for quercetin with a binding constant of 4.28×10 4 Lmol -1 at 298K, and the binding process was predominately driven by van der Waals forces and hydrogen bonds on account of the negative enthalpy and entropy changes. Moreover, molecular docking confirmed that the binding site for quercetin located in the isoalloxazine ring of the flavin adenine dinucleotide (FAD) domain of XOD, then the diffusion of O 2 - out of the FAD site was blocked in favor of another electron transferred from FADH 2 to O 2 - to form hydrogen peroxide (H 2 O 2 ). This study may clarify the role of quercetin on inhibiting XOD catalysis and provide a potential nutritional supplement for preventing gout and peroxidative damage. Copyright © 2018 Elsevier B.V. All rights reserved.

Gallic acid grafting modulates the oxidative potential of ferrimagnetic bioactive glass-ceramic SC-45.

PubMed

Corazzari, Ingrid; Tomatis, Maura; Turci, Francesco; Ferraris, Sara; Bertone, Elisa; Prenesti, Enrico; Vernè, Enrica

2016-12-01

Magnetite-containing glass-ceramics are promising bio-materials for replacing bone tissue after tumour resection. Thanks to their ferrimagnetic properties, they generate heat when subjected to an alternated magnetic field. In virtue of this they can be employed for the hyperthermic treatment of cancer. Moreover, grafting anti-cancer drugs onto their surface produces specific anti-neoplastic activity in these biomaterials. Gallic acid (GA) exhibits antiproliferative activity which renders it a promising candidate for anticancer applications. In the present paper, the reactivity of ferrimagnetic glass-ceramic SC-45 grafted with GA (SC-45+GA) was studied in terms of ROS release, rupture of the C-H bond of the formate molecule and Fenton reactivity by EPR/spin trapping in acellular systems. The ability of these materials to cause lipid peroxidation was assessed by UV-vis/TBA assay employing linoleic acid as a model of membrane lipid. The results, compared to those obtained with SC-45, showed that GA grafting (i) significantly enhanced the Fenton reactivity and (ii) restored the former reactivity of SC-45 towards both the C-H bond and linoleic acid which had been completely suppressed by prolonged contact with water. Fe 2+ centres at the surface are probably implicated. GA, acting as a pro-oxidant, reduces Fe 3+ to Fe 2+ by maintaining a supply of Fe 2+ at the surface of SC-45+GA. Copyright © 2016 Elsevier B.V. All rights reserved.

Ultrasound stimulated release of gallic acid from chitin hydrogel matrix.

PubMed

Jiang, Huixin; Kobayashi, Takaomi

2017-06-01

Ultrasound (US) stimulated drug release was examined in this study using a chitin hydrogel matrix loaded with gallic acid (GA), a drug used for wound healing and anticancer. Using phase inversion, GA-chitin hydrogels were prepared from chitin-dimethylacetamide (DMAc)/lithium chloride (LiCl) solution in the presence of GA, with 24h exposure of the solution to water vapor. The GA release from the GA-chitin hydrogel was examined under different US powers of 0-30W at 43kHz. The effects of GA loading amounts in the hydrogels (0.54, 0.43, and 0.25mg/cm 3 ) and chitin concentrations (0.1, 0.5, and 1wt%) on the release behaviors were recorded under 43kHz US exposure at 30W. Results show that US accelerated the release efficiencies for all samples. Furthermore, the release efficiency increased concomitantly with increasing US power, GA loading amount, and decrease of the chitin concentration. The highest release rate of 0.74μg/mL·min was obtained from 0.54mg/cm 3 of GA-loaded hydrogel fabricated from a 0.1wt% chitin mixture solution under 43kHz US exposure at 30W: nine times higher than that of the sample without US exposure. The hydrogel viscoelasticity demonstrated that the US irradiation rigidified the material. FT-IR showed that US can break the hydrogen bonds in the GA-chitin hydrogels. Copyright © 2017 Elsevier B.V. All rights reserved.

Green synthesis of gold and silver nanoparticles using gallic acid: catalytic activity and conversion yield toward the 4-nitrophenol reduction reaction

NASA Astrophysics Data System (ADS)

Park, Jisu; Cha, Song-Hyun; Cho, Seonho; Park, Youmie

2016-06-01

In the present report, gallic acid was used as both a reducing and stabilizing agent to synthesize gold and silver nanoparticles. The synthesized gold and silver nanoparticles exhibited characteristic surface plasmon resonance bands at 536 and 392 nm, respectively. Nanoparticles that were approximately spherical in shape were observed in high-resolution transmission electron microscopy and atomic force microscopy images. The hydrodynamic radius was determined to be 54.4 nm for gold nanoparticles and 33.7 nm for silver nanoparticles in aqueous medium. X-ray diffraction analyses confirmed that the synthesized nanoparticles possessed a face-centered cubic structure. FT-IR spectra demonstrated that the carboxylic acid functional groups of gallic acid contributed to the electrostatic binding onto the surface of the nanoparticles. Zeta potential values of -41.98 mV for the gold nanoparticles and -53.47 mV for the silver nanoparticles indicated that the synthesized nanoparticles possess excellent stability. On-the-shelf stability for 4 weeks also confirmed that the synthesized nanoparticles were quite stable without significant changes in their UV-visible spectra. The synthesized nanoparticles exhibited catalytic activity toward the reduction reaction of 4-nitrophenol to 4-aminophenol in the presence of sodium borohydride. The rate constant of the silver nanoparticles was higher than that of the gold nanoparticles in the catalytic reaction. Furthermore, the conversion yield (%) of 4-nitrophenol to 4-aminophenol was determined using reversed-phase high-performance liquid chromatography with UV detection at 254 nm. The silver nanoparticles exhibited an excellent conversion yield (96.7-99.9 %), suggesting that the synthesized silver nanoparticles are highly efficient catalysts for the 4-nitrophenol reduction reaction.

Quercetin-induced downregulation of phospholipase D1 inhibits proliferation and invasion in U87 glioma cells

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

Park, Mi Hee; Min, Do Sik, E-mail: minds@pusan.ac.kr

Highlights: {yields} Quercetin, a bioactive flavonoid, suppresses expression and enzymatic activity of phospholipase D1. {yields} Quercetin abolishes NFkB-induced phospholipase D1 expression via inhibition of NFkB transactivation. {yields} Quercetin-induced suppression of phospholipase D1 inhibits invasion and proliferation of human glioma cells. -- Abstract: Phospholipase D (PLD) has been recognized as a regulator of cell proliferation and tumorigenesis, but little is known about the molecules regulating PLD expression. Thus, the identification of small molecules inhibiting PLD expression would be an important advance in PLD-mediated physiology. Quercetin, a ubiquitous bioactive flavonoid, is known to inhibit proliferation and induce apoptosis in a variety ofmore » cancer cells. In the present study, we examined the effect of quercetin on the expression of PLD in U87 glioma cells. Quercetin significantly suppressed the expression of PLD1 at the transcriptional level. Moreover, quercetin abolished the protein expression of PLD1 in a time and dose-dependent manner, as well as inhibited PLD activity. Quercetin suppressed NF{kappa}B-induced PLD1 expression via inhibition of NFkB transactivation. Furthermore, quercetin inhibited activation and invasion of metalloproteinase-2 (MMP-2), a key modulator of glioma cell invasion, induced by phosphatidic acid (PA), a product of PLD activity. Taken together these data demonstrate that quercetin abolishes PLD1 expression and subsequently inhibits invasion and proliferation of glioma cells.« less

Quercetin affects glutathione levels and redox ratio in human aortic endothelial cells not through oxidation but formation and cellular export of quercetin-glutathione conjugates and upregulation of glutamate-cysteine ligase.

PubMed

Li, Chuan; Zhang, Wei-Jian; Choi, Jaewoo; Frei, Balz

2016-10-01

Endothelial dysfunction due to vascular inflammation and oxidative stress critically contributes to the etiology of atherosclerosis. The intracellular redox environment plays a key role in regulating endothelial cell function and is intimately linked to cellular thiol status, including and foremost glutathione (GSH). In the present study we investigated whether and how the dietary flavonoid, quercetin, affects GSH status of human aortic endothelial cells (HAEC) and their response to oxidative stress. We found that treating cells with buthionine sulfoximine to deplete cellular GSH levels significantly reduced the capacity of quercetin to inhibit lipopolysaccharide (LPS)-induced oxidant production. Furthermore, incubation of HAEC with quercetin caused a transient decrease and then full recovery of cellular GSH concentrations. The initial decline in GSH was not accompanied by a corresponding increase in glutathione disulfide (GSSG). To the contrary, GSSG levels, which were less than 0.5% of GSH levels at baseline (0.26±0.01 vs. 64.7±1.9nmol/mg protein, respectively), decreased by about 25% during incubation with quercetin. As a result, the GSH: GSSG ratio increased by about 70%, from 253±7 to 372±23. These quercetin-induced changes in GSH and GSSG levels were not affected by treating HAEC with 500µM ascorbic acid phosphate for 24h to increase intracellular ascorbate levels. Incubation of HAEC with quercetin also led to the appearance of extracellular quercetin-glutathione conjugates, which was paralleled by upregulation of the multidrug resistance protein 1 (MRP1). Furthermore, quercetin slightly but significantly increased mRNA and protein levels of glutamate-cysteine ligase (GCL) catalytic and modifier subunits. Taken together, our results suggest that quercetin causes loss of GSH in HAEC, not because of oxidation but due to formation and cellular export of quercetin-glutathione conjugates. Induction by quercetin of GCL subsequently restores GSH levels, thereby

Oral administration of quercetin is unable to protect against isoproterenol cardiotoxicity.

PubMed

Ríha, Michal; Vopršalová, Marie; Pilařová, Veronika; Semecký, Vladimír; Holečková, Magdalena; Vávrová, Jaroslava; Palicka, Vladimir; Filipský, Tomáš; Hrdina, Radomír; Nováková, Lucie; Mladěnka, Přemysl

2014-09-01

Catecholamines are endogenous amines that participate in the maintenance of cardiovascular system homeostasis. However, excessive release or exogenous administration of catecholamines is cardiotoxic. The synthetic catecholamine, isoprenaline (isoproterenol, ISO), with non-selective β-agonistic activity has been used as a viable model of acute myocardial toxicity for many years. Since the pathophysiology of ISO-cardiotoxicity is complex, the aim of this study was to elucidate the effect of oral quercetin pretreatment on myocardial ISO toxicity. Wistar-Han rats were randomly divided into four groups: solvent or quercetin administered orally by gavage in a dose of 10 mg kg(-1) daily for 7 days were followed by s.c. water for injection or ISO in a dose of 100 mg kg(-1). Haemodynamic, ECG and biochemical parameters were measured; effects on blood vessels and myocardial histology were assessed, and accompanying pharmacokinetic analysis was performed. Quercetin was unable to protect the cardiovascular system against acute ISO cardiotoxicity (stroke volume decrease, cardiac troponin T release, QRS-T junction elevation and histological impairment). The sole positive effect of quercetin on catecholamine-induced cardiotoxicity was the normalization of increased left ventricular end-diastolic pressure caused by ISO. Quercetin did not reverse the increased responsiveness of rat aorta to vasoconstriction in ISO-treated animals, but it decreased the same parameter in the control animals. Accompanying pharmacokinetic analysis showed absorption of quercetin and its metabolite 3-hydroxyphenylacetic acid formed by bacterial microflora. In conclusion, a daily oral dose of 10 mg kg(-1) of quercetin for 7 days did not ameliorate acute ISO-cardiovascular toxicity in rats despite minor positive cardiovascular effects.

Rapid dimerization of quercetin through an oxidative mechanism in the presence of serum albumin decreases its ability to induce cytotoxicity in MDA-MB-231 cells

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

Pham, Anh; Bortolazzo, Anthony; White, J. Brandon, E-mail: Brandon.White@sjsu.edu

Highlights: Black-Right-Pointing-Pointer Quercetin cannot be detected intracellularly despite killing MDA-MB-231 cells. Black-Right-Pointing-Pointer Quercetin forms a heterodimer through oxidation in media with serum. Black-Right-Pointing-Pointer The quercetin heterodimer does not kill MDA-MB-231 cells. Black-Right-Pointing-Pointer Ascorbic acid stabilizes quercetin increasing cell death in quercetin treated cells. Black-Right-Pointing-Pointer Quercetin, and not a modified form, is responsible for apoptosis and cell death. -- Abstract: Quercetin is a member of the flavonoid family and has been previously shown to have a variety of anti-cancer activities. We and others have reported anti-proliferation, cell cycle arrest, and induction of apoptosis of cancer cells after treatment with quercetin. Quercetinmore » has also been shown to undergo oxidation. However, it is unclear if quercetin or one of its oxidized forms is responsible for cell death. Here we report that quercetin rapidly oxidized in cell culture media to form a dimer. The quercetin dimer is identical to a dimer that is naturally produced by onions. The quercetin dimer and quercetin-3-O-glucopyranoside are unable to cross the cell membrane and do not kill MDA-MB-231 cells. Finally, supplementing the media with ascorbic acid increases quercetin's ability to induce cell death probably by reduction oxidative dimerization. Our results suggest that an unmodified quercetin is the compound that elicits cell death.« less

Simultaneous determination of phenolic acids and flavonoids in rice using solid-phase extraction and RP-HPLC with photodiode array detection.

PubMed

Irakli, Maria N; Samanidou, Victoria F; Biliaderis, Costas G; Papadoyannis, Ioannis N

2012-07-01

An analytical method based on an optimized solid-phase extraction procedure and followed by high-performance liquid chromatography (HPLC) separation with diode array detection was developed and validated for the simultaneous determination of phenolic acids (gallic, protocatechuic, 4-hydroxy-benzoic, vanillic, caffeic, syringic, p-coumaric, ferulic, sinapic, and cinnamic acids), flavanols (catechin and epicatechin), flavonols (myricetin, quercetin, kaempferol, quercetin-3-O-glucoside, hyperoside, and rutin), flavones (luteolin and apigenin) and flavanones (naringenin and hesperidin) in rice flour (Oryza sativa L.). Chromatographic separation was carried out on a PerfectSil Target ODS-3 (250 mm × 4.6 mm, 3 μm) column at temperature 25°C using a mobile phase, consisting of 0.5% (v/v) acetic acid in water, methanol, and acetonitrile at a flow rate 1 mL min(-1) , under gradient elution conditions. Application of optimum extraction conditions, elaborated on both Lichrolut C(18) and Oasis HLB cartridges, have led to extraction of phenolic acids and flavonoids from rice flour with mean recoveries 84.3-113.0%. The developed method was validated in terms of linearity, accuracy, precision, stability, and sensitivity. Repeatability (n = 5) and inter-day precision (n = 4) revealed relative standard deviation (RSD) <13%. The optimized method was successfully applied to the analysis of phenolic acids and flavonoids in pigmented (red and black rice) and non-pigmented rice (brown rice) samples. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dinuclear copper(II) octaazamacrocyclic complex in a PVC coated GCE and graphite as a voltammetric sensor for determination of gallic acid and antioxidant capacity of wine samples.

PubMed

Petković, B B; Stanković, D; Milčić, M; Sovilj, S P; Manojlović, D

2015-01-01

A novel efficient differential pulse voltammetric (DPV) method for determination gallic acid (GA) was developed by using an electrochemical sensor based on [Cu2tpmc](ClO4)4 immobilized in PVC matrix and coated on graphite (CGE) or classy carbon rod (CGCE). The proposed method is based on the gallic acid oxidation process at formed [Cu2tpmcGA](3+) complex at the electrode surface. The complexation was explored by molecular modeling and DFT calculations. Voltammograms for both sensors, recorded in a HNO3 as a supporting electrolyte at pH 2 and measured in 2.5×10(-7) to 1.0×10(-4) M of GA, resulted with two linear calibration curves (for higher and lower GA concentration range). The detection limit at CGE was 1.48×10(-7) M, while at CGCE was 4.6×10(-6) M. CGE was successfully applied for the determination of the antioxidant capacity based on GA equivalents for white, rosé and red wine samples. Copyright © 2014 Elsevier B.V. All rights reserved.

[Determination of quercetin and kaempferol in Dysosma plants by RP-HPLC].

PubMed

Luo, Jun; Zhang, Liyan; Wan, Mingxiang; He, Shunzhi; Yang, Yuqin

2010-11-01

To determine quercetin and kaempferol in the plant of genus Dysosma that come from different species, different plant parts or different growing areas, which provide the basis of rational utilization of Dysosma plants. The analysis was performed on a Diamonsil C18 column (4.6 mm x 150 mm, 5 microm) eluted with the mobile phase of methanol-water containing 0.1% phosphoric acid (60:40). The flow rate was 1 mL x min(-1), the detection wavelength was 360 nm; and the column temperature was set at 25 degrees C. The linear ranges of quercetin and kaempferol are 0.22-1.1 microg and 0.42-2.1 microg. The average recoveries of quercetin and kaempferol are 97.1% (RSD 1.4%) and 99.6% (RSD 2.4%); respectively. The contents of flavones in different species of Dysosma are significantly different.

Phytochemical constituents and chemosystematic significance of Chrozophora tinctoria (L.) Raf.

PubMed

Marzouk, Mona M; Hussein, Sameh R; Kassem, Mona E S; Kawashty, Salwa A; El Negoumy, Sabry I M

2016-07-01

Twelve compounds were isolated from Chrozophora tinctoria (L.) Raf. They were identified as kaempferol, kaempferol 3-O-β-glucopyranoside, kaempferol 3-O-(6″-α-rhamnopyranosyl)-β-glucopyranoside, quercetin, quercetin 3-O-β-glucopyranoside, quercetin 3-O-(6″-α-rhamnopyranosyl)-β-glucopyranoside, apigenin, apigenin 7-O-β-glucopyranoside, acacetin, gallic acid, methyl gallate and β-sitosterol-3-O-β-glucopyranoside. Their structures were elucidated by chemical and spectral methods. Furthermore, chemosystematics of the isolated compounds is briefly discussed. It was indicated that C. tinctoria is the only species of Chrozophora that has the capability to synthesis kaempferol aglycone and their glycosides, and the finding is supported by its distinct morphological and anatomical aspects.

Enhanced anticancer effect of fabricated gallic acid/CdS on the rGO nanosheets on human glomerular mesangial (IP15) and epithelial proximal (HK2) kidney cell lines - Cytotoxicity investigations.

PubMed

Peng, Wei; Luo, Pengcheng; Gui, Dingwen; Jiang, Weidong; Wu, Haixia; Zhang, Jie

2018-01-01

In spite of the technological innovation in the biomedical science, cancer remains a critical disease. In this study, we designed a gallic acid/cadmium sulfide (GA/CdS) nanocomposite fabricated on the reduced graphene oxide (GA/CdS-rGO) nanosheets for the treatment system of human kidney cancer cells. The GA/CdS-rGO nanosheets have been prepared using gallic acid as a reducing agent. The characterization of nanocomposites was studied using UV-Vis spectroscope, FT-IR, XRD, SEM and TEM. The microscopic images showed the spherical shape and nano-scaled CdS nanoparticles on the sheet like rGO nanomaterials. These structural and morphology investigations show that excellent properties of as-prepared GA/CdS-rGO has ability to treat the human glomerular mesangial (IP15) cancer cells at 50μg/ml as an IC 50 value, without affecting the epithelial proximal (HK-2) normal cells. In vitro cytotoxicity results showed that the variability of toxic effects after CdS exposure was strongly associated to the cellular Cd content. Release of Cd 2+ from nanocomposites depended to solubility and particle degradation of CdS nanoparticles were considered to be the main cause of these cytotoxicity. The in vitro analysis results indicated that heterogeneity of Cd and gallic acid toxicity that was highly dependent on the physico-chemical properties of the nanocomposites. The cytotoxicity results suggested that the prepared nanomaterials were toxic and inhibitory efficiency to human kidney cancer cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparative Effect of Quercetin and Quercetin-3-O-β-d-Glucoside on Fibrin Polymers, Blood Clots, and in Rodent Models.

PubMed

Choi, Jun-Hui; Kim, Kyung-Je; Kim, Seung

2016-11-01

The present study evaluates the in vitro, in vivo, and ex vivo antithrombotic and anticoagulant effect of two flavonoids: quercetin and quercetin-3-O-β-d-glucoside (isoquercetin). The present results have shown that quercetin and isoquercetin inhibit the enzymatic activity of thrombin and FXa and suppress fibrin clot formation and blood clotting. The prolongation effect of quercetin and isoquercetin against epinephrine and collagen-induced platelet activation may have been caused by intervention in intracellular signaling pathways including coagulation cascade and aggregation response on platelets and blood. The in vivo and ex vivo anticoagulant efficacy of quercetin and isoquercetin was evaluated in thrombin-induced acute thromboembolism model and in ICR mice. Our findings showed that in vitro and in vivo inhibitory effects of quercetin were slightly higher than that of quercetin glucoside, whereas in vitro and ex vivo anticoagulant effects of quercetin were weaker than that of quercetin glucoside because of their structural characteristics. © 2016 Wiley Periodicals, Inc.

Pharmacokinetic comparison between quercetin and quercetin 3-O-β-glucuronide in rats by UHPLC-MS/MS

NASA Astrophysics Data System (ADS)

Yang, Le-Le; Xiao, Na; Li, Xiao-Wei; Fan, Yong; Alolga, Raphael N.; Sun, Xiao-Yue; Wang, Shi-Lei; Li, Ping; Qi, Lian-Wen

2016-10-01

Quercetin is a natural flavonoid widely distributed in human diet and functional foods. Quercetin 3-O-β-glucuronide (Q3G) is present in wine and some medicinal plants. Quercetin and Q3G may be metabolized from each other in vivo. While quercetin has been the subject of many studies, the pharmacokinetic profiles of quercetin and Q3G (in animals) have not yet been compared. Herein, we prepared a column-based method for rapid isolation of Q3G from Nelumbo nucifera. Then, we developed an UHPLC-MS/MS method to compare the pharmacokinetics of quercetin and Q3G. Our results showed that the plasma concentration-time curves of quercetin and Q3G show two maxima (Tmax1 ≈ 0.75 h, Tmax2 ≈ 5 h). After oral administration of 100 mg/kg quercetin or 100 mg/kg Q3G in rats, predominantly Q3G was detected in plasma with AUC at 39529.2 ± 6108.2 mg·h·L-1 or 24625.1 ± 1563.8 mg·h·L-1, 18-fold higher than quercetin with AUC at 1583.9 ± 583.3 mg·h·L-1 or 1394.6 ± 868.1 mg·h·L-1, respectively. After intravenous injection of 10 mg/kg in rats, Q3G showed extensive tissue uptake in kidney (409.2 ± 118.4 ng/g), liver (166.1 ± 52.9 ng/g), heart (97.7 ± 22.6 ng/g), and brain (5.8 ± 1.2 ng/g). In conclusion, we have shown that Q3G is a major active component in plasma and tissue for oral administration of quercetin or Q3G.

Quercetin Lowers Plasma Triglycerides Accompanied by White Adipose Tissue Browning in Diet-Induced Obese Mice.

PubMed

Kuipers, Eline N; Dam, Andrea D van; Held, Ntsiki M; Mol, Isabel M; Houtkooper, Riekelt H; Rensen, Patrick C N; Boon, Mariëtte R

2018-06-16

Obesity and dyslipidemia are major risk factors for the development of cardiovascular diseases (CVD). Quercetin, a natural flavonoid, lowers plasma triglycerides (TG) in human intervention studies, and its intake is associated with lower CVD risk. The aim of this study was to elucidate the mechanism by which quercetin lowers plasma TG levels in diet-induced obesity. C57Bl/6J mice received a high-fat diet (45% of calories derived from fat) with or without quercetin (0.1% w / w ) for 12 weeks. Quercetin decreased plasma TG levels from nine weeks onwards (−19%, p < 0.05), without affecting food intake, body composition, or energy expenditure. Mechanistically, quercetin did not reduce intestinal fatty acid (FA) absorption. Rather, quercetin induced a slight reduction in liver Apob expression (−13%, p < 0.05), which suggests decreased very-low density lipoprotein-TG production. Interestingly, quercetin also markedly increased the uptake of [³H]oleate, which was derived from glycerol tri[³H]oleate-labeled lipoprotein-like particles by subcutaneous white adipose tissue (sWAT, +60%, p < 0.05). Furthermore, quercetin also markedly increased mRNA expression of Ucp1 (+229%, p < 0.05) and Elovl3 (+138%, p < 0.05), specifically in sWAT. Accordingly, only quercetin-treated animals showed uncoupling protein-1 protein-positive cells in sWAT, which is fully compatible with increased browning. Taken together, the TG-lowering effect of quercetin may, at least in part, be due to increased TG-derived FA uptake by sWAT as a consequence of browning.

Metabolic profile of the bioactive compounds of burdock (Arctium lappa) seeds, roots and leaves.

PubMed

Ferracane, Rosalia; Graziani, Giulia; Gallo, Monica; Fogliano, Vincenzo; Ritieni, Alberto

2010-01-20

In this work the bioactive metabolic profile, the antioxidant activity and total phenolic content of burdock (Arctium lappa) seeds, leaves and roots were obtained. TEAC values and total phenolic content for hydro-alcoholic extracts of burdock ranged from 67.39 to 1.63 micromol Trolox equivalent/100g dry weight (DW), and from 2.87 to 45 g of gallic acid equivalent/100g DW, respectively. Phytochemical compounds were analyzed by liquid chromatography coupled to electrospray tandem mass spectrometry (LC/MS/MS) in negative mode. The main compounds of burdock extracts were caffeoylquinic acid derivatives, lignans (mainly arctiin) and various flavonoids. The occurrence of some phenolic acids (caffeic acid, chlorogenic acid and cynarin) in burdock seeds; arctiin, luteolin and quercetin rhamnoside in burdock roots; phenolic acids, quercetin, quercitrin and luteolin in burdock leaves was reported for the first time.

