High-molecular-weight cocoa procyanidins possess enhanced insulin-enhancing and insulin mimetic activities in human primary skeletal muscle cells compared to smaller procyanidins.

PubMed

Bowser, Suzanne M; Moore, William T; McMillan, Ryan P; Dorenkott, Melanie R; Goodrich, Katheryn M; Ye, Liyun; O'Keefe, Sean F; Hulver, Matthew W; Neilson, Andrew P

2017-01-01

Dysregulation of glucose metabolism is a primary hallmark of metabolic disease (i.e., diabetes, obesity, etc.). Complementary nonpharmaceutical strategies are needed to prevent and/or ameliorate dysregulation of glucose metabolism and prevent progression from normoglycemia to prediabetes and type 2 diabetes across the lifespan. Cocoa compounds, particularly the procyanidins, have shown promise for improving insulin sensitivity and blood glucose homeostasis. However, the molecular mechanisms by which cocoa procyanidins exert these functions remain poorly understood. Furthermore, cocoa procyanidins exhibit size diversity, and evidence suggests that procyanidin bioactivity and size may be related. Here, we show that a procyanidin-rich cocoa extract elicits an antidiabetic effect by stimulating glycogen synthesis and glucose uptake, independent of insulin. Cocoa procyanidins did not appear to act via stimulation of AMPK or CaMKII activities. Additionally, in the presence of insulin, glycogen synthesis and AKT phosphorylation were affected. These mechanisms of action are most pronounced in response to oligomeric and polymeric procyanidins. These results demonstrate (1) specific mechanisms by which cocoa procyanidins improve glucose utilization in skeletal muscle and (2) that larger procyanidins appear to possess enhanced activities. These mechanistic insights suggest specific strategies and biological contexts that may be exploited to maximize the antidiabetic benefits of cocoa procyanidins. Copyright © 2016 Elsevier Inc. All rights reserved.

Tangeretin stimulates glucose uptake via regulation of AMPK signaling pathways in C2C12 myotubes and improves glucose tolerance in high-fat diet-induced obese mice.

PubMed

Kim, Myung Sunny; Hur, Haeng Jeon; Kwon, Dae Young; Hwang, Jin-Taek

2012-07-06

Although the flavonoid tangeretin (5, 6, 7, 8, 4'-pentamethoxyflavone) is known to possess beneficial health effects, the anti-diabetic effects and the mechanism of action have not been elucidated. Treatment with 100 μM tangeretin significantly increased the uptake of 2-NBDG in C2C12 myotubes. We also found that AMPK and AS160 were markedly phosphorylated by tangeretin treatment. In addition, pretreatment with an AMPK inhibitor significantly abrogated tangeretin-stimulated AS160 phosphorylation, glucose uptake, and Glut4 translocation from the cytosol to the plasma membrane. Furthermore, disruption of AMPK using siRNA transfection prevented the glucose uptake stimulated by tangeretin. We also examined the anti-diabetic properties of tangeretin in mice on HFD. Administration of HFD plus 200 mg/kg of tangeretin significantly altered weight gain, glucose tolerance, total cholesterol levels, and the secretion of adipocytokines, such as adiponectin, leptin, resistin, IL-6, and MCP-1. Moreover, AMPK was activated by 200 mg/kg of tangeretin in mouse muscle tissue, as expected from the cell system. These results suggest that tangeretin exerts anti-diabetic effects in both cell culture and mouse models, and these effects are necessary for activating AMPK. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Synthesis, spectroscopic, structural and thermal characterizations of vanadyl(IV) adenine complex prospective as antidiabetic drug agent

NASA Astrophysics Data System (ADS)

El-Megharbel, Samy M.; Hamza, Reham Z.; Refat, Moamen S.

2015-01-01

The vanadyl(IV) adenine complex; [VO(Adn)2]ṡSO4; was synthesized and characterized. The molar conductivity of this complex was measured in DMSO solution that showed an electrolyte nature. Spectroscopic investigation of the green solid complex studied here indicate that the adenine acts as a bidentate ligand, coordinated to vanadyl(IV) ions through the nitrogen atoms N7 and nitrogen atom of amino group. Thus, from the results presented the vanadyl(IV) complex has square pyramid geometry. Further characterizations using thermal analyses and scanning electron techniques was useful. The aim of this paper was to introduce a new drug model for the diabetic complications by synthesized a novel mononuclear vanadyl(IV) adenine complex to mimic insulin action and reducing blood sugar level. The antidiabetic ability of this complex was investigated in STZ-induced diabetic mice. The results suggested that VO(IV)/adenine complex has antidiabetic activity, it improved the lipid profile, it improved liver and kidney functions, also it ameliorated insulin hormone and blood glucose levels. The vanadyl(IV) complex possesses an antioxidant activity and this was clear through studying SOD, CAT, MDA, GSH and methionine synthase. The current results support the therapeutic potentiality of vanadyl(IV)/adenine complex for the management and treatment of diabetes.

Pistia stratiotes (Jalkumbhi)

PubMed Central

Tripathi, P.; Kumar, R.; Sharma, A. K.; Mishra, A.; Gupta, R.

2010-01-01

Pistia stratiotes (Family: Araceae) is commonly used in Ayurvedic medicine. This review article is a compilation of all the updated information on its phytochemical and pharmacological activities, which were performed by different methods. Studies indicate that P. stratiotes possesses diuretic, antidiabetic, antidermatophytic, antifungal, and antimicrobial properties. These results are very encouraging and indicate that this plant should be studied more extensively to confirm the reproducibility of these results and also to reveal other potential therapeutic effects, along with some “leads” with possible isolation of active biomoieties and their mechanism of action. PMID:22228955

Identification of Antidiabetic Compounds from Polyphenolic-rich Fractions of Bulbine abyssinica A. Rich Leaves

PubMed Central

Odeyemi, Samuel Wale; Afolayan, Anthony Jiede

2018-01-01

Background: Bulbine abyssinica has been reported to possess a variety of pharmacological activities traditionally. Previous work suggested its antidiabetic properties, but information on the antidiabetic compounds is still lacking. Objective: The present research exertion was aimed to isolate and identify biologically active polyphenols from B. abyssinica leaves and to evaluate their efficacy on carbohydrate digesting enzymes. Materials and Methods: Fractionation of the polyphenolic contents from the methanolic extract of B. abyssinica leaves was executed by the silica gel column chromatography to yield different fractions. The antioxidant activities of these fractions were carried out against 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) diammonium salt (ABTS), 2,2-diphenyl-1-picrylhydrazyl radicals, and ferric ion-reducing antioxidant power (FRAP). In vitro antidiabetic experimentation was performed by evaluating the α-amylase and α-glucosidase inhibitory capacity. The isolated polyphenols were then identified using liquid chromatography and mass spectroscopy (LC/MS). Results: Out of the eight polyphenolic fractions (BAL 1–8), BAL-4 has the highest inhibitory activity against ABTS radicals whereas BAL-6 showed potent ferric ion-reducing capacity. BAL-5 was the most effective fraction with antidiabetic activity with IC50of 140.0 and 68.58 ± 3.2 μg/ml for α-amylase and α-glucosidase inhibitory activities, respectively. All the fractions competitively inhibited α-amylase, BAL-5 and BAL-6 also inhibited α-glucosidase competitively, while BAL-4 and BAL-1 exhibited noncompetitive and near competitive inhibitions against α-glucosidase, respectively. The LC/MS analysis revealed the presence of carvone in all the fractions. Conclusions: The present study demonstrates the antioxidant and antidiabetic activities of the isolated polyphenols from B. abyssinica. SUMMARY Polyphenols were successfully isolated and identified from Bulbine abyssinica leavesThe isolated polyphenols are biologically active with high antioxidant as well as inhibitor of carbohydrate-digesting enzymesB. abyssinica can be a good source of amylase and glucosidase inhibitorsB. abyssinica can be used as complementary or alternative therapeutic agents especially for the treatment of diabetesCarvone, quercetin, and psoralen could be the compounds responsible for the α-amylase and α-glucosidase inhibitory activities. Abbreviations Used: ABTS: 2,2'-Azino-bis (3-ethylbenzthiazoline-6-sulfonic acid), DPPH: 2,2-diphenyl-1-picrylhydrazyl, FRAP: Ferric ion-reducing antioxidant power, LC/MS: Liquid chromatography and mass spectroscopy, AGEs: Advanced glycation end products, TLC: Thin-layer chromatography, MeOH: Methanol, PNP-G: ρ-Nitrophenyl-α-D-Glucoside, R2: Coefficient of determination, mgQE: Milligram quercetin equivalent, mgTAE: Milligram tannic acid equivalent, mgCE: Milligram catechin equivalent, g: Gram PMID:29568191

Evaluation of antidiabetic, antioxidant and antiglycating activities of the Eysenhardtia polystachya

PubMed Central

Gutierrez, Rosa Martha Perez; Baez, Efren Garcia

2014-01-01

Background: Many diseases are associated with oxidative stress caused by free radicals. The aim of the present study was to evaluate the antidiabetic, antioxidant and antiglycation properties of Eysenhardtia polystachya (EP) bark methanol-water extract. Materials and Methods : The antioxidant capacities were evaluated by studying in vitro the scavenging of DPPH and ABTS free radical, reactive oxygen species such as RO2, O2·-, H2O2, OH., H2O2, ONOO-, NO, HOCl,1 O2, chelating ability, ORAC, β-carotene-bleaching and lipid peroxidation. The antiglycation activities of EP were evaluated by haemoglobin, bovine serum albumin (BSA)-glucose, BSA-methylglyoxal and BSA-glucose assays. Oral administration of EP at the doses of 100 mg/kg, 200 mg/kg and 400 mg/g was studied in normal, glucose-loaded and antidiabetic effects on streptozotocin-induced mildly diabetic (MD) and severely diabetic (SD) mice. Results: EP showed Hdonor activity, free radical scavenging activity, metal chelating ability and lipid peroxidation Antioxidant activity may be attributed to the presence of phenolic and flavonoid compounds. EP is an inhibitor of fluorescent AGE, methylglyoxal and the glycation of haemoglobin. In STZ-induced diabetic mice, EP reduced the blood glucose, increased serum insulin, body weight, marker enzymes of hepatic function, glycogen, HDL, GK and HK while there was reduction in the levels of triglyceride, cholesterol, TBARS, LDL and G6Pase. Conclusions: Eysenhardtia polystachya possesses considerable antioxidant activity with reactive oxygen species (ROS) scavenging activity and demonstrated an anti-AGEs and hepatoprotective role, inhibits hyperglycemic, hyperlipidemic and oxidative stress indicating that these effects may be mediated by interacting with multiple targets operating in diabetes mellitus. PMID:24991120

Antidiabetic, antihyperlipidemic, and antioxidant activities of Musa balbisiana Colla. in Type 1 diabetic rats.

PubMed

Borah, Mukundam; Das, Swarnamoni

2017-01-01

To evaluate the antidiabetic, antihyperlipidemic, and antioxidant activities of the ethanolic extracts of the flowers and inflorescence stalk of Musa balbisiana Colla. in streptozotocin (STZ)-induced Type 1 diabetic rats. Diabetes was induced in male Wistar albino rats (150-200 g) by single intraperitoneal injection of STZ (60 mg/kg b.w. i.p.). Albino rats ( n = 25) were divided into five groups, of which five animals each. Group A (normal control) and Group B (diabetic control) received normal saline (10 ml/kg/day p.o.), whereas Group C and Group D received 250 mg/kg/day p.o. of flower and inflorescence stalk ethanolic extracts, respectively, for 2 weeks. Group E (diabetic standard) received 6 U/kg/day s.c of Neutral Protamine Hagedorn insulin. Fasting blood sugar, serum insulin, catalase (CAT), malondialdehyde (MDA), and serum lipid profile were estimated at specific intervals of time. Effect of the extracts on intestinal glucose absorption was also evaluated to know the probable mechanism of action. Diabetic control exhibited significant increase in blood glucose, serum cholesterol, triglycerides, low-density lipoprotein, serum MDA levels and decreased serum CAT, and high-density lipoprotein levels which were significantly reverted by flower and inflorescence stalk ethanolic extracts after 2 weeks. Serum insulin levels were in increased ( P < 0.05), and intestinal glucose absorption decreased significantly ( P < 0.01) in extract-treated groups. Flower and inflorescence stalk of M. balbisiana Colla. possess significant antidiabetic, antihyperlipidemic, and antioxidant activities in STZ-induced Type 1 diabetic rats.

Novel members of quinoline compound family enhance insulin secretion in RIN-5AH beta cells and in rat pancreatic islet microtissue

PubMed Central

Orfi, Z.; Waczek, F.; Baska, F.; Szabadkai, I.; Torka, R.; Hartmann, J.; Orfi, L.; Ullrich, A.

2017-01-01

According to clinical data, some tyrosine kinase inhibitors (TKIs) possess antidiabetic effects. Several proposed mechanisms were assigned to them, however their mode of action is not clear. Our hypothesis was that they directly stimulate insulin release in beta cells. In our screening approach we demonstrated that some commercially available TKIs and many novel synthesized analogues were able to induce insulin secretion in RIN-5AH beta cells. Our aim was to find efficient, more selective and less toxic compounds. Out of several hits, we chose members from a compound family with quinoline core structure for further investigation. Here we present the studies done with these novel compounds and reveal structure activity relationships and mechanism of action. One of the most potent compounds (compound 9) lost its affinity to kinases, but efficiently increased calcium influx. In the presence of calcium channel inhibitors, the insulinotropic effect was attenuated or completely abrogated. While the quinoline TKI, bosutinib substantially inhibited tyrosine phosphorylation, compound 9 had no such effect. Molecular docking studies further supported our data. We confirmed that some TKIs possess antidiabetic effects, moreover, we present a novel compound family developed from the TKI, bosutinib and optimized for the modulation of insulin secretion. PMID:28272433

Antidiabetic effect of polyphenolic extracts from selected edible plants as α-amylase, α -glucosidase and PTP1B inhibitors, and β pancreatic cells cytoprotective agents - a comparative study.

PubMed

Zakłos-Szyda, Małgorzata; Majewska, Iwona; Redzynia, Małgorzata; Koziołkiewicz, Maria

2015-01-01

Type 2 diabetes mellitus, which is usually a result of wrong dietary habits and reduced physical activity, represents 85-95% of all diabetes cases and among other diet related diseases is the major cause of deaths. The disease is characterized mainly by hyperglycemia, which is associated with attenuated insulin sensitivity or beta cells dysfunction caused by multiple stimuli, including oxidative stress and loss of insulin secretion. Since polyphenols possess multiple biological activities and constitute an important part of the human diet, they have recently emerged as critical phytochemicals in type 2 diabetes prevention and treatment. Their hypoglycemic action results from their antioxidative effect involved in recovering of altered antioxidant defenses and restoring insulin secreting machinery in pancreatic cells, or abilities to inhibit the activity of carbohydrates hydrolyzing enzymes (α-amylase and α-glucosidase) or protein tyrosine phosphatase 1B (PTP1B), which is known as the major negative regulator in insulin signaling. This study investigates the total phenolic content (Folin-Ciocalteu and HPLC methods) and antioxidant capacity (ABTS) of 20 polyphenolic extracts obtained from selected edible plants, which were screened in terms of α -amylase, α - glucosidase and protein tyrosine phosphatase 1B inhibitors or protective agents against oxidative stress induced by tertbutylhydroperoxide (t-BOOH) in βTC3 pancreatic beta cells used as a model target for antidiabetes drugs. The study concludes that Chaenomeles japonica, Oenothera paradoxa and Viburnum opulus may be promising natural sources for active compounds with antidiabetic properties.

Antidiabetic Effects of Aqueous Infusions of Artemisia herba-alba and Ajuga iva in Alloxan-Induced Diabetic Rats.

PubMed

Boudjelal, Amel; Siracusa, Laura; Henchiri, Cherifa; Sarri, Madani; Abderrahim, Benkhaled; Baali, Faiza; Ruberto, Giuseppe

2015-06-01

The aqueous infusions of the aerial parts of Artemisia herba-alba Asso and Ajuga iva Schreber, prepared in accordance with the traditional procedure used in the local folk medicine, have been analysed for their composition and content of phytochemical constituents and examined for their antidiabetic effectiveness in alloxan-induced diabetic rats. Oral administration of A. herba-alba and A. iva infusions was studied in normal and alloxan-induced diabetic rats, which were randomly divided into nine groups, each group consisting of six animals. The drug preparations (100, 200, and 300 mg/kg b. w.) of each plant were given orally to the rats of each group twice daily for 15 days. Compositional analysis of the aqueous infusions revealed the presence of several polyphenols as main components. A. herba-alba infusion was characterised by mono- and di-cinnamoylquinic acids, with 5-caffeoylquinic (chlorogenic) acid being the main compound, followed by 3,5-dicaffeoylquinic acid. Vicenin-2 (apigenin 6,8-di-C-glucoside) appeared to be the most abundant among flavonoids. On the other hand, A. iva showed the exclusive presence of flavonoids, with the flavanone naringin present in relatively high levels together with several apigenin (flavone) derivatives. Oral administration of 300 mg/kg b. w. of the aqueous infusions of A. herba-alba and A. iva exhibited a significant reduction in blood glucose content, showing a much more efficient antidiabetic activity compared to glibenclamide, the oral hypoglycaemic agent used as a positive control in this study. These results suggest that A. herba-alba and A. iva possess significant antidiabetic activity, as they were able to improve the biochemical damage in alloxan-induced diabetes in rats. Georg Thieme Verlag KG Stuttgart · New York.

Protective potential of Averrhoa bilimbi fruits in ameliorating the hepatic key enzymes in streptozotocin-induced diabetic rats.

PubMed

Kurup, Surya B; S, Mini

2017-01-01

Diabetes is a mutifactorial disease which leads to several complications. Currently available drug regimens for management of diabetes have certain drawbacks. Need for safer and effective medicines from natural sources having potent antidiabetic activity. Averrhoa bilimbi Linn. (Oxalidaceae) is a medicinal plant and is reported to possess hypoglycemic activity. To investigate the antidiabetic potential of Averrhoa bilimbi fruit extract in streptozotocin-induced diabetic rats. Diabetes was induced in male Sprague Dawley rats by single intraperitoneal injection of streptozotocin (STZ) (40mg/kg body weight). The diabetic rats were treated orally with ethyl acetate fraction of A. bilimbi fruits (ABE) (25mg/kg body weight) and metformin (100mg/kg body weight) by intragastric intubation for 60days. After 60days, the rats were sacrificed; blood, liver and pancreas were collected. Several indices such as blood glucose, plasma insulin, toxicity markers and the activities of carbohydrate-metabolizing enzymes were assayed. The phytochemicals present in the ABE was identified by gas chromatography-mass spectrometry analysis. ABE significantly (p<0.05) reduced the level of blood glucose and hepatic toxicity markers and increased plasma insulin in diabetic rats. ABE modulated the activities of carbohydrate-metabolizing enzymes, significantly increased the activities of hexokinase (59%) and pyruvate kinase (68%) and reduced the activities of glucose-6-phosphatase (32%) and fructose-1, 6-bisphosphatase (20%). The histological studies of the pancreas also supported our findings. The results were compared with metformin, a standard oral hypoglycemic drug. GC-MS analysis of ABE revealed the presence of 11 chemical constituents in the extract. ABE exerts its antidiabetic effect by promoting glucose metabolism via glycolysis and inhibiting hepatic endogenous glucose production via gluconeogenesis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Antidiabetic effect of Achillea millefollium through multitarget interactions: α-glucosidases inhibition, insulin sensitization and insulin secretagogue activities.

PubMed

Chávez-Silva, Fabiola; Cerón-Romero, Litzia; Arias-Durán, Luis; Navarrete-Vázquez, Gabriel; Almanza-Pérez, Julio; Román-Ramos, Rubén; Ramírez-Ávila, Guillermo; Perea-Arango, Irene; Villalobos-Molina, Rafael; Estrada-Soto, Samuel

2018-02-15

Achillea millefolium L. (Asteraceae) is a perennial herb used in Mexican folk medicine for treatment of several pathologies, including inflammatory and spasmodic gastrointestinal disorders, hepatobiliary complaints, overactive cardiovascular, respiratory ailments and diabetes. To evaluate the potential antidiabetic effect in vivo and to establish the potential mode of action through in vitro approaches of Achillea millefolium. The antidiabetic effect of hydroalcoholic extract of Achillea millefolium (HAEAm) was evaluated on the oral glucose tolerance tests, in normoglycemic and experimental Type 2 diabetic mice models. In addition, we evaluated the possible mode of action in in vitro assays to determine α-glucosidases inhibition, the insulin secretion and calcium mobilization in RINm5F cells and PPARγ and GLUT4 expression in 3T3-L1 cells. HAEAm showed significant glucose diminution on oral glucose tolerance test and in acute experimental Type 2 diabetic assay with respect to the control (p < 0.05). In addition, HAEAm promoted the α-glucosidases inhibition by 55% at 1mg/ml respect to control. On the other hand, HAEAm increased the PPARγ (five-times) and GLUT4 (two-fold) relative expression than control (p < 0.05). Finally, HAEAm significantly increased the insulin secretion and [Ca 2+ ] i compared with control. The HAEAm possesses in vivo antidiabetic effect, having such effect through multitarget modes of action that involve antihyperglycemic (α-glucosidases inhibition), hypoglycemic (insulin secretion) and potential insulin sensitizer (PPARγ/GLUT4 overexpression) actions. Copyright © 2017 Elsevier B.V. All rights reserved.

Antidiabetic effects of flavonoids from Sophora flavescens EtOAc extract in type 2 diabetic KK-ay mice.

PubMed

Yang, Xinzhou; Yang, Jing; Xu, Chan; Huang, Mi; Zhou, Qi; Lv, Jingnan; Ma, Xinhua; Ke, Changqiang; Ye, Yang; Shu, Guangwen; Zhao, Ping

2015-08-02

Bitter and cold Chinese medicines have been long used for the treatment for diabetes mellitus (DM) for thousands of years in China. The roots of Sophora flavescens Ait., one of bitter and cold Chinese medicines commonly used to remove lung heat have been used to counteract DM and exerted good clinical effects for diabetic patients in some folk hospitals in Fujian province, PR China. However, the corresponding active principles and antidiabetic mechanism of this Traditional Chinese Medicine remain unclear. Therefore, in this study, we aim at chemical profiling of the active principles, validating the potential antidiabetic effects of the active EtOAc extract (SF-EtOAc) in vitro and in vivo, and elucidating its probable antidiabetic mechanism as well as evaluating its acute oral toxicity. An off-line semi-preparative LC-NMR and LC-UV-ESI MS protocol was developed to determine the chemical principles of the active EtOAc extract rapidly and unambiguously. The effect of SF-EtOAc on the glucose transporter type 4 (GLUT4) translocation in L6 myotubes was examined. T2DM KK-Ay mice were induced by high-fat diet. SF-EtOAc was orally administration at the dose of 30, 60 and 120 mg/kg/d, for 21 days. Metformin was used as positive control. Body weight, plasma glucose, oral glucose tolerance test, serum insulin and blood-lipid indexes were measured. Phosphorylation of the AMP-activated protein kinase (AMPK) expression in liver was measured. We found that SF-EtOAc significantly improved oral glucose tolerance, increased serum high density lipoprotein cholesterol (HDL-C) and reduced body weight, blood glucose levels and other related blood-lipid indexes. Mechanistically, SF-EtOAc elevated phosphorylation of AMP-activated protein kinase (AMPK) and stimulated membrane translocation of GLUT4. Moreover, it was unveiled that oral median lethal dose (LD50) of SF-EtOAc was more than 7500 mg/kg, suggesting that SF-EtOAc was practically non-toxic for mice. SF-EtOAc improves glucose tolerance, reduces hyperglycemia and resumes insulin levels, at least in part, by activating GLUT4 translocation which may be modulated by AMPK pathway. According to the results of the present study, SF-EtOAc possesses a potent antidiabetic activity and could be used as a safe remedy for the treatment of diabetes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Loranthus micranthus Linn.: Biological Activities and Phytochemistry

PubMed Central

Zorofchian Moghadamtousi, Soheil; Hajrezaei, Maryam; Abdul Kadir, Habsah

2013-01-01

Loranthus micranthus Linn. is a medicinal plant from the Loranthaceae family commonly known as an eastern Nigeria species of the African mistletoe and is widely used in folkloric medicine to cure various ailments and diseases. It is semiparasitic plant because of growing on various host trees and shrubs and absorbing mineral nutrition and water from respective host. Hence, the phytochemicals and biological activities of L. micranthus demonstrated strong host and harvesting period dependency. The leaves have been proved to possess immunomodulatory, antidiabetic, antimicrobial, antihypertensive, antioxidant, antidiarrhoeal, and hypolipidemic activities. This review summarizes the information and findings concerning the current knowledge on the biological activities, pharmacological properties, toxicity, and chemical constituents of Loranthus micranthus. PMID:24109490

Alpinia calcarata Roscoe: A potential phytopharmacological source of natural medicine

PubMed Central

Rahman, Md Atiar; Islam, Md Shahidul

2015-01-01

Alpinia calcarata Roscoe (Family: Zingiberaceae), is a rhizomatous perennial herb, which is commonly used in the traditional medicinal systems in Sri Lanka. Alpinia calcarata is cultivated in tropical countries, including Sri Lanka, India, and Malaysia. Experimentally, rhizomes of Alpinia calcarata are shown to possess antibacterial, antifungal, anthelmintic, antinociceptive, anti-inflammatory, antioxidant, aphrodisiac, gastroprotective, and antidiabetic activities. Phytochemical screening revealed the presence of polyphenols, tannins, flavonoids, steroid glycosides and alkaloids in the extract and essential oil of this plant. Essential oil and extracts from this plant have been found to possess wide range of pharmacological and biological activities. This article provides a comprehensive review of its ethnomedical uses, chemical constituents and the pharmacological profile as a medicinal plant. Particular attention has been given to the pharmacological effects of the essential oil of Alpinia calcarata in this review so that the potential use of this plant either in pharmaceutics or as an agricultural resource can be evaluated. PMID:26009694

Antihyperglycaemic effect of Mangifera indica in rat.