The effect of quercetin dietary supplementation on meat oxidation processes and texture of fattening lambs.

PubMed

Andrés, S; Huerga, L; Mateo, J; Tejido, M L; Bodas, R; Morán, L; Prieto, N; Rotolo, L; Giráldez, F J

2014-02-01

Thirty two lambs were fed a total mixed ration (TMR) formulated either with palm oil (CTRL; 34 g palm oil kg(-1) TMR) or whole flaxseed (+FS, 85 g flaxseed kg(-1) TMR) alone or enriched with quercetin (+QCT, 34 g palm oil plus 2 g quercetin kg(-1) TMR; +FS+QCT, 85 g flaxseed plus 2 g quercetin kg(-1) TMR). Dietary flaxseed did not affect, in a significant manner, the lipid peroxidation of meat samples. Quercetin treatment reduced oxysterol content (P<0.05) after 7 days of refrigerated storage of fresh meat, but did not affect significantly (P>0.05) the level of lipid-derived volatiles in the headspace of the light-exposed stored cooked meat. Sensory evaluation showed flaxseed as being responsible for a negative effect on meat flavour, probably associated with a modification of the fatty acid profile whereas, unexpectedly, quercetin seemed to worsen meat tenderisation. © 2013.

Functionalized ZnO Nanoparticles with Gallic Acid for Antioxidant and Antibacterial Activity against Methicillin-Resistant S. aureus

PubMed Central

Lee, Joo Min; Choi, Kyong-Hoon; Min, Jeeeun; Kim, Ho-Joong; Jee, Jun-Pil; Park, Bong Joo

2017-01-01

In this study, we report a new multifunctional nanoparticle with antioxidative and antibacterial activities in vitro. ZnO@GA nanoparticles were fabricated by coordinated covalent bonding of the antioxidant gallic acid (GA) on the surface of ZnO nanoparticles. This addition imparts both antioxidant activity and high affinity for the bacterial cell membrane. Antioxidative activities at various concentrations were evaluated using a 2,2′-azino-bis(ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging method. Antibacterial activities were evaluated against Gram-positive bacteria (Staphylococcus aureus: S. aureus), including several strains of methicillin-resistant S. aureus (MRSA), and Gram-negative bacteria (Escherichia coli). The functionalized ZnO@GA nanoparticles showed good antioxidative activity (69.71%), and the bactericidal activity of these nanoparticles was also increased compared to that of non-functionalized ZnO nanoparticles, with particularly effective inhibition and high selectivity for MRSA strains. The results indicate that multifunctional ZnO nanoparticles conjugated to GA molecules via a simple surface modification process displaying both antioxidant and antibacterial activity, suggesting a possibility to use it as an antibacterial agent for removing MRSA. PMID:29099064

Characterization of putative receptors specific for quercetin on bovine aortic smooth-muscle cells

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

Yu, S.C.; Becker, C.G.

The authors have reported that tobacco glycoprotein (TGP), rutin-bovine serum albumin conjugates (R-BSA), quercetin, and chlorogenic acid are mitogenic for bovine aortic smooth-muscle cells (SMC). To investigate whether there are binding sites or receptors for these polyphenol-containing molecules on SMC, the authors have synthesized /sup 125/I-labeled rutin-bovine serum albumin ((/sup 125/I)R-BSA) of high specific activity (20 Ci/mmol). SMC were isolated from a bovine thoracic aorta and maintained in Eagle's minimum essential medium with 10% calf serum in culture. These SMC at early subpassages were suspended (3-5 x 10/sup 7/ cells/ml) in phosphate-buffered saline and incubated with (/sup 125/I)R-BSA (10 pmol)more » in the presence or absence of 200-fold unlabeled R-BSA, TGP, BSA, rutin, quercetin or related polyphenols, and catecholamines. Binding of (/sup 125/I)R-BSA to SMC was found to be reproducible and the radioligand was displaced by R-BSA, and also by TGP, rutin, quercetin, and chlorogenic acid, but not by BSA, ellagic acid, naringin, hesperetin, dopamine, epinephrine, or isoproterenol. The binding was saturable, reversible, and pH-dependent. These results demonstrate the presence of specific binding sites for quercetinon arterial SMC.« less

Gallic acid conjugated with gold nanoparticles: antibacterial activity and mechanism of action on foodborne pathogens

PubMed Central

Rattanata, Narintorn; Klaynongsruang, Sompong; Leelayuwat, Chanvit; Limpaiboon, Temduang; Lulitanond, Aroonlug; Boonsiri, Patcharee; Chio-Srichan, Sirinart; Soontaranon, Siriwat; Rugmai, Supagorn; Daduang, Jureerut

2016-01-01

Foodborne pathogens, including Plesiomonas shigelloides and Shigella flexneri B, are the major cause of diarrheal endemics worldwide. Antibiotic drug resistance is increasing. Therefore, bioactive compounds with antibacterial activity, such as gallic acid (GA), are needed. Gold nanoparticles (AuNPs) are used as drug delivery agents. This study aimed to conjugate and characterize AuNP–GA and to evaluate the antibacterial activity. AuNP was conjugated with GA, and the core–shell structures were characterized by small-angle X-ray scattering and transmission electron microscopy. Antibacterial activity of AuNP–GA against P. shigelloides and S. flexneri B was evaluated by well diffusion method. AuNP–GA bactericidal mechanism was elucidated by Fourier transform infrared microspectroscopic analysis. The results of small-angle X-ray scattering showed that AuNP–GA conjugation was successful. Antibacterial activity of GA against both bacteria was improved by conjugation with AuNP because the minimum inhibitory concentration value of AuNP–GA was significantly decreased (P<0.0001) compared to that of GA. Fourier transform infrared analysis revealed that AuNP–GA resulted in alterations of lipids, proteins, and nucleic acids at the bacterial cell membrane. Our findings show that AuNP–GA has potential for further application in biomedical sciences. PMID:27555764

Gallic acid conjugated with gold nanoparticles: antibacterial activity and mechanism of action on foodborne pathogens.

PubMed

Rattanata, Narintorn; Klaynongsruang, Sompong; Leelayuwat, Chanvit; Limpaiboon, Temduang; Lulitanond, Aroonlug; Boonsiri, Patcharee; Chio-Srichan, Sirinart; Soontaranon, Siriwat; Rugmai, Supagorn; Daduang, Jureerut

2016-01-01

Foodborne pathogens, including Plesiomonas shigelloides and Shigella flexneri B, are the major cause of diarrheal endemics worldwide. Antibiotic drug resistance is increasing. Therefore, bioactive compounds with antibacterial activity, such as gallic acid (GA), are needed. Gold nanoparticles (AuNPs) are used as drug delivery agents. This study aimed to conjugate and characterize AuNP-GA and to evaluate the antibacterial activity. AuNP was conjugated with GA, and the core-shell structures were characterized by small-angle X-ray scattering and transmission electron microscopy. Antibacterial activity of AuNP-GA against P. shigelloides and S. flexneri B was evaluated by well diffusion method. AuNP-GA bactericidal mechanism was elucidated by Fourier transform infrared microspectroscopic analysis. The results of small-angle X-ray scattering showed that AuNP-GA conjugation was successful. Antibacterial activity of GA against both bacteria was improved by conjugation with AuNP because the minimum inhibitory concentration value of AuNP-GA was significantly decreased (P<0.0001) compared to that of GA. Fourier transform infrared analysis revealed that AuNP-GA resulted in alterations of lipids, proteins, and nucleic acids at the bacterial cell membrane. Our findings show that AuNP-GA has potential for further application in biomedical sciences.

Quercetin Feeding in Newborn Dairy Calves Cannot Compensate Colostrum Deprivation: Study on Metabolic, Antioxidative and Inflammatory Traits

PubMed Central

Gruse, Jeannine; Kanitz, Ellen; Weitzel, Joachim M.; Tuchscherer, Armin; Stefaniak, Tadeusz; Jawor, Paulina; Wolffram, Siegfried; Hammon, Harald M.

2016-01-01

Immaturity of the neonatal immune system is causative for high morbidity in calves and colostrum intake is crucial for acquiring passive immunity. Pathogenesis is promoted by reactive oxygen species accumulating at birth if counter-regulation is inadequate. The flavonol quercetin exerts antioxidative and anti-inflammatory effects that may enhance neonatal health. The aim of this work was to study effects of quercetin feeding on metabolic, antioxidative and inflammatory parameters in neonatal calves to investigate whether quercetin could compensate for insufficient colostrum supply. Twenty-eight newborn calves were assigned to two dietary groups fed colostrum or milk-based formula on day 1 and 2 and milk replacer thereafter. From day 2 onwards, 7 calves per diet group were additionally fed quercetin aglycone (50 mg/(kg body weight × day)). Blood samples were taken repeatedly to measure plasma concentrations of flavonols, glucose, lactate, total protein, albumin, urea, non-esterified fatty acids, triglycerides, cholesterol, insulin, glucagon, cortisol, immunoglobulins, fibrinogen, haptoglobin and serum amyloid A. Trolox equivalent antioxidative capacity, ferric reducing ability of plasma, thiobarbituric acid reactive species and F2-isoprostanes were analyzed to evaluate plasma antioxidative status. Expression of tumor necrosis factor, interleukin-1α, interleukin-1β, serum amyloid A, haptoglobin, fibrinogen, C-reactive protein, catalase, glutathione peroxidase and superoxide dismutase mRNA were measured in liver tissue on day 8. Plasma flavonol concentrations were detectable only after quercetin-feeding without differences between colostrum and formula feeding. Plasma glucose, lactate, total protein, immunoglobulins, triglycerides, cholesterol, trolox equivalent antioxidative capacity and thiobarbituric acid reactive species were higher after colostrum feeding. Body temperature, fecal fluidity and plasma concentrations of cortisol and haptoglobin were higher in

The activity of ferulic and gallic acids in biofilm prevention and control of pathogenic bacteria.

PubMed

Borges, Anabela; Saavedra, Maria J; Simões, Manuel

2012-01-01

The activity of two phenolic acids, gallic acid (GA) and ferulic acid (FA) at 1000 μg ml(-1), was evaluated on the prevention and control of biofilms formed by Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Listeria monocytogenes. In addition, the effect of the two phenolic acids was tested on planktonic cell susceptibility, bacterial motility and adhesion. Biofilm prevention and control were tested using a microtiter plate assay and the effect of the phenolic acids was assessed on biofilm mass (crystal violet staining) and on the quantification of metabolic activity (alamar blue assay). The minimum bactericidal concentration for P. aeruginosa was 500 μg ml(-1) (for both phenolic acids), whilst for E. coli it was 2500 μg ml(-1) (FA) and 5000 μg ml(-1) (GA), for L. monocytogenes it was >5000 μg ml(-1) (for both phenolic acids), and for S. aureus it was 5000 μg ml(-1) (FA) and >5000 μg ml(-1) (GA). GA caused total inhibition of swimming (L. monocytogenes) and swarming (L. monocytogenes and E. coli) motilities. FA caused total inhibition of swimming (L. monocytogenes) and swarming (L. monocytogenes and E. coli) motilities. Colony spreading of S. aureus was completely inhibited by FA. The interference of GA and FA with bacterial adhesion was evaluated by the determination of the free energy of adhesion. Adhesion was less favorable when the bacteria were exposed to GA (P. aeruginosa, S. aureus and L. monocytogenes) and FA (P. aeruginosa and S. aureus). Both phenolics had preventive action on biofilm formation and showed a higher potential to reduce the mass of biofilms formed by the Gram-negative bacteria. GA and FA promoted reductions in biofilm activity >70% for all the biofilms tested. The two phenolic acids demonstrated the potential to inhibit bacterial motility and to prevent and control biofilms of four important human pathogenic bacteria. This study also emphasizes the potential of phytochemicals as an emergent source of biofilm

Nanoparticle mediated brain targeted delivery of gallic acid: in vivo behavioral and biochemical studies for improved antioxidant and antidepressant-like activity.

PubMed

Nagpal, Kalpana; Singh, Shailendra Kumar; Mishra, Dina Nath

2012-11-01

Gallic acid had been reported to possess antidepressant like activity, which may be attributed to its CNS effects like increase in reduced glutathione levels, increased catalase activity and decreased malonaldehyde levels in brain. This study was designed to enhance the antidepressant-like activity of gallic acid (GA) using nanoparticulate delivery system in swiss male albino mice and to explore the possible underlying mechanisms for this activity. GA loaded chitosan nanoparticles (GANP) and corresponding tween 80 coated batch (cGANP) were formulated for brain targeting of GA and characterized for physicochemical parameters, morphology, differential scanning calorimetry and in vitro drug release. GA, GANP, cGANP (dose equivalent to GA 10 mg/kg, i.p.) and positive control drug, Fluoxetine (10 mg/kg, i.p.) were administered for successive seven days to male swiss albino mice. Then, the in vivo antidepressant-like activity was evaluated using Despair Swim Test (DST) and Tail Suspension Test (TST); along with the evaluation of MAO-A activity, reduced glutathione, malonaldehyde level, catalase and locomotor activity in mice. KEYFINDINGS: cGANP (equivalent to 10 mg/kg, i.p.) significantly decreased immobility period of mice in DST and TST, indicating significant antidepressant-like activity. There was no significant effect on locomotor activity of the mice by GA and its nanoparticle formulations. cGANP (10 mg/kg, i.p.) significantly decreased Monoamine oxidase-A (MAO-A) activity, malondialdehyde levels, and catalase activity in mice. GA possess significant antidepressant like activity and ligand coated nanoparticle approach with improved brain targeting may serve as an effective approach to enhance such effect.

Quercetin-induced apoptosis prevents EBV infection

PubMed Central

Lee, Minjung; Son, Myoungki; Ryu, Eunhyun; Shin, Yu Su; Kim, Jong Gwang; Kang, Byung Woog; Sung, Gi-Ho; Cho, Hyosun; Kang, Hyojeung

2015-01-01

Epstein-Barr virus (EBV) is a human gamma-1 herpesvirus that establishes a lifelong latency in over 90% of the world's population. During latency, virus exists predominantly as a chromatin-associated, multicopy episome in the nuclei of a variety of tumor cells derived from B cells, T cells, natural killer (NK) cells, and epithelial cells. Licorice is the root of Glycyrrhiza uralensis or G. glabra that has traditionally cultivated in eastern part of Asia. Licorice was reported to have anti-viral, anti-inflammatory, anti-atopic, hepatoprotective, anti-neurodegenerative, anti-tumor, anti-diabetic effects and so forth. Quercetin and isoliquiritigenin are produced from licorice and highly similar in molecular structure. They have diverse bioactive effects such as antiviral activity, anti-asthmatic activity, anti-cancer activity, anti-inflammation activity, monoamine-oxidase inhibitor, and etc. To determine anti-EBV and anti-EBVaGC (Epstein-Barr virus associated gastric carcinoma) effects of licorice, we investigated antitumor and antiviral effects of quercetin and isoliquiritigenin against EBVaGC. Although both quercetin and isoliquiritigenin are cytotoxic to SNU719 cells, quercetin induced more apoptosis in SNU719 cells than isoliquiritigenin, more completely eliminated DNMT1 and DNMT3A expressions than isoliquiritigenin, and more strongly affects the cell cycle progression of SNU719 than isoliquiritigenin. Both quercetin and isoliquiritigenin induce signal transductions to stimulate apoptosis, and induce EBV gene transcription. Quercetin enhances frequency of F promoter use, whereas isoliquiritigenin enhances frequency of Q promoter use. Quercetin reduces EBV latency, whereas isoliquiritigenin increases the latency. Quercetin increases more the EBV progeny production, and inhibits more EBV infection than isoliquiritigenin. These results indicate that quercetin could be a promising candidate for antiviral and antitumor agents against EBV and human gastric carcinoma

Development and validation of High-performance Thin-layer Chromatography Method for Simultaneous Determination of Polyphenolic Compounds in Medicinal Plants.

PubMed

Jayachandran Nair, C V; Ahamad, Sayeed; Khan, Washim; Anjum, Varisha; Mathur, Rajani

2017-12-01

Quantitative standardization of plant-based products is challenging albeit essential to maintain their quality. This study aims to develop and validate high-performance thin-layer chromatography (HPTLC) method for the simultaneous determination of rutin (Ru), quercetin (Qu), and gallic acid (Ga) from Psidium guajava Linn. (PG) and Aegle marmelos (L.) Correa. (AM) and correlate with antioxidant activity. The stock solution (1 mg/mL) of standard Ru, Qu, and Ga in methanol: Water (1:1) was serially diluted and spotted (5 μL) on slica gel 60 F 254 thin-layer chromatography plates. Toluene: Ethyl acetate: Formic acid: Methanol (3:4:0.8:0.7, v/v/v) was selected as mobile phase for analysis at 254 nm. Hydroalcoholic (1:1) extracts of leaves of PG and AM were fractionated and similarly analyzed. Antioxidant activity was also determined using 2, 2-diphenyl-1-picrylhydrazyl assay. The developed method was robust and resolved Ru, Qu, and Ga at R f 0.08 ± 0.02, 0.76 ± 0.01, and 0.63 ± 0.02, respectively. The intra-day, interday precision, and interanalyst were <2% relative standard deviation. The limit of detection and limit of quantification for Ru, Qu, and Ga were 4.51, 4.2, 5.27, and 13.67, 12.73, 15.98 ng/spot, respectively. Antioxidant activity (Log 50% inhibition) of PG and AM was 4.947 ± 0.322 and 6.498 ± 0.295, respectively. The developed HPTLC method was rapid, accurate, precise, reproducible, and specific for the simultaneous estimation of Ru, Qu, and Ga. HPTLC method for simultaneous determination and quantification of Rutin, Quercetin and Gallic acid, is reported for quality control of herbal drugs. Abbreviations Used: A: Aqueous fraction; AM: Aegle marmelos L. Correa; B: Butanol fraction; C: Chloroform fraction; EA: Ethyl acetate fraction; Ga: Gallic acid; H: Hexane fraction; HA: Hydroalcoholic extract; HPTLC: High-performance thin-layer chromatography; PG: Psidium guajava ; Qu: Quercetin; Ru: Rutin.

Quercetin loaded biopolymeric colloidal particles prepared by simultaneous precipitation of quercetin with hydrophobic protein in aqueous medium.

PubMed

Patel, Ashok R; Heussen, Patricia C M; Hazekamp, Johan; Drost, Ellen; Velikov, Krassimir P

2012-07-15

Quercetin loaded biopolymeric colloidal particles were prepared by precipitating quercetin (water insoluble polyphenol) and zein (hydrophobic protein), simultaneously, by adding their hydro-alcoholic solution to aqueous solution in presence of sodium caseinate as an electrosteric stabiliser. The presence of protein resulted in altering the shape of quercetin precipitates from needle-like to spherical shape at higher zein proportions, as confirmed by transmission electron microscopy. The average particle size of zein:quercetin composite particles was below 200 nm (130-161 nm) with negative surface charge (-30 to -41 mV), as confirmed by dynamic light scattering and electrophoretic mobility data. Solid state characterisation (X-ray diffraction) and spectroscopic measurements (UV-Vis and IR spectroscopy) confirmed characteristic changes in quercetin due to the entrapment in the biopolymeric matrix of colloidal particles. Results from anti-oxidant study demonstrated the advantage of entrapping quercetin in the colloidal particles in terms of the chemical stability in the alkaline pH and against photodegradation under UV-light irradiation. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Tissue Distribution and Urinary Excretion Study of Gallic Acid and Protocatechuic Acid after Oral Administration of Polygonum Capitatum Extract in Rats.

PubMed

Ma, Feng-Wei; Deng, Qing-Fang; Zhou, Xin; Gong, Xiao-Jian; Zhao, Yang; Chen, Hua-Guo; Zhao, Chao

2016-03-24

In the present study, we investigated the tissue distribution and urinary excretion of gallic acid (GA) and protocatechuic acid (PCA) after rat oral administration of aqueous extract of Polygonum capitatum (P. capitatum, named Herba Polygoni Capitati in China). An UHPLC-MS/MS analytical method was developed and adopted for quantification of GA and PCA in different tissue homogenate and urine samples. Interestingly, we found that GA and PCA showed a relatively targeted distribution in kidney tissue after dosing 60 mg/kg P. capitatum extract (equivalent to 12 mg/kg of GA and 0.9 mg/kg of PCA). The concentrations of GA and PCA in the kidney tissue reached 1218.62 ng/g and 43.98 ng/g, respectively, at one hour after oral administration. The results helped explain the empirical use of P. capitatum for kidney diseases in folk medicine. Further studies on urinary excretion of P. capitatum extract indicated that GA and PCA followed a concentrated elimination over a 4-h period. The predominant metabolites were putatively identified to be 4-methylgallic acid (4-OMeGA) and 4-methylprotocatechuic acid (4-OMePCA) by analyzing their precursor ions and characteristic fragment ions using tandem mass spectrometry. However, the amount of unchanged GA and PCA that survived the metabolism were about 14.60% and 15.72% of the total intake, respectively, which is reported for the first time in this study.

Changes in composition and enamel demineralization inhibition activities of gallic acid at different pH values.

PubMed

Zhang, Jingyang; Huang, Xuelian; Huang, Shengbin; Deng, Meng; Xie, Xincheng; Liu, Mingdong; Liu, Hongling; Zhou, Xuedong; Li, Jiyao; Ten Cate, Jacob Martien

2015-01-01

Gallic acid (GA) has been shown to inhibit demineralization and enhance remineralization of enamel; however, GA solution is highly acidic. This study was to investigate the stability of GA solutions at various pH and to examine the resultant effects on enamel demineralization. The stability of GA in H2O or in phosphate buffer at pH 5.5, pH 7.0 and pH 10.0 was evaluated qualitatively by ultraviolet absorption spectra and quantified by high performance liquid chromatography with diode array detection (HPLC-DAD). Then, bovine enamel blocks were subjected to a pH-cycling regime of 12 cycles. Each cycle included 5 min applications with one of the following treatments: 1 g/L NaF (positive control), 4 g/L GA in H2O or buffered at pH 5.5, pH 7.0 and pH 10.0 and buffers without GA at the same pH (negative control), followed by a 60 min application with pH 5.0 acidic buffers and a 5 min application with neutral buffers. The acidic buffers were analysed for dissolved calcium. GA was stable in pure water and acidic condition, but was unstable in neutral and alkaline conditions, in which ultraviolet spectra changed and HPLC-DAD analysis revealed that most of the GA was degraded. All the GA groups significantly inhibited demineralization (p < 0.05) and there was no significant difference of the inhibition efficacy among different GA groups (p > 0.05). GA could inhibit enamel demineralization and the inhibition effect is not influenced by pH. GA could be a useful source as an anti-cariogenic agent for broad practical application.

Quantification of quercetin glycosides in 6 onion cultivars and comparisons of hydrolysis-HPLC and spectrophotometric methods in measuring total quercetin concentrations.

PubMed

Yoo, Kil Sun; Lee, Eun Jin; Patil, Bhimanagouda S

2010-03-01

This study was performed to purify and quantify quercetin glycosides (QG) and aglycone (free) quercetin (Q) in 6 selected onion cultivars and to compare analytical approaches based on high-performance liquid chromatography (HPLC) and spectrophotometry for the quantification of total quercetin (TQ) concentrations. Individual mono- and di-glycoside Q compounds were purified using a semipreparative HPLC and identified by comparing spectral data and by confirming corresponding peaks of QG and Q after incomplete enzyme-hydrolysis. Purified QG were quantified as Q by enzyme-hydrolysis/HPLC. TQ concentrations obtained from 20 onion bulbs with enzyme-hydrolysis/HPLC, no-hydrolysis/HPLC, and a spectrophotometric method without prior hydrolysis were significantly correlated (r(2)= 0.99) and were about 15% higher, identical, or 10% less than those concentrations by a standard acid-hydrolysis/HPLC method, respectively. During enzyme-hydrolysis of onion extracts, progressive reduction of the QG and formation of the corresponding mono-glycosides and Q were monitored using an analytical HPLC. TQ ranged from 83 to 330 microg/g F.W. in 6 selected cultivars of long-day or short-day onions. Q3,4'G and Q4'G were the 2 major compounds and comprised approximately between 94% and 97% of TQ in onions.

Fungal Pretreatment of Sweet Sorghum Bagasse with Combined CuSO4-Gallic Acid Supplement for Improvement in Lignin Degradation, Selectivity, and Enzymatic Saccharification.

PubMed

Mishra, Vartika; Jana, Asim K

2017-09-01

Sweet sorghum (Sorghum sp.) has high biomass yield. Hydrolysis of lignocellulosic sweet sorghum bagasse (SSB) to fermentable sugar could be useful for manufacture of biofuel or other fermentation products. Pretreatment of lignocellulosic biomass to degrade lignin before enzymatic hydrolysis is a key step. Fungal pretreatment of SSB with combined CuSO 4 -gallic acid supplements in solid-state fermentation (SSF) to achieve higher lignin degradation, selectivity value (SV), and enzymatic hydrolysis to sugar was studied. Coriolus versicolor was selected due to high activities of ligninolytic enzymes laccase, lignin peroxidase (LiP), manganese peroxidase (MnP), polyphenol oxidase (PPO), and arylalcohol oxidase (AAO) and low activities of cellulolytic enzymes CMCase, FPase, and β-glucosidase with high lignin degradation and SV in 20 days. CuSO 4 /gallic acid increased the activities of ligninolytic enzymes resulting in enhanced lignin degradations and SVs. Cumulative/synergistic effect of combined supplements further increased the activities of laccase, LiP, MnP, PPO, and AAO by 7.6, 14.6, 2.67, 2.06, and 2.15-folds, respectively (than control), resulting in highest lignin degradation 31.1 ± 1.4% w/w (1.56-fold) and SV 2.33 (3.58-fold). Enzymatic hydrolysis of pretreated SSB yielded higher (~2.2 times) fermentable sugar. The study showed combined supplements can improve fungal pretreatment of lignocellulosic biomass. XRD, SEM, FTIR, and TGA/DTG of SSB confirmed the results.

Gallic acid regulates skin photoaging in UVB-exposed fibroblast and hairless mice.

PubMed

Hwang, Eunson; Park, Sang-Yong; Lee, Hyun Ji; Lee, Tae Youp; Sun, Zheng-Wang; Yi, Tae Hoo

2014-12-01

Ultraviolet (UV) radiation is the primary factor in skin photoaging, which is characterized by wrinkle formation, dryness, and thickening. The mechanisms underlying skin photoaging are closely associated with degradation of collagen via upregulation of matrix metalloproteinase (MMP) activity, which is induced by reactive oxygen species (ROS) production. Gallic acid (GA), a phenolic compound, possesses a variety of biological activities including antioxidant and antiinflammatory activities. We investigated the protective effects of GA against photoaging caused by UVB irradiation using normal human dermal fibroblasts (NHDFs) in vitro and hairless mice in vivo. The production levels of ROS, interlukin-6, and MMP-1 were significantly suppressed, and type I procollagen expression was stimulated in UVB-irradiated and GA-treated NHDFs. GA treatment inhibited the activity of transcription factor activation protein 1. The effects of GA following topical application and dietary administration were examined by measuring wrinkle formation, histological modification, protein expression, and physiological changes such as stratum corneum hydration, transepidermal water loss, and erythema index. We found that GA decreased dryness, skin thickness, and wrinkle formation via negative modulation of MMP-1 secretion and positive regulation of elastin, type I procollagen, and transforming growth factor-β1. Our data indicate that GA is a potential candidate for the prevention of UVB-induced premature skin aging. Copyright © 2014 John Wiley & Sons, Ltd.

Gallic Acid as an Oxygen Scavenger in Bio-Based Multilayer Packaging Films

PubMed Central

Pant, Astrid F.; Sängerlaub, Sven; Müller, Kajetan

2017-01-01

Oxygen scavengers are used in food packaging to protect oxygen-sensitive food products. A mixture of gallic acid (GA) and sodium carbonate was used as an oxygen scavenger (OSc) in bio-based multilayer packaging films produced in a three-step process: compounding, flat film extrusion, and lamination. We investigated the film surface color as well as oxygen absorption at different relative humidities (RHs) and temperatures, and compared the oxygen absorption of OSc powder, monolayer films, and multilayer films. The films were initially brownish-red in color but changed to greenish-black during oxygen absorption under humid conditions. We observed a maximum absorption capacity of 447 mg O2/g GA at 21 °C and 100% RH. The incorporation of GA into a polymer matrix reduced the rate of oxygen absorption compared to the GA powder because the polymer acted as a barrier to oxygen and water vapor diffusion. As expected, the temperature had a significant effect on the initial absorption rate of the multilayer films; the corresponding activation energy was 75.4 kJ/mol. Higher RH significantly increased the oxygen absorption rate. These results demonstrate for the first time the production and the properties of a bio-based multilayer packaging film with GA as the oxygen scavenger. Potential applications include the packaging of food products with high water activity (aw > 0.86). PMID:28772849

Gallic Acid as an Oxygen Scavenger in Bio-Based Multilayer Packaging Films.

PubMed

Pant, Astrid F; Sängerlaub, Sven; Müller, Kajetan

2017-05-03

Oxygen scavengers are used in food packaging to protect oxygen-sensitive food products. A mixture of gallic acid (GA) and sodium carbonate was used as an oxygen scavenger (OSc) in bio-based multilayer packaging films produced in a three-step process: compounding, flat film extrusion, and lamination. We investigated the film surface color as well as oxygen absorption at different relative humidities (RHs) and temperatures, and compared the oxygen absorption of OSc powder, monolayer films, and multilayer films. The films were initially brownish-red in color but changed to greenish-black during oxygen absorption under humid conditions. We observed a maximum absorption capacity of 447 mg O₂/g GA at 21 °C and 100% RH. The incorporation of GA into a polymer matrix reduced the rate of oxygen absorption compared to the GA powder because the polymer acted as a barrier to oxygen and water vapor diffusion. As expected, the temperature had a significant effect on the initial absorption rate of the multilayer films; the corresponding activation energy was 75.4 kJ/mol. Higher RH significantly increased the oxygen absorption rate. These results demonstrate for the first time the production and the properties of a bio-based multilayer packaging film with GA as the oxygen scavenger. Potential applications include the packaging of food products with high water activity (a w > 0.86).

Influence of gallic acid on α-amylase and α-glucosidase inhibitory properties of acarbose.

PubMed

Oboh, Ganiyu; Ogunsuyi, Opeyemi Babatunde; Ogunbadejo, Mariam Damilola; Adefegha, Stephen Adeniyi

2016-07-01

Acarbose is an antidiabetic drug which acts by inhibiting α-amylase and α-glucosidase activities but with deleterious side effects. Gallic acid (GA) is a phenolic acid that is widespread in plant foods. We therefore investigated the influence of GA on α-amylase and α-glucosidase inhibitory properties of acarbose (in vitro). Aqueous solutions of acarbose and GA were prepared to a final concentration of 25μM each. Thereafter, mixtures of the samples (50% acarbose + 50% GA; 75% acarbose+25% GA; and 25% acarbose+75% GA) were prepared. The results revealed that the combination of 50% acarbose and 50% GA showed the highest α-glucosidase inhibitory effect, while 75% acarbose+25% GA showed the highest α-amylase inhibitory effect. Furthermore, all the samples caused the inhibition of Fe 2+ -induced lipid peroxidation (in vitro) in rat pancreatic tissue homogenate, with the combination of 50% acarbose and 50% GA causing the highest inhibition. All the samples also showed antioxidant properties (reducing property, 2,2'-azino-bis (-3-ethylbenzthiazoline-6-sulphonate [ABTS*] and 1,1-diphenyl-2-picrylhydrazyl [DPPH] free radicals scavenging abilities, and Fe 2+ chelating ability). Therefore, combinations of GA with acarbose could be employed as antidiabetic therapy, with a possible reduction of side effects of acarbose; nevertheless, the combination of 50% acarbose and 50% GA seems the best. Copyright © 2016. Published by Elsevier B.V.

Quercetin attenuates zymosan-induced arthritis in mice.

PubMed

Guazelli, Carla F S; Staurengo-Ferrari, Larissa; Zarpelon, Ana C; Pinho-Ribeiro, Felipe A; Ruiz-Miyazawa, Kenji W; Vicentini, Fabiana T M C; Vignoli, Josiane A; Camilios-Neto, Doumit; Georgetti, Sandra R; Baracat, Marcela M; Casagrande, Rubia; Verri, Waldiceu A

2018-06-01

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by articular lesions, recruitment of inflammatory cells and increased levels of pro-inflammatory cytokine. The intra-articular administration of zymosan is an experimental model that promotes inflammatory parameters resembling RA. Therefore, this model was used to investigate the efficacy of quercetin as a treatment of articular inflammation. Treatment with quercetin dose-dependently reduced zymosan-induced hyperalgesia, articular edema and the recruitment of neutrophils to the knee joint cavity. Histological analysis confirmed that quercetin inhibited zymosan-induced arthritis. The treatment with quercetin also inhibited zymosan-induced depletion of reduced glutathione (GSH) levels, TNFα and IL-1β production, and gp91 phox , prepro-endothelin-1 (preproET-1), and cyclooxygenase-2 mRNA expression. These molecular effects of quercetin were related to the inhibition of the nuclear factor kappa-B and induction of Nuclear factor erythroid 2- related factor (Nrf2)/home oxygenase (HO-1) pathway. Thus, quercetin exerted anti-inflammatory, analgesic and antioxidant effects in experimental arthritis, suggesting quercetin is a possible candidate for arthritis treatment. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Effect of stevia and citric acid on the stability of phenolic compounds and in vitro antioxidant and antidiabetic capacity of a roselle (Hibiscus sabdariffa L.) beverage.

PubMed

Pérez-Ramírez, Iza F; Castaño-Tostado, Eduardo; Ramírez-de León, José A; Rocha-Guzmán, Nuria E; Reynoso-Camacho, Rosalía

2015-04-01

Plant infusions are consumed due to their beneficial effects on health, which is attributed to their bioactive compounds content. However, these compounds are susceptible to degradation during processing and storage. The objective of this research was to evaluate the effect of stevia and citric acid on the stability of phenolic compounds, antioxidant capacity and carbohydrate-hydrolysing enzyme inhibitory activity of roselle beverages during storage. The optimum extraction conditions of roselle polyphenolic compounds was of 95 °C/60 min, which was obtained by a second order experimental design. The incorporation of stevia increased the stability of colour and some polyphenols, such as quercetin, gallic acid and rosmarinic acid, during storage. In addition, stevia decreased the loss of ABTS, DPPH scavenging activity and α-amylase inhibitory capacity, whereas the incorporation of citric acid showed no effect. These results may contribute to the improvement of technological processes for the elaboration of hypocaloric and functional beverages. Copyright © 2014 Elsevier Ltd. All rights reserved.

Enhanced skin delivery of quercetin by microemulsion.

PubMed

Kitagawa, Shuji; Tanaka, Yuko; Tanaka, Manami; Endo, Kanako; Yoshii, Akiko

2009-07-01

For topical application of quercetin it is necessary to improve the low efficiency of its intradermal delivery as well as its low solubility in aqueous and organic vesicles. The aim of this study was to determine the usefulness of a microemulsion for that purpose. A microemulsion consisting of isopropyl myristate, 150 mM NaCl solution, Tween 80 and ethanol was prepared. The skin delivery of quercetin by microemulsion using excised guinea-pig and Yucatan micropig skin in Franz diffusion cells was examined. Lipid peroxidation in skin was also tested using iron(II) and citrate. Using a w/o microemulsion as a vehicle, intradermal delivery of quercetin was significantly increased, as was its solubility. Quercetin penetrated deep into the skin, but no transfer was observed into the receptor compartment. It was confirmed that quercetin retained in the skin dose-dependently inhibited lipid peroxidation. The findings indicate the potential use of microemulsions for the skin delivery of quercetin, where it exerts antioxidative effects.

Antioxidant flavonol glycosides from Schinus molle.

PubMed

Marzouk, Mohamed S; Moharram, Fatma A; Haggag, Eman G; Ibrahim, Magda T; Badary, Osama A

2006-03-01

Chromatographic separation of aqueous MeOH extract of the leaves of Schinus molle L. has yielded two new acylated quercetin glycosides, named isoquercitrin 6''-O-p-hydroxybenzoate (12) and 2''-O-alpha-L-rhamnopyranosyl-hyperin 6''-O-gallate (13), together with 12 known polyphenolic metabolites for the first time from this species, namely gallic acid (1), methyl gallate (2), chlorogenic acid (3), 2''-alpha-L-rhamnopyranosyl-hyperin (4), quercetin 3-O-beta-D-neohesperidoside (5), miquelianin (6), quercetin 3-O-beta-D-galacturonopyranoside (7), isoquercitrin (8), hyperin (9), isoquercitrin 6''-gallate (10), hyperin 6''-O-gallate (11) and (+)-catechin (14). Their structures were established on the basis of chromatographic properties, chemical, spectroscopic (UV, 1H, 13C NMR) and ESI-MS (positive and negative modes) analyses. Compounds 4-9 and 11 exhibited moderate to strong radical scavenging properties on lipid peroxidation, hydroxyl radical and superoxide anion generations with the highest activities shown by 6 and 7 in comparison with that of quercetin as a positive control in vitro. Copyright 2006 John Wiley & Sons, Ltd.

Skin penetration and antioxidant effect of cosmeto-textiles with gallic acid.

PubMed

Alonso, C; Martí, M; Barba, C; Lis, M; Rubio, L; Coderch, L

2016-03-01

In this work, the antioxidant gallic acid (GA) has been encapsulated in microspheres prepared with poly-ε-caprolactone (PCL) and incorporated into polyamide (PA) obtaining the cosmeto-textile. The topical application of the cosmeto-textile provides a reservoir effect in the skin delivery of GA. The close contact of the cosmeto-textile, containing microsphere-encapsulated GA (ME-GA), with the skin and their corresponding occlusion, may be the main reasons that explain the crossing of active principle (GA) through the skin barrier, located in the stratum corneum, and its penetration into the different compartments of the skin, epidermis and dermis. An ex vivo assessment was performed to evaluate the antioxidant effect of the ME-GA on the stratum corneum (SC) using the thiobarbituric acid-reactive species (TBARS) test. The test is based on a non-invasive ex vivo methodology that evaluates lipid peroxides formed in the outermost layers of the SC from human volunteers after UV radiation to determine the effectiveness of an antioxidant. In this case, a ME-GA cosmeto-textile or ME-GA formulation were applied to the skin in vivo and lipid peroxidation (LPO) in the horny layer were determined after UV irradiation. This methodology may be used as a quality control tool to determine ex vivo the percentage of LPO inhibition on human SC for a variety of antioxidants that are topically applied, in this case GA. Results show that LPO formation was inhibited in human SC when GA was applied directly or embedded in the cosmeto-textile, demonstrating the effectiveness of both applications. The percentage of LPO inhibition obtained after both topical applications was approximately 10% for the cosmeto-textile and 41% for the direct application of microspheres containing GA. This methodology could be used to determine the effectiveness of topically applied antioxidants encapsulated in cosmeto-textiles on human SC. Copyright © 2016 Elsevier B.V. All rights reserved.

Characterization of the Interaction between Gallic Acid and Lysozyme by Molecular Dynamics Simulation and Optical Spectroscopy

PubMed Central

Zhan, Minzhong; Guo, Ming; Jiang, Yanke; Wang, Xiaomeng

2015-01-01

The binding interaction between gallic acid (GA) and lysozyme (LYS) was investigated and compared by molecular dynamics (MD) simulation and spectral techniques. The results from spectroscopy indicate that GA binds to LYS to generate a static complex. The binding constants and thermodynamic parameters were calculated. MD simulation revealed that the main driving forces for GA binding to LYS are hydrogen bonding and hydrophobic interactions. The root-mean-square deviation verified that GA and LYS bind to form a stable complex, while the root-mean-square fluctuation results showed that the stability of the GA-LYS complex at 298 K was higher than that at 310 K. The calculated free binding energies from the molecular mechanics/Poisson-Boltzmann surface area method showed that van der Waals forces and electrostatic interactions are the predominant intermolecular forces. The MD simulation was consistent with the spectral experiments. This study provides a reference for future study of the pharmacological mechanism of GA. PMID:26140374

Characterization of the Interaction between Gallic Acid and Lysozyme by Molecular Dynamics Simulation and Optical Spectroscopy.

PubMed

Zhan, Minzhong; Guo, Ming; Jiang, Yanke; Wang, Xiaomeng

2015-07-01

The binding interaction between gallic acid (GA) and lysozyme (LYS) was investigated and compared by molecular dynamics (MD) simulation and spectral techniques. The results from spectroscopy indicate that GA binds to LYS to generate a static complex. The binding constants and thermodynamic parameters were calculated. MD simulation revealed that the main driving forces for GA binding to LYS are hydrogen bonding and hydrophobic interactions. The root-mean-square deviation verified that GA and LYS bind to form a stable complex, while the root-mean-square fluctuation results showed that the stability of the GA-LYS complex at 298 K was higher than that at 310 K. The calculated free binding energies from the molecular mechanics/Poisson-Boltzmann surface area method showed that van der Waals forces and electrostatic interactions are the predominant intermolecular forces. The MD simulation was consistent with the spectral experiments. This study provides a reference for future study of the pharmacological mechanism of GA.

Design of titanium nitride- and wolfram carbide-doped RGO/GC electrodes for determination of gallic acid.

PubMed

Stanković, Dalibor M; Ognjanović, Miloš; Martin, Fabian; Švorc, Ľubomir; Mariano, José F M L; Antić, Bratislav

2017-12-15

In the present paper, the electrochemical behavior and the properties of two modified glassy carbon (GC) electrodes used for quantification of gallic acid in sweet wines were compared. A comparative study was conducted between titanium nitride- or wolfram carbide-doped reduced graphene oxide, labeled as TNrGO and WCrGO, respectively, modified GC electrodes, which are promising composite nanomaterials for electroanalytical applications. For the first time, WCrGO was synthesized and its electroanalytical properties compared with those of TNrGO. Results showed that the proposed materials exhibited enhanced characteristics, e.g., low limits of detection (1.1 μM and 3.1 μM for TNrGO and WCrGO, respectively), wide linear ranges (for TNrGO 4.5-76 μM and for WCrGO 10-100 μM), low adsorption, and low background current, which make them promising candidates for electrochemical sensing applications. Copyright © 2017 Elsevier Inc. All rights reserved.

Gallic acid loaded PEO-core/zein-shell nanofibers for chemopreventive action on gallbladder cancer cells.

PubMed

Acevedo, Francisca; Hermosilla, Jeyson; Sanhueza, Claudia; Mora-Lagos, Barbara; Fuentes, Irma; Rubilar, Mónica; Concheiro, Angel; Alvarez-Lorenzo, Carmen

2018-07-01

Coaxial electrospinning was used to develop gallic acid (GA) loaded poly(ethylene oxide)/zein nanofibers in order to improve its chemopreventive action on human gallbladder cancer cells. Using a Plackett-Burman design, the effects of poly(ethylene oxide) and zein concentration and applied voltage on the diameter and morphology index of nanofibers were investigated. Coaxial nanofibers were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). GA loading efficiency as high as 77% was obtained under optimal process conditions. The coaxial nanofibers controlled GA release in acid and neutral pH medium. Cytotoxicity and reactive oxygen species (ROS) production on gallbladder cancer cell lines GB-d1 and NOZ in the presence of GA-nanofibers were assessed. GA-nanofibers triggered an increase in the cellular cytotoxicity compared with free GA on GB-d1 and NOZ cells. Statistically significant differences were found in ROS levels of GA-nanofibers compared with free GA on NOZ cells. Differently, ROS production on GB-d1 cell line was similar. Based on these results, the coaxial nanofibers obtained in this study under optimized operational conditions offer an alternative for the development of a GA release system with improved chemopreventive action on gallbladder cancer cells. Copyright © 2018 Elsevier B.V. All rights reserved.

Quercetin and quercetin 3-O-glycosides from Bauhinia longifolia (Bong.) Steud. show anti-Mayaro virus activity.

PubMed

dos Santos, Alda E; Kuster, Ricardo M; Yamamoto, Kristie A; Salles, Tiago S; Campos, Renata; de Meneses, Marcelo D F; Soares, Márcia R; Ferreira, Davis

2014-03-28

The arthropod-borne Mayaro virus (MAYV) causes 'Mayaro fever', a disease of medical significance, primarily affecting individuals in permanent contact with forested areas in tropical South America. Recently, MAYV has attracted attention due to its likely urbanization. Currently, there are no licensed drugs against most mosquito-transmitted viruses. Here, we investigated the in vitro anti-MAYV activity of the flavonoids quercetin and its derivatives from the Brazilian shrub Bauhinia longifolia (Bong.) Steud. Flavonoids were purified by chromatographic fractionation from leaf extracts of B. longifolia and chemically identified as quercetin and quercetin glycosides using spectroscopic techniques. Cytotoxicity of purified flavonoids and of EtOAc- and n-BuOH-containing flavonoid mixtures was measured by the dye-uptake assay while their antiviral activity was evaluated by a virus yield inhibition assay. The following flavonoids were purified from B. longifolia leaves: non-glycosylated quercetin and its glycosides guaijaverin, quercitrin, isoquercitrin, and hyperin. EtOAc and n-BuOH fractions containing these flavonoids demonstrated the highest antiviral activity of all tested substances, while quercetin had the highest antiviral activity amongst purified flavonoids. Quercetin, EtOAc, or n-BuOH fractions inhibited MAYV production by more than 90% at 25 μg/mL, displaying a stronger antiviral effect than the licensed antiviral ribavirin. A mixture of the isomers isoquercitrin and hyperin had a modest antiviral effect (IC90 = 104.9), while guaijaverin and quercitrin did not show significant antiviral activity. B. longifolia is a good source of flavonoids with anti-Mayaro virus activity. This is the first report of the activity of quercetin and its derivatives against an alphavirus.

Quercetin and quercetin 3-O-glycosides from Bauhinia longifolia (Bong.) Steud. show anti-Mayaro virus activity

PubMed Central

2014-01-01

Background The arthropod-borne Mayaro virus (MAYV) causes ‘Mayaro fever’, a disease of medical significance, primarily affecting individuals in permanent contact with forested areas in tropical South America. Recently, MAYV has attracted attention due to its likely urbanization. Currently, there are no licensed drugs against most mosquito-transmitted viruses. Here, we investigated the in vitro anti-MAYV activity of the flavonoids quercetin and its derivatives from the Brazilian shrub Bauhinia longifolia (Bong.) Steud. Methods Flavonoids were purified by chromatographic fractionation from leaf extracts of B. longifolia and chemically identified as quercetin and quercetin glycosides using spectroscopic techniques. Cytotoxicity of purified flavonoids and of EtOAc- and n-BuOH-containing flavonoid mixtures was measured by the dye-uptake assay while their antiviral activity was evaluated by a virus yield inhibition assay. Results The following flavonoids were purified from B. longifolia leaves: non-glycosylated quercetin and its glycosides guaijaverin, quercitrin, isoquercitrin, and hyperin. EtOAc and n-BuOH fractions containing these flavonoids demonstrated the highest antiviral activity of all tested substances, while quercetin had the highest antiviral activity amongst purified flavonoids. Quercetin, EtOAc, or n-BuOH fractions inhibited MAYV production by more than 90% at 25 μg/mL, displaying a stronger antiviral effect than the licensed antiviral ribavirin. A mixture of the isomers isoquercitrin and hyperin had a modest antiviral effect (IC90 = 104.9), while guaijaverin and quercitrin did not show significant antiviral activity. Conclusions B. longifolia is a good source of flavonoids with anti-Mayaro virus activity. This is the first report of the activity of quercetin and its derivatives against an alphavirus. PMID:24678592

Effect of lemongrass water extract supplementation on atherogenic index and antioxidant status in rats.

PubMed

Somparn, Nuntiya; Saenthaweeuk, Suphaket; Naowaboot, Jarinyaporn; Thaeomor, Atcharaporn; Kukongviriyapan, Veerapol

2018-06-01

Cymbopogon citratus (DC) Stapf., commonly known as lemongrass, possesses strong antioxidant and cardiotonic properties. Lemongrass water extract contains several polyphenolic compounds including gallic acid, isoquercetin, quercetin, rutin, catechin and tannic acid. Rutin, isoquercetin catechin and quercetin are the flavonoids most abundantly found in the extract. The extract significantly decreased total cholesterol, low-density lipoprotein and atherogenic index in rats after treatment (p < 0.05). Expression of genes and protein of sterol regulatory element binding protein-1c (SREBP1c) and HMG-CoA reductase (HMGR) was also lowered significantly in treated groups (p < 0.05). Moreover, serum antioxidant capacity increased in treated rats in comparison with untreated ones (p < 0.05) and was associated with decreased serum lipid peroxidation.

Discovery of a new mitochondria permeability transition pore (mPTP) inhibitor based on gallic acid.

PubMed

Teixeira, José; Oliveira, Catarina; Cagide, Fernando; Amorim, Ricardo; Garrido, Jorge; Borges, Fernanda; Oliveira, Paulo J

2018-12-01

Pharmacological interventions targeting mitochondria present several barriers for a complete efficacy. Therefore, a new mitochondriotropic antioxidant (AntiOxBEN 3 ) based on the dietary antioxidant gallic acid was developed. AntiOxBEN 3 accumulated several thousand-fold inside isolated rat liver mitochondria, without causing disruption of the oxidative phosphorylation apparatus, as seen by the unchanged respiratory control ratio, phosphorylation efficiency, and transmembrane electric potential. AntiOxBEN 3 showed also limited toxicity on human hepatocarcinoma cells. Moreover, AntiOxBEN 3 presented robust iron-chelation and antioxidant properties in both isolated liver mitochondria and cultured rat and human cell lines. Along with its low toxicity profile and high antioxidant activity, AntiOxBEN 3 strongly inhibited the calcium-dependent mitochondrial permeability transition pore (mPTP) opening. From our data, AntiOxBEN 3 can be considered as a lead compound for the development of a new class of mPTP inhibitors and be used as mPTP de-sensitiser for basic research or clinical applications or emerge as a therapeutic application in mitochondria dysfunction-related disorders.

Free and Bound Phenolic Compound Content and Antioxidant Activity of Different Cultivated Blue Highland Barley Varieties from the Qinghai-Tibet Plateau.