PubMed

Aderibigbe, A O; Emudianughe, T S; Lawal, B A

1999-09-01

The leaves of Mangifera indica are used as an antidiabetic agent in Nigerian folk medicine. To determine whether or not there is a scientific basis for this use, the effect of the aqueous extract of the leaves on blood glucose level was assessed in normoglycaemic, glucose - induced hyperglycaemic and streptozotocin (STZ)-induced diabetic rats. The aqueous extract given orally (1 g/kg) did not alter the blood glucose levels in either normoglycaemic or STZ-induced diabetic rats. In glucose - induced hyperglycaemia, however, antidiabetic activity was seen when the extract and glucose were administered simultaneously and also when the extract was given to the rats 60 min before the glucose. The hypoglycaemic effect of the aqueous extract was compared with that of an oral dose of chlorpropamide (200 mg/kg) under the same conditions. The results of this study indicate that the aqueous extract of the leaves of Mangifera indica possess hypoglycaemic activity. This action may be due to an intestinal reduction of the absorption of glucose. However, other different mechanisms of action cannot be excluded. Copyright 1999 John Wiley & Sons, Ltd.

Anti-diabetic activity of Vaccinium bracteatum Thunb. leaves' polysaccharide in STZ-induced diabetic mice.

PubMed

Wang, Li; Zhang, Ying; Xu, Maochao; Wang, Yingyao; Cheng, Sujiao; Liebrecht, Alex; Qian, Haifeng; Zhang, Hui; Qi, Xiguang

2013-10-01

Vaccinium bracteatum Thunb. (VBT) is a traditional Chinese herbal medicine. The anti-diabetic activity of VBT leaves' polysaccharide (VBTLP) is studied in this paper. The results indicated VBTLP had a dose-dependent decrease on the blood glucose (BG) level, and the time effect of VBTLP on BG level was also significant. The insulin level of high dose group (HDG) was significantly higher (p<0.05) than that of model control (MC) group. Compared to MC, HDG and lose dose group (LDG) had significantly lower (p<0.05) TC and LDL-C levels, however, TG and HDL-C levels are similar. Compared to non-diabetic control (NC), HDG and LDG had similar plasma lipid levels except for higher LDL-C level. Although body weights of LDG and HDG were significant lower (p<0.05) than that of NC from week 2 to week 6, they were similar to that of PC. The results indicate VBTLP possesses a potential hypoglycemic effect in streptozotocin-induced diabetic mice. Copyright © 2013 Elsevier B.V. All rights reserved.

Management of diabetic complications through fruit flavonoids as a natural remedy.

PubMed

Tanveer, Amna; Akram, Kashif; Farooq, Umar; Hayat, Zafar; Shafi, Afshan

2017-05-03

Diabetes mellitus is a global disorder, and a major issue for health care systems. The current review outlooks the use of fruit flavonoids as natural remedy in the prevention of diabetes mellitus. The onset of diabetes mainly depends upon genetics and lifestyle issues. Currently used therapeutic options for the control of diabetes, like dietary amendments, oral hypoglycemic drugs, and insulin, have their own limitations. Fruit flavonoids possess various antidiabetic, anti-inflammatory, and antioxidant potentials and act on various cellular signaling pathways in pancreas, white adipose tissue, skeletal muscle, and liver function, which in result induces antidiabetic effects. Recently, antidiabetic effect of fruit flavonoids has been studied using various animal models and clinical trials. Research studies revealed a statistically significant potential of fruit flavonoids in managing the altered glucose and oxidative metabolisms in diabetes. Unlike synthetic antidiabetic agents, fruit flavonoids manage diabetes without compromising cellular homeostasis thereby posing no side effects. Further studies are required in purification and characterization of different fruit flavonoids with respect to their beneficial effect for diabetic patients.

Antidiabetic, antihyperlipidemic, and antioxidant activities of Musa balbisiana Colla. in Type 1 diabetic rats

PubMed Central

Borah, Mukundam; Das, Swarnamoni

2017-01-01

Objectives: To evaluate the antidiabetic, antihyperlipidemic, and antioxidant activities of the ethanolic extracts of the flowers and inflorescence stalk of Musa balbisiana Colla. in streptozotocin (STZ)-induced Type 1 diabetic rats. Materials and Methods: Diabetes was induced in male Wistar albino rats (150–200 g) by single intraperitoneal injection of STZ (60 mg/kg b.w. i.p.). Albino rats (n = 25) were divided into five groups, of which five animals each. Group A (normal control) and Group B (diabetic control) received normal saline (10 ml/kg/day p.o.), whereas Group C and Group D received 250 mg/kg/day p.o. of flower and inflorescence stalk ethanolic extracts, respectively, for 2 weeks. Group E (diabetic standard) received 6 U/kg/day s.c of Neutral Protamine Hagedorn insulin. Fasting blood sugar, serum insulin, catalase (CAT), malondialdehyde (MDA), and serum lipid profile were estimated at specific intervals of time. Effect of the extracts on intestinal glucose absorption was also evaluated to know the probable mechanism of action. Results: Diabetic control exhibited significant increase in blood glucose, serum cholesterol, triglycerides, low-density lipoprotein, serum MDA levels and decreased serum CAT, and high-density lipoprotein levels which were significantly reverted by flower and inflorescence stalk ethanolic extracts after 2 weeks. Serum insulin levels were in increased (P < 0.05), and intestinal glucose absorption decreased significantly (P < 0.01) in extract-treated groups. Conclusion: Flower and inflorescence stalk of M. balbisiana Colla. possess significant antidiabetic, antihyperlipidemic, and antioxidant activities in STZ-induced Type 1 diabetic rats. PMID:28458426

Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities: Identification of novel components of turmeric.

PubMed

Aggarwal, Bharat B; Yuan, Wei; Li, Shiyou; Gupta, Subash C

2013-09-01

Turmeric, a dried powder derived from the rhizome of Curcuma longa, has been used for centuries in certain parts of the world and has been linked to numerous biological activities including antioxidant, anti-inflammatory, anticancer, antigrowth, anti-arthritic, anti-atherosclerotic, antidepressant, anti-aging, antidiabetic, antimicrobial, wound healing, and memory-enhancing activities. One component of turmeric is curcumin, which has been extensively studied, as indicated by more than 5600 citations, most of which have appeared within the past decade. Recent research has identified numerous chemical entities from turmeric other than curcumin. It is unclear whether all of the activities ascribed to turmeric are due to curcumin or whether other compounds in turmeric can manifest these activities uniquely, additively, or synergistically with curcumin. However, studies have indicated that turmeric oil, present in turmeric, can enhance the bioavailability of curcumin. Studies over the past decade have indicated that curcumin-free turmeric (CFT) components possess numerous biological activities including anti-inflammatory, anticancer, and antidiabetic activities. Elemene derived from turmeric is approved in China for the treatment of cancer. The current review focuses on the anticancer and anti-inflammatory activities exhibited by CFT and by some individual components of turmeric, including turmerin, turmerone, elemene, furanodiene, curdione, bisacurone, cyclocurcumin, calebin A, and germacrone. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Identification of PPARgamma Partial Agonists of Natural Origin (II): In Silico Prediction in Natural Extracts with Known Antidiabetic Activity

PubMed Central

Guasch, Laura; Sala, Esther; Mulero, Miquel; Valls, Cristina; Salvadó, Maria Josepa; Pujadas, Gerard; Garcia-Vallvé, Santiago

2013-01-01

Background Natural extracts have played an important role in the prevention and treatment of diseases and are important sources for drug discovery. However, to be effectively used in these processes, natural extracts must be characterized through the identification of their active compounds and their modes of action. Methodology/Principal Findings From an initial set of 29,779 natural products that are annotated with their natural source and using a previously developed virtual screening procedure (carefully validated experimentally), we have predicted as potential peroxisome proliferators-activated receptor gamma (PPARγ) partial agonists 12 molecules from 11 extracts known to have antidiabetic activity. Six of these molecules are similar to molecules with described antidiabetic activity but whose mechanism of action is unknown. Therefore, it is plausible that these 12 molecules could be the bioactive molecules responsible, at least in part, for the antidiabetic activity of the extracts containing them. In addition, we have also identified as potential PPARγ partial agonists 10 molecules from 16 plants with undescribed antidiabetic activity but that are related (i.e., they are from the same genus) to plants with known antidiabetic properties. None of the 22 molecules that we predict as PPARγ partial agonists show chemical similarity with a group of 211 known PPARγ partial agonists obtained from the literature. Conclusions/Significance Our results provide a new hypothesis about the active molecules of natural extracts with antidiabetic properties and their mode of action. We also suggest plants with undescribed antidiabetic activity that may contain PPARγ partial agonists. These plants represent a new source of potential antidiabetic extracts. Consequently, our work opens the door to the discovery of new antidiabetic extracts and molecules that can be of use, for instance, in the design of new antidiabetic drugs or functional foods focused towards the prevention/treatment of type 2 Diabetes Mellitus. PMID:23405231

Anti-diabetic properties of Momordica charantia L. polysaccharide in alloxan-induced diabetic mice.

PubMed

Xu, Xin; Shan, Bin; Liao, Cai-Hu; Xie, Jian-Hua; Wen, Ping-Wei; Shi, Jia-Yi

2015-11-01

A water-soluble polysaccharide (MCP) was isolated from the fruits of Momordica charantia L., and the hypoglycemic effects of MCP were investigated in both normal healthy and alloxan-induced diabetic mice. MCP was orally administered once a day after 3 days of alloxan-induction at 100, 200 and 300mg/kg body weight for 28 day. Results showed that fasting blood glucose level (BGL) was significantly decreased, whereas the glucose tolerance was marked improvement in alloxan-induced diabetic mice, and loss in body weight was also prevented in diabetic mice compared to the diabetic control group. The dosage of 300mg/kg body weight exhibited the best effects. In addition, MCP did not exhibit any toxic symptoms in the limited toxicity evaluation in mice. The results suggest that MCP possess significantly dose-dependent anti-diabetic activity on alloxan-induced diabetic mice. Hence, MCP can be incorporated as a supplement in health-care food, drugs and/or combined with other hypoglycemic drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of salinity medium on antioxidant and antidiabetic activity marine endophytic fungus of asperegillus elegans ptf 9

NASA Astrophysics Data System (ADS)

Mulyani, Hani; Artanti, Nina; Fitria, Irni; Filailla, Euis; Kandace, Yoice Sri; Udin, Linar Zalinar

2017-11-01

Our previous studies on screening of antioxidant activities from various endophytic fungi isolated from marine bioata showed that A. elegans PTF9 isolated from sea weed is one of the fungus that has good antioxidant activity. In current study we reported the effect of medium salinity (0, 3 and 10% salt in PDB medium) on antioxidant and antidiabetes activity of mycelium and filtrate ethyl acetate extracts of A. elegans Ptf 9. The antioxidant assay was conducted using DPPH free radical scavenging activity method. The antidiabetes assay was conducted using a-glucosidase inhibitory activity method. The results showed that the best antioxidant activity was obtained from filtrate extract of fungus cultures with 0% salt (IC50=1.56 ppm), whereas the best antidiabetes activity was obtained from filtrate extract of fungus culture with 10% salt (IC50= 3.64 ppm). Addition of salt reduced the antioxidant activity, but not the antidiabetes activity. The results suggest that A. elegans PTF9 showed potential for further studies on isolation of antioxidant and antidiabetes lead compounds that could be use for further development of new drugs.

Aqueous extracts of Roselle (Hibiscus sabdariffa Linn.) varieties inhibit α-amylase and α-glucosidase activities in vitro.

PubMed

Ademiluyi, Adedayo O; Oboh, Ganiyu

2013-01-01

This study sought to investigate the inhibitory effect of aqueous extracts of two varieties (red and white) of Hibiscus sabdariffa (Roselle) calyces on carbohydrate hydrolyzing enzymes (α-amylase and α-glucosidase), with the aim of providing the possible mechanism for their antidiabetes properties. Aqueous extracts were prepared (1:100 w/v) and the supernatant used for the analysis. The extracts caused inhibition of α-amylase and α-glucosidase activities in vitro.The IC(50) revealed that the red variety (25.2 μg/mL) exhibited higher α-glucosidase inhibitory activity than the white variety (47.4 μg/mL), while the white variety (90.5 μg/mL) exhibited higher α-amylase inhibitory activity than the red variety (187.9 μg/mL). However, the α-glucosidase inhibitory activities of both calyces were higher than that of their α-amylase. In addition, the red variety possessed higher antioxidant capacity as exemplified by the (•)OH scavenging abilities, Fe(2+) chelating ability, and inhibition of Fe(2+)-induced pancreatic lipid peroxidation in vitro. The enzyme inhibitory activities and antioxidant properties of the roselle extracts agreed with their phenolic content. Hence, inhibition of α-amylase and α-glucosidase, coupled with strong antioxidant properties could be the possible underlying mechanism for the antidiabetes properties of H. sabdariffa calyces; however, the red variety appeared to be more potent.

Free Radicals Scavenging Capacity, Antidiabetic and Antihypertensive Activities of Flavonoid-Rich Fractions from Leaves of Trichilia emetica and Opilia amentacea in an Animal Model of Type 2 Diabetes Mellitus.

PubMed

Konaté, Kiessoun; Yomalan, Kassi; Sytar, Oksana; Zerbo, Patrice; Brestic, Marian; Patrick, Van Damme; Gagniuc, Paul; Barro, Nicolas

2014-01-01

Trichilia emetica and Opilia amentacea traditional Burkinabe medicinal plants were investigated to determine their therapeutic potential to inhibit key enzymes in carbohydrate metabolism, which has relevance to the management of type 2 diabetes. In vitro and in vivo antioxidant and antihypertensive potential and antilipidemia and antihyperglycemia activities in an animal model of type 2 diabetes mellitus have been studied. The antioxidant activity of the flavonoids from leaves of Trichilia emetica and Opilia amentacea has been evaluated using β -carotene-linoleic acid system, 1,1-diphenyl-2-picrylhydrazyl inhibitory activity, chelation of iron (II) ions, and lipid peroxidation which showed more pronounced antioxidant capacities of Trichilia emetica. Total cholesterol concentrations decreased in an animal model of type 2 diabetes mellitus under effects of flavonoid-rich fractions from leaves of Trichilia emetica and Opilia amentacea has been observed. Extract of flavonoid-rich fractions from Trichilia emetica shown maximum radical scavenging activity and possessed marked antiamylase activity which may be due to the presence of certain secondary metabolites. Suggested better antihyperglycemia, antilipidemia, and antihypertensive properties of flavonoid-rich fractions from Trichilia emetica compared to the extract of Opilia amentacea are demonstrating antidiabetic potential of Trichilia emetica as therapeutic targets for the management of type 2 diabetes.

In vitro antidiabetic activity of various crude extracts of Boletus variipes

NASA Astrophysics Data System (ADS)

Muniandy, Sutha; Fazry, Shazrul; Daud, Fauzi; Senafi, Sahidan

2015-09-01

Diabetes mellitus is a complex metabolic disease that progressively spread worldwide and difficult to treat due to various physical and metabolic complications. Current treatment using synthetic drugs has lead to various undesirable side effects. Here we determined the effect of Boletus variipes extracts on diabetes related enzymes. In this study, hot water, cold water and methanol extracts of B. variipes were utilized in order to assess their in vitro antidiabetic activity by measuring the effect on α-amylase and α-glucosidase enzyme. Hot water extract possessed the highest inhibition activity of α-amylase and α-glucosidase in a concentration dependent manner with the IC50 value 87 mg/mL and 89 mg/mL respectively. The methanol extract also showed inhibition activity of α-amylase and α-glucosidase but significantly lower than the hot water extract. Whereas cold water extract did not show any inhibition activity towards both the enzymes. Therefore, it is hypothesized that the hot water extract of Boletus variipes contains bioactive compound that can inhibit alpha-amylase and alpha-glucosidase enzyme activity. At the request of all authors of the paper an updated version was published on 11 May 2016. The original version identified the species of mushroom as Boletus variipes, but new findings have proved the species of mushroom to be Boletus qriseipurpureus. The species name has been updated throughout the revised version of this paper.

Antidiabetic effects of extracts from Psidium guajava.

PubMed

Oh, Won Keun; Lee, Chul Ho; Lee, Myung Sun; Bae, Eun Young; Sohn, Cheon Bae; Oh, Hyuncheol; Kim, Bo Yeon; Ahn, Jong Seog

2005-01-15

During a screening of medicinal plants for inhibition of protein tyrosine phosphatase1B (PTP1B), an extract from Psidium guajava (Myrtaceae) leaves exhibited significant inhibitory effect on PTP1B. Thus, its antidiabetic effect on Lepr(db)/Lepr(db) mice was evaluated. Significant blood glucose lowering effects of the extract were observed after intraperitoneal injection of the extract at a dose of 10mg/kg in both 1- and 3-month-old Lepr(db)/Lepr(db) mice. In addition, histological analysis of the liver from the butanol-soluble fraction treated Lepr(db)/Lepr(db) mice revealed a significant decrease in the number of lipid droplets compared to the control mice. Taken together, it was suggested that the extract from Psidium guajava leaves possesses antidiabetic effect in type 2 diabetic mice model and these effect is, at least in part, mediated via the inhibition of PTP1B.

Plant profile, phytochemistry and pharmacology of Cordia dichotoma (Indian cherry): A review

PubMed Central

Jamkhande, Prasad G.; Barde, Sonal R.; Patwekar, Shailesh L.; Tidke, Priti S.

2013-01-01

More than half of the world's population relies on the traditional medicine and major role of the traditional medicine including the use of plant extract and their active constituents. Among them, Cordia dichotoma Forst., a small to moderate size plant of family Boragenaceae, commonly called bhokar, lasura, gonda, Indian cherry and shlesmataka. Plant parts such as leaves, fruit, bark and seed have been reported for possessing antidiabetic, antiulcer, anti-inflammatory, immune-modulator and analgesic activity. Screening of fruit, leaves and seed shows the presence of pyrrolizidine alkaloids, coumarins, flavonoids, saponins, terpenes and sterols. Present review focuses on details of geographical distribution, physicochemical parameters, phytoconstituents and pharmacological properties of Cordia dichotoma reported so far. PMID:24093795

Chemical optimization of protein extraction from sweet potato (Ipomoea batatas) peel

USDA-ARS?s Scientific Manuscript database

Proteins isolated from sweet potatoes (Ipomoea batatas) have been shown to possess antidiabetic, antioxidant, and antiproliferative properties. The objective of this study was to chemically optimize a process for extracting proteins from sweet potato peel. The extraction procedure involved mixing pe...

Phytotherapy in diabetes: Review on potential mechanistic perspectives

PubMed Central

El-Abhar, Hanan S; Schaalan, Mona F

2014-01-01

Diabetes mellitus (DM) is a widely spread epidemic disease that results from the absence of insulin, decreased secretion and/or impaired function. Since DM is a multi-factorial disease, the available pharmaceuticals, despite their sensible treatment, target mostly one pathway to control hyperglycemia and encounter several side effects. Therefore, new therapeutic paradigms aim to hit several pathways using only one agent. Traditionally, antidiabetic plants and/or their active constituents may fulfill this need. More than 200 species of plants possess antidiabetic properties which were evaluated mostly by screening tests without digging far for the exact mode of action. Searching among the different literature resources and various database and in view of the above aspects, the present article provides a comprehensive review on the available antidiabetic plants that have been approved by pharmacological and clinical evaluations, and which their mechanism(s) of action is assured. These plants are categorized according to their proved mode of action and are classified into those that act by inhibiting glucose absorption from intestine, increasing insulin secretion from the pancreas, inhibiting glucose production from hepatocytes, or enhancing glucose uptake by adipose and muscle tissues. The current review also highlights those that mimic in their action the new peptide analogs, such as exenatide, liraglutide and dipeptidylpeptidase-4 inhibitors that increase glucagon-like peptide-1 serum concentration and slow down the gastric emptying. PMID:24748931

Susceptibility of sweetpotato (Ipomoea batatas) peel proteins to digestive enzymes

USDA-ARS?s Scientific Manuscript database

Sweet potato proteins have been shown to possess antioxidant and antidiabetic properties in vivo. The ability of a protein to exhibit systemic effects is somewhat unusual as proteins are typically susceptible to digestive enzymes. This study was undertaken to better understand how digestive enzymes ...

Phytochemistry, pharmacology, and clinical trials of Morus alba.

PubMed

Chan, Eric Wei-Chiang; Lye, Phui-Yan; Wong, Siu-Kuin

2016-01-01

The present review is aimed at providing a comprehensive summary on the botany, utility, phytochemistry, pharmacology, and clinical trials of Morus alba (mulberry or sang shu). The mulberry foliage has remained the primary food for silkworms for centuries. Its leaves have also been used as animal feed for livestock and its fruits have been made into a variety of food products. With flavonoids as major constituents, mulberry leaves possess various biological activities, including antioxidant, antimicrobial, skin-whitening, cytotoxic, anti-diabetic, glucosidase inhibition, anti-hyperlipidemic, anti-atherosclerotic, anti-obesity, cardioprotective, and cognitive enhancement activities. Rich in anthocyanins and alkaloids, mulberry fruits have pharmacological properties, such as antioxidant, anti-diabetic, anti-atherosclerotic, anti-obesity, and hepatoprotective activities. The root bark of mulberry, containing flavonoids, alkaloids and stilbenoids, has antimicrobial, skin-whitening, cytotoxic, anti-inflammatory, and anti-hyperlipidemic properties. Other pharmacological properties of M. alba include anti-platelet, anxiolytic, anti-asthmatic, anthelmintic, antidepressant, cardioprotective, and immunomodulatory activities. Clinical trials on the efficiency of M. alba extracts in reducing blood glucose and cholesterol levels and enhancing cognitive ability have been conducted. The phytochemistry and pharmacology of the different parts of the mulberry tree confer its traditional and current uses as fodder, food, cosmetics, and medicine. Overall, M. alba is a multi-functional plant with promising medicinal properties. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Anti-diabetic formulations of Nāga bhasma (lead calx): A brief review.

PubMed

Rajput, Dhirajsingh; Patgiri, B J; Galib, R; Prajapati, P K

2013-07-01

Ayurvedic formulations usually contain ingredients of herbal, mineral, metal or animal in origin. Nāga bhasma (lead calx) is a potent metallic formulation mainly indicated in the treatment of Prameha (~diabetes). Until date, no published information is available in compiled form on the formulations containing Nāga bhasma as an ingredient, their dose and indications. Therefore, in the present study, an attempt has been made to compile various formulations of Nāga bhasma indicated in treating Prameha. The present work aims to collect information on various formulations of Nāga bhasma mainly indicated in treating Prameha and to elaborate the safety and efficacy of Nāga bhasma as a Pramehaghna (antidiabetic) drug. Critical review of formulations of Nāga bhasma is compiled from various Ayurvedic texts and the therapeutic efficacy of Nāga bhasma is discussed on the basis of available data. Antidiabetic formulations of Nāga bhasma were discovered around 12(th) century CE. There are 44 formulations of Nāga bhasma mainly indicated for Prameha. Haridrā (Curcuma longa Linn), Āmalakī (Emblica officinalis), Guḍūci (Tinospora cordifolia) and Madhu (honey) enhance the antidiabetic action of Nāga bhasma and also help to prevent diabetic complications as well as any untoward effects of Nāga bhasma. On the basis of the reviewed research, it is concluded that Nāga bhasma possesses significant antidiabetic property.

Antibacterial activity of Momordica charantia (Curcubitaceae) extracts and fractions

PubMed Central

Costa, José Galberto M.; Nascimento, Eidla M. M.; Campos, Adriana R.; Rodrigues, Fabiola F. G.