PubMed

Yang, Xi-Juan; Dang, Bin; Fan, Ming-Tao

2018-04-11

In this study, the polyphenols composition and antioxidant properties of 12 blue highland barley varieties planted on the Qinghai-Tibet Plateau area were measured. The contents of the free, bound and total phenolic acids varied between 166.20-237.60, 170.10-240.75 and 336.29-453.94 mg of gallic acid equivalents per 100 g of dry weight (DW) blue highland barley grains, while the free and bound phenolic acids accounted for 50.09% and 49.91% of the total phenolic acids, respectively. The contents of the free, bound and total flavones varied among 20.61-25.59, 14.91-22.38 and 37.91-47.98 mg of catechin equivalents per 100 g of dry weight (DW) of blue highland barley grains, while the free and bound flavones accounted for 55.90% and 44.10% of the total flavones, respectively. The prominent phenolic compounds in the blue hulless barley grains were gallic acid, benzoic acid, syringic acid, 4-coumaric acid, naringenin, hesperidin, rutin, (+)-catechin and quercetin. Among these, protocatechuic acid, chlorogenic acid and (+)-catechin were the major phenolic compounds in the free phenolics extract. The most abundant bound phenolics were gallic acid, benzoic acid, syringic acid, 4-coumaric acid, benzoic acid, dimethoxybenzoic acid, naringenin, hesperidin, quercetin and rutin. The average contribution of the bound phenolic extract to the DPPH • free radical scavenging capacity was higher than 86%, that of free phenolic extract to the ABTS •+ free radical scavenging capacity was higher than 79%, and that of free phenolic (53%) to the FRAP antioxidant activity was equivalent to that of the bound phenol extract (47%). In addition, the planting environment exerts a very important influence on the polyphenol composition, content and antioxidant activity of blue highland barley. The correlation analysis showed that 2,4-hydroxybenzoic acid and protocatechuic acid were the main contributors to the DPPH • and ABTS •+ free radical scavenging capacity in the free phenolic extract

Inhibitory effect of gallic acid on CCl4-mediated liver fibrosis in mice.

PubMed

Wang, Jing; Tang, Long; White, James; Fang, Jing

2014-05-01

The aim of this study was to investigate the effect of gallic acid (GA) on liver fibrosis induced by carbon tetrachloride (CCl4). Male BALB/c mice were randomly divided into four groups: normal control group (group A), CCl4-induced liver injury control group (group B), and CCl4 induction with GA of low dose (5 mg/kg) and high dose (15 mg/kg) treatment group (group C and group D). GA was intra-gastric given for mice once a day after 2 weeks of CCl4 induction. Animals were killed at the eighth week. Degrees of fibrosis and collagen percentage were measured. Hyaluronic acid (HA), type IV collagen (cIV), malondialdehyde (MDA), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (γ-GT) were determined. Expression of matrix metalloproteinases-2 (MMP-2) and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) mRNA levels were examined by RT-PCR. Western blotting was carried out to evaluate the changes of MMP-2 protein. HE and VG stainings showed GA in a dose-dependent manner improved significantly the fibrosis condition in CCl4-injured mice (P < 0.05 or P < 0.01). Also, the concentrations of HA, cIV, and MDA, as well as the serum levels of ALT, AST, and γ-GT were markedly reduced by GA (P < 0.05 or P < 0.01), and decreases in MMP-2, TIMP-1 mRNA, and MMP-2 protein were observed as well (P < 0.05 or P < 0.01). GA could exert protective effect on liver injury and reduce liver fibrosis induced by CCl4 in mice, which might be through the inhibition of hepatic stellate cell activity.

Heterogeneous photocatalytic degradation of gallic acid under different experimental conditions.

PubMed

Quici, Natalia; Litter, Marta I

2009-07-01

UV/TiO(2)-heterogeneous photocatalysis was tested as a process to degrade gallic acid (Gal) in oxygenated solutions at pH 3. In the absence of oxidants other than oxygen, decay followed a zero order rate at different concentrations and was slow at concentrations higher than 0.5 mM. Addition of Fe(3+), H(2)O(2) and the combination Fe(3+)/H(2)O(2) improved Gal degradation. In the absence of H(2)O(2), an optimal Fe : Gal molar ratio of 0.33 : 1 was found for the photocatalytic decay, beyond which addition of Fe(3+) was detrimental and even worse in comparison with the system in the absence of Fe(3+). TiO(2) addition was beneficial compared with the same system in the absence of the photocatalyst if Fe(3+) was added at low concentration (0.33 : 1 Fe : Gal molar ratio), while at high concentration (1 : 1 Fe : Gal molar ratio) TiO(2) did not exert any significant effect. H(2)O(2) addition (1 : 0.33 Gal : H(2)O(2) molar ratio, absence of Fe(iii)) also enhanced the heterogeneous photocatalytic reaction. Simultaneous addition of Fe(3+) and H(2)O(2) was more effective than the addition of the separate oxidants. This system was compared with Fenton and photo-Fenton systems. At low H(2)O(2) concentration (0.33 : 1 : 0.2 Fe : Gal : H(2)O(2) molar ratio), the presence of TiO(2) also enhanced the reaction. The influence of the thermal charge transfer reaction between Gal and Fe(iii), which leads to an important Gal depletion in the dark with formation of quinones, was analysed. The mechanisms taking place in these complex systems are proposed, paying particular attention to the important charge transfer reaction of the Fe(iii)-Gal complex operative in dark conditions.

Deciphering the chemoselectivity of nickel-dependent quercetin 2,4-dioxygenase.

PubMed

Wang, Wen-Juan; Wei, Wen-Jie; Liao, Rong-Zhen

2018-06-13

The reaction mechanism and chemoselectivity of nickel-dependent quercetin 2,4-dioxygenase (2,4-QueD) have been investigated using the QM/MM approach. The protonation state of the Glu74 residue, a first-shell ligand of Ni, has been considered to be either neutral or deprotonated. QM/MM calculations predict that Glu74 must be deprotonated to rationalize the chemoselectivity and steer the 2,4-dioxygenolytic cleavage of quercetin, which harvests the experimentally-observed product, 2-protocatechuoylphloroglucinol carboxylic acid, coupled with the release of carbon monoxide. If the enzyme has a neutral Glu74 residue, the undesired 2,3-dioxygenolytic cleavage of quercetin becomes the dominant pathway, leading to the formation of α-keto acid. The calculations suggest that the reaction takes place via three major steps: (1) attack of the superoxide on the C2 of the substrate pyrone ring to generate a NiII-peroxide intermediate; (2) formation of the second C-O bond between C4 and the peroxide to produce a peroxide bridge; (3) simultaneous cleavage of the C2-C3, C3-C4, and O1-O2 bonds with the formation of 2-protocatechuoylphloroglucinol carboxylic acid and carbon monoxide. The third step was found to be rate-limiting, with a barrier of 17.4 kcal mol-1, which is in very good agreement with the experimental kinetic data. For the second C-O bond formation, an alternative pathway is that the peroxide attacks the C3 of the substrate pyrone ring, leading to the formation of a four-membered ring intermediate, which then undergoes concerted C2-C3 and O1-O2 bond cleavages to produce an α-keto acid. This pathway is associated with a barrier of 30.6 kcal mol-1, which is much higher than the major pathway. When Glu74 is protonated, the 2,3-dioxygenolytic pathway, however, has a lower barrier (21.8 kcal mol-1) than the 2,4-dioxygenolytic pathway.

Quercetin Attenuates Vascular Calcification through Suppressed Oxidative Stress in Adenine-Induced Chronic Renal Failure Rats.

PubMed

Chang, Xue-Ying; Cui, Lei; Wang, Xing-Zhi; Zhang, Lei; Zhu, Dan; Zhou, Xiao-Rong; Hao, Li-Rong

2017-01-01

This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine. 32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d), 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS)/p38 mitogen activated protein kinase (p38MAPK) pathway was determined to explore the potential mechanism. Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA) and creatinine levels, malonaldehyde (MDA) content, and superoxide dismutase (SOD) activity in serum and the increases of calcium and alkaline phosphatase (ALP) activity in the aorta ( P < 0.05) and attenuated calcification and calcium accumulation in the medial layer of vasculature in histopathology. Western blot analysis showed that iNOS/p38MAPK pathway was normalized by the quercetin supplementation. Quercetin exerted a protective effect on vascular calcification in adenine-induced chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway.

Quercetin Attenuates Vascular Calcification through Suppressed Oxidative Stress in Adenine-Induced Chronic Renal Failure Rats

PubMed Central

Chang, Xue-ying; Cui, Lei; Wang, Xing-zhi; Zhang, Lei; Zhu, Dan

2017-01-01

Background This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine. Methods 32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d), 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS)/p38 mitogen activated protein kinase (p38MAPK) pathway was determined to explore the potential mechanism. Results Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA) and creatinine levels, malonaldehyde (MDA) content, and superoxide dismutase (SOD) activity in serum and the increases of calcium and alkaline phosphatase (ALP) activity in the aorta (P < 0.05) and attenuated calcification and calcium accumulation in the medial layer of vasculature in histopathology. Western blot analysis showed that iNOS/p38MAPK pathway was normalized by the quercetin supplementation. Conclusions Quercetin exerted a protective effect on vascular calcification in adenine-induced chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway. PMID:28691026

Myricetin, quercetin and catechin-gallate inhibit glucose uptake in isolated rat adipocytes

PubMed Central

2004-01-01

The facilitative glucose transporter, GLUT4, mediates insulin-stimulated glucose uptake in adipocytes and muscles, and the participation of GLUT4 in the pathogenesis of various clinical conditions associated with obesity, visceral fat accumulation and insulin resistance has been proposed. Glucose uptake by some members of the GLUT family, mainly GLUT1, is inhibited by flavonoids, the natural polyphenols present in fruits, vegetables and wine. Therefore it is of interest to establish if these polyphenolic compounds present in the diet, known to be effective antioxidants but also endowed with several other biological activities such as protein-tyrosine kinase inhibition, interfere with GLUT4 function. In the present study, we show that three flavonoids, quercetin, myricetin and catechin-gallate, inhibit the uptake of methylglucose by adipocytes over the concentration range of 10–100 μM. These three flavonoids show a competitive pattern of inhibition, with Ki=16, 33.5 and 90 μM respectively. In contrast, neither catechin nor gallic acid inhibit methylglucose uptake. To obtain a better understanding of the interaction among GLUT4 and flavonoids, we have derived a GLUT4 three-dimensional molecular comparative model, using structural co-ordinates from a GLUT3 comparative model and a mechanosensitive ion channel [PDB (Protein Data Bank) code 1MSL] solved by X-ray diffraction. On the whole, the experimental evidence and computer simulation data favour a transport inhibition mechanism in which flavonoids and GLUT4 interact directly, rather than by a mechanism related to protein-tyrosine kinase and insulin signalling inhibition. Furthermore, the results suggest that GLUT transporters are involved in flavonoid incorporation into cells. PMID:15469417

Apigenin and quercetin promote. Delta. pH-dependent accumulation of IAA in membrane vesicles

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

Woolard, D.D.; Clark, K.A.

1990-05-01

Flavonoids may act as regulators of polar auxin transport. In the presence of a pH gradient (pH 8{sub in}/6{sub out}) the flavonoids quercetin and apigenin, as well as the synthetic herbicide napthylphthalamic acid (NPA), promote the accumulation of IAA in membrane vesicles from dark-grown zucchini hypocotyls. Simultaneous accumulation of {sup 3}H-IAA (10 nM) and {sup 14}C-butyric acid (5 {mu}M; included as a pH probe) was determined by a filtration assay after incubating the vesicles with 3 nM to 100 {mu}M quercetin, apigenin, NPA or unlabeled IAA. Maximal stimulation (% of Control) was observed with 3 {mu}M NPA (130%), 1 {mu}Mmore » quercetin (120%), or 3 {mu}M apigenin (115%); {Delta}pH was not affected by these concentrations. As reported by others, IAA uptake was saturable: 1 {mu}M unlabeled IAA eliminated {Delta}pH-dependent uptake of {sup 3}H-IAA without altering {Delta}pH. However, at 30 to 100 {mu}M, every compound tested collapsed the imposed pH gradient and therefore abolished specific {sup 3}H-IAA uptake.« less

Quercetin, not caffeine, is a major neuroprotective component in coffee.

PubMed

Lee, Moonhee; McGeer, Edith G; McGeer, Patrick L

2016-10-01

Epidemiologic studies indicate that coffee consumption reduces the risk of Parkinson's disease and Alzheimer's disease. To determine the factors involved, we examined the protective effects of coffee components. The test involved prevention of neurotoxicity to SH-SY5Y cells that was induced by lipopolysaccharide plus interferon-γ or interferon-γ released from activated microglia and astrocytes. We found that quercetin, flavones, chlorogenic acid, and caffeine protected SH-SY5Y cells from these toxins. They also reduced the release of tumor necrosis factor-α and interleukin-6 from the activated microglia and astrocytes and attenuated the activation of proteins from P38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa light chain enhancer of activated B cells (NFκB). After exposure to toxin containing glial-stimulated conditioned medium, we also found that quercetin reduced oxidative/nitrative damage to DNA, as well as to the lipids and proteins of SH-SY5Y cells. There was a resultant increase in [GSH]i in SH-SY5Y cells. The data indicate that quercetin is the major neuroprotective component in coffee against Parkinson's disease and Alzheimer's disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Gontscharovia popovii, a new source of carvacrol, its polyphenolic constituents, essential oil analysis, total phenolic content and antioxidant activity.

PubMed

Zareiyan, Faraneh; Rowshan, Vahid; Bahmanzadegan, Atefeh; Hatami, Ahmad

2017-09-28

The experiment was carried out using the shadow-dried aerial parts including leaves and shoots of Gontscharovia popovii collected in Fars province in order to investigate the polyphenolic compositions, antioxidant activity, total phenolic content and essential oil constituents. The result showed IC 50 of 395.77 μg mL -1 and total phenolic content of about 20.01 mg g -1 gallic acid equivalent dry weight. It also showed a wild range of polyphenols such as; Gallic acid, catechin, chloregenic acid, rutin, vanillin, trans-Ferulic acid, sinapic acid, coumarin, hesperedin, quercetin, hesperetin, eugenol and carvacrol as the main detected polyphenols. Some major compounds were also detected through essential oil analysis, such as; 76.7% carvacrol, 4.25% γ-Terpinene, 3.8% p-Cymene and 2.4% (E)-Caryophyllene. Qualitative and quantitative analyses of chemical compounds of G. popovii was performed using HPLC, GC, GC/MS and microplate reader.

Quercetin in brain diseases: Potential and limits.

PubMed

Dajas, Federico; Abin-Carriquiry, Juan Andrés; Arredondo, Florencia; Blasina, Fernanda; Echeverry, Carolina; Martínez, Marcela; Rivera, Felicia; Vaamonde, Lucía

2015-10-01

Quercetin is a ubiquitous flavonoid present in beverages, food and plants that has been demonstrated to have a role in the prevention of neurodegenerative and cerebrovascular diseases. In neuronal culture, quercetin increases survival against oxidative insults. Antioxidation appears to be a necessary but not sufficient condition for its neuroprotective action and modulation of intracellular signaling and transcription factors, increasing the expression of antioxidant and pro survival proteins and modulating inflammation, appears as important for neuronal protection. Quercetin also regulates the activity of kinases, changing the phosphorylation state of target molecules, resulting in modulation of cellular function and gene expression. Concentrations of quercetin higher than 100 μM consistently show cytotoxic and apoptotic effects by its autoxidation and generation of toxic quinones. In vivo, results are controversial with some studies showing neuroprotection by quercetin and others not, requiring a drug delivery system or chronic treatments to show neuroprotective effects. The blood and brain bioavailability of free quercetin after ingestion is a complex and controversial process that produces final low concentrations, a fact that has led to suggestions that metabolites would be active by themselves and/or as pro-drugs that would release the active aglycone in the brain. Available studies show that in normal or low oxidative conditions, chronic treatments with quercetin contributes to re-establish the redox regulation of proteins, transcription factors and survival signaling cascades that promote survival. In the presence of highly oxidative conditions such as in an ischemic tissue, quercetin could become pro-oxidant and toxic. At present, evidence points to quercetin as a preventive molecule for neuropathology when administered in natural matrices such as vegetables and food. More research is needed to support its use as a lead compound in its free form in

Molecular imaging of the biological effects of quercetin and quercetin-rich foods.

PubMed

Moskaug, Jan Øivind; Carlsen, Harald; Myhrstad, Mari; Blomhoff, Rune

2004-04-01

The human diet contains several thousands of organic plant molecules (i.e. phytochemicals), many of which have significant bioactivities. The specific physiological effects of these compounds are impossible to predict from in vitro studies using cell cultures and cell-free model systems. Nutrigenomics, which may be defined as the application of genomic tools to study the integrated effects of nutrients on gene regulation, however, holds great promise in increasing the understanding of how nutrients affect molecular events in an organism. Quercetin, a phytochemical belonging to the flavonoids, has antioxidant activities, inhibit protein kinases, inhibit DNA topoisomerases and regulate gene expression. The aim of the present review is to describe some of the many effects of quercetin, and how molecular imaging using transgenic reporter mice may serve as a tool to study the integrated influence of quercetin and other dietary phytochemicals on gene expression in vivo. We are using the bioluminescence emitted from firefly luciferase as the reporter since light originating from the inside of a cell or organism can be detected externally in an intact living organism. Molecular imaging using reporter models is therefore a unique technology to study the integrated effects of environmental insults and dietary substances on the influence of gene expression in disease development. We utilize these in vivo models to elucidate the role of various flavonoids, such as quercetin, for modulating gene expression related to oxidative stress and the antioxidant defence system.

Electrical characterization of Au/quercetin/n-Si heterojunction diode and optical analysis of quercetin thin film

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

Tombak, Ahmet, E-mail: tahmet@yahoo.com; Özaydin, C.; Boğa, M.

2016-03-25

Quercetin (3,5,7,3’,4’-pentahydroxyflavone, QE), one of the most widely distributed flavonoids in fruits and vegetables, has been reported to possess a wide variety of biological effects, including anti-oxidative, anti-inflammatory, anti-apoptosis, hepatoprotective, renoprotective and neuroprotective effects. In this study organic-inorganic junctions were fabricated by forming quercetin complex thin film using spin coating technique on n-Si and evaporating Au metal on the film. Optical properties of quercetin thin film were studied with the help of spectrophotometer. The current-voltage (I-V) characteristic of Au/quercetin/n-Si heterojunction diode was investigated at room temperature in dark. Some basic parameters of the diode such as ideality factor, rectification ratio,more » barrier height, series resistance and shunt resistance were calculated using dark current-voltage measurement. It was also seen that the device had good sensitivity to the light under 40-100 mW/cm{sup 2} illumination conditions.« less

Role of gallic and p-coumaric acids in the AHL-dependent expression of flgA gene and in the process of biofilm formation in food-associated Pseudomonas fluorescens KM120.

PubMed

Myszka, Kamila; Schmidt, Marcin T; Białas, Wojciech; Olkowicz, Mariola; Leja, Katarzyna; Czaczyk, Katarzyna

2016-09-01

In the process of Pseudomonas fluorescens biofilm formation, N-acyl-l-homoserine lactone (AHL)-mediated flagella synthesis plays a key role. Inhibition of AHL production may attenuate P. fluorescens biofilm on solid surfaces. This work validated the anti-biofilm properties of p-coumaric and gallic acids via the ability of phenolics to suppress AHL synthesis in P. fluorescens KM120. The dependence between synthesis of AHL molecules, expression of flagella gene (flgA) and the ability of biofilm formation by P. fluorescens KM120 on a stainless steel surface (type 304L) was also investigated. Research was carried out in a purpose-built flow cell device. Limitations on AHL synthesis in P. fluorescens KM120 were observed at concentrations of 120 and 240 µmol L(-1) of phenolic acids in medium. At such levels of gallic and p-coumaric acids the ability of P. fluorescens KM120 to synthesize 3-oxo-C6-homoserine lactone (HSL) was not observed. These concentrations caused decreased expression of flgA gene in P. fluorescens KM120. The changes in expression of AHL-dependent flgA gene significantly decreased the rate of microorganism colonization on the stainless steel surface. Phenolic acids are able to inhibit biofilm formation. The results obtained in the work may help to develop alternative techniques for anti-biofilm treatment in the food industry. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

Еvaluation of biocompatibility and antioxidant efficiency of chitosan-alginate nanoparticles loaded with quercetin.

PubMed

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

2017-10-01

The present study deals with development and evaluation of the safety profile of chitosan/alginate nanoparticles as a platform for delivery of a natural antioxidant quercetin. The nanoparticles were prepared by varying the ratios between both biopolymers giving different size and charge of the formulations. The biocompatibility was explored in vitro in cells from different origin: cultivated HepG2 cells, isolated primary rat hepatocytes, isolated murine spleen lymphocytes and macrophages. In vivo toxicological evaluation was performed after repeated 14-day oral administration to rats. The study revealed that chitosan/alginate nanoparticles did not change body weight, the relative weight of rat livers, liver histology, hematology and biochemical parameters. The protective effects of quercetin-loaded nanoparticles were investigated in the models of iron/ascorbic acid (Fe 2+ /AA) induced lipid peroxidation in microsomes and tert-butyl hydroperoxide oxidative stress in isolated rat hepatocytes. Interesting finding was that the empty chitosan/alginate nanoparticles possessed protective activity themselves. The antioxidant effects of quercetin loaded into the nanoparticles formulated with higher concentration of chitosan were superior compared to quercetin encapsulated in nanoparticles with higher amount of sodium alginate. In conclusion, chitosan/alginate nanoparticles can be considered appropriate carrier for quercetin, combining safety profile and improved protective activity of the encapsulated antioxidant. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of Gallic Acid on Dementia Type of Alzheimer Disease in Rats: Electrophysiological and Histological Studies.

PubMed

Hajipour, Somayeh; Sarkaki, Alireza; Farbood, Yaghoob; Eidi, Akram; Mortazavi, Pejman; Valizadeh, Zohreh

2016-04-01

To study the effect of gallic acid (GA) on hippocampal long-term potentiation (LTP) and histological changes in animal model of Alzheimer disease (AD) induced by beta-amyloid (Aβ). Sixty-four adult male Wistar rats (300±20 g) were divided into 8 groups: 1) Control (Cont); 2) AD; 3) Sham; 4-7) AD+GA (50, 100, and 200 mg/kg for 10 days, orally) or vehicle, 8) Cont+GA100, Aβ (1μg/μL in each site) was infused into hippocampus bilaterally. Changes of amplitude and slope of LTP induced in hippocampal dentate gyrus (DG) were evaluated by high frequency stimulation (HFS) of perforant path (PP). Data showed that LTP amplitude and area under curve significantly impaired in AD rats (P<0.001), while significantly improved in AD rats treated with GA (P<0.05, P<0.01). Current findings suggest that GA reduces neural damage and brain amyloid neuropathology and improves cognitive function via free radicals scavenging and inhibiting oligomerization of Aβ but with no effect on healthy rats.

Oxidized quercetin inhibits α-synuclein fibrillization.

PubMed

Zhu, Min; Han, Shubo; Fink, Anthony L

2013-04-01

α-Synucein is a small (14 kDa), abundant, intrinsically disordered presynaptic protein, whose aggregation is believed to be a critical step in Parkinson's disease (PD). Oxidative stress is reported to be a risk factor for dopamine cell degeneration in PD. Flavonoids are suggested to be important antioxidant against oxidative stress. Flavonoids were reported to inhibit fibrillization and disaggregate the preformed fibrils of α-synucein, but the molecular mechanism was still not clear. Quercetin, a well-recognized flavonoid antioxidant, was tested for its inhibition of α-synucein aggregation by thioflavin T assay, light scattering measurement, size-exclusion high performance liquid chromatography, atomic force microscopy, etc. The pre-incubated quercetin exhibited a noticeably stronger inhibition behavior to the fibril formation than that of the freshly prepared. The inhibition is significant in the presence of ortho- and para-benzenediol isomers and inconsiderable in the presence of meta-isomer. The oxidized quercetin species (i.e., chalcantrione, benzyfuranone, quercetinchinone, and other derivatives) cause stronger inhibition than quercetin does because of the elevated polarity and hydrophilicity. Presence of quercetin disaggregates α-synucein fibrils, rather than oligomers and amorphous aggregations. Instead of the antioxidant activity, the 1:1 covalent binding of quercetin with α-synucein, and the increased hydophilicity of the covalently modified α-synucein oligomers or monomers, account for the inhibition of α-synucein fibrillation. Clarification of the molecular mechanism of the inhibition and disaggregation may help to screen safer and more effective flavonoid therapeutic in combating PD. Copyright © 2012. Published by Elsevier B.V.

Dissection of the Effects of Quercetin on Mouse Myocardium.

PubMed

Santos, Michel Santana; Oliveira, Evaleide Diniz; Santos-Miranda, Artur; Cruz, Jader Santos; Gondim, Antônio Nei Santana; Menezes-Filho, José Evaldo Rodrigues; Souza, Diego Santos; Pinho-da-Silva, Leidiane; Jesus, Itamar Couto Guedes; Roman-Campos, Danilo; Guatimosim, Silvia; Lara, Aline; Conde-Garcia, Eduardo Antônio; Vasconcelos, Carla Maria Lins

2017-06-01

Quercetin is a plant flavonoid with several biological activities. This study aimed to describe quercetin effects on contractile and electrophysiological properties of the cardiac muscle as well as on calcium handling. Quercetin elicited positive inotropism that was significantly reduced by propranolol indicating an involvement of the sympathetic nervous system. In cardiomyocytes, 30 μM quercetin increased I Ca,L at 0 mV from -0.95 ± 0.01 A/F to -1.21 ± 0.08 A/F. The membrane potential at which 50% of the channels are activated (V 0.5 ) shifted towards more negative potentials from -13.06 ± 1.52 mV to -19.26 ± 1.72 mV and did not alter the slope factor. Furthermore, quercetin increased [Ca 2+ ] i transient by 28% when compared to control. Quercetin accelerated [Ca 2+ ] i transient decay time, which could be attributed to SERCA activation. In resting cardiomyocytes, quercetin did not change amplitude or frequency of Ca 2+ sparks. In isolated heart, quercetin increased heart rate and decreased PRi, QTc and duration of the QRS complex. Thus, we showed that quercetin activates β-adrenoceptors, leading to increased L-type Ca 2+ current and cell-wide intracellular Ca 2+ transient without visible changes in Ca 2+ sparks. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Interactions of quercetin, curcumin, epigallocatechin gallate and folic acid with gelatin.

PubMed

Yang, Tingting; Yang, Huiru; Fan, Yan; Li, Bafang; Hou, Hu

2018-06-15

Some small bioactive molecules from food show the potential health benefits, but with poor chemical stability and bioavailability. The interactions between small molecules and gelatin were investigated. Fluorescence experiments demonstrated that the bimolecular quenching constants (k q ) of complexes (gelatin-quercetin, gelatin-curcumin, gelatin-epigallocatechin gallate, gelatin-folic acid) were 3.7 × 10 12  L·mol -1 ·s -1 , 1.4 × 10 12  L·mol -1 ·s -1 , 2.7 × 10 12  L·mol -1 ·s -1 and 8.5 × 10 12  L·mol -1 ·s -1 , indicating that fluorescence quenching did not arise from a dynamical mechanism, but from gelatin-small molecules binding. Furthermore, the affinity with gelatin was ranked in the order of folic acid > quercetin > epigallocatechin gallate > curcumin. Fluorescence spectroscopy, ultraviolet and visible absorption spectroscopy, FTIR and circular dichroism showed that the interactions between small molecules and gelatin did not significantly alter the conformation and secondary structure of gelatin. Non-covalent interactions may result in the binding of gelatin with small molecules. The interactions were considered to be through two modes: (1) small molecules bound within the hydrophobic pockets of gelatin; (2) small molecules surrounded the gelatin molecule mainly through hydrogen bonds and hydrophobic interactions. Copyright © 2018 Elsevier B.V. All rights reserved.

Phenolic constituents of shea (Vitellaria paradoxa) kernels.

PubMed

Maranz, Steven; Wiesman, Zeev; Garti, Nissim

2003-10-08

Analysis of the phenolic constituents of shea (Vitellaria paradoxa) kernels by LC-MS revealed eight catechin compounds-gallic acid, catechin, epicatechin, epicatechin gallate, gallocatechin, epigallocatechin, gallocatechin gallate, and epigallocatechin gallate-as well as quercetin and trans-cinnamic acid. The mean kernel content of the eight catechin compounds was 4000 ppm (0.4% of kernel dry weight), with a 2100-9500 ppm range. Comparison of the profiles of the six major catechins from 40 Vitellaria provenances from 10 African countries showed that the relative proportions of these compounds varied from region to region. Gallic acid was the major phenolic compound, comprising an average of 27% of the measured total phenols and exceeding 70% in some populations. Colorimetric analysis (101 samples) of total polyphenols extracted from shea butter into hexane gave an average of 97 ppm, with the values for different provenances varying between 62 and 135 ppm of total polyphenols.

Quercetin Inhibits Peripheral and Spinal Cord Nociceptive Mechanisms to Reduce Intense Acute Swimming-Induced Muscle Pain in Mice

PubMed Central

Borghi, Sergio M.; Pinho-Ribeiro, Felipe A.; Fattori, Victor; Bussmann, Allan J. C.; Vignoli, Josiane A.; Camilios-Neto, Doumit; Casagrande, Rubia; Verri, Waldiceu A.

2016-01-01

The present study aimed to evaluate the effects of the flavonoid quercetin (3,3´,4´,5,7-pentahydroxyflavone) in a mice model of intense acute swimming-induced muscle pain, which resembles delayed onset muscle soreness. Quercetin intraperitoneal (i.p.) treatment dose-dependently reduced muscle mechanical hyperalgesia. Quercetin inhibited myeloperoxidase (MPO) and N-acetyl-β-D- glucosaminidase (NAG) activities, cytokine production, oxidative stress, cyclooxygenase-2 (COX-2) and gp91phox mRNA expression and muscle injury (creatinine kinase [CK] blood levels and myoblast determination protein [MyoD] mRNA expression) as well as inhibited NFκB activation and induced Nrf2 and HO-1 mRNA expression in the soleus muscle. Beyond inhibiting those peripheral effects, quercetin also inhibited spinal cord cytokine production, oxidative stress and glial cells activation (glial fibrillary acidic protein [GFAP] and ionized calcium-binding adapter molecule 1 [Iba-1] mRNA expression). Concluding, the present data demonstrate that quercetin is a potential molecule for the treatment of muscle pain conditions related to unaccustomed exercise. PMID:27583449

[Studies on chemical constituents of Taxillus sutchuenenisis].

PubMed

Chen, Jiang-tao; Feng, Feng

2007-11-01

To study the chemical constituents of Taxillus sutchuenenisis (Lecomte) Danser. Chromatography and spectrum analysis were employed to isolated and elucidate the chemical constituents in the plant. 9 compounds were isolated and identified as quercetin (I), quervetin 3-O-beta-D-galactoside (II), isoquercitrin (III), quercitrin (IV), rutin (V), gallic acid (VI), ferulic acid (VII), beta-sitosterol (VIII), daucosterol (IX), respectively. Compounds III-IX are isolated from this plant for the first time. The work provide evidence for the exploitation and utilization of this plant resouce.

Quercetin attenuates doxorubicin cardiotoxicity by modulating Bmi-1 expression

PubMed Central

Dong, Qinghua; Chen, Long; Lu, Qunwei; Sharma, Sherven; Li, Lei; Morimoto, Sachio; Wang, Guanyu

2014-01-01

Background and Purpose Doxorubicin-based chemotherapy induces cardiotoxicity, which limits its clinical application. We previously reported the protective effects of quercetin against doxorubicin-induced hepatotoxicity. In this study, we tested the effects of quercetin on the expression of Bmi-1, a protein regulating mitochondrial function and ROS generation, as a mechanism underlying quercetin-mediated protection against doxorubicin-induced cardiotoxicity. Experimental Approach Effects of quercetin on doxorubicin-induced cardiotoxicity was evaluated using H9c2 cardiomyocytes and C57BL/6 mice. Changes in apoptosis, mitochondrial function, oxidative stress and related signalling were evaluated in H9c2 cells. Cardiac function, serum enzyme activity and reactive oxygen species (ROS) generation were measured in mice after a single injection of doxorubicin with or without quercetin pre-treatment. Key Results In H9c2 cells, quercetin reduced doxorubicin-induced apoptosis, mitochondrial dysfunction, ROS generation and DNA double-strand breaks. The quercetin-mediated protection against doxorubicin toxicity was characterized by decreased expression of Bid, p53 and oxidase (p47 and Nox1) and by increased expression of Bcl-2 and Bmi-1. Bmi-1 siRNA abolished the protective effect of quercetin against doxorubicin-induced toxicity in H9c2 cells. Furthermore, quercetin protected mice from doxorubicin-induced cardiac dysfunction that was accompanied by reduced ROS levels and lipid peroxidation, but enhanced the expression of Bmi-1 and anti-oxidative superoxide dismutase. Conclusions and Implications Our results demonstrate that quercetin decreased doxorubicin-induced cardiotoxicity in vitro and in vivo by reducing oxidative stress by up-regulation of Bmi-1 expression. The findings presented in this study have potential applications in preventing doxorubicin-induced cardiomyopathy. PMID:24902966

Comparative assessment on in vitro antioxidant activities of ethanol extracts of Averrhoa bilimbi, Gymnema sylvestre and Capsicum frutescens.

PubMed

Rahman, Md Mominur; Habib, Md Razibul; Hasan, Md Anayet; Al Amin, Mohammad; Saha, Ayan; Mannan, Adnan

2014-01-01

Averrhoa bilimbi, Gymnema sylvestre and Capsicum frutescens are medicinal plants commonly used as traditional medicine for the treatment of various diseases. The present study was designed to investigate the antioxidant activities of Ethanolic extract of A. bilimbi, G. sylvestre and C. frutescens. The antioxidant activity of the extracts were evaluated using total phenolic and flavonoid contents, ferric reducing power and the free radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH). Total phenolic and flavonoid contents were higher in G. sylvestre (53.63636 ± 0.454545 mg/g gallic acid equivalent) and C. frutescens (26.66667 ± 2.081666 mg/g quercetin equivalent) respectively. Reducing power of the crude ethanol extracts increased with the concentrations of the extracts and all the extracts showed moderate free radical scavenging activity against DPPH. The plant extract displayed moderate phenolic and flavonoid contents compared to gallic acid and quercetin equivalent respectively, whereas also exhibited significant scavenging of DPPH radical and reducing power compared with ascorbic acid as standard. Our study suggests that G. sylvestre has significant antioxidant activity. The antioxidant compound of this plant might be a therapeutic candidate against oxidative stress related diseases. Different sub-fraction of A. bilimbi and C. frutescens should be studied further to assess the effect. Further study is necessary for isolation and characterization of the active antioxidant agents for better treatment.

Quercetin Reduces Ehrlich Tumor-Induced Cancer Pain in Mice

PubMed Central

Calixto-Campos, Cassia; Corrêa, Mab P.; Carvalho, Thacyana T.; Zarpelon, Ana C.; Hohmann, Miriam S. N.; Rossaneis, Ana C.; Coelho-Silva, Leticia; Pavanelli, Wander R.; Pinge-Filho, Phileno; Bernardy, Catia C. F.; Verri, Waldiceu A.

2015-01-01

Cancer pain directly affects the patient's quality of life. We have previously demonstrated that the subcutaneous administration of the mammary adenocarcinoma known as Ehrlich tumor induces pain in mice. Several studies have shown that the flavonoid quercetin presents important biological effects, including anti-inflammatory, antioxidant, analgesic, and antitumor activity. Therefore, the analgesic effect and mechanisms of quercetin were evaluated in Ehrlich tumor-induced cancer pain in mice. Intraperitoneal (i.p.) treatments with quercetin reduced Ehrlich tumor-induced mechanical and thermal hyperalgesia, but not paw thickness or histological alterations, indicating an analgesic effect without affecting tumor growth. Regarding the analgesic mechanisms of quercetin, it inhibited the production of hyperalgesic cytokines IL-1β and TNFα and decreased neutrophil recruitment (myeloperoxidase activity) and oxidative stress. Naloxone (opioid receptor antagonist) inhibited quercetin analgesia without interfering with neutrophil recruitment, cytokine production, and oxidative stress. Importantly, cotreatment with morphine and quercetin at doses that were ineffective as single treatment reduced the nociceptive responses. Concluding, quercetin reduces the Ehrlich tumor-induced cancer pain by reducing the production of hyperalgesic cytokines, neutrophil recruitment, and oxidative stress as well as by activating an opioid-dependent analgesic pathway and potentiation of morphine analgesia. Thus, quercetin treatment seems a suitable therapeutic approach for cancer pain that merits further investigation. PMID:26351625

Tryptamine-Gallic Acid Hybrid Prevents Non-steroidal Anti-inflammatory Drug-induced Gastropathy

PubMed Central

Pal, Chinmay; Bindu, Samik; Dey, Sumanta; Alam, Athar; Goyal, Manish; Iqbal, Mohd. Shameel; Sarkar, Souvik; Kumar, Rahul; Halder, Kamal Krishna; Debnath, Mita Chatterjee; Adhikari, Susanta; Bandyopadhyay, Uday

2012-01-01

We have investigated the gastroprotective effect of SEGA (3a), a newly synthesized tryptamine-gallic acid hybrid molecule against non-steroidal anti-inflammatory drug (NSAID)-induced gastropathy with mechanistic details. SEGA (3a) prevents indomethacin (NSAID)-induced mitochondrial oxidative stress (MOS) and dysfunctions in gastric mucosal cells, which play a pathogenic role in inducing gastropathy. SEGA (3a) offers this mitoprotective effect by scavenging of mitochondrial superoxide anion (O2˙̄) and intramitochondrial free iron released as a result of MOS. SEGA (3a) in vivo blocks indomethacin-mediated MOS, as is evident from the inhibition of indomethacin-induced mitochondrial protein carbonyl formation, lipid peroxidation, and thiol depletion. SEGA (3a) corrects indomethacin-mediated mitochondrial dysfunction in vivo by restoring defective electron transport chain function, collapse of transmembrane potential, and loss of dehydrogenase activity. SEGA (3a) not only corrects mitochondrial dysfunction but also inhibits the activation of the mitochondrial pathway of apoptosis by indomethacin. SEGA (3a) inhibits indomethacin-induced down-regulation of bcl-2 and up-regulation of bax genes in gastric mucosa. SEGA (3a) also inhibits indometacin-induced activation of caspase-9 and caspase-3 in gastric mucosa. Besides the gastroprotective effect against NSAID, SEGA (3a) also expedites the healing of already damaged gastric mucosa. Radiolabeled (99mTc-labeled SEGA (3a)) tracer studies confirm that SEGA (3a) enters into mitochondria of gastric mucosal cell in vivo, and it is quite stable in serum. Thus, SEGA (3a) bears an immense potential to be a novel gastroprotective agent against NSAID-induced gastropathy. PMID:22157011

Estimated Daily Intake and Seasonal Food Sources of Quercetin in Japan

PubMed Central

Nishimuro, Haruno; Ohnishi, Hirofumi; Sato, Midori; Ohnishi-Kameyama, Mayumi; Matsunaga, Izumi; Naito, Shigehiro; Ippoushi, Katsunari; Oike, Hideaki; Nagata, Tadahiro; Akasaka, Hiroshi; Saitoh, Shigeyuki; Shimamoto, Kazuaki; Kobori, Masuko

2015-01-01

Quercetin is a promising food component, which can prevent lifestyle related diseases. To understand the dietary intake of quercetin in the subjects of a population-based cohort study and in the Japanese population, we first determined the quercetin content in foods available in the market during June and July in or near a town in Hokkaido, Japan. Red leaf lettuce, asparagus, and onions contained high amounts of quercetin derivatives. We then estimated the daily quercetin intake by 570 residents aged 20–92 years old in the town using a food frequency questionnaire (FFQ). The average and median quercetin intakes were 16.2 and 15.5 mg day−1, respectively. The quercetin intakes by men were lower than those by women; the quercetin intakes showed a low correlation with age in both men and women. The estimated quercetin intake was similar during summer and winter. Quercetin was mainly ingested from onions and green tea, both in summer and in winter. Vegetables, such as asparagus, green pepper, tomatoes, and red leaf lettuce, were good sources of quercetin in summer. Our results will help to elucidate the association between quercetin intake and risks of lifestyle-related diseases by further prospective cohort study and establish healthy dietary requirements with the consumption of more physiologically useful components from foods. PMID:25849945

Gallic acid induced apoptotic events in HCT-15 colon cancer cells.

PubMed

Subramanian, Aruna Priyadharshni; Jaganathan, Saravana Kumar; Mandal, Mahitosh; Supriyanto, Eko; Muhamad, Ida Idayu

2016-04-21

To investigate the inhibitory action of diet-derived phenolic compound gallic acid (GA) against HCT-15 colon cancer cells. The antiproliferative effect of GA against colon cancer cells was determined by performing thiazolyl blue tetrazolium bromide (MTT) assay. The colony forming ability of GA treated colon cancer cells was evaluated using the colony forming assay. The cell cycle changes induced by GA in HCT-15 cells were analyzed by propidium iodide staining. Levels of reactive oxygen species (ROS) and mitochondrial membrane potential of HCT-15 exposed to GA was assessed using 2',7'-dichlorfluorescein-diacetate and rhodamine-123 respectively, with the help of flow cytometry. Morphological changes caused by GA treatment in the colon cancer cells were identified by scanning electron microscope and photomicrograph examination. Apoptosis was confirmed using flow cytometric analysis of GA treated HCT-15 cells after staining with Yo-Pro-1. MTT assay results illustrated that GA has an inhibitory effect on HCT-15 cells with IC50 value of 740 μmol/L. A time-dependent inhibition of colony formation was evident with GA treatment. Cell cycle arrest was evident from the accumulation of GA treated HCT-15 cells at sub-G1 phase (0.98 ± 1.03 vs 58.01 ± 2.05) with increasing exposure time. Flow cytometric analysis of GA treated HCT-15 cells depicted early events associated with apoptosis like lipid layer breakage and fall in mitochondrial membrane potential apart from an increase in the generation of ROS which were in a time dependent manner. SEM and photomicrograph images of the GA-treated cells displayed membrane blebbing and cell shrinking characteristics of apoptosis. Further apoptosis confirmation by Yo-Pro-1 staining also showed the time-dependent increase of apoptotic cells after treatment. These results show that GA induced ROS dependent apoptosis and inhibited the growth of colon cancer cells.

Quercetin solubilisation in bile salts: A comparison with sodium dodecyl sulphate.

PubMed

Buchweitz, Maria; Kroon, Paul A; Rich, Gillian T; Wilde, Peter J

2016-11-15

To understand the bioaccessibility of the flavonoid quercetin we studied its interaction with bile salt micelles. The environmental sensitivity of quercetin's UV-visible absorption spectrum gave information about quercetin partitioning. Two quercetin absorption peaks gave complementary information: Peak A (240-280nm) on the intermicellar phase and Peak B (340-440nm) on the micellar phase. Thus, by altering pH, we showed that only non-ionised quercetin partitions into micelles. We validated our interpretation by studying quercetin's interaction with SDS micelles. Pyrene fluorescence and the quercetin UV-visible spectra show that the adsorption site for pyrene and quercetin in bile salt micelles is more hydrophobic than that for SDS micelles. Also, both quercetin and pyrene reported a higher critical micelle concentration for bile salts than for SDS. Our method of using a flavonoid as an intrinsic probe, is generally applicable to other lipophilic bioactives, whenever they have observable environmental dependent properties. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Functionalities of chitosan conjugated with stearic acid and gallic acid and application of the modified chitosan in stabilizing labile aroma compounds in an oil-in-water emulsion.

PubMed

Yang, Tsung-Shi; Liu, Tai-Ti; Lin, I-Hwa

2017-08-01

The aims of this research were to conjugate chitosan (CT) with stearic acid (SA) and gallic acid (GA), and apply the modified chitosan to stabilize labile aroma compounds such as allyl isothiocyanate (AITC) and limonene in oil-in-water emulsions. Generally, the antioxidant activity of CT-SA-GA increased as the GA content in the conjugate increased. In most assays, GA had a lower IC 50 value than that of CT-SA-GA; however, CT-SA-GA exhibited better performance than GA in the Fe 2+ -chelating activity. In accelerated tests (heating or illumination) for evaluating the chemical stability of AITC and limonene during storage, CT-SA and CT-SA-GA were used to prepare AITC and limonene O/W emulsions, respectively. Tween 80 and Span 80 (T-S-80), an emulsifier mixture, were used as a control in both emulsions for comparison. The results show that CT-SA or CT-SA-GA could protect AITC or limonene from degradation or oxidation more effectively than T-S-80. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of quercetin and genistein on copper- and iron-induced lipid peroxidation in methyl linolenate.

PubMed

Boadi, William Y; Iyere, Peter A; Adunyah, Samuel E

2003-01-01

The single and combined effects of two abundant flavonoids, namely quercetin and genistein, were investigated according to their ability to inhibit the oxidation of methyl linolenate via Fenton's pathway. Antioxidative activity was determined by oxidizing methyl linolenate suspended in a buffer solution with either Fe2+ (50 microM) or Cu2+ (50 microM) and hydrogen peroxide (0.01 mM) without or with a flavonoid sample (10 or 20 microM). Lipid peroxidation products were measured by the thiobarbituric acid (TBA) assay and the amounts of thiobarbituric acid-reactive substances (TBARS) were calculated from a calibration curve using 1,1,3,3-tetraethoxypropane as the standard. Both quercetin and genistein at the 10 or 20 microM level decreased lipid peroxidation significantly compared with their respective controls. Of the two flavonoids tested, quercetin had a more marked effect on inhibiting lipid peroxides. Peroxidation products for the control samples were higher for the Fe2+-treated samples compared with the Cu2+ samples. Combination of both flavonoids at the same dose levels continued to decrease lipid peroxidation, the effect being the same for both metal ions. The data suggest that the combined flavonoids offered better protection than the single treatments and this may be attributed to the better radical scavenging or increased chelating capabilities of the combined over the single treatments. The differences in peroxide levels for the single treatment of quercetin compared with the genistein-treated samples may reflect the structural differences between these compounds in combating oxidative stress. Copyright 2003 John Wiley & Sons, Ltd.

Quercetin inhibits rhinovirus replication in vitro and in vivo

PubMed Central

Ganesan, Shyamala; Faris, Andrea N.; Comstock, Adam T.; Wang, Qiong; Nanua, Suparna; Hershenson, Marc B.; Sajjan, Uma S.

2012-01-01

Summary Rhinovirus (RV), which is responsible for the majority of common colds, also causes exacerbations in patients with asthma and chronic obstructive pulmonary disease. So far, there are no drugs available for treatment of rhinovirus infection. We examined the effect of quercetin, a plant flavanol on RV infection in vitro and in vivo. Pretreatment of airway epithelial cells with quercetin decreased Akt phosphosphorylation, viral endocytosis and IL-8 responses. Addition of quercetin 6 h after RV infection (after viral endocytosis) reduced viral load, IL-8 and IFN responses in airway epithelial cells. This was associated with decreased levels of negative and positive strand viral RNA, and RV capsid protein, abrogation of RV-induced eIF4GI cleavage and increased phosphorylation of eIF2α. In mice infected with RV, quercetin treatment decreased viral replication as well as expression of chemokines and cytokines. Quercetin treatment also attenuated RV-induced airway cholinergic hyperresponsiveness. Together, our results suggest that quercetin inhibits RV endocytosis and replication in airway epithelial cells at multiple stages of the RV life cycle. Quercetin also decreases expression of pro-inflammatory cytokines and improves lung function in RV-infected mice. Based on these observations, further studies examining the potential benefits of quercetin in the prevention and treatment of RV infection are warranted. PMID:22465313

Enhancement of Phenolic Production and Antioxidant Activity from Buckwheat Leaves by Subcritical Water Extraction.

PubMed

Kim, Dong-Shin; Kim, Mi-Bo; Lim, Sang-Bin

2017-12-01

To enhance the production of phenolic compounds with high antioxidant activity and reduce the level of phototoxic fagopyrin, buckwheat leaves were extracted with subcritical water (SW) at 100~220°C for 10~50 min. The major phenolic compounds were quercetin, gallic acid, and protocatechuic acid. The cumulative amount of individual phenolic compounds increased with increasing extraction temperature from 100°C to 180°C and did not change significantly at 200°C and 220°C. The highest yield of individual phenolic compounds was 1,632.2 μg/g dry sample at 180°C, which was 4.7-fold higher than that (348.4 μg/g dry sample) at 100°C. Total phenolic content and total flavonoid content increased with increasing extraction temperature and decreased with increasing extraction time, and peaked at 41.1 mg gallic acid equivalents/g and 26.9 mg quercetin equivalents/g at 180°C/10 min, respectively. 2,2-Diphenyl-1-picrylhydrazyl free radical scavenging activity and ferric reducing ability of plasma reached 46.4 mg ascorbic acid equivalents/g and 72.3 mmol Fe 2+ /100 g at 180°C/10 min, respectively. The fagopyrin contents were reduced by 92.5~95.7%. Color values L * and b * decreased, and a * increased with increasing extraction temperature. SW extraction enhanced the yield of phenolic compounds with high antioxidant activity and reduced the fagopyrin content from buckwheat leaves.

Fabrication of chitosan/gallic acid 3D microporous scaffold for tissue engineering applications.

PubMed

Thangavel, Ponrasu; Ramachandran, Balaji; Muthuvijayan, Vignesh

2016-05-01

This study explores the potential of gallic acid incorporated chitosan (CS/GA) 3D scaffolds for tissue engineering applications. Scaffolds were prepared by freezing and lyophilization technique and characterized. FTIR spectra confirmed the presence of GA in chitosan (CS) gel. DSC and TGA analysis revealed that the structure of chitosan was not altered due to the incorporation of GA, but thermal stability was significantly increased compared to the CS scaffold. SEM micrographs showed smooth, homogeneous, and microporous architecture of the scaffolds with good interconnectivity. CS/GA scaffolds exhibited approximately 90% porosity on average, increased swelling (600-900%) and controlled biodegradation (15-40%) in PBS (pH 7.4 at 37°C) with 1 mg/mL of lysozyme. CS/GA scaffolds showed 2-4 fold decrease in CFUs (p < 0.05) for both gram positive and gram negative bacteria compared to the CS scaffold. Cytotoxicity of these scaffolds was evaluated using NIH 3T3 L1 fibroblast cells. CS/GA 0.25% scaffold showed similar viability with CS scaffold at 24 and 48 h. CS/GA scaffolds (0.5-1.0%) showed 60-75% viability at 24 h and 90% at 48 h. SEM images showed that an increased cell attachment was observed for CS/GA scaffolds compared to CS scaffolds. These findings authenticate that CS/GA scaffolds were cytocompatible and would be useful for tissue engineering applications. © 2015 Wiley Periodicals, Inc.