2010-01-01

Momordica charantia L. belongs to the family Curcubitaceae and it is very common in many Brazilian regions. The plant is a liana with flowers and yellow fruits that present red seeds when are ripe. Popularly known as “melão-de-sãocaetano”, “melão amargo” or “cabaço-amargo”, it possesses many uses: antidiabetic, antihelmintic, antmicrobial, anticancerigenous and antioxidant. The phytochemical prospection of the fresh and dried leaves extracts showed the presence of different classes of secondary metabolites, as flavonoids, alkaloids and tannins, that have demonstrated antimicrobial action. Fresh and dried leaves presented significantly antimicrobial activity against all bacterial strains tested, specially Escherichia coli. Ethyl acetate fractions were effective against Escherichia coli and Bacillus cereus. The modulatory activity was significative too PMID:24826002

Pea, Pisum sativum, and Its Anticancer Activity

PubMed Central

Rungruangmaitree, Runchana; Jiraungkoorskul, Wannee

2017-01-01

Pisum sativum (Family: Fabaceae), as known as green pea or garden pea, has long been important in diet due to its content of fiber, protein, starch, trace elements, and many phytochemical substances. It has been shown to possess antibacterial, antidiabetic, antifungal, anti-inflammatory, antihypercholesterolemia, and antioxidant activities and also shown anticancer property. Its nonnutritive biologically active components include alkaloids, flavonoids, glycosides, isoflavones, phenols, phytosterols, phytic acid, protease inhibitors, saponins, and tannins. This plant is rich in apigenin, hydroxybenzoic, hydroxycinnamic, luteolin, and quercetin, all of which have been reported to contribute to its remedial properties including anticarcinogenesis property. Based on established literature on the anticancer property of P. sativum and possible mode of action, this review article has focused to demonstrate that P. sativum could be further explored for the development of anticancer treatment. PMID:28503053

Antidiabetic and antihyperlipidemic activity of Piper longum root aqueous extract in STZ induced diabetic rats

PubMed Central

2013-01-01

Background The available drugs for diabetes, Insulin or Oral hypoglycemic agents have one or more side effects. Search for new antidiabetic drugs with minimal or no side effects from medicinal plants is a challenge according to WHO recommendations. In this aspect, the present study was undertaken to evaluate the antihyperglycemic and antihyperlipidemic effects of Piper longum root aqueous extract (PlrAqe) in streptozotocin (STZ) induced diabetic rats. Methods Diabetes was induced in male Wister albino rats by intraperitoneal administration of STZ (50 mg/kg.b.w). Fasting blood glucose (FBG) levels were measured by glucose-oxidase & peroxidase reactive strips. Serum biochemical parameters such as glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG), very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol were estimated. The activities of liver and kidney functional markers were measured. The statistical analysis of results was carried out using Student t-test and one-way analysis (ANOVA) followed by DMRT. Results During the short term study the aqueous extract at a dosage of 200 mg/kg.b.w was found to possess significant antidiabetic activity after 6 h of the treatment. The administration of aqueous extract at the same dose for 30 days in STZ induced diabetic rats resulted in a significant decrease in FBG levels with the corrections of diabetic dyslipidemia compared to untreated diabetic rats. There was a significant decrease in the activities of liver and renal functional markers in diabetic treated rats compared to untreated diabetic rats indicating the protective role of the aqueous extract against liver and kidney damage and its non-toxic property. Conclusions From the above results it is concluded that the plant extract is capable of managing hyperglycemia and complications of diabetes in STZ induced diabetic rats. Hence this plant may be considered as one of the potential sources for the isolation of new oral anti hypoglycemic agent(s). PMID:23414307

A novel dihydroxy gymnemic triacetate isolated from Gymnema sylvestre possessing normoglycemic and hypolipidemic activity on STZ-induced diabetic rats.

PubMed

Daisy, Pitchai; Eliza, James; Mohamed Farook, Khanzan Abdul Majeed

2009-11-12

Gymnema sylvestre (Asclepiadaceae) is emerging as a potential treatment for the management of diabetes. The leaves are used in herbal medicine preparations. The present study was carried out to isolate and identify the putative antidiabetic compound based on bioassay-guided fractionation. An active compound dihydroxy gymnemic triacetate has been isolated from Gymnema sylvestre acetone extract and its optimum dose has been determined and patented. An optimum dose of dihydroxy gymnemic triacetate (20mg/kg body weight) was orally administered for 45 days to streptozotocin diabetic rats for the assessment of plasma glucose, insulin, glycated hemoglobin (HbA1c), tissue glycogen, lipid parameters such as triglycerides, total cholesterol, LDL-cholesterol, HDL-cholesterol and activities of hepatic marker enzymes, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and acid phosphatase (ACP) in normal and streptozotocin diabetic rats. Dihydroxy gymnemic triacetate at 20mg dose produced significant effects on all biochemical parameters studied compared to diabetic control group. These results indicate that dihydroxy gymnemic triacetate, the compound from Gymnema sylvestre, possessed hypoglycemic and hypolipidemic activity in long-term treatment and hence it could be used as a drug for treating diabetes.

[Research advances of Tasmayi].

PubMed

Kizaibek, Murat

2013-02-01

Tasmayi (mumie, shilajit) is a pale brown to black substance which leaks from the layers of rocks in many mountain ranges during the warm summer months. In traditional Kazakh medicine, it is used for the treatment of bone fracture and many inflammatory ailments. It is also used as a remedy in the traditional medical systems of many countries such as India, Russia and Kazakhstan. According to the literatures, Tasmayi possesses anti-inflammatory, antiulcerogenic, antibacterial, free radical scavenging, antioxidative, memory enhancing, antidiabetic, antistress, antiallergic, immunomodulative, anti AIDS, anabolic and regeneration stimulating activities. The major physiological action of Tasmayi could be belonging to the presence of dibenzo-alpha-pyrones along with humic and fulvic acids.

Hypoglycaemic, antihyperglycaemic and hypolipidemic activities of Caesalpinia bonducella seeds in rats.

PubMed

Sharma, S R; Dwivedi, S K; Swarup, D

1997-09-01

Hypoglycaemic, antihyperglycaemic and hypolipidemic activities of the aqueous and 50% ethanolic extracts of Caesalpinia bonducella Fleming (Leguminosae) seeds were studied in normal and streptozotocin (SZ)-diabetic rats. In normal rats, both the extracts exhibited hypoglycaemic activity as early as 4 h after administration at a lower dose of 100 mg/kg. The hypoglycaemia produced by the aqueous extract was of prolonged duration as compared to ethanolic extract. In diabetic rats, both the extracts produced significant (P < 0.01) antihyperglycaemic effect from day 5 onwards. Aqueous extract also exhibited antihypercholesterolemic and antihypertriglyceridemic effects in SZ-diabetic rats. These results suggest that C. bonducella seeds possess an antidiabetic principle and can be useful for treatment of diabetes. Further studies are warranted to fractionate the active principle and to find out its exact mechanism of action.

Evaluation of Biological Effects of Hydroalcoholic Extract of Hibiscus Rosa Sinensis Flowers on Alloxan Induced Diabetes in Rats.

PubMed

Pethe, Mohan; Yelwatkar, Samir; Manchalwar, Smita; Gujar, Vijay

2017-08-01

Aim and Objective The current study sought to investigate antidiabetic, hypolipidimic, antioxidant and histopathological effects of floral extract of Hibiscus rosa sinensis in Alloxan induced Diabetes in rats. Materials and Methods Study was conducted on 6 groups with 6 wistar rats in each group for the period of 4 weeks. Group I: served as normal control (NC), rats administered with gum acacia 1 ml daily, group II: consider as diabetic control (DC) treated with alloxon 150 mg/kg body wt. Whereas Hibiscus rosa-sinensis flower extract was given orally in group III (DE1), group IV (DE2), group V (DE3) at doses of 50, 100 and 200 mg/kg body weight dissolved in distilled water respectively. Group VI (DG) was given glibenclamide (5 mg/kg) as a standard drug and results were compared in reference to it. Results The results indicate that the test compound HEFHR (Hydroalcoholic extract of flower Hibiscus rosa-sinensis) has significant and sustained oral antidiabetic activity, comparable with the hypoglycemic effect of Glibenclamide and Sulphonylurea. Flower extract of HRS was more efficacious in lipid lowering effect and in antioxidative activity than glibenclamide. After 28 day treatment with flower extract, size of islets was significantly increased and necrosis and atrophy of islets were significantly improved; also increase in number and diameter of cell islets appeared to be regular as compared to the diabetic group. Conclusion HEFHR possesses significant antidiabetic, hypolipidemic and antioxidant properties as well as regeneration of beta cells in rats. Further evaluation of HEFHR is in progress. © Georg Thieme Verlag KG Stuttgart · New York.

Antidiabetic and hypolipidaemic effects of a methanol/methylene-chloride extract of Laportea ovalifolia (Urticaceae), measured in rats with alloxan-induced diabetes.

PubMed

Momo, C E N; Oben, J E; Tazoo, D; Dongo, E

2006-01-01

A decoction of the leaves of Laportea ovalifolia is widely used in Cameroon for the treatment of several illnesses, including diabetes mellitus. The antidiabetic and hypolipidaemic effects of a methanol/methylene-chloride extract of the aerial parts of L. ovalifolia have now been investigated, in normal rats and rats with diabetes induced by the intraperitoneal injection of alloxan (at 150 mg/kg bodyweight). In the diabetic rats, 2 weeks of daily, intragastric treatment with the L. ovalifolia extract not only produced a significant reduction in the fasting serum glucose concentrations but also lowered the serum concentrations of total cholesterol, triglycerides, and low-density-lipoprotein cholesterol, lowered the ratio of total cholesterol to high-density-lipoprotein (HDL) cholesterol, and increased the serum concentration of HDL cholesterol. At least in rats with alloxan-induced diabetes, the methanol/methylene-chloride extract of L. ovalifolia therefore appears to possess antidiabetic and hypolipidaemic properties.

Indexing Natural Products for Their Potential Anti-Diabetic Activity: Filtering and Mapping Discriminative Physicochemical Properties.

PubMed

Zeidan, Mouhammad; Rayan, Mahmoud; Zeidan, Nuha; Falah, Mizied; Rayan, Anwar

2017-09-17

Diabetes mellitus (DM) poses a major health problem, for which there is an unmet need to develop novel drugs. The application of in silico techniques and optimization algorithms is instrumental to achieving this goal. A set of 97 approved anti-diabetic drugs, representing the active domain, and a set of 2892 natural products, representing the inactive domain, were used to construct predictive models and to index anti-diabetic bioactivity. Our recently-developed approach of 'iterative stochastic elimination' was utilized. This article describes a highly discriminative and robust model, with an area under the curve above 0.96. Using the indexing model and a mix ratio of 1:1000 (active/inactive), 65% of the anti-diabetic drugs in the sample were captured in the top 1% of the screened compounds, compared to 1% in the random model. Some of the natural products that scored highly as potential anti-diabetic drug candidates are disclosed. One of those natural products is caffeine, which is noted in the scientific literature as having the capability to decrease blood glucose levels. The other nine phytochemicals await evaluation in a wet lab for their anti-diabetic activity. The indexing model proposed herein is useful for the virtual screening of large chemical databases and for the construction of anti-diabetes focused libraries.

Marine Pharmacology in 2009–2011: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and other Miscellaneous Mechanisms of Action †

PubMed Central

Mayer, Alejandro M. S.; Rodríguez, Abimael D.; Taglialatela-Scafati, Orazio; Fusetani, Nobuhiro

2013-01-01

The peer-reviewed marine pharmacology literature from 2009 to 2011 is presented in this review, following the format used in the 1998–2008 reviews of this series. The pharmacology of structurally-characterized compounds isolated from marine animals, algae, fungi and bacteria is discussed in a comprehensive manner. Antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral pharmacological activities were reported for 102 marine natural products. Additionally, 60 marine compounds were observed to affect the immune and nervous system as well as possess antidiabetic and anti-inflammatory effects. Finally, 68 marine metabolites were shown to interact with a variety of receptors and molecular targets, and thus will probably contribute to multiple pharmacological classes upon further mechanism of action studies. Marine pharmacology during 2009–2011 remained a global enterprise, with researchers from 35 countries, and the United States, contributing to the preclinical pharmacology of 262 marine compounds which are part of the preclinical pharmaceutical pipeline. Continued pharmacological research with marine natural products will contribute to enhance the marine pharmaceutical clinical pipeline, which in 2013 consisted of 17 marine natural products, analogs or derivatives targeting a limited number of disease categories. PMID:23880931

Moringa oleifera from Cambodia Ameliorates Oxidative Stress, Hyperglycemia, and Kidney Dysfunction in Type 2 Diabetic Mice.

PubMed

Tang, Yujiao; Choi, Eun-Ju; Han, Weon Cheol; Oh, Mirae; Kim, Jin; Hwang, Ji-Young; Park, Pyo-Jam; Moon, Sang-Ho; Kim, Yon-Suk; Kim, Eun-Kyung

2017-05-01

Recent reports have shown the antidiabetic effect of Moringa oleifera from various parts of the world. However, M. oleifera from Cambodia has never determined. Therefore, the aim of this study was to assess the antidiabetic effect of M. oleifera extract from Cambodia. The leaf ethanolic extract contained flavonoids (31.90 mg/mL), polyphenols (53.03 mg/mL), lycopene (0.042 mg/mL), and ß-carotene (0.170 mg/mL), and possessed 2,2-diphenyl-1-picrylhydrazyl, hydrogen peroxide, and hydroxyl radical scavenging activities of 92.40, 99.25, and 83.57 TE/μM at 1 mg/mL, respectively. Db/db mice were orally administered the leaf extract (150 mg/kg/day) for 5 weeks. M. oleifera treatment significantly ameliorated the altered fasting plasma glucose (from 483 to 312 mg/dL), triglyceride (from 42.12 to 23.00 mg/dL), and low-density lipoprotein cholesterol (from 107.21 to 64.25 mg/dL) compared to control group, and increased the insulin levels from 946 ± 92 to 1678 ± 268 pg/mL. The histopathological damage and expression levels of tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6, cyclooxygenase-2, and inducible nitric oxide synthase in renal tissue decreased. These results indicate the potential antidiabetic benefits of M. oleifera ethanolic leaf extract.

Pharmacological importance of sulphated polysaccharide carrageenan from red seaweed Kappaphycus alvarezii in comparison with commercial carrageenan.

PubMed

Suganya, Arumugampillai Manimehalai; Sanjivkumar, Muthusamy; Chandran, Manohar Navin; Palavesam, Arunachalam; Immanuel, Grasian

2016-12-01

Pharmacological properties of native carrageenan (κ) extracted from Kappaphycus alvarezii and commercial carrageenan (Sigma-Aldrich) were evaluated using in vitro antioxidant, anticancer and antidiabetic studies. Phytochemical analysis of native and commercial carrageenans showed the presence of alkaloids, saponins, steroids, gums & mucilages and carbohydrate. Both native and commercial carrageenans exhibited better antioxidant activities such as total antioxidant capacity (87±0.47 and 82.6±0.47μg A.A/g), hydroxyl radical scavenging activity (61.4±0.27 and 58.66±0.31μg/ml), nitric oxide radical scavenging activity (80.42±0.22 and 73.66±0.22μg/ml), DPPH radical scavenging activity (56.26±0.20 and 53.67±0.082μg/ml) and reducing power assay (46.57±0.32 and 42.54±0.27μg/ml) at the maximum concentration of 100μg/ml carrageenans. These results indicated that native carrageenan from K. alvarezii possessed better antioxidant potential in comparison with commercial carrageenan. Anticancer activities of both carrageenans showed excellent inhibition on the growth of breast, colon, liver and osteosarcoma cell lines at the maximum concentration of 150μg/ml. Native carrageenan exhibited an excellent anticancer activity on colon carcinoma cell lines (67.66±0.168%) with the IC 50 value of 73.87μg/ml and commercial carrageenan possessed a potent inhibition on the growth of breast cancer cell lines (67.33±0.077%) with the IC 50 value of 123.8μg/ml. These results clearly indicated the beneficial effect of native and commercial carrageenans as anticancer agents being a free radical scavenger. Anti-diabetic property of both carrageenans showed inhibition effect on α- glucosidase enzyme. The inhibitory effect depends on concentration of carrageenans and it was recorded that maximum (74.49±1.05 and 67.42±0.63) inhibitory effect of α- glucosidase enzyme at 500μg/ml concentration. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Nano-preparation of Andrographis paniculata extract by casein micelle for antidiabetic agent

NASA Astrophysics Data System (ADS)

Arbianti, Rita; Dewi, Veronica; Imansari, Farisa; Hermansyah, Heri; Sahlan, Muhamad

2017-02-01

Side effects caused by oral medications for person with diabetic are the background of the development of alternative treatments by traditional medicine, herbs. Andrographis paniculata (AP) is one of the herbs that is potent to be anti-diabetic agent. The active compound of AP, andrographolide have been examined to have anti-diabetic activity as α-glucosidase enzyme inhibitor. This research aims to encapsulate sambiloto's extract with casein micelle and produce nanoparticles which have anti-diabetic activity as α-glucosidase inhibitor. Extract of AP is encapsulated by casein micelle and made into nano size using sonicator. The dominant active compounds in AP extract coated by casein are andrographolide, neoandrographolide, 14-deoxy-11,12didehydroandrographolide with encapsulation efficiency of 68.83%, 89.15% and 81.69%, the average diameter of the particles is about 120.57 nm and its loading capacity is 28.85%. AP's extract has antidiabetic activity as α-glucosidase inhibitor with percent inhibition of 95%. The morphology of nanoencapsulated AP's extract analyzed by FE-SEM, were similar with casein micelle.

Anti-diabetic formulations of Nāga bhasma (lead calx): A brief review

PubMed Central

Rajput, Dhirajsingh; Patgiri, B. J.; Galib, R; Prajapati, P. K.

2013-01-01

Introduction: Ayurvedic formulations usually contain ingredients of herbal, mineral, metal or animal in origin. Nāga bhasma (lead calx) is a potent metallic formulation mainly indicated in the treatment of Prameha (~diabetes). Until date, no published information is available in compiled form on the formulations containing Nāga bhasma as an ingredient, their dose and indications. Therefore, in the present study, an attempt has been made to compile various formulations of Nāga bhasma indicated in treating Prameha. Aim: The present work aims to collect information on various formulations of Nāga bhasma mainly indicated in treating Prameha and to elaborate the safety and efficacy of Nāga bhasma as a Pramehaghna (antidiabetic) drug. Materials and Methods Critical review of formulations of Nāga bhasma is compiled from various Ayurvedic texts and the therapeutic efficacy of Nāga bhasma is discussed on the basis of available data. Result and Conclusion: Antidiabetic formulations of Nāga bhasma were discovered around 12th century CE. There are 44 formulations of Nāga bhasma mainly indicated for Prameha. Haridrā (Curcuma longa Linn), Āmalakī (Emblica officinalis), Guḍūci (Tinospora cordifolia) and Madhu (honey) enhance the antidiabetic action of Nāga bhasma and also help to prevent diabetic complications as well as any untoward effects of Nāga bhasma. On the basis of the reviewed research, it is concluded that Nāga bhasma possesses significant antidiabetic property. PMID:25161332

Identification of Novel Human Dipeptidyl Peptidase-IV Inhibitors of Natural Origin (Part II): In Silico Prediction in Antidiabetic Extracts

PubMed Central

Guasch, Laura; Sala, Esther; Ojeda, María José; Valls, Cristina; Bladé, Cinta; Mulero, Miquel; Blay, Mayte; Ardévol, Anna; Garcia-Vallvé, Santiago; Pujadas, Gerard

2012-01-01

Background Natural extracts play an important role in traditional medicines for the treatment of diabetes mellitus and are also an essential resource for new drug discovery. Dipeptidyl peptidase IV (DPP-IV) inhibitors are potential candidates for the treatment of type 2 diabetes mellitus, and the effectiveness of certain antidiabetic extracts of natural origin could be, at least partially, explained by the inhibition of DPP-IV. Methodology/Principal Findings Using an initial set of 29,779 natural products that are annotated with their natural source and an experimentally validated virtual screening procedure previously developed in our lab (Guasch et al.; 2012) [1], we have predicted 12 potential DPP-IV inhibitors from 12 different plant extracts that are known to have antidiabetic activity. Seven of these molecules are identical or similar to molecules with described antidiabetic activity (although their role as DPP-IV inhibitors has not been suggested as an explanation for their bioactivity). Therefore, it is plausible that these 12 molecules could be responsible, at least in part, for the antidiabetic activity of these extracts through their inhibitory effect on DPP-IV. In addition, we also identified as potential DPP-IV inhibitors 6 molecules from 6 different plants with no described antidiabetic activity but that share the same genus as plants with known antidiabetic properties. Moreover, none of the 18 molecules that we predicted as DPP-IV inhibitors exhibits chemical similarity with a group of 2,342 known DPP-IV inhibitors. Conclusions/Significance Our study identified 18 potential DPP-IV inhibitors in 18 different plant extracts (12 of these plants have known antidiabetic properties, whereas, for the remaining 6, antidiabetic activity has been reported for other plant species from the same genus). Moreover, none of the 18 molecules exhibits chemical similarity with a large group of known DPP-IV inhibitors. PMID:23028712

Comparative Analysis of Chemical Profile, Antioxidant, In-vitro and In-vivo Antidiabetic Activities of Juniperus foetidissima Willd. and Juniperus sabina L.

PubMed Central

Orhan, Nilüfer; Deliorman Orhan, Didem; Gökbulut, Alper; Aslan, Mustafa; Ergun, Fatma

2017-01-01

Fruit and leaves of junipers are commonly used internally as tea and pounded fruits are eaten to lower blood glucose levels in Anatolia. Thus, we aimed to evaluate antidiabetic and antioxidant potential and the chemical profile of Juniperus foetidissima Willd. and J. sabina L. in this study. In-vitro antidiabetic activities of leaf and fruit extracts were examined by their inhibitory activity on α-glucosidase and α-amylase enzymes. Then, in-vivo antidiabetic activities of leaf and fruit extracts of Juniperus species were investigated on streptozotocin-induced diabetic rats. Additionally, antioxidant activities (phosphomolybdenum, ferric-reducing antioxidant power and ABTS radical scavenging activity assays), phytochemical screening tests and high performance liquid chromatography analysis (HPLC) were done. In-vitro enzyme inhibitory effects of the extracts were supported by the results of in-vivo antidiabetic activity studies. Phytochemical screening tests indicated presence of flavonoids, tannins, terpenoids and carbohydrates in the extracts. Amentoflavone was identified as the major compound in the extracts and content of amentoflavone was determined. As a result, Juniperus extracts and its active constituents might be beneficial for diabetes and its complications. PMID:29844777

Evaluation of antioxidant, antibacterial, and antidiabetic potential of two traditional medicinal plants of India: Swertia cordata and Swertia chirayita.

PubMed

Roy, Priyanka; Abdulsalam, Fatima I; Pandey, D K; Bhattacharjee, Aniruddha; Eruvaram, Naveen Reddy; Malik, Tabarak

2015-06-01

Swertia cordata and Swertia chirayita are temperate Himalayan medicinal plants used as potent herbal drugs in Indian traditional systems of medicine (Ayurvedic, Unani and Siddha). Assessment of Antioxidant, antibacterial, and antidiabetic potential of Swertia cordata and Swertia chirayita. Phytochemicals of methanolic and aqueous extracts of the two Swertia species were analyzed. The antioxidant potential of all the extracts was assessed by measuring total phenolic content, total flavonoid content and free radical scavenging potential was assessed by 1,1-diphenyl-2-picrilhydrazyl (DPPH) assay, antibacterial activity was assessed against various pathogenic and nonpathogenic bacteria in vitro by Kirby-Bauer agar well diffusion method and antidiabetic activity was assessed by α-amylase inhibition. Methanolic leaf extracts of both the species of Swertia contain significant antibacterial as well as anti-diabetic potential, whereas methanolic root extracts of both species were found to have potential antioxidant activity. However, Swertia chirayita showed better activities than Swertia cordata although both species have good reputation in traditional Indian medicine. Both the species are having high medicinal potential in terms of their antioxidant, antibacterial and antidiabetic activities. Studies are required to further elucidate antioxidant, anti-diabetic and antibacterial potentials using various in-vitro, in-vivo biochemical and molecular biology techniques.

Evaluation of antioxidant, antibacterial, and antidiabetic potential of two traditional medicinal plants of India: Swertia cordata and Swertia chirayita

PubMed Central

Roy, Priyanka; Abdulsalam, Fatima I.; Pandey, D. K.; Bhattacharjee, Aniruddha; Eruvaram, Naveen Reddy; Malik, Tabarak

2015-01-01

Background: Swertia cordata and Swertia chirayita are temperate Himalayan medicinal plants used as potent herbal drugs in Indian traditional systems of medicine (Ayurvedic, Unani and Siddha). Objective: Assessment of Antioxidant, antibacterial, and antidiabetic potential of Swertia cordata and Swertia chirayita. Materials and Methods: Phytochemicals of methanolic and aqueous extracts of the two Swertia species were analyzed. The antioxidant potential of all the extracts was assessed by measuring total phenolic content, total flavonoid content and free radical scavenging potential was assessed by 1,1-diphenyl-2-picrilhydrazyl (DPPH) assay, antibacterial activity was assessed against various pathogenic and nonpathogenic bacteria in vitro by Kirby-Bauer agar well diffusion method and antidiabetic activity was assessed by α-amylase inhibition. Results: Methanolic leaf extracts of both the species of Swertia contain significant antibacterial as well as anti-diabetic potential, whereas methanolic root extracts of both species were found to have potential antioxidant activity. However, Swertia chirayita showed better activities than Swertia cordata although both species have good reputation in traditional Indian medicine. Conclusion: Both the species are having high medicinal potential in terms of their antioxidant, antibacterial and antidiabetic activities. Studies are required to further elucidate antioxidant, anti-diabetic and antibacterial potentials using various in-vitro, in-vivo biochemical and molecular biology techniques. PMID:26109789

Mangiferin: a natural miracle bioactive compound against lifestyle related disorders.

PubMed

Imran, Muhammad; Arshad, Muhammad Sajid; Butt, Masood Sadiq; Kwon, Joong-Ho; Arshad, Muhammad Umair; Sultan, Muhammad Tauseef

2017-05-02

The current review article is an attempt to explain the therapeutic potential of mangiferin, a bioactive compound of the mango, against lifestyle-related disorders. Mangiferin (2-β-D-glucopyranosyl-1,3,6,7-tetrahydroxy-9H-xanthen-9-one) can be isolated from higher plants as well as the mango fruit and their byproducts (i.e. peel, seed, and kernel). It possesses several health endorsing properties such as antioxidant, antimicrobial, antidiabetic, antiallergic, anticancer, hypocholesterolemic, and immunomodulatory. It suppresses the activation of peroxisome proliferator activated receptor isoforms by changing the transcription process. Mangiferin protects against different human cancers, including lung, colon, breast, and neuronal cancers, through the suppression of tumor necrosis factor α expression, inducible nitric oxide synthase potential, and proliferation and induction of apoptosis. It also protects against neural and breast cancers by suppressing the expression of matrix metalloproteinase (MMP)-9 and MMP-7 and inhibiting enzymatic activity, metastatic potential, and activation of the β-catenin pathway. It has the capacity to block lipid peroxidation, in order to provide a shielding effect against physiological threats. Additionally, mangiferin enhances the capacity of the monocyte-macrophage system and possesses antibacterial activity against gram-positive and gram-negative bacteria. This review summarizes the literature pertaining to mangiferin and its associated health claims.

An Update Review on the Anthelmintic Activity of Bitter Gourd, Momordica charantia

PubMed Central

Poolperm, Sutthaya; Jiraungkoorskul, Wannee

2017-01-01

Momordica charantia (Family: Cucurbitales), as known as bitter melon or gourd, is a daily consumption as food and traditional medicinal plant in Southeast Asia and Indo-China. It has been shown to possess anticancer, antidepressant, antidiabetic, anti-inflammatory, antimicrobial, antiobesity, antioxidant, and antiulcer properties. Its common phytochemical components include alkaloids, charantin, flavonoids, glycosides, phenolics, tannins, and terpenoids. This plant is rich in various saponins including momordicin, momordin, momordicoside, karavilagenin, karaviloside, and kuguacin, all of which have been reported to contribute to its remedial properties including antibacterial, antifungal, antiviral, and antiparasitic infections. Based on established literature on the anthelmintic activity of M. charantia and possible mode of action, this review article has attempted to compile M. charantia could be further explored for the development of potential anthelmintic drug. PMID:28503051

An Update Review on the Anthelmintic Activity of Bitter Gourd, Momordica charantia.

PubMed

Poolperm, Sutthaya; Jiraungkoorskul, Wannee

2017-01-01

Momordica charantia (Family: Cucurbitales ), as known as bitter melon or gourd, is a daily consumption as food and traditional medicinal plant in Southeast Asia and Indo-China. It has been shown to possess anticancer, antidepressant, antidiabetic, anti-inflammatory, antimicrobial, antiobesity, antioxidant, and antiulcer properties. Its common phytochemical components include alkaloids, charantin, flavonoids, glycosides, phenolics, tannins, and terpenoids. This plant is rich in various saponins including momordicin, momordin, momordicoside, karavilagenin, karaviloside, and kuguacin, all of which have been reported to contribute to its remedial properties including antibacterial, antifungal, antiviral, and antiparasitic infections. Based on established literature on the anthelmintic activity of M. charantia and possible mode of action, this review article has attempted to compile M. charantia could be further explored for the development of potential anthelmintic drug.

Plant profile, phytochemistry and pharmacology of Cordia dichotoma (Indian cherry): a review.

PubMed

Jamkhande, Prasad G; Barde, Sonal R; Patwekar, Shailesh L; Tidke, Priti S

2013-12-01

More than half of the world's population relies on the traditional medicine and major role of the traditional medicine including the use of plant extract and their active constituents. Among them, Cordia dichotoma Forst., a small to moderate size plant of family Boragenaceae, commonly called bhokar, lasura, gonda, Indian cherry and shlesmataka. Plant parts such as leaves, fruit, bark and seed have been reported for possessing antidiabetic, antiulcer, anti-inflammatory, immune-modulator and analgesic activity. Screening of fruit, leaves and seed shows the presence of pyrrolizidine alkaloids, coumarins, flavonoids, saponins, terpenes and sterols. Present review focuses on details of geographical distribution, physicochemical parameters, phytoconstituents and pharmacological properties of Cordia dichotoma reported so far. Copyright © 2013 Asian Pacific Tropical Biomedical Magazine. Published by Elsevier B.V. All rights reserved.

Azadirachta indica: A herbal panacea in dentistry – An update

PubMed Central

Lakshmi, T.; Krishnan, Vidya; Rajendran, R; Madhusudhanan, N.

2015-01-01

Azadirachta indica commonly known as Neem, is an evergreen tree. Since time immemorial it has been used by Indian people for treatment of various diseases due to its medicinal properties. It possesses anti-bacterial, anti-cariogenic, anti-helminthic, anti-diabetic, anti-oxidant, astringent, anti-viral, cytotoxic, and anti-inflammatory activity. Nimbidin, Azadirachtin and nimbinin are active compounds present in Neem which are responsible for antibacterial activity. Neem bark is used as an active ingredient in a number of toothpastes and toothpowders. Neem bark has anti-bacterial properties, it is quite useful in dentistry for curing gingival problems and maintaining oral health in a natural way. Neem twigs are used as oral deodorant, toothache reliever and for cleaning of teeth. The objective of this article is to focus on the various aspects of Azadirachta indica in dentistry in order to provide a tool for future research. PMID:26009692

Azadirachta indica: A herbal panacea in dentistry - An update.

PubMed

Lakshmi, T; Krishnan, Vidya; Rajendran, R; Madhusudhanan, N

2015-01-01

Azadirachta indica commonly known as Neem, is an evergreen tree. Since time immemorial it has been used by Indian people for treatment of various diseases due to its medicinal properties. It possesses anti-bacterial, anti-cariogenic, anti-helminthic, anti-diabetic, anti-oxidant, astringent, anti-viral, cytotoxic, and anti-inflammatory activity. Nimbidin, Azadirachtin and nimbinin are active compounds present in Neem which are responsible for antibacterial activity. Neem bark is used as an active ingredient in a number of toothpastes and toothpowders. Neem bark has anti-bacterial properties, it is quite useful in dentistry for curing gingival problems and maintaining oral health in a natural way. Neem twigs are used as oral deodorant, toothache reliever and for cleaning of teeth. The objective of this article is to focus on the various aspects of Azadirachta indica in dentistry in order to provide a tool for future research.

The metabolism of berberine and its contribution to the pharmacological effects.

PubMed

Wang, Kun; Feng, Xinchi; Chai, Liwei; Cao, Shijie; Qiu, Feng

2017-05-01

Berberine, a bioactive alkaloid isolated from several herbal substances, possesses multiple pharmacological effects, including antimicrobial, antidiabetic, anticancer activities. Meanwhile, berberine undergoes extensive metabolism after oral administration which results in its extremely low plasma exposure. Therefore, it is believed that the metabolites of berberine also contribute a lot to its pharmacological effects. Along these lines, this review covers the metabolism studies of berberine in terms of its metabolic pathways and metabolic organs based on the identified metabolites, and it also covers the pharmacological activities of its active metabolites. In brief, the predominant metabolic pathways of berberine are demethylation, demethylenation, reduction, hydroxylation and subsequent conjugation in vivo. Active metabolites such as columbamine, berberrubine and demethyleneberberine also exhibit similar pharmacological effects by comparison with berberine, such as antioxidant, anti-inflammatory, antitumor, antimicrobial, hepatoprotective, neuroprotective, hypolipidemic and hypoglycemic effects. Overall, berberine together with its metabolites formed the material basis of berberine in vivo.

New insights into the ameliorative effects of ferulic acid in pathophysiological conditions.

PubMed

Ghosh, Sumit; Basak, Priyanka; Dutta, Sayanta; Chowdhury, Sayantani; Sil, Parames C

2017-05-01

Ferulic acid, a natural phytochemical has gained importance as a potential therapeutic agent by virtue of its easy commercial availability, low cost and minimal side-effects. It is a derivative of curcumin and possesses the necessary pharmacokinetic properties to be retained in the general circulation for several hours. The therapeutic effects of ferulic acid are mediated through its antioxidant and anti-inflammatory properties. It exhibits different biological activities such as anti-inflammatory, anti-apoptotic, anti-carcinogenic, anti-diabetic, hepatoprotective, cardioprotective, neuroprotective actions, etc. The current review addresses its therapeutic effects under different pathophysiological conditions (eg. cancer, cardiomyopathy, skin disorders, brain disorders, viral infections, diabetes etc.). Copyright © 2017 Elsevier Ltd. All rights reserved.

Mangifera Indica (Mango)

PubMed Central

Shah, K. A.; Patel, M. B.; Patel, R. J.; Parmar, P. K.

2010-01-01

Mangifera indica, commonly used herb in ayurvedic medicine. Although review articles on this plant are already published, but this review article is presented to compile all the updated information on its phytochemical and pharmacological activities, which were performed widely by different methods. Studies indicate mango possesses antidiabetic, anti-oxidant, anti-viral, cardiotonic, hypotensive, anti-inflammatory properties. Various effects like antibacterial, anti fungal, anthelmintic, anti parasitic, anti tumor, anti HIV, antibone resorption, antispasmodic, antipyretic, antidiarrhoeal, antiallergic, immunomodulation, hypolipidemic, anti microbial, hepatoprotective, gastroprotective have also been studied. These studies are very encouraging and indicate this herb should be studied more extensively to confirm these results and reveal other potential therapeutic effects. Clinical trials using mango for a variety of conditions should also be conducted. PMID:22228940

Profertility and antidiabetic properties of Gynura procumbens on streptozotocin induced male rats

NASA Astrophysics Data System (ADS)

Khaidatul Akmar, K.; Mahanem, M. N.

2016-11-01

Gynura procumbens (GP) is an herbal plant that is used for treating diseases such as diabetes mellitus, cardiovascular and also fertility. The objective of this study was to determine the anti-diabetic and pro-fertility effect of GP on streptozotocin induced male rats within 14 days. A total of 42 male rats were randomly assigned into six groups; normal, negative, and positive control, and three treated groups of different dosages of GP; 150 mg/kg, 300 mg/kg and 450 mg/kg. The treated groups were given aqueous extract GP via oral gavage for 14 consecutive days. The fasting blood glucose (FBG) level in all treated groups showed significant decreased compared to negative and positive group after 14 days treatment. Sperm quality parameters in GP treated group (450 mg/kg) showed significant increase when compared to negative and positive group. It was observed that the histology of testes in the treated group (450 mg/kg) produced a significant result whereby the germinal cell layer shown an arranged order of cells compared to the negative and positive control groups. It appeared that aqueous extract of GP have a pro-fertility effect and possess anti-hyperglycemic activity within 14 days of treatment.

Phytochemical Screening, Alpha-Glucosidase Inhibition, Antibacterial and Antioxidant Potential of Ajuga bracteosa Extracts.

PubMed

Hafeez, Kokab; Andleeb, Saiqa; Ghousa, Tahseen; Mustafa, Rozina G; Naseer, Anum; Shafique, Irsa; Akhter, Kalsoom

2017-01-01

Ajuga bracteosa, a medicinal herb, is used by local community to cure a number of diseases such as inflammation, jaundice bronchial asthma, cancer and diabetes. The aim of present work was to evaluate the antioxidant potential, in vitro antidiabetic and antimicrobial effects of A. bracteosa. n-hexane, ethyl acetate, chloroform, acetone, methanol and aqueous extracts of Ajuga bracteosa roots, were prepared via maceration. Antibacterial activity was carried out by agar well diffusion method. Quantitative and qualitative phytochemical screening was done. The antioxidant activity was determined by iron (II) chelating activity, iron reducing power, DPPH, and ABTS free radical scavenging methods, Antidiabetic activity was evaluated through inhibition of α-glucosidase assay. Phytochemical analysis showed the presence of phenols, flavonoids, tannins, saponins, quinines, terpenoids, xanthoproteins, glycosides, carbohydrates, steroids, phytosterols and amino acids. DPPH and ABTS potential values were recorded as 61.92% to 88.84% and 0.11% to 38.82%, respectively. Total phenolic and total flavonoid contents were expressed as gallic acid and rutin equivalents. Total iron content was expressed as FeSO4 equivalents. Chloroform and n-hexane extracts showed significant enzyme inhibition potential with IC50 values of 29.92 μg/ml and 131.7 μg/ml respectively. Aqueous extract showed maximum inhibition of E. coli, S. typhimurium, E. amnigenus, S. pyogenes, and S. aureus, (18.0±1.0 mm, 12.5±0.7 mm, 17.0±0.0 mm, 11.0±0.0 mm and 15.3±2.0 mm mm), respectively. Similarly, n-hexane extract showed maximum inhibition of E. coli, E. amnigenus, S. aureus (11.6±1.5 mm; 11.3±1.5 mm; 13.3±0.5 mm). This study also shows that n-hexane, chloroform, ethyl acetate and aqueous extracts of A. bracteosa root possess α-glucosidase inhibitory activities and therefore it may be used as hypoglycemic agents in the management of postprandial hyperglycemia. Ajuga bracteosa root extracts may provide a basis for development of antioxidant, antimicrobial and antidiabetic drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Antidiabetic and antihyperlipidemic effects of ethanolic extract of leaves of Punica granatum in alloxan-induced non–insulin-dependent diabetes mellitus albino rats

PubMed Central

Das, Swarnamoni; Barman, Sarajita

2012-01-01

Objectives: Punica granatum L., (Family: Punicaceae) is used in Indian Unani medicine for treatment of diabetes mellitus. Therefore, the present study was done to evaluate the antidiabetic and antihyperlipidemic effects of ethanolic extract of leaves of P. granatum in alloxan-induced diabetic rats. Materials and Methods: Healthy Wistar albino rats (100-150 g) were divided into four groups of six animals each. Groups A and B received normal saline [(10 ml/kg/day/per oral (p.o.)]; group C received ethanolic extract of leaves of P. granatum (500 mg/kg/p.o.); and group D received glibenclamide (0.5 mg/kg/day/p.o.). The extracts were given for 1 week in all groups. To induce diabetes, alloxan 150 mg/kg, intraperitoneal (i.p.) single dose was administered to groups B, C, and D. Blood glucose and serum lipids [Total Cholesterol (TC), Triglycerides (TG), Low Density Lipoproteins (LDL), and High Density Lipoproteins (HDL)] and the atherogenic index were estimated after one week. For mechanism of antidiabetic action glycogen estimation on the liver, cardiac and skeletal muscle, and intestinal glucose absorption was done. Results: Group B showed a significant (P<0.01) increase in blood glucose as compared to group A. Groups C and D showed significant decrease (P<0.01) in blood glucose level in comparison to group B. The test drug showed a significant (P<0.01) increase in glycogen content in the liver, cardiac, and skeletal muscle; it significantly (P<0.01) reduced intestinal glucose absorption. Groups C and D showed significant (P<0.01) decrease in serum TC, TG, LDL, and AI as compared to Group B, which showed a significant (P<0.01) increase. Groups C and D showed significant (P<0.01) increase in serum HDL as compared to Group B, which showed a significant (P<0.01) decrease in all values. Conclusion: P. granatum leaves possess significant antidiabetic and antihyperlipidemic activity. PMID:22529479

Next generation sequencing and de novo transcriptome analysis of Costus pictus D. Don, a non-model plant with potent anti-diabetic properties

PubMed Central

2012-01-01

Background Phyto-remedies for diabetic control are popular among patients with Type II Diabetes mellitus (DM), in addition to other diabetic control measures. A number of plant species are known to possess diabetic control properties. Costus pictus D. Don is popularly known as “Insulin Plant” in Southern India whose leaves have been reported to increase insulin pools in blood plasma. Next Generation Sequencing is employed as a powerful tool for identifying molecular signatures in the transcriptome related to physiological functions of plant tissues. We sequenced the leaf transcriptome of C. pictus using Illumina reversible dye terminator sequencing technology and used combination of bioinformatics tools for identifying transcripts related to anti-diabetic properties of C. pictus. Results A total of 55,006 transcripts were identified, of which 69.15% transcripts could be annotated. We identified transcripts related to pathways of bixin biosynthesis and geraniol and geranial biosynthesis as major transcripts from the class of isoprenoid secondary metabolites and validated the presence of putative norbixin methyltransferase, a precursor of Bixin. The transcripts encoding these terpenoids are known to be Peroxisome Proliferator-Activated Receptor (PPAR) agonists and anti-glycation agents. Sequential extraction and High Performance Liquid Chromatography (HPLC) confirmed the presence of bixin in C. pictus methanolic extracts. Another significant transcript identified in relation to anti-diabetic, anti-obesity and immuno-modulation is of Abscisic Acid biosynthetic pathway. We also report many other transcripts for the biosynthesis of antitumor, anti-oxidant and antimicrobial metabolites of C. pictus leaves. Conclusion Solid molecular signatures (transcripts related to bixin, abscisic acid, and geranial and geraniol biosynthesis) for the anti-diabetic properties of C. pictus leaves and vital clues related to the other phytochemical functions like antitumor, anti-oxidant, immuno-modulatory, anti-microbial and anti-malarial properties through the secondary metabolite pathway annotations are reported. The data provided will be of immense help to researchers working in the treatment of DM using herbal therapies. PMID:23176672

Evaluation of Antidiabetic and Antihyperlipidemic Effects of Hydroalcoholic Extract of Leaves of Ocimum tenuiflorum (Lamiaceae) and Prediction of Biological Activity of its Phytoconstituents

PubMed Central

Parasuraman, Subramani; Balamurugan, Subramani; Christapher, Parayil Varghese; Petchi, Rajendran Ramesh; Yeng, Wong Yeng; Sujithra, Jeyabalan; Vijaya, Chockalingam

2015-01-01

Objective: The aim was to evaluate the anti-diabetic and anti-hyperlipidemic effects of hydroalcoholic extract of leaves of Ocimum tenuiflorum (Lamiaceae) and prediction of biological activities of its phytoconstituents using in vivo anti-diabetic model and in silico analysis respectively. Materials and Methods: The leaves of O. tenuiflorum were extracted with 60% ethanol, and the extract was used for further pharmacological screening. The acute toxicity of the extract was evaluated as per the guidelines set by the Organization for Economic Co-operation and Development, revised draft guidelines 423. The oral anti-diabetic activity of the hydroalcoholic extract of O. tenuiflorum (125, 250 and 500 mg/kg) was studied against streptozotocin (STZ) (50 mg/kg; i.p.) + nicotinamide (120 mg/kg; i.p.) induced diabetes mellitus. The animals were treated with the investigational plant extract and standard drug (glibenclamide) for 21 consecutive days and the effect of hydroalcoholic extract of O. tenuiflorum on blood glucose levels was measured at regular intervals. At the end of the study, blood samples were collected from all the animals for biochemical estimation, then the animals were sacrificed and the liver and kidney were collected for organ weight analysis. Prediction for pharmacological and toxicological properties of phytoconstituents of O. tenuiflorum was carried out using online web tools such as online pass prediction and lazar toxicity prediction. Results: The hydroalcoholic extract of O. tenuiflorum showed significant anti-diabetic and anti-hyperlipidemic activity at 250 and 500 mg/kg, and this effect was comparable with that of glibenclamide. Predicted biological activities of phytoconstituents of O. tenuiflorum showed presence of various pharmacological actions, which includes anti-diabetic and anti-hyperlipidemic activities. Prediction of toxicological properties of phytoconstituents of O. tenuiflorum did not show any major toxic effects. Conclusion: The hydroalcoholic extract of O. tenuiflorum showed significant anti-diabetic and anti-hyperlipidemic activity against STZ + nicotinamide induced diabetes mellitus in rats. Further studies are required to confirm the anti-diabetic and anti-hyperlipidemic activities of individual phytoconstituents of O. tenuiflorum. PMID:25829789

Antidiabetic effect of total flavonoids from Sanguis draxonis in type 2 diabetic rats.

PubMed

Chen, Fufeng; Xiong, Hui; Wang, Jianxia; Ding, Xin; Shu, Guangwen; Mei, Zhinan

2013-10-07

Sanguis draxonis (SD) is a kind of red resin obtained from the wood of Dracaena cochinchinensis (Lour.) S. C. Chen (Dracaena cochinchinensis). It is a Chinese traditional herb that is prescribed for the handling of diabetic disorders, which is also supported by an array of scientific studies published in recent years. Although chemical constituents of this plant material have also been previously evaluated (Tang et al., 1995; Wei et al., 1998), it still remains poorly understood which constituent is the major contributor to its antidiabetic activities. Moreover, very little is known about the molecular mechanisms underlying antidiabetic activities of SD. Flavonoids exist at a high level in SD. The aim of this study is to evaluate the antidiabetic effects of total flavonoids from SD (SDF) in type 2 Diabetes mellitus (T2DM) rats. T2DM rats were induced by 4 weeks high-fat diet and a singular injection of streptozotocin (STZ) (35mg/kg). Then T2DM rats were treated with SDF for 21 days, using normal saline as the negative control. For comparison, a standard antidiabetic drug, metformin (200mg/kg), was used as a positive control. Three weeks later, relative biochemical indexes were determined and histopathological examinations were performed to assess the antidiabetic activities of SDF. SDF not only exhibited a significant hypoglycemic activity, but also alleviated dyslipidemia, tissue steatosis, and oxidative stress associated with T2DM. Moreover, considerable pancreatic islet protecting effects could be observed after SDF treatment. Further investigations revealed a potential anti-inflammation activity of SDF by determining serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP). This study demonstrates both hypoglycemic and hypolipidemic effects of SDF in T2DM rats, suggesting that flavonoids are the major active ingredients accounting for the antidiabetic activity of SD. Alleviating chronic inflammation responses and protecting pancreatic islets are possible mechanisms involved in the antidiabetic activity of SDF. © 2013 Elsevier Ireland Ltd. All rights reserved.

Computational and Pharmacological Evaluation of Ferrocene-Based Acyl Ureas and Homoleptic Cadmium Carboxylate Derivatives for Anti-diabetic Potential.

PubMed

Bano, Shahar; Khan, Arif-Ullah; Asghar, Faiza; Usman, Muhammad; Badshah, Amin; Ali, Saqib

2017-01-01

We investigated possible anti-diabetic effect of ferrocene-based acyl ureas: 4-ferrocenyl aniline (PFA), 1-(4-chlorobenzoyl)-3-(4-ferrocenylphenyl) urea (DPC1), 1-(3-chlorobenzoyl)-3-(4-ferrocenylphenyl) urea (DMC1), 1-(2-chlorobenzoyl)-3-(4-ferrocenylphenyl) urea (DOC1) and homoleptic cadmium carboxylates: bis (diphenylacetato) cadmium (II) (DPAA), bis (4-chlorophenylacetato) cadmium (II) (CPAA), using in silico and in vivo techniques. PFA, DPC1, DMC1, DOC1, DPAA and CPAA exhibited high binding affinities (ACE ≥ -350 Kcal/mol) against targets: aldose reductase, peroxisome proliferator-activated receptor γ, 11β-hydroxysteroid dehydrogenase-1, C-alpha glucosidase and glucokinase, while showed moderate affinities (ACE ≥ -250 Kcal/mol) against N-alpha glucosidase, dipeptidyl peptidase-IV, phosphorylated-Akt, glycogen synthase kinase-3β, fructose-1,6-bisphosphatase and phosphoenolpyruvate carboxykinase, whereas revealed lower affinities (ACE < -250 Kcal/mol) vs. alpha amylase, protein tyrosine phosphatases 1B, glycogen phosphorylase and phosphatidylinositol 3 kinase. In alloxan (300 mg/Kg)-induced diabetic mice, DPAA and DPC1 (1-10 mg/Kg) at day 1, 5, 10, 15, and 20th decreased blood glucose levels, compared to diabetic control group and improved the treated animals body weight. DPAA (10 mg/Kg) and DPC1 (5 mg/Kg) in time-dependent manner (30-120 min.) enhanced tolerance of oral glucose overload in mice. DPAA and DPCI dose-dependently at 1, 5, and 10 mg/Kg decreased glycosylated hemoglobin levels in diabetic animals, as caused by metformin. These results indicate that aforementioned derivatives of ferrocene and cadmium possess anti-diabetic potential.

In vitro and in silico analyses of Vicia faba L. on Peroxisome proliferator-activated receptor gamma.