Neuroprotective effects of Quercetin on radiation-induced brain injury in rats.

PubMed

Kale, Aydemir; Piskin, Özcan; Bas, Yilmaz; Aydin, Bengü Gülhan; Can, Murat; Elmas, Özlem; Büyükuysal, Çagatay

2018-04-24

Extensive research has been focused on radiation-induced brain injury. Animal and human studies have shown that flavonoids have remarkable toxicological profiles. This study aims to investigate the neuroprotective effects of quercetin in an experimental radiation-induced brain injury. A total of 32 adult male Wistar-Albino rats were randomly divided into four groups (control, quercetin, radiation, and radiation+quercetin groups, with eight rats in each group). Doses (50 mg/kg) of quercetin were administered to the animals in the quercetin and radiation+quercetin groups; radiation and radiation+quercetin groups were exposed to a dose of 20 Gy to the cranium region. Tissue samples, and biochemical levels of tissue injury markers in the four groups were compared. In all measured parameters of oxidative stress, administration of quercetin significantly demonstrated favorable effects. Both plasma and tissue levels of malondialdehyde and total antioxidant status significantly changed in favor of antioxidant activity. Histopathological evaluation of the tissues also demonstrated a significant decrease in cellular degeneration and infiltration parameters after quercetin administration. Quercetin demonstrated significant neuroprotection after radiation-induced brain injury. Further studies of neurological outcomes under different experimental settings are required in order to achieve conclusive results.

Surface functionalization of bioactive glasses with natural molecules of biological significance, Part I: Gallic acid as model molecule

NASA Astrophysics Data System (ADS)

Zhang, Xin; Ferraris, Sara; Prenesti, Enrico; Verné, Enrica

2013-12-01

Gallic acid (3,4,5-trihydroxybenzoic acid, GA) and its derivatives are a group of biomolecules (polyphenols) obtained from plants. They have effects which are potentially beneficial to heath, for example they are antioxidant, anticarcinogenic and antibacterial, as recently investigated in many fields such as medicine, food and plant sciences. The main drawbacks of these molecules are both low stability and bioavailability. In this research work the opportunity to graft GA to bioactive glasses is investigated, in order to deliver the undamaged biological molecule into the body, using the biomaterial surfaces as a localized carrier. GA was considered for functionalization since it is a good model molecule for polyphenols and presents several interesting biological activities, like antibacterial, antioxidant and anticarcinogenic properties. Two different silica based bioactive glasses (SCNA and CEL2), with different reactivity, were employed as substrates. UV photometry combined with the Folin&Ciocalteu reagent was adopted to test the concentration of GA in uptake solution after functionalization. This test verified how much GA consumption occurred with surface modification and it was also used on solid samples to test the presence of GA on functionalized glasses. XPS and SEM-EDS techniques were employed to characterize the modification of material surface properties and functional group composition before and after functionalization.

Antioxidant properties and phenolic profile characterization by LC-MS/MS of selected Tunisian pomegranate peels.

PubMed

Abid, Mouna; Yaich, Héla; Cheikhrouhou, Salma; Khemakhem, Ibtihel; Bouaziz, Mohamed; Attia, Hamadi; Ayadi, M A

2017-08-01

Antioxidant contents and activities of different extracts from four Tunisian pomegranate peels, locally called "Acide", "Gabsi", "Nebli" and "Tounsi", were studied. Peels samples were extracted with three solvents (water, ethanol and acetone). For each extract, the total phenol contents and antioxidant activity were evaluated. The highest values of polyphenol, tannins, flavonoids and anthocyanins were recorded in the acetone extract of Acide ecotype with 304.6 mg gallic acid equivalent/g; 292.23 mg gallic acid equivalent/g; 15.46 mg Quercetin/g and 54.51 mg cy-3-glu/100 g, respectively. The acetone extract of Acide ecotype also showed the highest free radical-scavenging and reducing power activity compared to other extracts. Besides, the phytochemical analysis by LC-MS/MS revealed a high content of ellagitannins with punicalagin and punicalagin derivatives as the major compounds that might be responsible for promising antioxidant activity of pomegranate peel extracts. Two compounds (Castalagin derivative and Galloyl-bis-HHDP-hex derivative) were detected only in "Acide" ecotype in important contents.

Quercetin inhibits the invasion of murine melanoma B16-BL6 cells by decreasing pro-MMP-9 via the PKC pathway.

PubMed

Zhang, Xian-Ming; Huang, Shao-Peng; Xu, Qiang

2004-01-01

On the basis of the inhibitory effect of quercetin on the invasion of melanoma B16-BL6 cells previously reported by us, the mechanisms of quercetin-mediated inhibition of invasion were further investigated in the present study. The ability of B16-BL6 cells to invade and migrate was evaluated in terms of the numbers of cells penetrating a reconstituted basement membrane in the Transwell coculture system. The relative levels and activities of matrix metalloproteinase-9 (MMP-9) and MMP-2 were determined by gelatin zymography and quantified using LabWorks 4.0 software. The quercetin-mediated inhibition of invasion was partially blocked by phorbol-12,13-dibutyrate (PDB), a PKC (protein kinase C) activator, and by doxorubicin, a PKC inhibitor. Only the proforms of MMP-9 (92 kDa) and MMP-2 (72 kDa) were detected by gelatin zymography. Quercetin dose-dependently decreased the gelatinolytic activity of pro-MMP-9. Doxorubicin also markedly reversed the quercetin-induced decrease. Quercetin showed a dose-dependent antagonism of increases in gelatinolytic activity of pro-MMP-9 induced by PDB and free fatty acid (another PKC activator). Together with the report that quercetin directly reduces PKC activity, the results reported here suggest that quercetin may inhibit the invasion of B16-BL6 cells by decreasing pro-MMP-9 via the PKC pathway.

Formation of redispersible polyelectrolyte complex nanoparticles from gallic acid-chitosan conjugate and gum arabic.

PubMed

Hu, Qiaobin; Wang, Taoran; Zhou, Mingyong; Xue, Jingyi; Luo, Yangchao

2016-11-01

Polyelectrolyte complex (PEC) nanoparticles between chitosan (CS) and biomacromolecules offer better physicochemical properties as delivery vehicles for nutrients than other CS-based nanoparticles. Our major objective was to fabricate PEC nanoparticles between water soluble gallic acid-chitosan conjugate (GA-CS) and gum arabic. The optimal fabrication method, physicochemical characteristics and stability were investigated. Furthermore, we also evaluated the effects of nano spray drying technology on the morphology and redispersibility of nanoparticle powders using Buchi B-90 Nano Spray Dryer. Results showed that the mass ratio between GA-CS and gum arabic and the preparation pH had significant contributions in determining the particle size and count rate of the nanoparticles, with the ratio of 3:1 and pH 5.0 being the optimal conditions that resulted in 112.2nm and 122.9kcps. The polyethylene glycol (PEG) played a vital role in forming the well-separated spray dried nanoparticles. The most homogeneous nanoparticles with the smoothest surface were obtained when the mass ratio of GA-CS and PEG was 1:0.5. In addition, the GA-CS/gum arabic spray dried nanoparticles exhibited excellent water-redispersibiliy compared to native CS/gum arabic nanoparticles. Our results demonstrated GA-CS/gum arabic nanoparticles were successfully fabricated with promising physicochemical properties and great potential for their applications in food and pharmaceutical industries. Copyright © 2016 Elsevier B.V. All rights reserved.

Role of Quercetin Benefits in Neurodegeneration.

PubMed

Elumalai, Preetham; Lakshmi, Sreeja

2016-01-01

Neurodegenerative disorders are often life threatening and hired as an economic burden to the health-care system. Nutritional interventions principally involving polyphenols were practiced to arrest or reverse the age-related health disorders. Flavonoids, a class of dietary polyphenols, are rising to superstardom in preventing brain disorders with their potent antioxidant defense mechanism. Quercetin is a ubiquitous flavonoid reported to have all-natural myriad of health benefits. Citrus fruits, apple, onion, parsley, berries, green tea, and red wine comprise the major dietary supplements of quercetin apart from some herbal remedies like Ginkgo biloba. Appositeness of quercetin in reducing risks of neurodegenerative disorders, cancer, cardiovascular diseases, allergic disorders, thrombosis, atherosclerosis, hypertension, and arrhythmia, to name a few, is attributed to its highly pronounced antioxidant and anti-inflammatory properties. Neurodegeneration, characterized by progressive deterioration of the structure and function of neurons, is crucially accompanied by severe cognitive deficits. Aging is the major risk factor for neurodegenerative disorders in Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) being coequal high hands. Oxidative stress and mitochondrial dysfunction are the key players in triggering neurodegeneration. The upsurge of neurodegenerative disorders is always appalling since there exists a paucity in effective treatment practices. Past few years' studies have underpinned the mechanisms through which quercetin boons the brain health in many aspects including betterment in cognitive output. Undoubtedly, quercetin will be escalating as an arable field, both in scientific research and in pharmacological and clinical applications.

Free radical scavenging potency of quercetin catecholic colonic metabolites: Thermodynamics of 2H+/2e- processes.

PubMed

Amić, Ana; Lučić, Bono; Stepanić, Višnja; Marković, Zoran; Marković, Svetlana; Dimitrić Marković, Jasmina M; Amić, Dragan

2017-03-01

Reaction energetics of the double (2H + /2e - ), i.e., the first 1H + /1e - (catechol→ phenoxyl radical) and the second 1H + /1e - (phenoxyl radical→ quinone) free radical scavenging mechanisms of quercetin and its six colonic catecholic metabolites (caffeic acid, hydrocaffeic acid, homoprotocatechuic acid, protocatechuic acid, 4-methylcatechol, and catechol) were computationally studied using density functional theory, with the aim to estimate the antiradical potency of these molecules. We found that second hydrogen atom transfer (HAT) and second sequential proton loss electron transfer (SPLET) mechanisms are less energy demanding than the first ones indicating 2H + /2e - processes as inherent to catechol moiety. The Gibbs free energy change for reactions of inactivation of selected free radicals indicate that catecholic colonic metabolites constitute an efficient group of more potent scavengers than quercetin itself, able to deactivate various free radicals, under different biological conditions. They could be responsible for the health benefits associated with regular intake of flavonoid-rich diet. Copyright © 2016 Elsevier Ltd. All rights reserved.

Chemotherapeutic potential of quercetin on human bladder cancer cells.

PubMed

Oršolić, Nada; Karač, Ivo; Sirovina, Damir; Kukolj, Marina; Kunštić, Martina; Gajski, Goran; Garaj-Vrhovac, Vera; Štajcar, Damir

2016-07-28

In an effort to improve local bladder cancer control, we investigated the cytotoxic and genotoxic effects of quercetin on human bladder cancer T24 cells. The cytotoxic effect of quercetin against T24 cells was examined by MTT test, clonogenic assay as well as DNA damaging effect by comet assay. In addition, the cytotoxic effect of quercetin on the primary culture of papillary urothelial carcinoma (PUC), histopathological stage T1 of low- or high-grade tumours, was investigated. Our analysis demonstrated a high correlation between reduced number of colony and cell viability and an increase in DNA damage of T24 cells incubated with quercetin at doses of 1 and 50 µM during short term incubation (2 h). At all exposure times (24, 48 and 72 h), the efficacy of quercetin, administered at a 10× higher dose compared to T24 cells, was statistically significant (P < 0.05) for the primary culture of PUC. In conclusion, our study suggests that quercetin could inhibit cell proliferation and colony formation of human bladder cancer cells by inducing DNA damage and that quercetin may be an effective chemopreventive and chemotherapeutic agent for papillary urothelial bladder cancer after transurethral resection.

Tunicate-Inspired Gallic Acid/Metal Ion Complex for Instant and Efficient Treatment of Dentin Hypersensitivity.

PubMed

Prajatelistia, Ekavianty; Ju, Sung-Won; Sanandiya, Naresh D; Jun, Sang Ho; Ahn, Jin-Soo; Hwang, Dong Soo

2016-04-20

Dentin hypersensitivity is sharp and unpleasant pains caused by exposed dentinal tubules when enamel outside of the tooth wears away. The occlusion of dentinal tubules via in situ remineralization of hydroxyapatite is the best method to alleviate the symptoms caused by dentin hypersensitivity. Commercially available dental desensitizers are generally effective only on a specific area and are relatively toxic, and their performance usually depends on the skill of the clinician. Here, a facile and efficient dentin hypersensitivity treatment with remarkable aesthetic improvement inspired by the tunicate-self-healing process is reported. As pyrogallol groups in tunicate proteins conjugate with metal ions to heal the torn body armor of a tunicate, the ingenious mechanism by introducing gallic acid (GA) as a cheap, abundant, and edible alternative to the pyrogallol groups of the tunicate combined with a varied daily intake of metal ion sources is mimicked. In particular, the GA/Fe(3+) complex exhibits the most promising results, to the instant ≈52% blockage in tubules within 4 min and ≈87% after 7 d of immersion in artificial saliva. Overall, the GA/metal ion complex-mediated coating is facile, instant, and effective, and is suggested as an aesthetic solution for treating dentin hypersensitivity. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rational engineering of p-hydroxybenzoate hydroxylase to enable efficient gallic acid synthesis via a novel artificial biosynthetic pathway.

PubMed

Chen, Zhenya; Shen, Xiaolin; Wang, Jian; Wang, Jia; Yuan, Qipeng; Yan, Yajun

2017-11-01

Gallic acid (GA) is a naturally occurring phytochemical that has strong antioxidant and antibacterial activities. It is also used as a potential platform chemical for the synthesis of diverse high-value compounds. Hydrolytic degradation of tannins by acids, bases or microorganisms serves as a major way for GA production, which however, might cause environmental pollution and low yield and efficiency. Here, we report a novel approach for efficient microbial production of GA. First, structure-based rational engineering of PobA, a p-hydroxybenzoate hydroxylase from Pseudomonas aeruginosa, generated a new mutant, Y385F/T294A PobA, which displayed much higher activity toward 3,4-dihydroxybenzoic acid (3,4-DHBA) than the wild-type and any other reported mutants. Remarkably, expression of this mutant in Escherichia coli enabled generation of 1149.59 mg/L GA from 1000 mg/L 4-hydroxybenzoic acid (4-HBA), representing a 93% molar conversion ratio. Based on that, we designed and reconstituted a novel artificial biosynthetic pathway of GA and achieved 440.53 mg/L GA production from simple carbon sources in E. coli. Further enhancement of precursor supply through reinforcing shikimate pathway was able to improve GA de novo production to 1266.39 mg/L in shake flasks. Overall, this study not only led to the development of a highly active PobA variant for hydroxylating 3,4-DHBA into GA via structure-based protein engineering approach, but also demonstrated a promising pathway for bio-based manufacturing of GA and its derived compounds. Biotechnol. Bioeng. 2017;114: 2571-2580. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Neurite Outgrowth and Neuroprotective Effects of Quercetin from Caesalpinia mimosoides Lamk. on Cultured P19-Derived Neurons

PubMed Central

Tangsaengvit, Napat; Kitphati, Worawan; Tadtong, Sarin; Bunyapraphatsara, Nuntavan; Nukoolkarn, Veena

2013-01-01

Quercetin has been isolated for the first time from ethyl acetate extract of Caesalpinia mimosoides Lamk. C. mimosoides Lamk. (Fabaceae) or Cha rueat (Thai name) is an indigenous plant found in mixed deciduous forest in northern and north-eastern parts of Thailand. Thai rural people consume its young shoots and leaves as a fresh vegetable, as well as it is used for medicinal purposes.The antioxidant capacity in terms of radical scavenging activity of quercetin was determined as IC50 of 3.18 ± 0.07 µg/mL, which was higher than that of Trolox and ascorbic acid (12.54 ± 0.89 and 10.52 ± 0.48 µg/mL, resp.). The suppressive effect of quercetin on both purified and cellular acetylcholinesterase (AChE) enzymes was investigated as IC50 56.84 ± 2.64 and 36.60 ± 2.78 µg/mL, respectively. In order to further investigate the protective ability of quercetin on neuronal cells, P19-derived neurons were used as a neuronal model in this study. As a result, quercetin at a very low dose of 1 nM enhanced survival and induced neurite outgrowth of P19-derived neurons. Furthermore, this flavonoid also possessed significant protection against oxidative stress induced by serum deprivation. Altogether, these findings suggest that quercetin is a multifunctional compound and promising valuable drugs candidate for the treatment of neurodegenerative disease. PMID:23840266

Quercetin and Its Anti-Allergic Immune Response.

PubMed

Mlcek, Jiri; Jurikova, Tunde; Skrovankova, Sona; Sochor, Jiri

2016-05-12

Quercetin is the great representative of polyphenols, flavonoids subgroup, flavonols. Its main natural sources in foods are vegetables such as onions, the most studied quercetin containing foods, and broccoli; fruits (apples, berry crops, and grapes); some herbs; tea; and wine. Quercetin is known for its antioxidant activity in radical scavenging and anti-allergic properties characterized by stimulation of immune system, antiviral activity, inhibition of histamine release, decrease in pro-inflammatory cytokines, leukotrienes creation, and suppresses interleukin IL-4 production. It can improve the Th1/Th2 balance, and restrain antigen-specific IgE antibody formation. It is also effective in the inhibition of enzymes such as lipoxygenase, eosinophil and peroxidase and the suppression of inflammatory mediators. All mentioned mechanisms of action contribute to the anti-inflammatory and immunomodulating properties of quercetin that can be effectively utilized in treatment of late-phase, and late-late-phase bronchial asthma responses, allergic rhinitis and restricted peanut-induced anaphylactic reactions. Plant extract of quercetin is the main ingredient of many potential anti-allergic drugs, supplements and enriched products, which is more competent in inhibiting of IL-8 than cromolyn (anti-allergic drug disodium cromoglycate) and suppresses IL-6 and cytosolic calcium level increase.

Topical application of quercetin improves wound healing in pressure ulcer lesions.

PubMed

Yin, Guimei; Wang, Zhijing; Wang, Zhaoxia; Wang, Xirui

2018-05-07

The ischemia-reperfusion (I/R) induced skin lesion has been identified as primary cause of pressure ulcers. To date, attempts to prevent pressure ulcers have not produced a significant improvement. Quercetin, one of the most widely distributed flavonoids in fruits and vegetables, exhibits its antioxidant and anti-inflammatory properties against many diseases, including ischemic heart disease, atherosclerosis, and renal injury. In vitro wound scratch assay was first used to assess the function of quercetin in wounding cell model. Next, animal pressure ulcers model was established with two cycles of I/R. The impact of quercetin in the wound recovery, immune cell infiltration and pro-inflammatory cytokines production was investigated in this model. Mechanistic regulation of quercetin at the wound site was also studied. Quercetin accelerated wound closure in cell scratch assay. Dose response study suggested 1 μM quercetin for in vivo study. In I/R injury model, quercetin treatment significantly accelerated wound closure, reduced immune cell infiltration and pro-inflammatory cytokines production. Signaling study showed quercetin treatment inhibited MAPK but not NFĸB activation. Quercetin treatment improved the wound healing process in I/R lesions by suppressing MAPK pathway. Our results supported that quercetin could be a potential therapeutic agent for pressure ulcers. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Quercetin Suppresses Twist to Induce Apoptosis in MCF-7 Breast Cancer Cells

PubMed Central

Ranganathan, Santhalakshmi; Halagowder, Devaraj; Sivasithambaram, Niranjali Devaraj

2015-01-01

Quercetin is a dietary flavonoid which exerts anti-oxidant, anti-inflammatory and anti-cancer properties. In this study, we investigated the anti-proliferative effect of quercetin in two breast cancer cell lines (MCF-7 and MDA-MB-231), which differed in hormone receptor. IC50 value (37μM) of quercetin showed significant cytotoxicity in MCF-7 cells, which was not observed in MDA-MB-231 cells even at 100μM of quercetin treatment. To study the response of cancer cells to quercetin, with respect to different hormone receptors, both the cell lines were treated with a fixed concentration (40μM) of quercetin. MCF-7 cells on quercetin treatment showed more apoptotic cells with G1 phase arrest. In addition, quercetin effectively suppressed the expression of CyclinD1, p21, Twist and phospho p38MAPK, which was not observed in MDA-MB-231 cells. To analyse the molecular mechanism of quercetin in exerting an apoptotic effect in MCF-7 cells, Twist was over-expressed and the molecular changes were observed after quercetin administration. Quercetin effectively regulated the expression of Twist, in turn p16 and p21 which induced apoptosis in MCF-7 cells. In conclusion, quercetin induces apoptosis in breast cancer cells through suppression of Twist via p38MAPK pathway. PMID:26491966

Ameliorative Effect of Gallic Acid on Cyclophosphamide-Induced Oxidative Injury and Hepatic Dysfunction in Rats

PubMed Central

Olayinka, Ebenezer Tunde; Ore, Ayokanmi; Ola, Olaniyi Solomon; Adeyemo, Oluwatobi Adewumi

2015-01-01

Cyclophosphamide (CP), a bifunctional alkylating agent used in chemotherapy has been reported to induce organ toxicity mediated by generation of reactive oxygen species and oxidative stress. Gallic acid (GA), a phenolic substance, is a natural antioxidant with proven free radical scavenging activity and offers protection against oxidative damage. This research study was designed to investigate the ameliorative effect of GA against CP-induced toxicity in rats. Twenty-five male Wistar rats (180–200 g) were randomized into five treatment groups: (A) control, (B) CP, 2 mg/kg body weight (b.w.), (C) pre-treatment with GA (20 mg/kg b.w.) for seven days followed by CP (2 mg/kg b.w.) for seven days, (D) co-treatment with GA (20 mg/kg b.w) and CP (2 mg/kg b.w.) for seven days, and (E) GA (20 mg/kg b.w.) for seven days. CP induced marked renal and hepatic damages as plasma levels of urea, creatinine, bilirubin and activities of AST, ALT, ALP and GGT were significantly elevated (p < 0.05) in the CP-treated group relative to control. In addition, hepatic levels of GSH, vitamin C and activities of SOD, catalase and GST significantly reduced in the CP-treated group when compared with control. This was accompanied with a significant increase in hepatic lipid peroxidation. The restoration of the markers of renal and hepatic damages as well as antioxidant indices and lipid peroxidation by pre- and co-treatment with GA clearly shows that GA offers ameliorative effect by scavenging the reactive oxygen species generated by CP. This protective effect may be attributed to the antioxidant property of gllic acid. PMID:29083393

The Content of Dietary Fibre and Polyphenols in Morphological Parts of Buckwheat (Fagopyrum tataricum).

PubMed

Dziedzic, Krzysztof; Górecka, Danuta; Szwengiel, Artur; Sulewska, Hanna; Kreft, Ivan; Gujska, Elżbieta; Walkowiak, Jarosław

2018-03-01

In this report, we presented the profile of polyphenolic substances in flowers, leaves, stalk and roots of Fagopyrum tataricum estimated by using RP-UHPLC-ESI-MS equipment (reversed-phase ultra-high-performance liquid chromatography electrospray ionisation mass spectrometry). The neutral detergent fibre, acid detergent fibre, acid detergent lignin, cellulose and hemicellulose were also determined. Flowers, leaves, stalk and roots showed varying levels of dietary fibre and polyphenols. The highest content of neutral and acid detergent fibre were found in the roots (63.92 and 45.45% d.m., respectively) while the most rich in phenolic compounds were flowers (4.8 mg/1 g d.m.). Root and stalk contained the highest level of cellulose, 38.70 and 25.57% d.m., respectively. Among the investigated polyphenolic substances such as: 2,6-dihydroxybenzoic acid, 3,4-dihydroxybenzoic acid, 3,5-dihydroxybenzoic acid, 4-hydrobenzoic acid, caffeic acid, catechin, chlorogenic acid, fagopyrin, ferulic acid, myricetin, gallic acid, isovanilic acid, isovitexin, kaempferol, luteolin, p-coumaric acid, procyanidin B2, quercetin, quercetin 3-D galactoside, rutin, syringic acid and vitexin, we observed that the contents of rutin and chlorogenic acid were the highest. We found some correlation between dietary fibre fractions and individual phenolic substances. The levels of acid detergent fibre (ADF), cellulose and hemicellulose were negatively correlated with isovitexin, kaempferol, vitexin, fagopyrin, caffeic acid and procyanidin B2 content. In this investigation, two solvents (water and methanol) were estimated regarding their extraction efficiency of phenolic compounds. Taking these results into consideration, we recommend using methanol as the extractor to isolate chlorogenic acid, fagopyrin, kaempferol, procyanidin B2, quercetin, quercetin 3-D-galactoside, rutin, vitexin, and water for other investigated polyphenolic substances obtained from Fagopyrum tataricum.

Preparation and evaluation of quercetin-loaded lecithin-chitosan nanoparticles for topical delivery.