PubMed

Prabhu, D Sathya; Rajeswari, V Devi

2018-06-20

The agonists of peroxisome proliferator-activated receptor gamma (PPARγ) from natural victual products were used as antidiabetic agents. Faba bean (Vicia faba L.) is a consequential legume that was known to possess potential antidiabetic activity, whose mechanism of action was unknown. The current study was focused to ascertain gene expression of the nuclear receptor PPARγ by Faba bean pod extract in rat cell lines (RINm5F).The real-time polymerase chain reaction analysis demonstrated that Faba bean pod extract in concentrations of 160 µg/mL have shown 4.97-fold stimulation compared with control. The cells treated with 320 µg/mL has shown 5.89-fold upregulation, respectively. Furthermore, in silico docking analysis was carried out against PPARγ, using the bioactive compounds identified from Faba bean pod extracts, which were known reported compounds from the literature. The results suggest that gene expression of PPARγ was inhibited by the constituents in Faba bean. In silico analysis prognosticates, butein has a high binding energy (-8.6 kcal/mol) with an atomic contact energy of -214.10, followed by Apigenin and Quercetin against PPARγ. Similarly, the percentage of interaction was high for butein, followed by Apigenin and Quercetin than other compounds comparatively. Hence, the results conclude inhibition of PPARγ by the bioactive compounds from Faba bean, which may provide insights into developing future therapeutic molecules for diabetes mellitus. © 2018 Wiley Periodicals, Inc.

Marine pharmacology in 2001–2002: Marine compounds with anthelmintic, antibacterial, anticoagulant, antidiabetic, antifungal, anti-inflammatory, antimalarial, antiplatelet, antiprotozoal, antituberculosis, and antiviral activities; affecting the cardiovascular, immune and nervous systems and other miscellaneous mechanisms of action

PubMed Central

Mayer, Alejandro M.S.; Hamann, Mark T.

2016-01-01

During 2001–2002, research on the pharmacology of marine chemicals continued to be global in nature involving investigators from Argentina, Australia, Brazil, Canada, China, Denmark, France, Germany, India, Indonesia, Israel, Italy, Japan, Mexico, Netherlands, New Zealand, Pakistan, the Philippines, Russia, Singapore, Slovenia, South Africa, South Korea, Spain, Sweden, Switzerland, Thailand, United Kingdom, and the United States. This current article, a sequel to the authors’ 1998, 1999 and 2000 marine pharmacology reviews, classifies 106 marine chemicals derived from a diverse group of marine animals, algae, fungi and bacteria, on the basis of peer-reviewed preclinical pharmacology. Anthelmintic, antibacterial, anticoagulant, antifungal, antimalarial, antiplatelet, antiprotozoal, antituberculosis or antiviral activities were reported for 56 marine chemicals. An additional 19 marine compounds were shown to have significant effects on the cardiovascular, immune and nervous system as well as to possess anti-inflammatory and antidiabetic effects. Finally, 31 marine compounds were reported to act on a variety of molecular targets and thus may potentially contribute to several pharmacological classes. Thus, during 2001–2002 pharmacological research with marine chemicals continued to contribute potentially novel chemical leads for the ongoing global search for therapeutic agents for the treatment of multiple disease categories. PMID:15919242

Date Palm Tree (Phoenix dactylifera L.): Natural Products and Therapeutic Options

PubMed Central

Al-Alawi, Reem A.; Al-Mashiqri, Jawhara H.; Al-Nadabi, Jawaher S. M.; Al-Shihi, Badria I.; Baqi, Younis

2017-01-01

Many plants, including some of the commonly consumed herbs and spices in our daily food, can be safely and effectively used to prevent and/or treat some health concerns. For example, caffeine the active ingredient found in coffee beans (Coffea), shows biological activity in the treatment of the central nervous system (CNS) disorders, indole-3-carbinol, and 3,3′-diindolylmethane are both broccoli (Brassica oleracea) derived phytochemicals with potential anti-cancer activity, and resveratrol, isolated from grape (Vitis vinifera), is reported to extend lifespan and provide cardio-neuro-protective, anti-diabetic, and anti-cancer effects. Date palm fruits possess high nutritional and therapeutic value with significant antioxidant, antibacterial, antifungal, and anti-proliferative properties. This review focuses on the date fruit extracts and their benefits in individual health promoting conditions and highlights their applications as useful to the pharmaceutical and nutraceutical industries in the development of natural compound-based industrial products. PMID:28588600

Date Palm Tree (Phoenix dactylifera L.): Natural Products and Therapeutic Options.

PubMed

Al-Alawi, Reem A; Al-Mashiqri, Jawhara H; Al-Nadabi, Jawaher S M; Al-Shihi, Badria I; Baqi, Younis

2017-01-01

Many plants, including some of the commonly consumed herbs and spices in our daily food, can be safely and effectively used to prevent and/or treat some health concerns. For example, caffeine the active ingredient found in coffee beans ( Coffea ), shows biological activity in the treatment of the central nervous system (CNS) disorders, indole-3-carbinol, and 3,3'-diindolylmethane are both broccoli ( Brassica oleracea ) derived phytochemicals with potential anti-cancer activity, and resveratrol, isolated from grape ( Vitis vinifera ), is reported to extend lifespan and provide cardio-neuro-protective, anti-diabetic, and anti-cancer effects. Date palm fruits possess high nutritional and therapeutic value with significant antioxidant, antibacterial, antifungal, and anti-proliferative properties. This review focuses on the date fruit extracts and their benefits in individual health promoting conditions and highlights their applications as useful to the pharmaceutical and nutraceutical industries in the development of natural compound-based industrial products.

Antinociceptive, anti-inflammatory and antidiabetic effects of Bryophyllum pinnatum (Crassulaceae) leaf aqueous extract.

PubMed

Ojewole, John A O

2005-05-13

In order to scientifically appraise some of the ethnomedical uses of Bryophyllum pinnatum leaves, the present study was undertaken to investigate the antinociceptive, anti-inflammatory and antidiabetic properties of the plant's leaf aqueous extract in experimental animal models. The antinociceptive effect of the herb's leaf extract was evaluated by the 'hot-plate' and 'acetic acid' test models of pain in mice. The anti-inflammatory and antidiabetic effects of the plant's extract were investigated in rats, using fresh egg albumin-induced pedal (paw) oedema, and streptozotocin (STZ)-induced diabetes mellitus. Diclofenac (DIC, 100 mg/kg) and chlorpropamide (250 mg/kg) were used respectively as reference drugs for comparison. Bryophyllum pinnatum leaf aqueous extract (BPE, 25-800 mg/kg i.p.) produced significant (P<0.05-0.001) antinociceptive effects against thermally- and chemically-induced nociceptive pain stimuli in mice. The plant extract (BPE, 25-800 mg/kg p.o. or i.p.) also significantly (P<0.05-0.001) inhibited fresh egg albumin-induced acute inflammation and caused significant (P<0.05-0.001) hypoglycaemia in rats. The results of this experimental animal study suggest that Bryophyllum pinnatum leaf aqueous extract possesses antinociceptive, anti-inflammatory and hypoglycaemic properties. The different flavonoids, polyphenols, triterpenoids and other chemical constituents of the herb are speculated to account for the observed antinociceptive, anti-inflammatory and antidiabetic properties of the plant.

Amarogentin, a secoiridoid glycoside, abrogates platelet activation through PLC γ 2-PKC and MAPK pathways.

PubMed

Yen, Ting-Lin; Lu, Wan-Jung; Lien, Li-Ming; Thomas, Philip Aloysius; Lee, Tzu-Yin; Chiu, Hou-Chang; Sheu, Joen-Rong; Lin, Kuan-Hung

2014-01-01

Amarogentin, an active principle of Gentiana lutea, possess antitumorigenic, antidiabetic, and antioxidative properties. Activation of platelets is associated with intravascular thrombosis and cardiovascular diseases. The present study examined the effects of amarogentin on platelet activation. Amarogentin treatment (15~60  μM) inhibited platelet aggregation induced by collagen, but not thrombin, arachidonic acid, and U46619. Amarogentin inhibited collagen-induced phosphorylation of phospholipase C (PLC) γ2, protein kinase C (PKC), and mitogen-activated protein kinases (MAPKs). It also inhibits in vivo thrombus formation in mice. In addition, neither the guanylate cyclase inhibitor ODQ nor the adenylate cyclase inhibitor SQ22536 affected the amarogentin-mediated inhibition of platelet aggregation, which suggests that amarogentin does not regulate the levels of cyclic AMP and cyclic GMP. In conclusion, amarogentin prevents platelet activation through the inhibition of PLC γ2-PKC cascade and MAPK pathway. Our findings suggest that amarogentin may offer therapeutic potential for preventing or treating thromboembolic disorders.

Amarogentin, a Secoiridoid Glycoside, Abrogates Platelet Activation through PLCγ2-PKC and MAPK Pathways

PubMed Central

Yen, Ting-Lin; Lu, Wan-Jung; Lien, Li-Ming; Thomas, Philip Aloysius; Lee, Tzu-Yin; Chiu, Hou-Chang; Sheu, Joen-Rong

2014-01-01

Amarogentin, an active principle of Gentiana lutea, possess antitumorigenic, antidiabetic, and antioxidative properties. Activation of platelets is associated with intravascular thrombosis and cardiovascular diseases. The present study examined the effects of amarogentin on platelet activation. Amarogentin treatment (15~60 μM) inhibited platelet aggregation induced by collagen, but not thrombin, arachidonic acid, and U46619. Amarogentin inhibited collagen-induced phosphorylation of phospholipase C (PLC)γ2, protein kinase C (PKC), and mitogen-activated protein kinases (MAPKs). It also inhibits in vivo thrombus formation in mice. In addition, neither the guanylate cyclase inhibitor ODQ nor the adenylate cyclase inhibitor SQ22536 affected the amarogentin-mediated inhibition of platelet aggregation, which suggests that amarogentin does not regulate the levels of cyclic AMP and cyclic GMP. In conclusion, amarogentin prevents platelet activation through the inhibition of PLCγ2-PKC cascade and MAPK pathway. Our findings suggest that amarogentin may offer therapeutic potential for preventing or treating thromboembolic disorders. PMID:24868545

Comparison of antioxidant, anticholinesterase, and antidiabetic activities of three curcuminoids isolated from Curcuma longa L.

PubMed

Kalaycıoğlu, Zeynep; Gazioğlu, Işıl; Erim, F Bedia

2017-12-01

Antioxidant, anticholinesterase and antidiabetic activities of three curcuminoids isolated from the Curcuma longa were simultaneously tested and compared in this study. The highest antioxidant power was detected for curcumin with the applied methods. The drug potentials of curcuminoids for Alzheimer's disease were controlled. Bisdemethoxycurcumin (BDMC) showed substantial inhibitory activity. The activity of demethoxycurcumin (DMC) followed BDMC, whereas curcumin showed very little acetylcholinesterase inhibition activity. Antidiabetic activity of curcuminoids was evaluated by their α-glucosidase inhibitory activities. All curcuminoids show activities with decreasing order as BDMC > curcumin > DMC. The significant activities of BDMC compared to its isomers and examination of chemical structures of isomers might be a starting point in designing new drugs for Alzheimer's and Diabetes Mellitus.

Metformin - a Future Therapy for Neurodegenerative Diseases : Theme: Drug Discovery, Development and Delivery in Alzheimer's Disease Guest Editor: Davide Brambilla.

PubMed

Markowicz-Piasecka, Magdalena; Sikora, Joanna; Szydłowska, Aleksandra; Skupień, Agata; Mikiciuk-Olasik, Elżbieta; Huttunen, Kristiina M

2017-12-01

Type 2 diabetes mellitus (T2DM) is a complex, chronic and progressive metabolic disease, which is characterized by relative insulin deficiency, insulin resistance, and high glucose levels in blood. Esteemed published articles and epidemiological data exhibit an increased risk of developing Alzheimer's disease (AD) in diabetic pateints. Metformin is the most frequently used oral anti-diabetic drug, which apart from hypoglycaemic activity, improves serum lipid profiles, positively influences the process of haemostasis, and possesses anti-inflammatory properties. Recently, scientists have put their efforts in establishing metformin's role in the treatment of neurodegenerative diseases, such as AD, amnestic mild cognitive impairment and Parkinson's disease. Results of several clinical studies confirm that long term use of metformin in diabetic patients contributes to better cognitive function, compared to participants using other anti-diabetic drugs. The exact mechanism of metformin's advantageous activity in AD is not fully understood, but scientists claim that activation of AMPK-dependent pathways in human neural stem cells might be responsible for the neuroprotective activity of metformin. Metformin was also found to markedly decease Beta-secretase 1 (BACE1) protein expression and activity in cell culture models and in vivo, thereby reducing BACE1 cleavage products and the production of Aβ (β-amyloid). Furthermore, there is also some evidence that metformin decreases the activity of acetylcholinesterase (AChE), which is responsible for the degradation of acetylcholine (Ach), a neurotransmitter involved in the process of learning and memory. In regard to the beneficial effects of metformin, its anti-inflammatory and anti-oxidative properties cannot be omitted. Numerous in vitro and in vivo studies have confirmed that metformin ameliorates oxidative damage.

Characterization of a Novel Polysaccharide-Iron(III) Complex and Its Anti-Anemia and Nonspecific Immune Regulating Activities.

PubMed

Zhang, Yun; Ma, Fanyi; Zhu, Jinhua; Du, Zuliang; Zhao, Ying-Yong; Liu, Xiuhua

2017-01-01

Dioscorea opposita Thunb is the famous food and traditional medicine in China and it was rich in polysaccharides. Polysaccharides of Dioscorea Opposita Thunb possess immunoregulatory activity, free radical scavenging activity and anti-diabetic activity. A novel polysaccharide- iron(III) complex (CYPIC) was synthesized by using crude polysaccharide extracted from Dioscorea opposita Thunb. The component, structure, morphology and molecular weights of CYPIC were analysed, and the anti-anemia, acute toxicity and nonspecific immune regulating activities of CYPIC were assayed. The results showed that CYPIC could increase red blood cell count (RBC), hemoglobin (Hb), hematocrit (HCT), thymus and spleen index of mice with iron deficiency anemia (IDA). Although the structure and deeper mechanisms of CYPIC should be further studied, CYPIC has the potential to be used as an iron supplement for the treatment of iron deficiency anemia. The large scale industrial production was suggested due to the simple preparation processing of CYPIC. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Antidiabetic and Beta Cell-Protection Activities of Purple Corn Anthocyanins

PubMed Central

Hong, Su Hee; Heo, Jee-In; Kim, Jeong-Hyeon; Kwon, Sang-Oh; Yeo, Kyung-Mok; Bakowska-Barczak, Anna M.; Kolodziejczyk, Paul; Ryu, Ok-Hyun; Choi, Moon-Ki; Kang, Young-Hee; Lim, Soon Sung; Suh, Hong-Won; Huh, Sung-Oh; Lee, Jae-Yong

2013-01-01

Antidiabetic and beta cell-protection activities of purple corn anthocyanins (PCA) were examined in pancreatic beta cell culture and db/db mice. Only PCA among several plant anthocyanins and polyphenols showed insulin secretion activity in culture of HIT-T15 cells. PCA had excellent antihyperglycemic activity (in terms of blood glucose level and OGTT) and HbA1c-decreasing activity when compared with glimepiride, a sulfonylurea in db/db mice. In addition, PCA showed efficient protection activity of pancreatic beta cell from cell death in HIT-T15 cell culture and db/db mice. The result showed that PCA had antidiabetic and beta cell-protection activities in pancreatic beta cell culture and db/db mice. PMID:24244813

Synthesis, Characterisation, Molecular Docking, Anti-microbial and Anti-diabetic Screening of Substituted 4-indolylphenyl-6-arylpyrimidine-2-imine Derivatives.

PubMed

Ramya, Veerasamy; Vembu, Santhirakasu; Ariharasivakumar, Ganesan; Gopalakrishnan, Manathusamy

2017-09-01

The purpose of the research is to synthesise a novel series of (E)-2-(4-(1H-indol-3-yl)-6-p-substituted phenylpyrimidin-2-yl)dimethylguanidine derivatives since 3-(1H-indol-3-yl)-1-p-substituted phenylprop-2-en-1-one and evaluate their molecular docking studies, antimicrobial, and anti-diabetic activities. Among all the synthesized compounds ( 11a-g ), compound 11a exhibits excellent CDOCKER energy (-11.36 kcal/mol). The entire compounds ( 11a-g ) confirm very good antimicrobial activity towards the tested microorganisms. In the in vitro anti-diabetic studies, compounds (11a, 11c, and 11g) confirm higher alpha-amylase and alpha-glucosidase inhibition activity. In the in vivo anti-diabetic activities, the synthesized compounds (11a-g) (10 mg/kg, p.o.) investigated by the streptozotocin (60 mg/kg, ip) -nicotinamide (120 mg/kg, p.o.) - induced model in adult male albino Wistar rat and these derivatives show considerable fasting blood glucose level when compared to metformin hydrochloride a potent and well-known anti-diabetic drug as a reference. © Georg Thieme Verlag KG Stuttgart · New York.

Chlorogenic Acid and Rutin Play a Major Role in the In Vivo Anti-Diabetic Activity of Morus alba Leaf Extract on Type II Diabetic Rats

PubMed Central

Hunyadi, Attila; Martins, Ana; Hsieh, Tusty-Jiuan; Seres, Adrienn; Zupkó, István

2012-01-01

The leaves of the white mulberry tree (Morus alba L.) are used worldwide in traditional medicine as anti-diabetics. Various constituents of mulberry leaves, such as iminosugars (i.e. 1-deoxynojirimicin), flavonoids and related compounds, polysaccharides, glycopeptides and ecdysteroids, have been reported to exert anti-diabetic activity, but knowledge about their contribution to the overall activity is limited. The objective of the present work was to determine the in vivo anti-diabetic activity of an extract of mulberry leaves (MA), and to examine to what extent three major constituents, chlorogenic acid, rutin and isoquercitrin, might contribute to the observed activity. Quantities of the three constituents of interest in the extract were determined by using HPLC-DAD. Activity was determined by using a type II diabetic rat model. After 11 days of per os administration of 250 or 750 mg/kg of MA or the corresponding amounts of each individual compound, a dose dependent decrease of non-fasting blood glucose levels were found for MA, chlorogenic acid and rutin, but not for isoquercitrin. Based on our results, chlorogenic acid and rutin might account for as much as half the observed anti-diabetic activity of MA, hence they can be considered as excellent markers for the quality control of mulberry products. PMID:23185641

Peroxisome Proliferator-Activated Receptor γ (PPARγ) and Ligand Choreography: Newcomers Take the Stage.

PubMed

Garcia-Vallvé, Santiago; Guasch, Laura; Tomas-Hernández, Sarah; del Bas, Josep Maria; Ollendorff, Vincent; Arola, Lluís; Pujadas, Gerard; Mulero, Miquel

2015-07-23

Thiazolidinediones (TZDs), such as rosiglitazone and pioglitazone, are peroxisome proliferator-activated receptor γ (PPARγ) full agonists that have been widely used in the treatment of type 2 diabetes mellitus. Despite the demonstrated beneficial effect of reducing glucose levels in the plasma, TZDs also induce several adverse effects. Consequently, the search for new compounds with potent antidiabetic effects but fewer undesired effects is an active field of research. Interestingly, the novel proposed mechanisms for the antidiabetic activity of PPARγ agonists, consisting of PPARγ Ser273 phosphorylation inhibition, ligand and receptor mutual dynamics, and the presence of an alternate binding site, have recently changed the view regarding the optimal characteristics for the screening of novel PPARγ ligands. Furthermore, transcriptional genomics could bring essential information about the genome-wide effects of PPARγ ligands. Consequently, facing the new mechanistic scenario proposed for these compounds is essential for resolving the paradoxes among their agonistic function, antidiabetic activities, and side effects and should allow the rational development of better and safer PPARγ-mediated antidiabetic drugs.

Heterocyclic Compounds: Effective α-Amylase and α-Glucosidase Inhibitors.

PubMed

Saeedi, Mina; Hadjiakhondi, Abbas; Nabavi, Seyed Mohammad; Manayi, Azadeh

2017-01-01

Diabetes Mellitus (DM) is a metabolic disease characterized by high blood sugar levels. Recently, it has emerged as an important and global health problem with long-term complications and high economic burden. α-Amylase (α-Amy) and α-glucosidase (α-Gls) are two enzymes which are involved in the hydrolysis of starch into sugars and disaccharides leading to the increase of blood glucose level. Hence, inhibition of α-amylase and α-glucosidase plays key role in the treatment of type 2 diabetes. Heterocyclic compounds -both synthetic and naturally occurring derivatives- possess efficient biological properties. At this juncture, they have demonstrated potent inhibitory activity against α-Amy and α-Gls and were found to be versatile tools for the development of novel anti-diabetic agents.

Enzymes inhibition and antidiabetic effect of isolated constituents from Dillenia indica.

PubMed

Kumar, Sunil; Kumar, Vipin; Prakash, Om

2013-01-01

This study was designed to investigate the enzyme inhibitory and antidiabetic activity for the constituents isolated from Dillenia indica. The leaves of D. indica were extracted with methanol and subjected to fractionation and chromatographic separation, which led to the isolation of seven compounds: betulinic acid (1), n-heptacosan-7-one (2), n-nonatriacontan-18-one (3), quercetin (4), β sitosterol (5), stigmasterol (6), and stigmasteryl palmitate (7). Among these isolates, compounds 1, 4, 5, and 6 were evaluated for in vitro enzyme inhibition and compounds 4, 5 and 6 were evaluated for antidiabetic activity in streptozotocin-nicotinamide induced diabetic mice. Compounds 1, 4, 5, and 6 showed 47.4, 55.2, 48.8, and 44.3% α -amylase inhibition, respectively, and 52.2, 78.2, 52.5, and 34.2% α -glucosidase inhibition, respectively, at the dose of 50 µg/kg. Compounds 4, 5 and 6 also showed significant (∗P < 0.05) antidiabetic activity in streptozotocin-nicotinamide induced diabetic mice at the dose of 10 mg/kg. These results provide evidence that Dillenia indica might be a potential source of antidiabetic agents.

Marine Organisms with Anti-Diabetes Properties

PubMed Central

Lauritano, Chiara; Ianora, Adrianna

2016-01-01

Diabetes is a chronic degenerative metabolic disease with high morbidity and mortality rates caused by its complications. In recent years, there has been a growing interest in looking for new bioactive compounds to treat this disease, including metabolites of marine origin. Several aquatic organisms have been screened to evaluate their possible anti-diabetes activities, such as bacteria, microalgae, macroalgae, seagrasses, sponges, corals, sea anemones, fish, salmon skin, a shark fusion protein as well as fish and shellfish wastes. Both in vitro and in vivo screenings have been used to test anti-hyperglycemic and anti-diabetic activities of marine organisms. This review summarizes recent discoveries in anti-diabetes properties of several marine organisms as well as marine wastes, existing patents and possible future research directions in this field. PMID:27916864

Phytochemicals and antidiabetic activity of Eusideroxylon zwageri stem bark collected from East Kalimantan, Indonesia

NASA Astrophysics Data System (ADS)

Kusuma, I. W.; Rahmini; Ramadhan, R.; Rahmawati, N.; Suwasono, R. A.; Sari, NM

2018-04-01

Eusideroxylon zwagery (Lauraceae), a tropical tree species known as ulin or borneo iron wood and traditionally used for the treatment of diabetes in the Ethnic of Kutai. Plant extract was prepared by maceration using ethanol. The plant extract was evaluated its DPPH and superoxide radicals scavenging activity, the inhibition on α-glucosidase and α-amylase activity as antidiabetic potential and the analysis of the total phenolic, total flavonoids and proanthocyanidin contents. The ethanolic extract of the stem bark was 8.62% on the dry weight basis. The IC50 values of antioxidant activity of the extract in DPPH and superoxide radical scavenging mechanisms were 44.90 µg/ml and 30.47 µg/ml. In antidiabetic assay, the E. zwageri stem bark extract showed IC50 value 58.45µg/ml in ɑ-glucosidase inhibition, and 9.04 µg/ml in ɑ-amylase inhibition. Quercetin, an antidiabetic activity-having flavonoid, displayed IC50 values 2.00 µg/ml and 4.04 µg/ml in ɑ-glucosidase and ɑ-amylase inhibitory assays. In phytochemical assay, the extract had 31.28 GAE/g extract (mg), 30.48 CE/g extract (mg) and 183.3 PE/g extract (mg) for the total phenolic, total flavonoid and total proanthocyanidin contents. The limited reports of E. zwageri indicated the needs to search the active compounds from plant as potential antidiabetic agents by considering plant conservation status.

Effects of butanol fraction of Ziziphus mucronata root ethanol extract on glucose homeostasis, serum insulin and other diabetes-related parameters in a murine model for type 2 diabetes.