PubMed

Tan, Qi; Liu, Weidong; Guo, Chenyu; Zhai, Guangxi

2011-01-01

The purpose of this study was to investigate lecithin-chitosan nanoparticles as a topical delivery system for quercetin. Tocopheryl propylene glycol succinate was chosen to be the surfactant for the nanosystem. The mean particle size of the nanoparticles was 95.3 nm, and the entrapment efficiency and drug loading for quercetin were 48.5% and 2.45%, respectively. Topical delivery in vitro and in vivo of the quercetin-loaded nanoparticles was evaluated using quercetin propylene glycol solution as the control. Compared with quercetin solution, the quercetin-loaded nanoparticles showed higher permeation ability, and significantly increased accumulation of quercetin in the skin, especially in the epidermis. Microstructure observation of the skin surface after administration indicated that the interaction between ingredients of the nanoparticles and the skin surface markedly changed the morphology of the stratum corneum and disrupted the corneocyte layers, thus facilitating the permeation and accumulation of quercetin in skin. Lecithin-chitosan nanoparticles are a promising carrier for topical delivery of quercetin.

Preparation and evaluation of quercetin-loaded lecithin-chitosan nanoparticles for topical delivery

PubMed Central

Tan, Qi; Liu, Weidong; Guo, Chenyu; Zhai, Guangxi

2011-01-01

Background The purpose of this study was to investigate lecithin-chitosan nanoparticles as a topical delivery system for quercetin. Methods Tocopheryl propylene glycol succinate was chosen to be the surfactant for the nanosystem. The mean particle size of the nanoparticles was 95.3 nm, and the entrapment efficiency and drug loading for quercetin were 48.5% and 2.45%, respectively. Topical delivery in vitro and in vivo of the quercetin-loaded nanoparticles was evaluated using quercetin propylene glycol solution as the control. Results Compared with quercetin solution, the quercetin-loaded nanoparticles showed higher permeation ability, and significantly increased accumulation of quercetin in the skin, especially in the epidermis. Microstructure observation of the skin surface after administration indicated that the interaction between ingredients of the nanoparticles and the skin surface markedly changed the morphology of the stratum corneum and disrupted the corneocyte layers, thus facilitating the permeation and accumulation of quercetin in skin. Conclusion Lecithin-chitosan nanoparticles are a promising carrier for topical delivery of quercetin. PMID:21904452

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.

Effect of tannic and gallic acids alone or in combination with carbenicillin or tetracycline on Chromobacterium violaceum CV026 growth, motility, and biofilm formation.

PubMed

Dusane, Devendra H; O'May, Che; Tufenkji, Nathalie

2015-07-01

Chromobacterium violaceum is an opportunistic pathogen that causes infections that are difficult to treat. The goal of this research was to evaluate the effect of selected tannins (tannic acid (TA) and gallic acid (GA)) on bacterial growth, motility, antibiotic (carbenicillin, tetracycline) susceptibility, and biofilm formation. Both tannins, particularly TA, impaired bacterial growth levels and swimming motilities at sub-minimum inhibitory concentrations (sub-MICs). In combination with tannins, antibiotics showed increased MICs, suggesting that tannins interfered with antibacterial activity. Sub-MICs of tetracycline or TA alone enhanced biofilm formation of C. violaceum; however, in combination, these compounds inhibited biofilm formation. In contrast, carbenicillin at sub-MICs was effective in inhibiting C. violaceum biofilm formation; however, in combination with lower concentrations of TA or GA, biofilms were enhanced. These results provide insights into the effects of tannins on C. violaceum growth and their varying interaction with antibiotics used to target C. violaceum infections.

Preparation and in vitro characterization of gallic acid-loaded human serum albumin nanoparticles

NASA Astrophysics Data System (ADS)

Mohammad-Beigi, Hossein; Shojaosadati, Seyed Abbas; Morshedi, Dina; Arpanaei, Ayyoob; Marvian, Amir Tayaranian

2015-04-01

Gallic acid (GA), as an antioxidant and antiparkinson agent, was loaded onto cationic human serum albumin nanoparticles (HSA NPs). Polyethylenimine (PEI)-coated HSA (PEI-HSA) NPs were prepared using three different methods: (I) coating negatively charged HSA NPs with positively charged PEI through attractive electrostatic interactions, (II) coating HSA NPs with PEI via covalent amide bond formation using N-(3-dimethylaminopropyl)- N-ethylcarbodiimide hydrochloride, and (III) coating HSA NPs with PEI via covalent bonding using glutaraldehyde for linking amine groups of PEI and amine groups of albumin NPs. Method II was selected since it resulted in a higher shift in the zeta potential value (mV) and less zeta potential value deviation, and also less size polydispersity. GA was loaded by adsorption onto the surface of PEI-HSA NPs of two different sizes: 117 ± 2.9 nm (PEI-P1) and 180 ± 3.1 nm (PEI-P2) NPs. Both GA-entrapment and GA-loading efficiencies increased slightly with the increasing size of NPs, and were affected intensely by the mass ratio of GA to PEI-HSA NPs. Free radical scavenging of GA was quantified based on the 2,2-diphenyl-1-picrylhydrazyl method. The obtained results showed that GA remains active during the preparation of GA-loaded PEI-HSA NPs. The cytotoxicities of HSA, PEI-HSA, and GA-loaded PEI-HSA NPs on the PC-12 cells, as the neuroendocrine cell line, were measured. Our results indicate that positively charged PEI-HSA NPs are good candidates for efficient and safe delivery of GA to the brain.

Preparation and antibacterial activities of chitosan-gallic acid/polyvinyl alcohol blend film by LED-UV irradiation.

PubMed

Yoon, Soon-Do; Kim, Young-Mog; Kim, Boo Il; Je, Jae-Young

2017-11-01

Active blend films from chitosan-gallic acid (CGA) and polyvinyl alcohol (PVA) were prepared via a simple mixing and casting method through the addition of citric acid as a plasticizer. The CGA/PVA blend films were characterized using Fourier transform infrared spectroscopy (FT-IR). The mechanical properties including tensile strength (TS) and elongation at break (%E), degree of solubility (S) and swelling behavior (DS), water vapor adsorption, and antimicrobial activities of the CGA/PVA blend films with and without LED (light emitting diode)-UV irradiation were also investigated. The CGA/PVA blend films exposed to UV irradiation exerted a higher TS (43.5MPa) and lower %E (50.40), S (0.38) and DS (2.73) compared to the CGA/PVA blend films (TS=41.7MPa, %E=55.40, S=0.42, and DS=3.16) not exposed LED-UV irradiation, indicating that the cross-linkage between CGA and PVA had been strengthened by LED-UV irradiation. However, the water vapor adsorption in the CGA/PVA blend films increased due to the changes of surface roughness and pore volume after LED-UV irradiation, and all values increased by increasing the CGA concentrations in the CGA/PVA blend films. The antimicrobial activities of the CGA/PVA blend films showed that the efficient concentration of CGA in the CGA/PVA blend films was over 1.0%. Taken together, the CGA/PVA blend films have potential for use as food packing materials. Copyright © 2017 Elsevier B.V. All rights reserved.

The Teratogenicity and the Action Mechanism of Gallic Acid Relating with Brain and Cervical Muscles

PubMed Central

Hsieh, Chiu Lan; Lin, Chien-Hong; Chen, Kuan Chou; Peng, Chiung-Chi; Peng, Robert Y.

2015-01-01

Gallic acid (3,4,5-trihydroxybenzoic acid) (GA) and other flavanoids are extensively used in nutraceuticals because of their antioxidant and antiinflammatory properties. While examining whether GA is effective in alleviating valproic-acid-induced teratogenesis in a chicken embryo model (CEM), we observed embryo hemorrhage and liposis in the musculi longissimus cervicis. We conducted this study to determine whether GA is inherently teratogenic and the extent to which the risk can be transferred to fetuses. A CEM was used to administer GA at 2, 6, 10, and 14 μM. GA at 2 μM did not exhibit cytotoxicity. At 6, 10, and 14 μM, GA caused severe decreases in body and liver weights, causing -5.6%, -21.3%, and -27.5% body weights and 4.0, 3.8, and 3.2-g, liver weights, respectively, in day-1 chicks. The optimal alive birth rate (or damaging rate) reached 33.3%, 39.4%, and 29.2% at 6, 10, and 14 μM GA, respectively. The damaged tissue was primarily cervical muscle (musculi longissimus cervicis), as evidenced by liposis, Zenker’s necrosis, and hemolysis. The erythrocyte, hemoglobin, eosinophil, lymphocyte, and monocyte counts were severely reduced and PPAR-α was downregulated, whereas the Ras/Raf/JAK/STAT pathway was upregulated. The GA dose required to induce teratogenesis was ≥ 6 μM (1.02 mg/kg), which can be easily consumed by pregnant women in typical teas such as Chinese Pu-’Er and Chinese black teas, indicating a potential risk to human fetuses. GA at doses ≥ 1.02 mg/kg of body weight potentially causes characteristic cerebral hemolysis and liposis in the musculi longissimus cervicis. The mechanism of action of GA is multidisciplinary: The liposis can be ascribed to downregulation of PPAR-α; the erythrocyte hemolysis can be attributed to its unique autooxidative and prooxidant behavior and the inhibition of carbonic anhydrase; and the proliferation and differentiation deficits can be attributed to the upregulation of the Ras/Raf/JAK/STAT pathway. PMID

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.

Ellagic acid, phenolic acids, and flavonoids in Malaysian honey extracts demonstrate in vitro anti-inflammatory activity.

PubMed

Kassim, Mustafa; Achoui, Mouna; Mustafa, Mohd Rais; Mohd, Mustafa Ali; Yusoff, Kamaruddin Mohd

2010-09-01

Natural honey has been used in traditional medicine of different cultures throughout the world. This study looked into the extraction of Malaysian honey and the evaluation of the anti-inflammatory activity of these extracts. It was hypothesized that honey extracts contain varying amounts of phenolic compounds and that they possess different in vitro anti-inflammatory activities. Honey extracts were analyzed using liquid chromatography-mass spectrometry to identify and compare phenolic compounds, whereas high-performance liquid chromatography was used for their quantification. Subsequently, honey methanol extract (HME) and honey ethyl acetate extract (HEAE) were tested in vitro for their effect on nitric oxide production in stimulated macrophages. The extracts were also tested for their effects on tumor necrosis factor-α (TNF) cytotoxicity in L929 cells. The major phenolics in the extracts were ellagic, gallic, and ferulic acids; myricetin; chlorogenic acid; and caffeic acid. Other compounds found in lower concentrations were hesperetin, p-coumaric acid, chrysin, quercetin, luteolin, and kaempferol. Ellagic acid was the most abundant of the phenolic compounds recorded, with mean concentrations of 3295.83 and 626.74 μg/100 g of honey in HME and HEAE, respectively. The median maximal effective concentrations for in vitro nitric oxide inhibition by HEAE and HME were calculated to be 37.5 and 271.7 μg/mL, respectively. The median maximal effective concentrations for protection from TNF cytotoxicity by HEAE and HME were 168.1 and 235.4 μg/mL, respectively. In conclusion, HEAE exhibited greater activity in vitro, whereas HME contained a higher concentration of phenolic compounds per 100 g of honey. Copyright © 2010 Elsevier Inc. All rights reserved.

Enhancing oral bioavailability of quercetin using novel soluplus polymeric micelles

NASA Astrophysics Data System (ADS)

Dian, Linghui; Yu, Enjiang; Chen, Xiaona; Wen, Xinguo; Zhang, Zhengzan; Qin, Lingzhen; Wang, Qingqing; Li, Ge; Wu, Chuanbin

2014-12-01

To improve its poor aqueous solubility and stability, the potential chemotherapeutic drug quercetin was encapsulated in soluplus polymeric micelles by a modified film dispersion method. With the encapsulation efficiency over 90%, the quercetin-loaded polymeric micelles (Qu-PMs) with drug loading of 6.7% had a narrow size distribution around mean size of 79.00 ± 2.24 nm, suggesting the complete dispersibility of quercetin in water. X-ray diffraction (XRD) patterns illustrated that quercetin was in amorphous or molecular form within PMs. Fourier transform infrared spectroscopy (FTIR) indicated that quercetin formed intermolecular hydrogen bonding with carriers. An in vitro dialysis test showed the Qu-PMs possessed significant sustained-release property, and the formulation was stable for at least 6 months under accelerated conditions. The pharmacokinetic study in beagle dogs showed that absorption of quercetin after oral administration of Qu-PMs was improved significantly, with a half-life 2.19-fold longer and a relative oral bioavailability of 286% as compared to free quercetin. Therefore, these novel soluplus polymeric micelles can be applied to encapsulate various poorly water-soluble drugs towards a development of more applicable therapeutic formulations.

Islet protection and amelioration of type 2 diabetes mellitus by treatment with quercetin from the flowers of Edgeworthia gardneri.

PubMed

Zhuang, Manjiao; Qiu, Honghong; Li, Ping; Hu, Lihua; Wang, Yayu; Rao, Lei

2018-01-01

The traditional Chinese medicine - the flower of Edgeworthia gardneri - is reported as an effective therapeutic for type 2 diabetes mellitus (T2DM). Nevertheless, most constituents of the flowers of E. gardneri have not yet been studied. This study was conducted to investigate the effect of quercetin extracted from the flowers of E. gardneri on islet protection and amelioration in T2DM and explore its mechanism. Quercetin was extracted from the flowers of E. gardneri and verified by high-performance liquid chromatography. Quercetin or crude extract's effect on insulin secretion was investigated. ERK1/2 and phospho-ERK1/2 were detected by Western blot analysis, and fluo-3 AM was used to detect intracellular Ca 2+ . The anti-apoptosis effect of quercetin or crude extract on MIN-6 cells was investigated by thiazolyl blue tetrazolium bromide (MTT) assay and flow cytometry analysis. Activation of caspases and expression of Bcl-2 and BAX were tested by Western blot analysis. In addition, the mitochondrial membrane potential was determined by JC-1 probe. Moreover, in vivo activity was also tested in db/db mice. A quercetin level of >10 μmol/L could induce insulin secretion. Intracellular Ca 2+ and ERK1/2 were involved in the signaling pathway of quercetin-induced insulin secretion. We also observed that quercetin could inhibit palmitic acid-induced cell apoptosis via suppressing the activation of caspase-3, -9, -12; increasing the ratio of Bcl-2/BAX and reversing the impaired mitochondrial membrane potential. Crude extract's effect on insulin secretion was similar to that of pure extracted quercetin, while it possessed higher anti-apoptosis activity. Additionally, intraperitoneal glucose tolerance, plasma insulin level, hepatic triglyceride, hepatic glycogen and the pathological histology of both pancreatic islet and liver in db/db mice were significantly improved by the administration of the extracted quercetin. Our study indicated that quercetin extracted from the

Comparative assessment on in vitro antioxidant activities of ethanol extracts of Averrhoa bilimbi, Gymnema sylvestre and Capsicum frutescens

PubMed Central

Rahman, Md. Mominur; Habib, Md. Razibul; Hasan, Md. Anayet; Al Amin, Mohammad; Saha, Ayan; Mannan, Adnan

2014-01-01

Background: Averrhoa bilimbi, Gymnema sylvestre and Capsicum frutescens are medicinal plants commonly used as traditional medicine for the treatment of various diseases. The present study was designed to investigate the antioxidant activities of Ethanolic extract of A. bilimbi, G. sylvestre and C. frutescens. Materials and Methods: The antioxidant activity of the extracts were evaluated using total phenolic and flavonoid contents, ferric reducing power and the free radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH). Results: Total phenolic and flavonoid contents were higher in G. sylvestre (53.63636 ± 0.454545 mg/g gallic acid equivalent) and C. frutescens (26.66667 ± 2.081666 mg/g quercetin equivalent) respectively. Reducing power of the crude ethanol extracts increased with the concentrations of the extracts and all the extracts showed moderate free radical scavenging activity against DPPH. The plant extract displayed moderate phenolic and flavonoid contents compared to gallic acid and quercetin equivalent respectively, whereas also exhibited significant scavenging of DPPH radical and reducing power compared with ascorbic acid as standard. Conclusion: Our study suggests that G. sylvestre has significant antioxidant activity. The antioxidant compound of this plant might be a therapeutic candidate against oxidative stress related diseases. Different sub-fraction of A. bilimbi and C. frutescens should be studied further to assess the effect. Further study is necessary for isolation and characterization of the active antioxidant agents for better treatment. PMID:24497740

Dietary Quercetin Reduces Chemotherapy-Induced Fatigue in Mice

PubMed Central

Mahoney, Sara E.; Davis, J. Mark; Murphy, E. Angela; McClellan, Jamie L.; Pena, Marjory M.

2014-01-01

Purpose While fatigue is the most commonly reported symptom of chemotherapy, there are currently no effective treatments for chemotherapy-induced fatigue (CIF). We used a mouse model to examine the benefits of quercetin on CIF as measured by voluntary wheel running activity and sought to determine whether quercetin may be associated with a decrease in inflammation and/or anemia. Methods Mice were assigned to 1 of 4 groups: placebo-vehicle (Plac-PBS), placebo-5-fluorouracil (Plac-5FU), quercetin-vehicle (Quer-PBS), or quercetin-5-fluorouracil (Quer-5FU). All mice were given a daily injection of either 60 mg/kg of 5-FU or phosphate buffered saline (PBS) for 5 days. Quercetin (0.02%) treatment was administered in the food 3 days prior to 5-FU administration and for the duration of the experiment (ie, days −2 to 14). A second group of mice was sacrificed at 5 and 14 days post initial injection for assessment of monocyte chemoattractant protein-1 (MCP-1) and anemia. Results Voluntary wheel running was reduced in both the Plac-5FU and Quer-5FU groups following 5-FU injection (P < .05). However, the Quer-5FU group recovered to baseline levels by approximately day 7, whereas the Plac-5FU group remained suppressed. MCP-1 was significantly elevated at 14 days in Plac-5FU (P < .001), but no changes were seen with Quer-5FU. Treatment with 5-FU resulted in anemia at both 5 days and 14 days; however, quercetin blocked this effect at 14 days (P < .001). Conclusion These results demonstrate the beneficial effect of quercetin on improving recovery of voluntary physical activity following 5-FU treatment, which may be linked to a decrease in inflammation and anemia. PMID:24626097

Gallic acid/hydroxypropyl-β-cyclodextrin complex: Improving solubility for application on in vitro/ in vivo Candida albicans biofilms

PubMed Central

Teodoro, Guilherme Rodrigues; Salvador, Marcos José; Koga-Ito, Cristiane Yumi

2017-01-01

The aim of this study was to increase the solubility of gallic acid (GA) for the treatment of Candida albicans biofilm, which is very difficult to treat and requires high drug concentrations. Cyclodextrins (CDs) were used for this purpose. Complexes were evaluated by phase-solubility studies, prepared by spray drying and characterized by drug loading, scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). The complexes were tested on C. albicans biofilm using in vitro and in vivo models. HPβCD formed soluble inclusion complexes with GA. The percentage of GA in GA/HPβCD was 10.8 ± 0.01%. The SEM and DSC analyses confirmed the formation of inclusion complexes. GA/HPβCD maintained the antimicrobial activity of the pure GA. GA/HPβCD was effective on C. albicans biofilms of 24 and 48h. The in vivo results showed an anti-inflammatory activity of GA/HPβCD with no difference in invading hypha counting among the groups. This study encourages the development of new antifungal agents. PMID:28700692

Gallic acid induced apoptotic events in HCT-15 colon cancer cells

PubMed Central

Subramanian, Aruna Priyadharshni; Jaganathan, Saravana Kumar; Mandal, Mahitosh; Supriyanto, Eko; Muhamad, Ida Idayu

2016-01-01

AIM: To investigate the inhibitory action of diet-derived phenolic compound gallic acid (GA) against HCT-15 colon cancer cells. METHODS: The antiproliferative effect of GA against colon cancer cells was determined by performing thiazolyl blue tetrazolium bromide (MTT) assay. The colony forming ability of GA treated colon cancer cells was evaluated using the colony forming assay. The cell cycle changes induced by GA in HCT-15 cells were analyzed by propidium iodide staining. Levels of reactive oxygen species (ROS) and mitochondrial membrane potential of HCT-15 exposed to GA was assessed using 2’,7’-dichlorfluorescein-diacetate and rhodamine-123 respectively, with the help of flow cytometry. Morphological changes caused by GA treatment in the colon cancer cells were identified by scanning electron microscope and photomicrograph examination. Apoptosis was confirmed using flow cytometric analysis of GA treated HCT-15 cells after staining with Yo-Pro-1. RESULTS: MTT assay results illustrated that GA has an inhibitory effect on HCT-15 cells with IC50 value of 740 μmol/L. A time-dependent inhibition of colony formation was evident with GA treatment. Cell cycle arrest was evident from the accumulation of GA treated HCT-15 cells at sub-G1 phase (0.98 ± 1.03 vs 58.01 ± 2.05) with increasing exposure time. Flow cytometric analysis of GA treated HCT-15 cells depicted early events associated with apoptosis like lipid layer breakage and fall in mitochondrial membrane potential apart from an increase in the generation of ROS which were in a time dependent manner. SEM and photomicrograph images of the GA-treated cells displayed membrane blebbing and cell shrinking characteristics of apoptosis. Further apoptosis confirmation by Yo-Pro-1 staining also showed the time-dependent increase of apoptotic cells after treatment. CONCLUSION: These results show that GA induced ROS dependent apoptosis and inhibited the growth of colon cancer cells. PMID:27099438

Metabolic variation and antioxidant potential of Malus prunifolia (wild apple) compared with high flavon-3-ol containing fruits (apple, grapes) and beverage (black tea).

PubMed

Maria John, K M; Enkhtaivan, Gansukh; Kim, Ju Jin; Kim, Doo Hwan

2014-11-15

Secondary metabolic variation of wild apple (Malus prunifolia) was compared with fruits that contained high flavan-3-ol like grapes (GR), apple (App) and the beverage, black tea (BT). The polyphenol contents in wild apple was higher than in GR and App but less than BT. The identified phenolic acids (gallic, protocatechuic, chlorogenic, p-coumaric and ferulic acids) and flavonoids (quercetin and myricetin) indicate that wild apple was higher than that of App. Among all the samples, BT had highest antioxidant potential in terms of 2,2'-Azinobis (3-thylbenzothiazoline-6-sulfonic acid) diammonium salt (95.36%), metal chelating (45.36%) and phosphomolybdenum activity (95.8 mg/g) because of the high flavan-3-ol content. The gallic acid and epigallocatechin gallate were highly correlated with antioxidant potential and these metabolites levels are higher in wild apple than that of App. Wild apples being a non-commercial natural source, a detailed study of this plant will be helpful for the food additive and preservative industry. Copyright © 2014 Elsevier Ltd. All rights reserved.

Anti- and pro-oxidant effects of quercetin in copper-induced low density lipoprotein oxidation. Quercetin as an effective antioxidant against pro-oxidant effects of urate.

PubMed

Filipe, Paulo; Haigle, Josiane; Silva, João Nuno; Freitas, João; Fernandes, Afonso; Mazière, Jean-Claude; Mazière, Cécile; Santus, René; Morlière, Patrice

2004-05-01

We recently reported that, depending on its concentration, urate is either a pro- or an antioxidant in Cu(2+)-induced low-density lipoprotein (LDL) oxidation. We also previously demonstrated an antioxidant synergy between urate and some flavonoids in the Cu(2+)-induced oxidation of diluted serum. As a result, the effect of the flavonoid quercetin on the Cu(2+)-induced oxidation of isolated LDL has been studied either in the presence or absence of urate. We demonstrate that, like urate, quercetin alone, at low concentration, exhibits a pro-oxidant activity. The pro-oxidant behavior depends on the Cu(2+) concentration but it is not observed at high Cu(2+) concentration. When compared with urate, the switch between the pro- and the antioxidant activities occurs at much lower quercetin concentrations. As for urate, the pro-oxidant character of quercetin is related to its ability to reduce Cu(2+) with the formation of semioxidized quercetin and Cu(+) with an expected yield larger than that obtained with urate owing to a more favorable redox potential. It is also shown that the pro-oxidant activity of urate can be inhibited by quercetin. An electron transfer between quercetin and semioxidized urate leading to the repair of urate could account for this observation as suggested by recently published pulse radiolysis data. It is anticipated that the interactions between quercetin-Cu(2+)-LDL and urate, which are tightly controlled by their respective concentration, determine the balance between the pro- and antioxidant behaviors. Moreover, as already observed with other antioxidants, it is demonstrated that quercetin alone behaves as a pro-oxidant towards preoxidized LDL.

Analysis of hydrolyzable tannins and other phenolic compounds in emblic leafflower (Phyllanthus emblica L.) fruits by high performance liquid chromatography-electrospray ionization mass spectrometry.

PubMed

Yang, Baoru; Kortesniemi, Maaria; Liu, Pengzhan; Karonen, Maarit; Salminen, Juha-Pekka

2012-09-05

Phenolic compounds were extracted from dried emblic leafflower (Phyllanthus emblica L.) fruits with methanol and separated by Sephadex LH-20 column chromatography. The raw extracts and fractions were analyzed with HPLC coupled with diode array UV spectroscopy, electrospray ionization mass spectrometry, and tandem mass spectrometry. Mucic acid gallate, mucic acid lactone gallate, monogalloylglucose, gallic acid, digalloylglucose, putranjivain A, galloyl-HHDP-glucose, elaeocarpusin, and chebulagic acid were suggested to be the most abundant compounds in the crude methanol extracts of the fruits. In addition, 144 peaks were detected, of which 67 were tentatively identified mostly as ellagitannins, flavonoids, and simple gallic acid derivatives in the fractions. The results indicated the presence of neochebulagic acid, isomers of neochebuloyl galloylglucose, chebuloyl neochebuloyl galloylglucose, ellagic acid glycosides, quercetin glycosides, and eriodictyol coumaroyl glycosides in the fruits. The study provides a systematic report of the retention data and characteristics of UV, MS, and MS/MS spectra of the phenolic compounds in the fruits of emblic leafflower. The fruits of two varieties (Ping Dan No 1 and Fruity) from Guangxi Province differed from those of wild Tian Chuan emblic leafflower from Fujian Province in the content and profile of phenolic compounds.