PubMed

Ibrahim, Mohammed Auwal; Islam, Md Shahidul

2017-12-01

Ziziphus mucronata Willd (Rhamnaceae) is currently used in Nigerian traditional treatment of diabetes mellitus. However, detailed information on the antidiabetic potential of the plant parts is presently unknown. The present study investigated the antidiabetic effects of the butanol fraction of Z. mucronata root (ZMBF) in a type 2 diabetes (T2D) model of rats. T2D was induced in rats by feeding a 10% fructose solution ad libitum for two weeks followed by an intraperitoneal injection of streptozotocin (40 mg/kg bw) and the animals were orally treated with ZMBF 150 or 300 mg/kg bw for five days a week for four weeks. Food and fluid intake, body weight changes and blood glucose levels were monitored during the experiment while other blood and organ specific diabetes-associated parameters were measured at the end of the experiment. After four-week treatment, significantly (p < 0.05) lower blood glucose (19.24 vs 28.96 mmol/L), improved glucose tolerance ability (21.26 vs 28.56 mmol/L), higher serum insulin (131.37 vs 64.20 pmol/L) and liver glycogen (2.40 vs 1.54 mg/g tissue) were observed in the 300 mg/kg ZMBF ingested group compared with the diabetic control group. However, food and fluid intake, body weight gain, HOMA-β, HOMA-IR, serum fructosamine level, hepatic and renal function tests were not significantly (p > 0.05) affected by the treatment of ZMBF. Results of this study suggest that ZMBF treatment, at 300 mg/kg bw, possess antidiabetic activity, but could not ameliorate some diabetes-related parameters in type 2 diabetic rats.

Oral administration of Dictyostelium differentiation-inducing factor 1 lowers blood glucose levels in streptozotocin-induced diabetic rats.

PubMed

Kawaharada, Ritsuko; Nakamura, Akio; Takahashi, Katsunori; Kikuchi, Haruhisa; Oshima, Yoshiteru; Kubohara, Yuzuru

2016-06-15

Differentiation-inducing factor 1 (DIF-1), originally discovered in the cellular slime mold Dictyostelium discoideum, and its derivatives possess pharmacological activities, such as the promotion of glucose uptake in non-transformed mammalian cells in vitro. Accordingly, DIFs are considered promising lead candidates for novel anti-diabetic drugs. The aim of this study was to assess the anti-diabetic and toxic effects of DIF-1 in mouse 3T3-L1 fibroblast cells in vitro and in diabetic rats in vivo. Main methods We investigated the in vitro effects of DIF-1 and DIF-1(3M), a derivative of DIF-1, on glucose metabolism in 3T3-L1 cells by using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS). We also examined the effects of DIF-1 on blood glucose levels in streptozotocin (STZ)-induced rats. CE-TOF-MS revealed that 20μM DIF-1 and 20μM DIF-1(3M) promoted glucose uptake and metabolism in 3T3-L1 cells. Oral administration of DIF-1 (30mg/kg) significantly lowered basal blood glucose levels in STZ-treated rats and promoted a decrease in blood glucose levels after oral glucose loading (2.5g/kg) in the rats. In addition, daily oral administration of DIF-1 (30mg/kg/day) for 1wk significantly lowered the blood glucose levels in STZ-treated rats but did not affect their body weight and caused only minor alterations in the levels of other blood analytes. These results indicate that DIF-1 may be a good lead compound for the development of anti-diabetic drugs. Copyright © 2016 Elsevier Inc. All rights reserved.

Mushroom Polysaccharides: Chemistry and Antiobesity, Antidiabetes, Anticancer, and Antibiotic Properties in Cells, Rodents, and Humans.

PubMed

Friedman, Mendel

2016-11-29

More than 2000 species of edible and/or medicinal mushrooms have been identified to date, many of which are widely consumed, stimulating much research on their health-promoting properties. These properties are associated with bioactive compounds produced by the mushrooms, including polysaccharides. Although β-glucans (homopolysaccharides) are believed to be the major bioactive polysaccharides of mushrooms, other types of mushroom polysaccharides (heteropolysaccharides) also possess biological properties. Here we survey the chemistry of such health-promoting polysaccharides and their reported antiobesity and antidiabetic properties as well as selected anticarcinogenic, antimicrobial, and antiviral effects that demonstrate their multiple health-promoting potential. The associated antioxidative, anti-inflammatory, and immunomodulating activities in fat cells, rodents, and humans are also discussed. The mechanisms of action involve the gut microbiota, meaning the polysaccharides act as prebiotics in the digestive system. Also covered here are the nutritional, functional food, clinical, and epidemiological studies designed to assess the health-promoting properties of polysaccharides, individually and as blended mixtures, against obesity, diabetes, cancer, and infectious diseases, and suggestions for further research. The collated information and suggested research needs might guide further studies needed for a better understanding of the health-promoting properties of mushroom polysaccharides and enhance their use to help prevent and treat human chronic diseases.

Mushroom Polysaccharides: Chemistry and Antiobesity, Antidiabetes, Anticancer, and Antibiotic Properties in Cells, Rodents, and Humans

PubMed Central

Friedman, Mendel

2016-01-01

More than 2000 species of edible and/or medicinal mushrooms have been identified to date, many of which are widely consumed, stimulating much research on their health-promoting properties. These properties are associated with bioactive compounds produced by the mushrooms, including polysaccharides. Although β-glucans (homopolysaccharides) are believed to be the major bioactive polysaccharides of mushrooms, other types of mushroom polysaccharides (heteropolysaccharides) also possess biological properties. Here we survey the chemistry of such health-promoting polysaccharides and their reported antiobesity and antidiabetic properties as well as selected anticarcinogenic, antimicrobial, and antiviral effects that demonstrate their multiple health-promoting potential. The associated antioxidative, anti-inflammatory, and immunomodulating activities in fat cells, rodents, and humans are also discussed. The mechanisms of action involve the gut microbiota, meaning the polysaccharides act as prebiotics in the digestive system. Also covered here are the nutritional, functional food, clinical, and epidemiological studies designed to assess the health-promoting properties of polysaccharides, individually and as blended mixtures, against obesity, diabetes, cancer, and infectious diseases, and suggestions for further research. The collated information and suggested research needs might guide further studies needed for a better understanding of the health-promoting properties of mushroom polysaccharides and enhance their use to help prevent and treat human chronic diseases. PMID:28231175

In silico-based combinatorial pharmacophore modelling and docking studies of GSK-3β and GK inhibitors of Hippophae.

PubMed

Middha, Sushil Kumar; Goyal, Arvind Kumar; Faizan, Syed Ahmed; Sanghamitra, Nethramurthy; Basistha, Bharat Chandra; Usha, Talambedu

2013-11-01

Type 2 diabetes is an inevitably progressive disease, with irreversible beta cell failure. Glycogen synthase kinase and Glukokinase, two important enzymes with diverse biological actions in carbohydrate metabolism, are promising targets for developing novel antidiabetic drugs. A combinatorial structure-based molecular docking and pharmacophore modelling study was performed with the compounds of Hippophae salicifolia and H. rhamnoides as inhibitors. Docking with Discovery Studio 3.5 revealed that two compounds from H. salicifolia, viz Lutein D and an analogue of Zeaxanthin, and two compounds from H. rhamnoides, viz Isorhamnetin-3-rhamnoside and Isorhamnetin-7-glucoside, bind significantly to the GSK-3 beta receptor and play a role in its inhibition; whereas in the case of Glucokinase, only one compound from both the plants, i.e. vitamin C, had good binding characteristics capable of activation. The results help to understand the type of interactions that occur between the ligands and the receptors. Toxicity predictions revealed that none of the compounds had hepatotoxic effects and had good absorption as well as solubility characteristics. The compounds did not possess plasma protein-binding, crossing blood-brain barrier ability. Further, in vivo and in vitro studies need to be performed to prove that these compounds can be used effectively as antidiabetic drugs.

Comparative Study of Antidiabetic Activity and Oxidative Stress Induced by Zinc Oxide Nanoparticles and Zinc Sulfate in Diabetic Rats.

PubMed

Nazarizadeh, Ali; Asri-Rezaie, Siamak

2016-08-01

In the current study, antidiabetic activity and toxic effects of zinc oxide nanoparticles (ZnO) were investigated in diabetic rats compared to zinc sulfate (ZnSO4) with particular emphasis on oxidative stress parameters. One hundred and twenty male Wistar rats were divided into two healthy and diabetic groups, randomly. Each major group was further subdivided into five subgroups and then orally supplemented with various doses of ZnO (1, 3, and 10 mg/kg) and ZnSO4 (30 mg/kg) for 56 consecutive days. ZnO showed greater antidiabetic activity compared to ZnSO4 evidenced by improved glucose disposal, insulin levels, and zinc status. The altered activities of erythrocyte antioxidant enzymes as well as raised levels of lipid peroxidation and a marked reduction of total antioxidant capacity were observed in rats receiving ZnO. ZnO nanoparticles acted as a potent antidiabetic agent, however, severely elicited oxidative stress particularly at higher doses.

Inhibitory effects of Piper betle on production of allergic mediators by bone marrow-derived mast cells and lung epithelial cells.

PubMed

Wirotesangthong, Mali; Inagaki, Naoki; Tanaka, Hiroyuki; Thanakijcharoenpath, Witchuda; Nagai, Hiroichi

2008-03-01

The leaves of the Piper betle Linn. (Piperaceae) are used in traditional medicine and possess anti-oxidant, anti-bacterial, anti-fungal, anti-diabetic and radioprotective activities. However, little is known about their anti-allergic activity. Therefore, the effects of P. betle ethanolic extract (PE) on the production of histamine and granulocyte macrophage-colony-stimulating factor (GM-CSF) by murine bone marrow mast cells (BMMCs) and on the secretion of eotaxin and IL-8 by the human lung epithelial cell line, BEAS-2B, were investigated in vitro. PE significantly decreased histamine and GM-CSF produced by an IgE-mediated hypersensitive reaction, and inhibited eotaxin and IL-8 secretion in a TNF-alpha and IL-4-induced allergic reaction. The results suggest that P. betle may offer a new therapeutic approach for the control of allergic diseases through inhibition of production of allergic mediators.

Metabolomic Investigation of Rat Serum Following Oral Administration of the Willow Bracket Medicinal Mushroom, Phellinus igniarius (Agaricomycetes), by UPLC-HDMS.

PubMed

Dong, Yu; He, Ying; Yu, Zhongming; Zhang, Yang; Wang, Nani; Shou, Dan; Li, Changyu

2016-01-01

The medicinal willow bracket mushroom, Phellinus igniarius, is a species that has been reported to possess antibacterial, antioxidative, antitumor, antidiabetic, and antihyperlipidemia activities. The aim of this study was to elucidate the changes in endogenous metabolites after oral administration of a decoction of Ph. Igniarius. Ultraperformance liquid chromatography (UPLC)/electrospray ionization synapt high-definition mass spectrometry (ESI-HDMS) combined with pattern recognition approaches, including principal component analysis and orthogonal partial least squares discriminant analysis, were integrated to discover differentiating metabolites. The current metabolomics approach identified 16 ions (5 in the negative mode, 11 in the positive mode) as "differentiating metabolites". The results illustrated that Ph. Igniarius is likely to increase the biosynthesis and secretion of bile acids that provide hypolipidemic activity and showed that robust UPLC/ESI-HDMS techniques are promising for profiling analysis of medicinal mushroom metabolites.

Levels of Tannins and Flavonoids in Medicinal Plants: Evaluating Bioprospecting Strategies

PubMed Central

Siqueira, Clarissa Fernanda de Queiroz; Cabral, Daniela Lyra Vasconcelos; Peixoto Sobrinho, Tadeu José da Silva; de Amorim, Elba Lúcia Cavalcanti; de Melo, Joabe Gomes; Araújo, Thiago Antônio de Sousa; de Albuquerque, Ulysses Paulino

2012-01-01

There are several species of plants used by traditional communities in the Brazilian semiarid. An approach used in the search for natural substances that possess therapeutic value is ethnobotany or ethnopharmacology. Active substances that have phenolic groups in their structure have great pharmacological potential. To establish a quantitative relationship between the species popularly considered to be antimicrobial, antidiabetic, and antidiarrheal, the contents of tannins and flavonoids were determined. The plant selection was based on an ethnobotanical survey conducted in a community located in the municipality of Altinho, northeastern Brazil. For determination of tannin content was utilized the technique of radial diffusion, and for flavonoids, an assay based on the complexation of aluminum chloride. The group of plants with antimicrobial indications showed a higher content of tannins compared to the control groups. The results evidence suggests a possible relationship between these compounds and the observed activity. PMID:21969842

Antidiabetic activities of aqueous ethanol and n-butanol fraction of Moringa stenopetala leaves in streptozotocin-induced diabetic rats.

PubMed

Toma, Alemayehu; Makonnen, Eyasu; Mekonnen, Yelamtsehay; Debella, Asfaw; Adisakwattana, Sirichai

2015-07-18

Moringa stenopetala has been used in traditional health systems to treat diabetes mellitus. The aim of this study was to investigate the antidiabetic activity of aqueous ethanol and n-butanol fraction of Moringa stenopetala leaves in streptozotocin (STZ) induced diabetic rats. The aqueous ethanol extract and n-butanol fraction of Moringa stenopetala leaves hydroalcoholic (500 mg/kg body weight) and metformin (150 mg/kg body weight) were administered to diabetic rats. Blood glucose, lipid profiles, liver and kidney function were examined after 14 days of experiment. Histopathological profile of the pancreas was also observed in diabetic rats at the end of study. An oral sucrose challenge test was also carried out to assess the post prandial effect of the extract. Oral administration of the aqueous ethanol and n-butanol extracts of Moringa stenopetala leaves (500 mg/kg body weight) and metformin (150 mg/kg) significantly reduced blood glucose level (P<0.05), improved serum lipid profiles, liver enzymes and kidney functions in diabetic rats after 14 days. The extracts also improved damage of islet of Langerhan's in diabetic rats. The plant material reduced the post-prandial glucose level (P<0.001) at the dose of 750 mg/kg. These findings revealed that both the aqueous ethanol and n-butanol extracts of Moringa stenopetala leaves possess antihyperglycemic and antihyperlipidemic properties, and alleviate STZ-induced pancreatic damage in diabetic rats. The beneficial effects of plant material in inhibition of diabetes-induced complications are being investigated.

Marine Algae As A Prospective Source For Antidiabetic Compounds - A Brief Review.

PubMed

Unnikrishnan, Pulikkaparambil Sasidharan; Jayasri, Mangalam Achuthananda

2018-01-01

Diabetes Mellitus (DM) is a metabolic disorder characterized by chronic hyperglycaemia, which is attributed to several life threatening complications including atherosclerosis, nephropathy, and retinopathy. The current therapies available for the management of DM mainly include oral antidiabetic drugs and insulin injections. However, continuous use of synthetic drugs provides lower healing with many side effects. Therefore, there is an urge for safe and efficient antidiabetic drugs for the management of DM. In the continuing search for effective antidiabetic drugs, marine algae (seaweeds) remains as a promising source with potent bioactivity. It is anticipated that the isolation, characterization, and pharmacological study of unexplored marine algae can be useful in the discovery of novel antidiabetic compounds with high biomedical value. Among marine algae, brown and red algae are reported to exhibit antidiabetic activity. Majority of the investigations on algal derived compounds controls the blood glucose levels through the inhbition of carbohydrate hydroloyzing enzymes and protein tyrosine phosphatase 1B enzymes, insulin sensitization, glucose uptake effect and other protective effects against diabetic complications. Based on the above perspective this review provides; profiles for various marine algae posessing antidiabetic activity. This study also highlights the therapeutic potential of compounds isolated from marine algae for the effective management of diabetes and its associated complications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Enzymes Inhibition and Antidiabetic Effect of Isolated Constituents from Dillenia indica

PubMed Central

Kumar, Sunil; Kumar, Vipin; Prakash, Om

2013-01-01

Aims. This study was designed to investigate the enzyme inhibitory and antidiabetic activity for the constituents isolated from Dillenia indica. Methods. The leaves of D. indica were extracted with methanol and subjected to fractionation and chromatographic separation, which led to the isolation of seven compounds: betulinic acid (1), n-heptacosan-7-one (2), n-nonatriacontan-18-one (3), quercetin (4), β sitosterol (5), stigmasterol (6), and stigmasteryl palmitate (7). Among these isolates, compounds 1, 4, 5, and 6 were evaluated for in vitro enzyme inhibition and compounds 4, 5 and 6 were evaluated for antidiabetic activity in streptozotocin-nicotinamide induced diabetic mice. Results. Compounds 1, 4, 5, and 6 showed 47.4, 55.2, 48.8, and 44.3% α-amylase inhibition, respectively, and 52.2, 78.2, 52.5, and 34.2% α-glucosidase inhibition, respectively, at the dose of 50 µg/kg. Compounds 4, 5 and 6 also showed significant (∗P < 0.05) antidiabetic activity in streptozotocin-nicotinamide induced diabetic mice at the dose of 10 mg/kg. Conclusion. These results provide evidence that Dillenia indica might be a potential source of antidiabetic agents. PMID:24307994

Erythritol reduces small intestinal glucose absorption, increases muscle glucose uptake, improves glucose metabolic enzymes activities and increases expression of Glut-4 and IRS-1 in type 2 diabetic rats.

PubMed

Chukwuma, Chika Ifeanyi; Mopuri, Ramgopal; Nagiah, Savania; Chuturgoon, Anil Amichund; Islam, Md Shahidul

2017-08-02

Studies have reported that erythritol, a low or non-glycemic sugar alcohol possesses anti-hyperglycemic and anti-diabetic potentials but the underlying mode of actions is not clear. This study investigated the underlying mode of actions behind the anti-hyperglycemic and anti-diabetic potentials of erythritol using different experimental models (experiment 1, 2 and 3). Experiment 1 examined the effects of increasing concentrations (2.5-20%) of erythritol on glucose absorption and uptake in isolated rat jejunum and psoas muscle, respectively. Experiments 2 and 3 examined the effects of a single oral dose of erythritol (1 g/kg bw) on intestinal glucose absorption, gastric emptying and postprandial blood glucose increase, glucose tolerance, serum insulin level, muscle/liver hexokinase and liver glucose-6 phosphatase activities, liver and muscle glycogen contents and mRNA and protein expression of muscle Glut-4 and IRS-1 in normal and type 2 diabetic animals. Experiment 1 revealed that erythritol dose dependently enhanced muscle glucose ex vivo. Experiment 2 demonstrated that erythritol feeding delayed gastric emptying and reduced small intestinal glucose absorption as well as postprandial blood glucose rise, especially in diabetic animals. Experiment 3 showed that erythritol feeding improved glucose tolerance, muscle/liver hexokinase and liver glucose-6 phosphatase activities, glycogen storage and also modulated expression of muscle Glut-4 and IRS-1 in diabetic animals. Data suggest that erythritol may exert anti-hyperglycemic effects not only via reducing small intestinal glucose absorption, but also by increasing muscle glucose uptake, improving glucose metabolic enzymes activity and modulating muscle Glut-4 and IRS-1 mRNA and protein expression. Hence, erythritol may be a useful dietary supplement for managing hyperglycemia, particularly for T2D.

The 21st century form of vitamin E--tocotrienol.

PubMed

Bardhan, Jayeeta; Chakraborty, Runu; Raychaudhuri, Utpal

2011-01-01

Vitamin E family constitutes of tocopherol and tocotrienol. Each form has several isomers: alpha,beta, gamma, delta, desmo and didesmo. Although tocopherol is known much earlier, tocotrienol has been discovered more recently.Tocotrienol has higher antioxidant potential than tocopherol. Research shows that tocotrienol can inhibit the induced oxidative damage to lipids and proteins. Cholesterol biosynthesis pathway requires HMG Co A reductase. Tocotrienol degrades HMG Co A reductase protein and in turn lowers cholesterol synthesis. Tocotrienol can reverse ischemia-reperfusion which mediates cardiac dysfunction and induces c-Src protein expression. Tocotrienol prevents oxytosis and offers protection against Alzheimer's disease, Parkinson's disease, Hungtington's disease. Tocotrienol exerts anticancer property through cell cycle arrest, induction of apoptosis, inhibition of angiogenesis; antitumor activity. Tocotrienol also possesses anti-inflammatory, antidiabetic, antiadipogenic and antiatherogenic effect.

Antidiabetic and Antioxidant Effects and Phytochemicals of Mulberry Fruit (Morus alba L.) Polyphenol Enhanced Extract

PubMed Central

Wang, Yihai; Xiang, Limin; Wang, Chunhua; Tang, Chao; He, Xiangjiu

2013-01-01

The antidiabetic and antioxidant activities of the ethyl acetate-soluble extract (MFE) of mulberry fruit (Morus alba L.) were investigated. In vitro, MFE showed potent α-glucosidase inhibitory activity and radical-scavenging activities against DPPH and superoxide anion radicals. In vivo, MFE could significantly decrease fasting blood glucose (FBG) and glycosylated serum protein (GSP), and increase antioxidant enzymatic activities (SOD, CAT, GSH-Px) in streptozotocin (STZ)-induced diabetic mice. Bioactivity-guided fractionation of the MFE led to the isolation of 25 phenolic compounds, and their structures were identified on the basis of MS and NMR data. All the 25 compounds were isolated from mulberry fruit for the first time. Also, the α-glucosidase inhibitory activity and antioxidant activity of the phenolics were evaluated. Potent α-glucosidase inhibitory and radical-scavenging activities of these phenolics suggested that they may be partially responsible for the antidiabetic and antioxidant activities of mulberry fruit. PMID:23936259

Antidiabetic and antioxidant effects and phytochemicals of mulberry fruit (Morus alba L.) polyphenol enhanced extract.

PubMed

Wang, Yihai; Xiang, Limin; Wang, Chunhua; Tang, Chao; He, Xiangjiu

2013-01-01

The antidiabetic and antioxidant activities of the ethyl acetate-soluble extract (MFE) of mulberry fruit (Morus alba L.) were investigated. In vitro, MFE showed potent α-glucosidase inhibitory activity and radical-scavenging activities against DPPH and superoxide anion radicals. In vivo, MFE could significantly decrease fasting blood glucose (FBG) and glycosylated serum protein (GSP), and increase antioxidant enzymatic activities (SOD, CAT, GSH-Px) in streptozotocin (STZ)-induced diabetic mice. Bioactivity-guided fractionation of the MFE led to the isolation of 25 phenolic compounds, and their structures were identified on the basis of MS and NMR data. All the 25 compounds were isolated from mulberry fruit for the first time. Also, the α-glucosidase inhibitory activity and antioxidant activity of the phenolics were evaluated. Potent α-glucosidase inhibitory and radical-scavenging activities of these phenolics suggested that they may be partially responsible for the antidiabetic and antioxidant activities of mulberry fruit.

Inhibitory effect of alliin from Allium sativum on the glycation of superoxide dismutase.

PubMed

Anwar, Shehwaz; Younus, Hina

2017-10-01

Inhibition of glycation is an important approach for alleviating diabetic complications. Alliin, the most abundant sulphur compound in garlic has been demonstrated to possess antidiabetic activity. However, there is no scientific evidence supporting its antiglycating activity. The objective of this study was to determine the inhibitory effect of alliin on glucose and methyglyoxal (MG)-induced glycation of an important antioxidant enzyme, superoxide dismutase (SOD). Glycation of SOD resulted in a decrease in enzyme activity, fragmentation/cross-linking, reduced cross-reactivity with anti-SOD antibodies, both tertiary and secondary structural changes, and formation of AGEs and fibrils. Alliin offered protection against glucose or MG induced glycation of SOD. The antiglycating potential of alliin appears to be comparable with that of quercetin which is reported to be a potent natural inhibitor of glycation. Alliin has a good antiglycating effect and hence is expected to have therapeutic potential in the prevention of glycation-mediated diabetic complications. Copyright © 2017 Elsevier B.V. All rights reserved.

Anti-Diabetic, Anti-Oxidant and Anti-Hyperlipidemic Activities of Flavonoids from Corn Silk on STZ-Induced Diabetic Mice.

PubMed

Zhang, Yan; Wu, Liying; Ma, Zhongsu; Cheng, Jia; Liu, Jingbo

2015-12-23

Corn silk is a well-known ingredient frequently used in traditional Chinese herbal medicines. This study was designed to evaluate the anti-diabetic, anti-oxidant and anti-hyperlipidemic activities of crude flavonoids extracted from corn silk (CSFs) on streptozotocin (STZ)-induced diabetic mice. The results revealed that treatment with 300 mg/kg or 500 mg/kg of CSFs significantly reduced the body weight loss, water consumption, and especially the blood glucose (BG) concentration of diabetic mice, which indicated their potential anti-diabetic activities. Serum total superoxide dismutase (SOD) and malondialdehyde (MDA) assays were also performed to evaluate the anti-oxidant effects. Besides, several serum lipid values including total cholesterol (TC), triacylglycerol (TG), low density lipoprotein cholesterol (LDL-C) were reduced and the high density lipoprotein cholesterol level (HDL-C) was increased. The anti-diabetic, anti-oxidant and anti-hyperlipidemic effect of the CSFs suggest a potential therapeutic treatment for diabetic conditions.

Updates on Managing Type 2 Diabetes Mellitus with Natural Products: Towards Antidiabetic Drug Development.

PubMed

Alam, Fahmida; Islam, Md Asiful; Kamal, M A; Gan, Siew Hua

2016-08-13

Over the years, natural products have shown success as antidiabetics in vitro, in vivo and in clinical trials. Because natural product-derived drugs are more affordable and effective with fewer side-effects compared to conventional therapies, pharmaceutical research is increasingly leaning towards the discovery of new antidiabetic drugs from natural products targeting pathways or components associated with type 2 diabetes mellitus (T2DM) pathophysiology. However, the drug discovery process is very lengthy and costly with significant challenges. Therefore, various techniques are currently being developed for the preclinical research phase of drug discovery with the aim of drug development with less time and efforts from natural products. In this review, we have provided an update on natural products including fruits, vegetables, spices, nuts, beverages and mushrooms with potential antidiabetic activities from in vivo, in vitro and clinical studies. Synergistic interactions between natural products and antidiabetic drugs; and potential antidiabetic active compounds from natural products are also documented to pave the way for combination treatment and new drug discovery, respectively. Additionally, a brief idea of the drug discovery process along with the challenges that arise during drug development from natural products and the methods to conquer those challenges are discussed to create a more convenient future drug discovery process.

Farmer to Pharmacist: Curcumin as an Anti-invasive and Antimetastatic Agent for the Treatment of Cancer

NASA Astrophysics Data System (ADS)

Bandyopadhyay, Debasish

2014-12-01

A huge number of compounds are widely distributed in nature and many of these possess medicinal/biological/pharmacological activity. Curcumin, a polyphenol derived from the rhizomes (underground stems) of Curcuma longa Linn (a member of the ginger family, commonly known as turmeric) is a culinary spice and therapeutic used in India for thousands of years to induce color and flavor in food as well as to treat a wide array of diseases. The origin of turmeric as spice and folklore medicine is so old that it is lost in legend. Curcumin has many beneficial pharmacological effects which includes, but are not limited with, antimicrobial, anti-inflammatory, antioxidant, antiviral, antiangiogenic, and antidiabetic activities. Most importantly curcumin possesses immense antitumorigenic effect. It prevents tumor invasion and metastasis in a number of animal models, including models of lung, liver, stomach, colon, breast, esophageal cancer etc. Invasion and metastasis are considered as one of the hallmarks in cancer biology. The pertinent recent applications of curcumin as anti-invasive and antimetastatic agent in in vitro and in vivo and ex vivo studies as well as associated molecular mechanisms have been discussed in this review. Curcumin has also demonstrated the ability to improve patient outcomes in clinical trials.

Farmer to pharmacist: curcumin as an anti-invasive and antimetastatic agent for the treatment of cancer1

PubMed Central

Bandyopadhyay, Debasish

2014-01-01

A huge number of compounds are widely distributed in nature and many of these possess medicinal/biological/pharmacological activity. Curcumin, a polyphenol derived from the rhizomes (underground stems) of Curcuma longa Linn (a member of the ginger family, commonly known as turmeric) is a culinary spice and therapeutic used in India for thousands of years to induce color and flavor in food as well as to treat a wide array of diseases. The origin of turmeric as spice and folklore medicine is so old that it is lost in legend. Curcumin has many beneficial pharmacological effects which includes, but are not limited with, antimicrobial, anti-inflammatory, antioxidant, antiviral, antiangiogenic, neurodegenerative diseases such as Alzheimer disease, and antidiabetic activities. Most importantly curcumin possesses immense antitumorigenic effect. It prevents tumor invasion and metastasis in a number of animal models, including models of lung, liver, stomach, colon, breast, esophageal cancer etc. Invasion and metastasis are considered as one of the hallmarks in cancer biology. The pertinent recent applications of curcumin as anti-invasive and antimetastatic agent in in vitro and in vivo and ex vivo studies as well as associated molecular mechanisms have been discussed in this review. Curcumin has also demonstrated the ability to improve patient outcomes in clinical trials. PMID:25566531

Hypoglycemic effect of methanolic extract of Musa paradisiaca (Musaceae) green fruits in normal and diabetic mice.

PubMed

Ojewole, J A O; Adewunmi, C O

2003-01-01

Diabetes mellitus is a debilitating hormonal disorder in which strict glycemic control and prevention of associated complications are of crucial importance. This study was designed to evaluate the hypoglycemic effect of methanolic extract of mature, green fruits of Musa paradisiaca (MEMP) in normal (normoglycemic) and streptozotocin (STZ)-treated, diabetic (hyperglycemic) mice, using chlorpropamide as the reference antidiabetic agent. MEMP (100-800 mg/kg p.o.) induced significant, dose-related (p < 0.05-0.001) reductions in the blood glucose concentrations of both normal and diabetic mice. Chlorpropamide (250 mg/kg p.o.) also produced significant (p < 0.01-0.001) reductions in the blood glucose concentrations of normal and diabetic mice. The results of this experimental study indicate that, in the mammalian model used, MEMP possesses hypoglycemic activity. Although the precise mechanism of the hypoglycemic action of MEMP is still unclear and will have to await further studies, it could be due, at least in part, to stimulation of insulin production and subsequent glucose utilization. Nevertheless, the findings of this experimental animal study indicate that MEMP possesses hypoglycemic activity, and thus lends credence to the suggested folkloric use of the plant in the management and/or control of adult-onset, type-2 diabetic mellitus among the Yoruba-speaking people of South-Western Nigeria.

Antioxidant and α-glucosidase activities of benzoic acid derivate from the bark of Myristica fatua Houtt

NASA Astrophysics Data System (ADS)

Megawati, Darmawan, Akhmad; Fajriah, Sofa; Primahana, Gian; Dewi, Rizna Triana; Minarti, Meiliawati, Lia

2017-11-01

Myrictica fatua Houtt widely used in Indonesian as one of the traditional medicinal plants. Cancer and diabetic mellitus (DM) type 2 are two degenerative diseases caused by the presence of excessive free radicals in the body. Antioxidant and anti-diabetic active compounds were needed to reduce the risk of the diseases. One of the chemical compound groups that can be used as antioxidant and antidiabetic is phenolic compound. Isolation of the methanolic extract of the bark of M. fatua Houtt using chromatography methods led to the isolation of phenolic compound. Methyl 3,4-dihydroxybenzoate showed antioxidant and antidiabetic activities through DPPH free radicals scavenger and α-glucosidase inhibitions activities test showed IC50 value 7.96 and 7.68 ug / mL, respectively

Anti-diabetic property of Methanol extract of Musa sapientum leaves and its fractions in alloxan-induced diabetic rats.

PubMed

Adewoye, E O; Ige, A O

2013-06-30

Diabetes mellitus is a metabolic disorder resulting from necrosis of β-cell and insulin resistance at the cellular level. Musa sapientum has been shown to possess anti-diabetic properties, however, the mechanism of its action is unknown. The effect of Methanolic extract of Musa sapientum leaves (MEMSL) and its fractions were assessed for in vitro inhibitory activity of α-amylase enzyme, in vivo hypoglycemic properties and liver glycogen content in alloxan-induced diabetic rats. Dried plant powder of Musa sapientum was successively extracted using n-hexane, ethyl acetate, dichloromethane and methanol respectively. The filtrate obtained was evaporated using rotary evaporator and the extract was stored at 4°C until use. The methanolic extract obtained was further fractionated using column chromatography. In vitro alpha amylase inhibitory activity of the methanolic extract at different doses (2.5mg/ml, 5mg/ml, 10mg/ml, 25mg/ml and 50mg/ml) and column fractions (100ug/ml) were assessed and compared with that of acarbose (5mg/ml), a standard oral α-amylase inhibitor. Hypoglycemic activity and liver glycogen content was studied using alloxan -induced diabetic male rats treated with MEMSL (250mg/kg and 500mg/kg), column fractions F2 and F5 (100μg/kg) for 14 days respectively. Results obtained showed a dose -dependent increase in α-amylase inhibitory activity of the methanolic extract at 5, 10, 25 and 50mg/ml exhibiting 29%, 61%, and 72% and 80% inhibitory activities respectively. Column fractions 2 and 5 showed the highest α-amylase inhibitory activity of 79% and 74% respectively. The MEMSL at 250mg/kg and 500mg/kg exhibited 66% and 59% hypoglycemic activities respectively compared with diabetic controls. Fractions 2 and 5 showed 48% and 75% reduction in blood glucose level respectively. Liver glycogen in diabetic animals treated with MEMSL (250mg/kg and 500mg/kg), F2 and F5 were significantly increased (5.5±0.5, 5.9±0.7, 3.6±0.5, 8.0±0.4 mg/100gwt. liver) compared with Diabetic controls (1.2±0.3 mg/100gwt. liver) respectively suggesting an increase in glucose storage or reduction in glycogen breakdown. It seems possible that the anti-diabetic properties in the leaf extract of Musa sapientum and its fractions maybe due to the inhibition of α-amylase, increased storage of glucose as glycogen in the liver and/or reduced breakdown of liver glycogen stores.

Aqueous Extract of Phyllanthus niruri Leaves Displays In Vitro Antioxidant Activity and Prevents the Elevation of Oxidative Stress in the Kidney of Streptozotocin-Induced Diabetic Male Rats

PubMed Central

Giribabu, Nelli; Rao, Pasupuleti Visweswara; Kumar, Korla Praveen; Muniandy, Sekaran; Swapna Rekha, Somesula; Salleh, Naguib

2014-01-01

P. niruri has been reported to possess antidiabetic and kidney protective effects. In the present study, the phytochemical constituents and in vitro antioxidant activity of P. niruri leaf aqueous extract were investigated together with its effect on oxidative stress and antioxidant enzymes levels in diabetic rat kidney. Results. Treatment of diabetic male rats with P. niruri leaf aqueous extract (200 and 400 mg/kg) for 28 consecutive days prevents the increase in the amount of lipid peroxidation (LPO) product, malondialdehyde (MDA), and the diminution of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity levels in the kidney of diabetic rats. The amount of LPO showed strong negative correlation with SOD, CAT, and GPx activity levels. P. niruri leaf aqueous extract exhibits in vitro antioxidant activity with IC50 slightly lower than ascorbic acid. Phytochemical screening of plant extract indicates the presence of polyphenols. Conclusion. P. niruri leaf extract protects the kidney from oxidative stress induced by diabetes. PMID:24991228

α-Glucosidase inhibitory activity of selected Philippine plants.

PubMed

Lawag, Ivan L; Aguinaldo, Alicia M; Naheed, Suad; Mosihuzzaman, Mohammad

2012-10-31

Antidesma bunius Spreng. (Phyllantaceae), Averrhoa bilimbi L. (Oxalidaceae), Biophytum sensitivum (L.) DC. (Oxalidaceae), Ceriops tagal (Perr.) C.B. Rob. (Rhizophoraceae), Kyllinga monocephala Rottb. (Cyperaceae), and Rhizophora mucronata Lam. (Rhizophoraceae) are used as remedies to control diabetes. In the present study, these plants were screened for their potential α-glucosidase inhibitory activity. The 80% aqueous ethanolic extracts were screened for their α-glucosidase enzyme inhibitory activity using yeast alpha glucosidase enzyme. Except for A. bilimbi with IC(50) at 519.86±3.07, all manifested a significant enzyme inhibitory activity. R. mucronata manifested the highest activity with IC(50) at 0.08±1.82 μg mL(-1), followed by C. tagal with IC(50) at 0.85±1.46 μg mL(-1) and B. sensitivum with IC(50) at 2.24±1.58 μg mL(-1). This is the first report on the α-glucosidase inhibitory effect of the six Philippine plants; thus, partly defining the mechanism on why these medicinal plants possess antidiabetic properties. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Comparative Efficacy and Acceptability of Anti-Diabetic Agents for Alzheimer's Disease and Mild Cognitive Impairment: A Systematic Review and Network Meta-analysis.

PubMed

Cao, Bing; Rosenblat, Joshua D; Brietzke, Elisa; Park, Caroline; Lee, Yena; Musial, Natalie; Pan, Zihang; Mansur, Rodrigo B; McIntyre, Roger S

2018-05-23

The current meta-analysis compares the efficacy (i.e., pro-cognitive effects) and acceptability of anti-diabetic agents for Alzheimer's disease (AD) and mild cognitive impairment (MCI). Cochrane Library (CENTRAL), PubMed/MEDLINE, EMBASE and PsycINFO were searched from inception to January 15, 2018 for randomized controlled trials (RCTs) comparing anti-diabetic agents with placebo and/or another active anti-diabetic agent for the treatment of AD or MCI. Nineteen eligible studies (n = 4,855) evaluating the effects of six different anti-diabetic drugs (i.e., intranasal insulin, pioglitazone, rosiglitazone, metformin, sitagliptin and liraglutide) were included. The results of 29 pairwise comparisons indicated that cognition was significantly improved in subjects treated with anti-diabetic agents compared to placebo. Pioglitazone 15-30 mg demonstrated the greatest efficacy compared to placebo in network meta-analysis. No significant differences in acceptability were identified when comparing agents with each other and with placebo. The current findings indicate a pro-cognitive class effect of anti-diabetic agents in AD/MCI. Other anti-diabetic agents should also be investigated in future studies. This study is registered with PROSPERO (CRD42018085967). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Therapeutic and cosmetic applications of Evodiamine and its derivatives--A patent review.

PubMed

Gavaraskar, Kirti; Dhulap, Sivakami; Hirwani, R R

2015-10-01

Evodiamine, ((+)-(S)-8,13,13b,14-tetrahydro-14-methylindolo[2',3':3,4]pyrido[2,1-b]quinazolin-5(7H)-one) indoloquinazoline alkaloid, is the major component isolated from the fruits of Evodia rutaecarpa, family Rutaceae. Broad spectrum of pharmacological activities of Evodiamine suggests its imperative role in treating a variety of diseases influencing the function of diverse targets. A comprehensive search was carried out to collect patent information regarding Evodiamine and its derivatives using different patent databases covering priority years to till date. The patents claiming therapeutic as well as cosmetic applications of Evodiamine and its derivatives were analyzed in detail and were classified technically based on the its application such as treatment of metabolic disorders, cancer, neurological disorders, and cardiovascular disorders, etc. The analysis revealed that the use and the mode of actions of Evodiamine and its derivatives in weight management treatments are currently well established. For example the fat reducing property of this alkaloid is primarily due to its mode of actions such as prevention of muscle protein catabolism, enhancement of thermogenesis and lipid oxidation. Apart from its use for treating obesity, Evodiamine and its derivatives are also experimentally explored for their anti-cancer, anti-diabetic and anti-inflammatory properties. The possible mechanisms related to its anti-cancer activity as illustrated by different experimental studies include its potential action as modulator of specific receptors such as topoisomerase I, NF-kappa B and B-cell lymphoma 2 (Bcl2). The analysis hence highlights that, clinical studies pertaining to the anti-cancer, anti-diabetes as well as anti-inflammatory activities of the Evodiamine and its derivatives would possess important market potential for the development of Evodiamine based therapeutics. Copyright © 2015 Elsevier B.V. All rights reserved.

Mangiferin: A xanthonoid with multipotent anti-inflammatory potential.

PubMed

Saha, Sukanya; Sadhukhan, Pritam; Sil, Parames C

2016-09-10

Over the last era, small molecules sourced from different plants have gained attention for their varied and long-term medicinal benefits. Their advantageous therapeutic effects in diverse pathological complications lead researchers to give an ever-increasing emphasis on them and discover their novel therapeutic potentials. Among these, the heat stable, xanthonoid group of organic molecules has gained special importance with distinctive regards to the bioactive molecule mangiferin due to its solubility in water. Mangiferin, a yellow polyphenol having C-glycosyl xanthone structure, is widely present in different edible sources like mango, and possesses numerous biological activities. Extensive research with this molecule shows its antioxidant, anti-inflammatory, antidiabetic, anticancer, antimicrobial, analgesic, and immunomodulatory properties. Thus, it provides protection against a wide range of physiological disorders. The C-glucosyl linkage and polyhydroxy groups in mangiferin's structure contribute essentially to its free radical-scavenging activity. Moreover, its ability in regulating various transcription factors like NF-κB, Nrf-2, etc. and modulating the expression of different proinflammatory signaling intermediates like tumor necrosis factor-α, COX-2, etc. contribute to its anti-inflammatory, anticancer, and antidiabetic potentials. In this comprehensive article, information has been provided about the sources, chemical structure, metabolism, and different biological activities of mangiferin with special emphasis on the underlying cellular signal transduction pathways. Insights into an in-depth assessment of mangiferin's anti-inflammatory therapeutic potential have also been discussed in detail. On an overall perspective, this review aims to stage mangiferin's diversified therapeutic applications and its emerging possibility as a promising drug in future based on its anti-inflammatory property. © 2016 BioFactors, 42(5):459-474, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

Novel coumarin modified GLP-1 derivatives with enhanced plasma stability and prolonged in vivo glucose-lowering ability.

PubMed

Han, Jing; Sun, Lidan; Huang, Xun; Li, Zheng; Zhang, Chenyu; Qian, Hai; Huang, Wenlong

2014-12-01

The short biological half-life limits the therapeutic use of glucagon-like peptide-1 (GLP-1) and chemical modification to improve the interaction of peptides with serum albumin represents an effective strategy to develop long-acting peptide analogues. Coumarin, a natural product, is known to bind tightly to plasma proteins and possesses many biological activities. Therefore, we designed and synthesized a series of coumarin-modified GLP-1 derivatives, hypothesizing that conjugation with coumarin would retain the therapeutic effects and prolong the biological half-life of the conjugates. Four cysteine-modified GLP-1 analogues (1-4) were prepared using Gly8 -GLP-1(7-36)-NH2 peptide as a starting point. These analogues were conjugated with two coumarin maleimides to yield eight compounds (conjugates 6-13) for testing. Activation of human GLP-1 receptors, stability to enzymic inactivation in plasma and binding to human albumin were assessed in vitro. In vivo, effects on oral glucose tolerance tests (OGTT) in rats and on blood glucose levels in db/db mice were studied. Most conjugates showed well preserved receptor activation efficacy, enhanced albumin-binding properties and improved in vitro plasma stability and conjugate 7 was selected to undergo further assessment. In rats, conjugate 7 had a longer circulating t1/2 than exendin-4 or liraglutide. A prolonged antidiabetic effect of conjugate 7 was observed after OGTT in rats and a prolonged hypoglycaemic effect in db/db mice. Cysteine-specific coumarin conjugation with GLP-1 offers a useful approach to the development of long-acting incretin-based antidiabetic agents. Conjugate 7 is a promising long-lasting GLP-1 derivative deserving further investigation. © 2014 The British Pharmacological Society.

Novel coumarin modified GLP-1 derivatives with enhanced plasma stability and prolonged in vivo glucose-lowering ability

PubMed Central

Han, Jing; Sun, Lidan; Huang, Xun; Li, Zheng; Zhang, Chenyu; Qian, Hai; Huang, Wenlong

2014-01-01

Background and Purpose The short biological half-life limits the therapeutic use of glucagon-like peptide-1 (GLP-1) and chemical modification to improve the interaction of peptides with serum albumin represents an effective strategy to develop long-acting peptide analogues. Coumarin, a natural product, is known to bind tightly to plasma proteins and possesses many biological activities. Therefore, we designed and synthesized a series of coumarin-modified GLP-1 derivatives, hypothesizing that conjugation with coumarin would retain the therapeutic effects and prolong the biological half-life of the conjugates. Experimental Approach Four cysteine-modified GLP-1 analogues (1–4) were prepared using Gly8-GLP-1(7–36)-NH2 peptide as a starting point. These analogues were conjugated with two coumarin maleimides to yield eight compounds (conjugates 6–13) for testing. Activation of human GLP-1 receptors, stability to enzymic inactivation in plasma and binding to human albumin were assessed in vitro. In vivo, effects on oral glucose tolerance tests (OGTT) in rats and on blood glucose levels in db/db mice were studied. Key Results Most conjugates showed well preserved receptor activation efficacy, enhanced albumin-binding properties and improved in vitro plasma stability and conjugate 7 was selected to undergo further assessment. In rats, conjugate 7 had a longer circulating t1/2 than exendin-4 or liraglutide. A prolonged antidiabetic effect of conjugate 7 was observed after OGTT in rats and a prolonged hypoglycaemic effect in db/db mice. Conclusions and Implications Cysteine-specific coumarin conjugation with GLP-1 offers a useful approach to the development of long-acting incretin-based antidiabetic agents. Conjugate 7 is a promising long-lasting GLP-1 derivative deserving further investigation. PMID:25039358

Piperine, a Natural Bioenhancer, Nullifies the Antidiabetic and Antioxidant Activities of Curcumin in Streptozotocin-Diabetic Rats

PubMed Central

Arcaro, Carlos Alberto; Gutierres, Vânia Ortega; Assis, Renata Pires; Moreira, Thais Fernanda; Costa, Paulo Inácio; Baviera, Amanda Martins; Brunetti, Iguatemy Lourenço

2014-01-01

Knowing that curcumin has low bioavailability when administered orally, and that piperine has bioenhancer activity by inhibition of hepatic and intestinal biotransformation processes, the aim of this study was to investigate the antidiabetic and antioxidant activities of curcumin (90 mg/kg) and piperine (20 or 40 mg/kg), alone or co-administered, incorporated in yoghurt, in streptozotocin (STZ)-diabetic rats. The treatment for 45 days of STZ-diabetic rats with curcumin-enriched yoghurt improved all parameters altered in this experimental model of diabetes: the body weight was increased in association with the weight of skeletal muscles and white adipose tissues; the progressive increase in the glycemia levels was avoided, as well as in the glycosuria, urinary urea, dyslipidemia, and markers of liver (alanine and aspartate aminotransferases and alkaline phosphatase) and kidney (urinary protein) dysfunction; the hepatic oxidative stress was decreased, since the activities of the antioxidant enzymes superoxide dismutase, catalase and gluthatione peroxidase were increased, and the levels of malondialdehyde and protein carbonyl groups were reduced. The dose of 20 mg/kg piperine also showed antidiabetic and antioxidant activities. The treatment of STZ-diabetic rats with both curcumin and 20 mg/kg piperine in yoghurt did not change the antidiabetic and antioxidant activities of curcumin; notably, the treatment with both curcumin and 40 mg/kg piperine abrogated the beneficial effects of curcumin. In addition, the alanine aminotransferase levels were further increased in diabetic rats treated with curcumin and 40 mg/kg piperine in comparison with untreated diabetic rats. These findings support that the co-administration of curcumin with a bioenhancer did not bring any advantage to the curcumin effects, at least about the antidiabetic and antioxidant activities, which could be related to changes on its biotransformation. PMID:25469699

Cinnamaldehyde--a potential antidiabetic agent.

PubMed

Subash Babu, P; Prabuseenivasan, S; Ignacimuthu, S

2007-01-01

Cinnamonum zeylanicum (cinnamon) is widely used in traditional system of medicine to treat diabetes in India. The present study was carried out to isolate and identify the putative antidiabetic compounds based on bioassay-guided fractionation; the compound identified decreased the plasma glucose levels. The active compound was purified by repeat column and structure of cinnamaldehyde was determined on the basis of chemical and physiochemical evidence. The LD(50) value of cinnamaldehyde was determined as 1850+/-37 mg/kg bw. Cinnamaldehyde was administered at different doses (5, 10 and 20 mg/kg bw) for 45 days to streptozotocin (STZ) (60 mg/kg bw)-induced male diabetic wistar rats. It was found that plasma glucose concentration was significantly (p<0.05) decreased in a dose-dependent manner (63.29%) compared to the control. In addition, oral administration of cinnamaldehyde (20 mg/kg bw) significantly decreased glycosylated hemoglobin (HbA(1C)), serum total cholesterol, triglyceride levels and at the same time markedly increased plasma insulin, hepatic glycogen and high-density lipoprotein-cholesterol levels. Also cinnamaldehyde restored the altered plasma enzyme (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase and acid phosphatase) levels to near normal. Administration of glibenclamide, a reference drug (0.6 mg/kg bw) also produced a significant (p<0.05) reduction in blood glucose concentration in STZ-induced diabetic rats. The results of this experimental study indicate that cinnamaldehyde possesses hypoglycemic and hypolipidemic effects in STZ-induced diabetic rats.

Antidiabetic and antioxidant functionality associated with phenolic constituents from fruit parts of indigenous black jamun (Syzygium cumini L.) landraces.

PubMed

Gajera, H P; Gevariya, Shila N; Hirpara, Darshna G; Patel, S V; Golakiya, B A

2017-09-01

Fruit phenolics are important dietary antioxidant and antidiabetic constituents. The fruit parts (pulp, seed, seed coat, kernel) of underutilized indigenous six black jamun landraces ( Syzygium cumini L.), found in Gir forest region of India and differed in their fruit size, shape and weight, are evaluated and correlated with antidiabetic, DPPH radical scavenging and phenolic constituents. The α-amylase inhibitors propose an efficient antidiabetic strategy and the levels of postprandial hyperglycemia were lowered by restraining starch breakdown. The sequential solvent systems with ascending polarity-petroleum ether, ethyl acetate, methanol and water were performed for soxhlet extraction by hot percolation method and extractive yield was found maximum with methanolic fruit part extracts of six landraces. The methanolic extracts of fruit parts also evidenced higher antidiabetic activity and hence utilized for further characterization. Among the six landraces, pulp and kernel of BJLR-6 (very small, oblong fruits) evidenced maximum 53.8 and 98.2% inhibition of α-amylase activity, respectively. The seed attained inhibitory activity mostly contributed by the kernel fraction. The inhibition of DPPH radical scavenging activity was positively correlated with phenol constituents. An HPLC-PDA technique was used to quantify the seven individual phenolics. The seed and kernel of BJLR-6 exhibited higher individual phenolics-gallic, catechin, ellagic, ferulic acids and quercetin, whereas pulp evidenced higher with gallic acid and catechin as α-amylase inhibitors. The IC 50 value indicates concentration of fruit extracts exhibiting ≥50% inhibition on porcine pancreatic α-amylase (PPA) activity. The kernel fraction of BJLR6 evidenced lowest (8.3 µg ml -1 ) IC 50 value followed by seed (12.9 µg ml -1 ), seed coat (50.8 µg ml -1 ) and pulp (270 µg ml -1 ). The seed and kernel of BJLR-6 inhibited PPA at much lower concentrations than standard acarbose (24.7 µg ml -1 ) considering good candidates for antidiabetic herbal formulations.