Quercetin protects rat cortical neurons against traumatic brain injury.

PubMed

Du, Guoliang; Zhao, Zongmao; Chen, Yonghan; Li, Zonghao; Tian, Yaohui; Liu, Zhifeng; Liu, Bin; Song, Jianqiang

2018-06-01

Previous studies have demonstrated that traumatic brain injury (TBI) may cause neurological deficits and neuronal cell apoptosis. Quercetin, one of the most widely distributed flavonoids, possesses anti‑inflammatory, anti‑blood coagulation, anti‑ischemic and anti‑cancer activities, and neuroprotective effects in the context of brain injury. The purpose of the present study was to investigate the neuroprotective effects of quercetin in TBI. A total of 75 rats were randomly arranged into 3 groups as follows: Sham group (Sham); TBI group (TBI); and TBI + quercetin group (Que). Brain edema was evaluated by analysis of brain water content. The neurobehavioral status of the rats was evaluated by Neurological Severity Scoring. Immunohistochemical and western blot analyses were used to measure the expression of certain proteins. The results of the present study demonstrated that post‑TBI administration of quercetin may attenuate brain edema, in addition to improving motor function in rats. Additionally, quercetin caused a marked inhibition of extracellular signal‑regulated kinase 1/2 phosphorylation and activated Akt serine/threonine protein kinase phosphorylation, which may result in attenuation of neuronal apoptosis. The present study provided novel insights into the mechanism through which quercetin may exert its neuroprotective activity in a rat model of TBI.

Antiviral Effects of Black Raspberry (Rubus coreanus) Seed and Its Gallic Acid against Influenza Virus Infection.

PubMed

Lee, Ji-Hye; Oh, Mi; Seok, Jong Hyeon; Kim, Sella; Lee, Dan Bi; Bae, Garam; Bae, Hae-In; Bae, Seon Young; Hong, Young-Min; Kwon, Sang-Oh; Lee, Dong-Hun; Song, Chang-Seon; Mun, Ji Young; Chung, Mi Sook; Kim, Kyung Hyun

2016-06-06

Influenza is a serious public health concern worldwide, as it causes significant morbidity and mortality. The emergence of drug-resistant viral strains requires new approaches for the treatment of influenza. In this study, Rubus coreanus seed (RCS) that is left over from the production of wine or juice was found to show antiviral activities against influenza type A and B viruses. Using the time-of-addition plaque assay, viral replication was almost completely abolished by simultaneous treatment with the RCS fraction of less than a 1-kDa molecular weight (RCSF1). One of the polyphenols derived from RCSF1, gallic acid (GA), identified by liquid chromatography-tandem mass spectrometry, showed inhibitory effects against both influenza type A and B viruses, albeit at relatively high concentrations. RCSF1 was bound to hemagglutinin protein, inhibited hemagglutination significantly and disrupted viral particles, whereas GA was found to only disrupt the viral particles by using transmission electron microscopy. In BALB/c mice infected with influenza virus, oral administration of RCSF1 significantly improved the survival rate and reduced the viral titers in the lungs. Our results demonstrate that RCSF1 and GA show potent and broad antiviral activity against influenza A and B type viruses and are promising sources of agents that target virus particles.

Antiviral Effects of Black Raspberry (Rubus coreanus) Seed and Its Gallic Acid against Influenza Virus Infection

PubMed Central

Lee, Ji-Hye; Oh, Mi; Seok, Jong Hyeon; Kim, Sella; Lee, Dan Bi; Bae, Garam; Bae, Hae-In; Bae, Seon Young; Hong, Young-Min; Kwon, Sang-Oh; Lee, Dong-Hun; Song, Chang-Seon; Mun, Ji Young; Chung, Mi Sook; Kim, Kyung Hyun

2016-01-01

Influenza is a serious public health concern worldwide, as it causes significant morbidity and mortality. The emergence of drug-resistant viral strains requires new approaches for the treatment of influenza. In this study, Rubus coreanus seed (RCS) that is left over from the production of wine or juice was found to show antiviral activities against influenza type A and B viruses. Using the time-of-addition plaque assay, viral replication was almost completely abolished by simultaneous treatment with the RCS fraction of less than a 1-kDa molecular weight (RCSF1). One of the polyphenols derived from RCSF1, gallic acid (GA), identified by liquid chromatography-tandem mass spectrometry, showed inhibitory effects against both influenza type A and B viruses, albeit at relatively high concentrations. RCSF1 was bound to hemagglutinin protein, inhibited hemagglutination significantly and disrupted viral particles, whereas GA was found to only disrupt the viral particles by using transmission electron microscopy. In BALB/c mice infected with influenza virus, oral administration of RCSF1 significantly improved the survival rate and reduced the viral titers in the lungs. Our results demonstrate that RCSF1 and GA show potent and broad antiviral activity against influenza A and B type viruses and are promising sources of agents that target virus particles. PMID:27275830

Association of Dietary Quercetin with Reduced Risk of Proximal Colon Cancer

PubMed Central

Djuric, Zora; Severson, Richard K.; Kato, Ikuko

2012-01-01

Quercetin is a flavonol that appears to be protective against several cancers, but its possible role in prevention of colorectal cancer is not yet well studied. We evaluated dietary intakes of quercetin and risk of colorectal cancer in a large case-control study conducted in Metropolitan Detroit, MI (n = 2664). The protective effects of quercetin intake, as assessed by food frequency questionnaire, were confined to risk of proximal colon cancer. Stratified analyses showed that the protective effects of quercetin on risk of proximal colon cancer were significant only when fruit intake or the Healthy Eating Index score were high, or when tea intake was low, with odds ratios (OR) for the highest versus the lowest quartile = 0.49, 0.44, and 0.51, respectively. Increased quercetin intake had no protective effects when tea intake was high. Interestingly, increased intake of quercetin was associated with increased risk of distal colon cancer when total fruit intake was low (OR for the highest versus the lowest quartile = 1.99). These results suggest that quercetin can have disparate effects on colon cancer risk depending on whether dietary intakes of fruit or tea are high, and that quercetin had protective effects only on proximal, not distal, colon cancer. PMID:22429001

On the causes and consequences of the uncoupler-like effects of quercetin and dehydrosilybin in H9c2 cells

PubMed Central

Mouithys-Mickalad, Ange; Dostal, Zdenek; Serteyn, Didier; Modriansky, Martin

2017-01-01

Quercetin and dehydrosilybin are polyphenols which are known to behave like uncouplers of respiration in isolated mitochondria. Here we investigated whether the effect is conserved in whole cells. Following short term incubation, neither compound uncouples mitochondrial respiration in whole H9c2 cells below 50μM. However, following hypoxia, or long term incubation, leak (state IV with oligomycin) oxygen consumption is increased by quercetin. Both compounds partially protected complex I respiration, but not complex II in H9c2 cells following hypoxia. In a permeabilised H9c2 cell model, the increase in leak respiration caused by quercetin is lowered by increased [ADP] and is increased by adenine nucleotide transporter inhibitor, atractyloside, but not bongkrekic acid. Both quercetin and dehydrosilybin dissipate mitochondrial membrane potential in whole cells. In the case of quercetin, the effect is potentiated post hypoxia. Genetically encoded Ca++ sensors, targeted to the mitochondria, enabled the use of fluorescence microscopy to show that quercetin decreased mitochondrial [Ca++] while dehydrosilybin did not. Likewise, quercetin decreases accumulation of [Ca++] in mitochondria following hypoxia. Fluorescent probes were used to show that both compounds decrease plasma membrane potential and increase cytosolic [Ca++]. We conclude that the uncoupler-like effects of these polyphenols are attenuated in whole cells compared to isolated mitochondria, but downstream effects are nevertheless apparent. Results suggest that the effect of quercetin observed in whole and permeabilised cells may originate in the mitochondria, while the mechanism of action of cardioprotection by dehydrosilybin may be less dependent on mitochondrial uncoupling than originally thought. Rather, protective effects may originate due to interactions at the plasma membrane. PMID:28977033

Frost decreases content of sugars, ascorbic acid and some quercetin glycosides but stimulates selected carotenes in Rosa canina hips.

PubMed

Cunja, Vlasta; Mikulic-Petkovsek, Maja; Zupan, Anka; Stampar, Franci; Schmitzer, Valentina

2015-04-15

Primary and secondary metabolites of Rosa canina hips were determined by HPLC/MS during ripening and after frost damage. Rose hips were harvested six times from the beginning of September until the beginning of December. Color parameters a*, b* and L* decreased during maturation. Glucose and fructose were the predominant sugars representing up to 92% total sugars, and citric acid was the major organic acid detected in rose hips (constituting up to 58% total organic acids). Total sugar and ascorbic acid content significantly decreased after frost damage; from 42.2 to 25.9 g 100 g(-1) DW for sugars and from 716.8 to 176.0 mg 100 g(-1) DW for ascorbic acid. Conversely, β-carotene and lycopene levels increased in frostbitten rose hips to 22.1 and 113.2 mg 100 g(-1) DW, respectively. In addition to cyanidin-3-glucoside (highest level in hips was 125.7 μg 100 g (-1) DW), 45 different phenolic compounds have been identified. The most abundant were proanthocyanidins (their levels amounted up to 90% of total flavanol content) and their content showed no significant differences during maturation. The levels of catechin, phloridzin, flavanones and several quercetin glycosides were highest on the first three sampling dates and decreased after frost. Antioxidant capacity similarly decreased in frostbitten rose hips. Total phenolic content increased until the third sampling and decreased on later samplings. Copyright © 2015 Elsevier GmbH. All rights reserved.

Efficacy of an orally administered combination of hyaluronic acid, chondroitin sulfate, curcumin and quercetin for the prevention of recurrent urinary tract infections in postmenopausal women.

PubMed

Torella, M; Del Deo, F; Grimaldi, A; Iervolino, S A; Pezzella, M; Tammaro, C; Gallo, P; Rappa, C; De Franciscis, P; Colacurci, N

2016-12-01

To assess whether the orally administered combination of hyaluronic acid (HA), chondroitin sulfate (CS), curcumin and quercetin could be effective in preventing recurrent cystitis in postmenopausal women and whether its efficacy was conditioned by the concurrent use of local estrogen therapy. This was a prospective evaluation of 145 postmenopausal women consecutively recruited from the database of three different investigators. All women should have mild-to-moderate urogenital atrophy and a history of recurrent urinary tract infections (≥2 episodes within 6 months or ≥3 episodes within 12 months documented by positive urine cultures) during the last year. Patients were assigned to three different therapeutic regimens: the first group was treated only with vaginal estrogens, the second group only with HA, CS, curcumin and quercetin per os, and the third group was treated with HA, CS, curcumin and quercetin associated with local estrogens. We evaluated the number of patients with <2 infective episodes in the 6-month follow-up and <3 episodes in the 12-month follow-up (main aim definition) and the reduction of related symptoms through a Visual Analog Scale (VAS) and the Pelvic Pain and Urgency/Frequency (PUF) patient symptom scale. Student's t-test and chi-squared test were used for data analysis as appropriate. At 6-month follow up, the main aim rate was 8%, 11.1% and 25% in the three groups, respectively (p<0.05 compared to baseline only in group 3). Although the reduction in the number of recurrent episodes became significant in all groups at 1 year follow-up, the main aim rate was almost double in women receiving both local estrogens and oral therapy (group 3) compared to those receiving single treatments. The improvement of related symptoms was significant in all groups at 12-month follow-up. In postmenopausal women, the combination of HA, CS, curcumin and quercetin per os was effective in preventing recurrent urinary tract infections, especially if

Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential.

PubMed

Caltagirone, S; Rossi, C; Poggi, A; Ranelletti, F O; Natali, P G; Brunetti, M; Aiello, F B; Piantelli, M

2000-08-15

Flavonoids are a class of polyphenolic compounds widely distributed in the plant kingdom, which display a variety of biological activities, including chemoprevention and tumor growth inhibition. Our aim was to investigate the effects of several polyphenols on the growth and metastatic potential of B16-BL6 melanoma cells in vivo. Intraperitoneal administration of quercetin, apigenin, (-)-epigallocathechin-3-gallate (EGCG), resveratrol, and the anti-estrogen tamoxifen, at the time of i.m. injection of B16-BL6 cells into syngeneic mice, resulted in a significant, dose-dependent delay of tumor growth, without toxicity. The relative descending order of potency was EGCG > apigenin = quercetin = tamoxifen > resveratrol > control. Furthermore, polyphenols significantly potentiated the inhibitory effect of a non-toxic dose of cisplatin. When tested for the ability to inhibit lung colonization, quercetin, apigenin, and tamoxifen (but not EGCG or resveratrol) significantly decreased the number of B16-BL6 colonies in the lungs in a dose-dependent manner, with quercetin and apigenin being more effective than tamoxifen. Interestingly, quercetin, apigenin, and tamoxifen (but not EGCG or resveratrol) significantly decreased the invasion of B16-BL6 cells in vitro, with quercetin and apigenin being more effective than tamoxifen. This suggests that anti-invasive activity is one of the mechanisms underlying inhibition of lung colonization by quercetin and apigenin. In conclusion, quercetin and apigenin inhibit melanoma growth and invasive and metastatic potential; therefore, they may constitute a valuable tool in the combination therapy of metastatic melanoma. Copyright 2000 Wiley-Liss, Inc.

A Study of the Modulating Action of Quercetin on Biochemical and Histological Alterations Induced by Lead Exposure in the Liver and Kidney of Rats.

PubMed

Mohammed, Ghena M.; Sedky, Azza; Elsawy, Hany

2017-06-30

Lead is a highly toxic metal and a very potent poison. Lead poisoning is a serious condition but can be treated. Quercetin is a flavonoid with many beneficial uses. The aim of the present study was to investigate the possible modulating action of quercetin as a model of an antioxidant against the toxic effects of lead acetate on liver and kidneys of rats. Rats were randomly divided into four groups: (i) saline group (control); (ii) lead group received i.p. lead acetate (20 mg/kg b.w.); (iii) quercetin group received i.p. quercetin (50 mg/kg b.w.); (iv) lead and quercetin group received i.p. lead acetate (20 mg/kg b.w.) followed by i.p. quercetin (50 mg/kg b.w.) for 4 weeks. The lead concentrations were determined in the liver and kidney tissues. Liver marker enzymes, bilirubin, albumin, total protein, creatinine, uric acid and urea, were assessed in the serum and light microscopic studies were performed. The results showed that lead acetate administration was associated with an increase in serum alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST) activities, total bilirubin, creatinine, uric acid, urea levels. Lead accumulation in kidneys and liver tissues was also found, but were associated with decrease in albumin and total protein in comparison with the respective mean values of the control. Lead acetate caused numerous histological alterations in the liver, including chronic inflammation, bilary hyperplasia, edema, congestion, Kupffer cells hyperplasia and hemosiderosis, and in the kidney, including tubular dilation, atrophy of glomerular tuft, widening of urinary space and mild fibroblast. In contrary, administration of lead acetate along with quercetin partially restored the studied parameters to normal values and improved structure of liver and kidney with significant decreases in the severity of histopathological changes when compared with the lead acetate group. In conclusion, treatment with quercetin may provide a

Quercetin suppresses HeLa cells by blocking PI3K/Akt pathway.

PubMed

Xiang, Tao; Fang, Yong; Wang, Shi-Xuan

2014-10-01

To explore the effect of quercetin on the proliferation and apoptosis of HeLa cells, HeLa cells were incubated with quercetin at different concentrations. Cell viability was evaluated by MTT assay, cell apoptosis was detected by Annexin-V/PI double labeled cytometry and DNA ladder assay. Cell cycle was flow cytometrically determined and the morphological changes of the cells were observed under a fluorescence microscope after Hoechst 33258 staining and the apoptosis-related proteins in the HeLa cells were assessed by Western blotting. The results showed that quercetin significantly inhibited the growth of HeLa cells and induced obvious apoptosis in vitro in a time- and dose-dependent manner. Moreover, quercetin induced apoptosis of HeLa cells in cell cycle-dependent manner because quercetin could induce arrest of HeLa cells at G0/G1 phase. Quercetin treatment down-regulated the expression of the PI3K and p-Akt. In addition, quercetin could down-regulate expression of bcl-2, up-regulate Bax, but exerted no effect on the overall expression of Akt. We are led to conclude that quercetin induces apoptosis via PI3k/Akt pathways, and quercetin has potential to be used as an anti-tumor agent against human cervix cancer.

Effect of dietary supplementation of gallic acid on nitrogen balance, nitrogen excretion pattern and urinary nitrogenous constituents in beef cattle.

PubMed

Wei, Chen; Yang, Kai; Zhao, Guangyong; Lin, Shixin; Xu, Zhiwei

2016-10-01

The objective of the trial was to study the effects of dietary supplementation of gallic acid (GA) on nitrogen (N) balance, N excretion pattern and urinary N constituents in beef cattle. In a 4 × 4 Latin square design, four male 30-month-old Simmental cattle (443 ± 22 kg live weight) received four levels of GA (purity ≥ 98.5%), i.e. 0, 5.3, 10.5, 21.1 g/kg DM, added to a basal ration. Each experimental period lasted 17 d, consisting of 12 d adaptation and 5 d sampling. The results showed that supplementation of GA at 5.3, 10.5 or 21.1 g/kg DM did not affect the N balance but regulated the N excretion pattern by increasing the ratio of faecal N/urinary N and decreasing the ratio of urinary urea N/total urinary N in beef cattle fed at maintenance level.

Hot-melt extrusion microencapsulation of quercetin for taste-masking.

PubMed

Khor, Chia Miang; Ng, Wai Kiong; Kanaujia, Parijat; Chan, Kok Ping; Dong, Yuancai

2017-02-01

Besides its poor dissolution rate, the bitterness of quercetin also poses a challenge for further development. Using carnauba wax, shellac or zein as the shell-forming excipient, this work aimed to microencapsulate quercetin by hot-melt extrusion for taste-masking. In comparison with non-encapsulated quercetin, the microencapsulated powders exhibited significantly reduced dissolution in the simulated salivary pH 6.8 medium indicative of their potentially good taste-masking efficiency in the order of zein > carnauba wax > shellac. In vitro bitterness analysis by electronic tongue confirmed the good taste-masking efficiency of the microencapsulated powders. In vitro digestion results showed that carnauba wax and shellac-microencapsulated powders presented comparable dissolution rate with the pure quercetin in pH 1.0 (gastric) and 6.8 (intestine) medium; while zein-microencapsulated powders exhibited a remarkably slower dissolution rate. Crystallinity of quercetin was slightly reduced after microencapsulation while its chemical structure remained unchanged. Hot-melt extrusion microencapsulation could thus be an attractive technique to produce taste-masked bioactive powders.

Quercetin inhibits glucose transport by binding to an exofacial site on GLUT1.

PubMed

Hamilton, Kathryn E; Rekman, Janelle F; Gunnink, Leesha K; Busscher, Brianna M; Scott, Jordan L; Tidball, Andrew M; Stehouwer, Nathan R; Johnecheck, Grace N; Looyenga, Brendan D; Louters, Larry L

2018-05-29

Quercetin, a common dietary flavone, is a competitive inhibitor of glucose uptake and is also thought to be transported into cells by GLUT1. In this study, we confirm that quercetin is a competitive inhibitor of GLUT1 and also demonstrate that newly synthesized compounds, WZB-117 and BAY-876 are robust inhibitors of GLUT1 in L929 cells. To measure quercetin interaction with L929 cells, we develop a new fluorescent assay using flow cytometry. The binding of quercetin and its inhibitory effects on 2-deoxyglucose (2DG) uptake showed nearly identical dose dependent effects, with both having maximum effects between 50 and 100 μM and similar half maximum effects at 8.9 and 8.5 μM respectively. The interaction of quercetin was rapid with t 1/2 of 54 s and the onset and loss of its inhibitory effects on 2DG uptake were equally fast. This suggests that either quercetin is simply binding to surface GLUT1 or its transport in and out of the cell reaches equilibrium very quickly. If quercetin is transported, the co-incubation of quercetin with other glucose inhibitors should block quercetin uptake. However, we observed that WZB-117, an exofacial binding inhibitor of GLUT1 reduced quercetin interaction, while cytochalasin B, an endofacial binding inhibitor, enhanced quercetin interaction, and BAY-876 had no effect on quercetin interaction. Taken together, these data are more consistent with quercetin simply binding to GLUT1, but not actually being transported into L929 cells via the glucose channel in GLUT1. Copyright © 2018. Published by Elsevier B.V.

Ameliorative Effect of Quercetin on Neurochemical and Behavioral Deficits in Rotenone Rat Model of Parkinson's Disease: Modulating Autophagy (Quercetin on Experimental Parkinson's Disease).

PubMed

El-Horany, Hemat E; El-Latif, Rania N Abd; ElBatsh, Maha M; Emam, Marwa N

2016-07-01

Autophagy is necessary for neuronal homeostasis and its dysfunction has been implicated in Parkinson's disease (PD) as it can exacerbate endoplasmic reticulum (ER) stress and ER stress-induced apoptosis. Quercetin is a flavonoid known for its neuroprotective and antioxidant effects. The present study investigated the protective, autophagy-modulating effects of quercetin in the rotenone rat model of PD. Rotenone was intraperitoneally injected at dose of 2 ml/kg/day for 4 weeks. Simultaneous intraperitoneal injection of quercetin was given at a dose of 50 mg/kg/day also for 4 weeks. Neurobehavioral changes were studied. Oxidative/antioxidant status, C/EBP homologous protein (CHOP), Beclin-1, and dopamine levels were assessed. DNA fragmentation and histopathological changes were evaluated. This research work revealed that quercetin significantly attenuated rotenone-induced behavioral impairment, augmented autophagy, ameliorated ER stress- induced apoptosis with attenuated oxidative stress. From the current study, quercetin can act as an autophagy enhancer in PD rat model and modulates the microenvironment that leads to neuronal death. © 2016 Wiley Periodicals, Inc.

Quercetin Protects Yeast Saccharomyces cerevisiae pep4 Mutant from Oxidative and Apoptotic Stress and Extends Chronological Lifespan.

PubMed

Alugoju, Phaniendra; Janardhanshetty, Sudharshan Setra; Subaramanian, Subasri; Periyasamy, Latha; Dyavaiah, Madhu

2018-05-01

The yeast Saccharomyces cerevisiae PEP4 gene encodes vacuolar endopeptidase proteinase A (Pep4p), which is a homolog of the human CTSD gene that encodes cathepsin D. Mutation of CTSD gene in human resulted in a number of neurodegenerative diseases. In this study, we have shown that yeast pep4 mutant cells are highly sensitive to oxidative and apoptotic stress induced by hydrogen peroxide and acetic acid, respectively. pep4∆ cells also showed accumulation of reactive oxygen species (ROS), apoptotic markers, and reduced chronological lifespan. In contrast, quercetin pretreatment protected the pep4 mutant from oxidative and apoptotic stress-induced sensitivity by scavenging ROS and reducing apoptotic markers. The percentage viability of quercetin-treated pep4∆ cells was more pronounced and increased stress resistance against oxidant, apoptotic, and heat stress during chronological aging. From our experimental results, we concluded that quercetin protects yeast pep4 mutant cells from oxidative stress and apoptosis, thereby increasing viability during chronological aging.

Quercetin Represses Apolipoprotein B Expression by Inhibiting the Transcriptional Activity of C/EBPβ

PubMed Central

Inoue, Jun; Sato, Ryuichiro

2015-01-01

Quercetin is one of the most abundant polyphenolic flavonoids found in fruits and vegetables and has anti-oxidative and anti-obesity effects. Because the small intestine is a major absorptive organ of dietary nutrients, it is likely that highly concentrated food constituents, including polyphenols, are present in the small intestinal epithelial cells, suggesting that food factors may have a profound effect in this tissue. To identify novel targets of quercetin in the intestinal enterocytes, mRNA profiling using human intestinal epithelial Caco-2 cells was performed. We found that mRNA levels of some apolipoproteins, particularly apolipoprotein B (apoB), are downregulated in the presence of quercetin. On the exposure of Caco-2 cells to quercetin, both mRNA and protein levels of apoB were decreased. Promoter analysis of the human apoB revealed that quercetin response element is localized at the 5′-proximal promoter region, which contains a conserved CCAAT enhancer-binding protein (C/EBP)-response element. We found that quercetin reduces the promoter activity of apoB, driven by the enforced expression of C/EBPβ. Quercetin had no effect on either mRNA or protein levels of C/EBPβ. In contrast, we found that quercetin inhibits the transcriptional activity of C/EBPβ but not its recruitment to the apoB promoter. On the exposure of Caco-2 cells to quercetin 3-O-glucuronide, which is in a cell-impermeable form, no notable change in apoB mRNA was observed, suggesting an intracellular action of quercetin. In vitro interaction experiments using quercetin-conjugated beads revealed that quercetin binds to C/EBPβ. Our results describe a novel regulatory mechanism of transcription of apolipoprotein genes by quercetin in the intestinal enterocytes. PMID:25875015

Assessment of exposure to oak wood dust using gallic acid as a chemical marker.