Mangiferin and its aglycone, norathyriol, improve glucose metabolism by activation of AMP-activated protein kinase.

PubMed

Wang, Fang; Yan, Juming; Niu, Yanfen; Li, Yan; Lin, Hua; Liu, Xu; Liu, Jikai; Li, Ling

2014-01-01

Mangiferin has been reported to possess antidiabetic activities. Norathyriol, a xanthone aglycone, has the same structure as mangiferin, except for a C-glucosyl bond. To our best knowledge, no study has been conducted to determine and compare those two compounds on glucose consumption in vitro. In this study, the effects of norathyriol and mangiferin on glucose consumption in normal and insulin resistance (IR) L6 myotubes were evaluated. Simultaneously, the potential mechanism of this effect was also investigated. Normal or IR L6 myotubes were incubated with norathyriol (2.5 ∼ 10 μM, 0.625 ∼ 2.5 μM), mangiferin (10 ∼ 40 μM, 2.5 ∼ 10 μM) or rosiglitazone (20 μM) and/or 0.05 nM insulin for 24 h, respectively. The glucose consumption was assessed using the glucose oxidase method. Immunoblotting was performed to detect protein kinase B (PKB/Akt) and AMP-activated protein kinase (AMPK) phosphorylation in L6 myotubes cells. Norathyriol and mangiferin treatment alone increased the glucose consumption 61.9 and 56.3%, respectively, in L6 myotubes and made additional increasing with 0.05 nM insulin. In IR L6 myotubes, norathyriol treatment made increasing with or without insulin, mangiferin treatment also made increasing but only when co-treated with insulin. Immunoblotting results showed that norathyriol and mangiferin produced an increase of 1.9 - and 1.8-fold in the phosphorylation levels of the AMPK, but not in Akt. Our findings suggest that norathyriol and mangiferin could improve the glucose utilization and insulin sensitivity by up-regulation of the phosphorylation of AMPK. Norathyriol may be considered as an active metabolite responsible for the antidiabetic activity of mangiferin.

Averrhoa bilimbi fruits attenuate hyperglycemia-mediated oxidative stress in streptozotocin-induced diabetic rats.

PubMed

Kurup, Surya B; Mini, S

2017-04-01

Hyperglycemia-mediated oxidative stress plays a major role in the development of diabetic complications. Averrhoa bilimbi Linn. (Oxalidaceae) is a medicinal plant with fruits reported to possess antidiabetic activity. This study evaluated the beneficial effects of the ethyl acetate fraction of A. bilimbi fruit (ABAEE) on the antioxidant/oxidant status in diabetes mellitus. Diabetic rats were treated orally with the ethyl acetate fraction of A. bilimbi fruits at a dose of 25 mg/kg body weight for 60 days. Serum glucose, glycated hemoglobin, plasma insulin, hepatic toxicity markers, antioxidant enzymes, lipid peroxidation products, and liver histopathology were assayed checked after 60 days of extract treatment. Diabetic rats administered ABAEE showed a significant decline in serum glucose, glycated hemoglobin, and also significantly increases the level of plasma insulin, as well as a notable attenuation in thiobarbituric acid-reactive substances, conjugated dienes, and hydroperoxides. ABAEE also modulated hepatic antioxidant potential by significantly increasing the activities of catalase, glutathione peroxidase, glutathione reductase, superoxide dismutase, and reducing glutathione content. The results associated with ABAEE were more significant than those observed following treatment with the standard drug metformin. Histopathological observations showed that ABAEE effectively rescued hepatocytes from oxidative damage without affecting cellular function and structural integrity. High-performance liquid chromatography analysis of ABAEE indicated the presence of phenolic compound, quercetin, indicating that the antidiabetic effect of the extract might be related to quercetin. These results demonstrated the potential beneficial effect of ABAEE on streptozotocin-induced diabetes in rats. Copyright © 2016. Published by Elsevier B.V.

Bitter melon: a panacea for inflammation and cancer

PubMed Central

Dandawate, Prasad R.; Subramaniam, Dharmalingam; Padhye, Subhash B.; Anant, Shrikant

2017-01-01

Nature is a rich source of medicinal plants and their products that are useful for treatment of various diseases and disorders. Momordica charantia, commonly known as bitter melon or bitter gourd, is one of such plants known for its biological activities used in traditional system of medicines. This plant is cultivated in all over the world, including tropical areas of Asia, Amazon, east Africa, and the Caribbean and used as a vegetable as well as folk medicine. All parts of the plant, including the fruit, are commonly consumed and cooked with different vegetables, stir-fried, stuffed or used in small quantities in soups or beans to give a slightly bitter flavor and taste. The plant is reported to possess anti-oxidant, anti-inflammatory, anti-cancer, anti-diabetic, anti-bacterial, anti-obesity, and immunomodulatory activities. The plant extract inhibits cancer cell growth by inducing apoptosis, cell cycle arrest, autophagy and inhibiting cancer stem cells. The plant is rich in bioactive chemical constituents like cucurbitane type triterpenoids, triterpene glycosides, phenolic acids, flavonoids, essential oils, saponins, fatty acids, and proteins. Some of the isolated compounds (Kuguacin J, Karaviloside XI, Kuguaglycoside C, Momordicoside Q–U, Charantin, α-eleostearic acid) and proteins (α-Momorcharin, RNase MC2, MAP30) possess potent biological activity. In the present review, we are summarizing the anti-oxidant, anti-inflammatory, and anti-cancer activities of Momordica charantia along with a short account of important chemical constituents, providing a basis for establishing detail biological activities of the plant and developing novel drug molecules based on the active chemical constituents. PMID:26968675

Fermentation, Isolation, Structure, and antidiabetic activity of NFAT-133 produced by Streptomyces strain PM0324667

PubMed Central

2011-01-01

Type-2 diabetes is mediated by defects in either insulin secretion or insulin action. In an effort to identify extracts that may stimulate glucose uptake, similar to insulin, a high throughput-screening assay for measuring glucose uptake in skeletal muscle cells was established. During the screening studies to discover novel antidiabetic compounds from microbial resources a Streptomyces strain PM0324667 (MTCC 5543, the Strain accession number at Institute of Microbial Technology, Chandigarh, India), an isolate from arid soil was identified which expressed a secondary metabolite that induced glucose uptake in L6 skeletal muscle cells. By employing bioactivity guided fractionation techniques, a tri-substituted simple aromatic compound with anti-diabetic potential was isolated. It was characterized based on MS and 2D NMR spectral data and identified as NFAT-133 which is a known immunosuppressive agent that inhibits NFAT-dependent transcription in vitro. Our investigations revealed the antidiabetic potential of NFAT-133. The compound induced glucose uptake in differentiated L6 myotubes with an EC50 of 6.3 ± 1.8 μM without activating the peroxisome proliferator-activated receptor-γ. Further, NFAT-133 was also efficacious in vivo in diabetic animals and reduced systemic glucose levels. Thus it is a potential lead compound which can be considered for development as a therapeutic for the treatment of type-2 diabetes. We have reported herewith the isolation of the producer microbe, fermentation, purification, in vitro, and in vivo antidiabetic activity of the compound. PMID:22104600

Study on antidiabetic activity of wheat and barley starch using asymmetrical flow field-flow fractionation coupled with multiangle light scattering.

PubMed

Dou, Haiyang; Zhou, Bing; Jang, Hae-Dong; Lee, Seungho

2014-05-02

The ability of asymmetrical flow field-flow fractionation (AF4) coupled online with multiangle light scattering (MALS) and refractive index detector (RI) (AF4-MALS-RI) for monitoring of change in molecular conformation of wheat and barley starch during germination process was evaluated. AF4 provides separation of starch molecules based on their hydrodynamic sizes, and MALS yields the molar mass and molecular size (radius of gyration, Rg). In vitro and in vivo anti-hyperglycemic effect of germinated wheat and barley was studied. The relationship between antidiabetic activity and molecular conformation was, for the first time, investigated. The ratio of Rg to the hydrodynamic radius (Rh) and the apparent density were proven to be important parameters as they offer an insight into molecular conformation. Results showed that, when geminated, the apparent density and the antidiabetic activity of barley were significantly increased, suggesting germination makes the molecules more compact which could contribute to enhancement of their antidiabetic activity. The information obtained by AF4-MALS-RI is valuable for understanding of germination mechanism, and thus for developing functional foods. Copyright © 2014 Elsevier B.V. All rights reserved.

Pharmacological Modulation of Lung Carcinogenesis in Smokers: Preclinical and Clinical Evidence

PubMed Central

De Flora, Silvio; Ganchev, Gancho; Iltcheva, Marietta; La Maestra, Sebastiano; Micale, Rosanna T.; Steele, Vernon E.; Balansky, Roumen

2016-01-01

Many drugs in common use possess pleiotropic properties that make them capable of interfering with carcinogenesis mechanisms. We discuss here the ability of pharmacological agents to mitigate the pulmonary carcinogenicity of mainstream cigarette smoke. The evaluated agents included antiinflammatory drugs (budesonide, celecoxib, aspirin, naproxen, licofelone), antidiabetic drugs (metformin, pioglitazone), antineoplastic agents (lapatinib, bexarotene, vorinostat), and other drugs and supplements (phenethyl isothiocyanate, myo-inositol, N-acetylcysteine, ascorbic acid, berry extracts). The drugs have been evaluated in mouse models mimicking interventions either in current smokers or in ex-smokers or a prenatal chemoprevention. They displayed a broad spectrum of activities by attenuating either smoke-induced preneoplastic lesions or benign tumors and/or malignant tumors. Together with epidemiological data, these findings provide useful information to predict the potential effects of pharmacological agents in smokers. PMID:26726119

Stereospermum fimbriatum as a Potential Source of Phytochemicals: A Review of Stereospermum Genus.

PubMed

Awang, Anis F I; Ferdosh, Sahena; Sarker, Md Zaidul I; Sheikh, Hassan I; Ghafoor, Kashif; Yunus, Kamaruzzaman

Stereospermum fimbriatum is one of the medicinal plants that has been claimed to be used traditionally to treat several illnesses such as stomachache, earache, skin irritation and postpartum illness. The genus of this plant is known to possess medicinal properties in every part of the plant. Therapeutic potential of S. fimbriatum is anticipated based on numerous previous studies that documented variety of phytochemical contents and bioactivity of the genus. The most reported bioactivities of its genus are antimicrobial, antioxidant, anti-diabetic, anti-inflammatory, anti-diarrheal and analgesic activities. S. fimbriatum is a rare species that has not been discovered yet. Thus, this review aims at highlighting the potentials of S. fimbriatum by collecting available data on the bioactivities of its genus and set the directions for future research on this plant.

Functional significance of bioactive peptides derived from soybean.

PubMed

Singh, Brij Pal; Vij, Shilpa; Hati, Subrota

2014-04-01

Biologically active peptides play an important role in metabolic regulation and modulation. Several studies have shown that during gastrointestinal digestion, food processing and microbial proteolysis of various animals and plant proteins, small peptides can be released which possess biofunctional properties. These peptides are to prove potential health-enhancing nutraceutical for food and pharmaceutical applications. The beneficial health effects of bioactive peptides may be several like antihypertensive, antioxidative, antiobesity, immunomodulatory, antidiabetic, hypocholesterolemic and anticancer. Soybeans, one of the most abundant plant sources of dietary protein, contain 36-56% of protein. Recent studies showed that soy milk, an aqueous extract of soybean, and its fermented product have great biological properties and are a good source of bioactive peptides. This review focuses on bioactive peptides derived from soybean; we illustrate their production and biofunctional attributes. Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical and Biological Aspects of Extracts from Medicinal Plants with Antidiabetic Effects

PubMed Central

Gushiken, Lucas F.; Beserra, Fernando P.; Rozza, Ariane L.; Bérgamo, Patrícia L.; Bérgamo, Danilo A.; Pellizzon, Claudia H.

2016-01-01

Diabetes mellitus is a chronic disease and a leading cause of death in western countries. Despite advancements in the clinical management of the disease, it is not possible to control the late complications of diabetes. The main characteristic feature of diabetes is hyperglycemia, which reflects the deterioration in the use of glucose due to a faulty or poor response to insulin secretion. Alloxan and streptozotocin (STZ) are the chemical tools that are most commonly used to study the disease in rodents. Many plant species have been used in ethnopharmacology or to treat experimentally symptoms of this disease. When evaluated pharmacologically, most of the plants employed as antidiabetic substances have been shown to exhibit hypoglycemic and antihyperglycemic activities, and to contain chemical constituents that may be used as new antidiabetic agents. There are many substances extracted from plants that offer antidiabetic potential, whereas others may result in hypoglycemia as a side effect due to their toxicity, particularly their hepatotoxicity. In this article we present an updated overview of the studies on extracts from medicinal plants, relating the mechanisms of action by which these substances act and the natural principles of antidiabetic activity. PMID:28012277

Fucoxanthin, a Marine Carotenoid, Reverses Scopolamine-Induced Cognitive Impairments in Mice and Inhibits Acetylcholinesterase in Vitro

PubMed Central

Lin, Jiajia; Huang, Ling; Yu, Jie; Xiang, Siying; Wang, Jialing; Zhang, Jinrong; Yan, Xiaojun; Cui, Wei; He, Shan; Wang, Qinwen

2016-01-01

Fucoxanthin, a natural carotenoid abundant in edible brown seaweeds, has been shown to possess anti-cancer, anti-oxidant, anti-obesity and anti-diabetic effects. In this study, we report for the first time that fucoxanthin effectively protects against scopolamine-induced cognitive impairments in mice. In addition, fucoxanthin significantly reversed the scopolamine-induced increase of acetylcholinesterase (AChE) activity and decreased both choline acetyltransferase activity and brain-derived neurotrophic factor (BDNF) expression. Using an in vitro AChE activity assay, we discovered that fucoxanthin directly inhibits AChE with an IC50 value of 81.2 μM. Molecular docking analysis suggests that fucoxanthin likely interacts with the peripheral anionic site within AChE, which is in accordance with enzymatic activity results showing that fucoxanthin inhibits AChE in a non-competitive manner. Based on our current findings, we anticipate that fucoxanthin might exhibit great therapeutic efficacy for the treatment of Alzheimer’s disease by acting on multiple targets, including inhibiting AChE and increasing BDNF expression. PMID:27023569

Chlorogenic Acid: Recent Advances on Its Dual Role as a Food Additive and a Nutraceutical against Metabolic Syndrome.

PubMed

Santana-Gálvez, Jesús; Cisneros-Zevallos, Luis; Jacobo-Velázquez, Daniel A

2017-02-26

Chlorogenic acid (5-O-caffeoylquinic acid) is a phenolic compound from thehydroxycinnamic acid family. This polyphenol possesses many health-promoting properties, mostof them related to the treatment of metabolic syndrome, including anti-oxidant, anti-inflammatory,antilipidemic, antidiabetic, and antihypertensive activities. The first part of this review will discussthe role of chlorogenic acid as a nutraceutical for the prevention and treatment of metabolicsyndrome and associated disorders, including in vivo studies, clinical trials, and mechanisms ofaction. The second part of the review will be dealing with the role of chlorogenic acid as a foodadditive. Chlorogenic acid has shown antimicrobial activity against a wide range of organisms,including bacteria, yeasts, molds, viruses, and amoebas. These antimicrobial properties can beuseful for the food industry in its constant search for new and natural molecules for thepreservation of food products. In addition, chlorogenic acid has antioxidant activity, particularlyagainst lipid oxidation; protective properties against degradation of other bioactive compoundspresent in food, and prebiotic activity. The combination of these properties makes chlorogenic acidan excellent candidate for the formulation of dietary supplements and functional foods.

The Hypoglycemic, Hypolipidemic, and Anti-Diabetic Nephritic Activities of Zeaxanthin in Diet-Streptozotocin-Induced Diabetic Sprague Dawley Rats.

PubMed

Kou, Ling; Du, Mingzhao; Zhang, Chaopu; Dai, Zhiyin; Li, Xuan; Zhang, Baohai

2017-07-01

Zeaxanthin (ZA), an important compound found in Lycium barbarum, shows various pharmacodynamic effects. In our present study, a high-fat, high-sucrose diet and streptozotocin (STZ)-induced diabetic rat model was used to investigate the antidiabetic activities of ZA. After a 4-week administration of 200 and 400 mg/kg of ZA and 100 mg/kg of metformin hydrochloride, various blood biochemical indexes were detected. ZA strongly normalized the reduced bodyweight and enhanced fasting blood glucose in diabetic rats. The positive data obtained from the oral glucose tolerance test further confirmed its antidiabetic effects. ZA displayed significant hypolipidemic activities indicated by its modulation of serum levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and total cholesterol. The antidiabetic nephropathy of ZA was confirmed by its regulation of pathological kidney structures, urine levels of n-acetyl-β-d-glucosaminidase and albuminuria, and serum levels of urea nitrogen. ZA inhibited the serum levels of inflammatory factors including interleukin-2 (IL-2), IL-6, tumor necrosis factor-α, and nuclear factor kappa B, further confirming its renal protection. Moreover, the serum imbalances in superoxide dismutase, glutathione peroxidase, methane dicarboxylic aldehyde, and catalase were normalized by ZA, suggesting its antioxidant properties. Altogether, ZA produced hypoglycemic, hypolipidemic, and antidiabetic nephritic effects in a diet-STZ-induced diabetic rat model.

Characteristics and in vitro Anti-diabetic Properties of the Korean Rice Wine, Makgeolli Fermented with Laminaria japonica.

PubMed

Choi, Jae-Suk; Seo, Hyo Ju; Lee, Yu-Ri; Kwon, Su-Jung; Moon, Sun Hwa; Park, Sun-Mee; Sohn, Jae Hak

2014-06-01

New in vitro anti-diabetes makgeolli was produced from rice by adding various quantities of Laminaria japonica, and the fermentation characteristics of the L. japonica makgeolli during the fermentation process were investigated. The contents of alcohol and reducing sugar, and viable count of yeast, of L. japonica makgeolli were not significantly changed when the proportion of L. japonica was increased. The total acid content decreased with an increase in L. japonica concentration; the pH and total bacterial cell count increased in proportion with the increase in L. japonica concentration. The L. japonica makgeolli contents of free sugars, such as fructose, glucose, and sucrose, and of organic acids, such as acetic acid, citric acid, succinic acid, and lactic acid, were altered during fermentation and showed various patterns. The effects of the quantity of L. japonica added on the acceptability and anti-diabetes activities of L. japonica makgeolli were also investigated. In a sensory evaluation, L. japonica makgeolli brewed by adding 2.5 or 5% L. japonica to the mash showed the best overall acceptability; the 12.5% L. japonica sample was least favored due to its seaweed flavor. L. japonica addition did not increase the peroxynitrite-scavenging activity of makgeolli. L. japonica makgeolli showed potent anti-diabetes activity, particularly that containing >7.5% L. japonica. Therefore, L. japonica makgeolli may represent a new functional makgeolli with anti-diabetes properties.

Bioactivities examination of Cinchona leaves ethanol extracts

NASA Astrophysics Data System (ADS)

Artanti, Nina; Udin, Linar Z.; Hanafi, M.; Jamilah, Kurniasih, Ida Rahmi; Primahana, Gian; Anita, Yulia; Sundowo, Andini; Kandace, Yoice Sri

2017-01-01

Cinchona species especially the barks are commonly known for commercial production of quinine as antimalarial. Although it is also reported for treatment of depurative, whooping cough, influenza and dysentery. In this paper we reported in vitro examination of other bioactivities (antidiabetes, antioxidant and in vitro cytotoxicity) of 70% ethanol extract of Cinchona ledgeriana and C. succirubra leaves as well as qunine, quinidine, and cinchonine the major alkaloids found in Cinchona species. Antidiabetes was conducted using α-glucosidase inhibitory activity assay. Antioxidant was conducted using DPPH free radical scavenging activity assay. In vitro cytotoxic activity was concucted by microscopic observation on growth of breast cancer cell line MCF-7. The results showed that at concentration of 100 µg/ml, C. ledgeriana leaves ethanol extracts showed the best activity as antidiabetes (98% inhibitory of α-glucosidase activity) and antioxidant (92% DPPH free radical scavenging activity), whereas at the same concentration C. succirubra, quinine, quinidine and cinchonine showed very low activities of antidiabetes and antioxidant. Microscopic observation of in vitro cytotoxicity showed that C. ledgeriana also has excellent cytotoxicity to breast cancer cell line MCF-7 which better than quinine, quinidine and cinchonine, whereas C. succirubra showed low cytotoxicity. These results suggest that cinchona species have many potential as the source of drugs discovery and development other than just for malaria treatment. Therefore it is important to conduct further studies and to maintain the available Cinchona plantation in Indonesia.

Fumosorinone, a novel PTP1B inhibitor, activates insulin signaling in insulin-resistance HepG2 cells and shows anti-diabetic effect in diabetic KKAy mice

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

Liu, Zhi-Qin; College of Pharmaceutical Sciences, key laboratory of pharmaceutical quality control of Hebei province, Hebei University, Baoding 071002; Liu, Ting

Insulin resistance is a characteristic feature of type 2 diabetes mellitus (T2DM) and is characterized by defects in insulin signaling. Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of the insulin signaling pathways, and its increased activity and expression are implicated in the pathogenesis of insulin resistance. Therefore, the inhibition of PTP1B is anticipated to become a potential therapeutic strategy to treat T2DM. Fumosorinone (FU), a new natural product isolated from insect fungi Isaria fumosorosea, was found to inhibit PTP1B activity in our previous study. Herein, the effects of FU on insulin resistance and mechanism in vitro andmore » in vivo were investigated. FU increased the insulin-provoked glucose uptake in insulin-resistant HepG2 cells, and also reduced blood glucose and lipid levels of type 2 diabetic KKAy mice. FU decreased the expression of PTP1B both in insulin-resistant HepG2 cells and in liver tissues of diabetic KKAy mice. Furthermore, FU increased the phosphorylation of IRβ, IRS-2, Akt, GSK3β and Erk1/2 in insulin-resistant HepG2 cells, as well as the phosphorylation of IRβ, IRS-2, Akt in liver tissues of diabetic KKAy mice. These results showed that FU increased glucose uptake and improved insulin resistance by down-regulating the expression of PTP1B and activating the insulin signaling pathway, suggesting that it may possess antidiabetic properties. - Highlights: • Fumosorinone is a new PTP1B inhibitor isolated from insect pathogenic fungi. • Fumosorinone attenuated the insulin resistance both in vitro and in vivo. • Fumosorinone decreased the expression of PTP1B both in vitro and in vivo. • Fumosorinone activated the insulin signaling pathway both in vitro and in vivo.« less

The significance of compliance and persistence in the treatment of diabetes, hypertension and dyslipidaemia: a review

PubMed Central

Cramer, J A; Benedict, Á; Muszbek, N; Keskinaslan, A; Khan, Z M

2008-01-01

Objectives To review studies of patient compliance/persistence with cardiovascular or antidiabetic medication published since the year 2000; to compare the methods used to measure compliance/persistence across studies; to compare reported compliance/persistence rates across therapeutic classes and to assess whether compliance/persistence correlates with clinical outcomes. Methods English language papers published between January 2000 and November 2005 investigating patient compliance/persistence with cardiovascular or antidiabetic medication were identified through searches of the MEDLINE and EMBASE databases. Definitions and measurements of compliance/persistence were compared across therapeutic areas using contingency tables. Results Of the 139 studies analysed, 32% focused on hypertension, 27% on diabetes and 13% on dyslipidaemia. The remainder covered coronary heart disease and cardiovascular disease (CVD) in general. The most frequently reported measure of compliance was the 12-month medication possession ratio (MPR). The overall mean MPR was 72%, and the MPR did not differ significantly between treatment classes (range: 67–76%). The average proportion of patients with an MPR of > 80% was 59% overall, 64% for antihypertensives, 58% for oral antidiabetics, 51% for lipid-lowering agents and 69% in studies of multiple treatments, again with no significant difference between treatment classes. The average 12-month persistence rate was 63% and was similar across therapeutic classes. Good compliance had a positive effect on outcome in 73% of the studies examining clinical outcomes. Conclusions Non-compliance with cardiovascular and antidiabetic medication is a significant problem, with around 30% of days ‘on therapy’ not covered by medication and only 59% of patients taking medication for more than 80% of their days ‘on therapy’ in a year. Good compliance has a positive effect on clinical outcome, suggesting that the management of CVD may be improved by improving patient compliance. PMID:17983433

Comparison of the Chemical Profiles and Antioxidant and Antidiabetic Activities of Extracts from Two Ganoderma Species (Agaricomycetes).

PubMed

Tang, Xiaoqing; Cai, Weixi; Xu, Baojun

2016-01-01

The objective of this study was to compare the mycochemical profiles, antioxidant activities, and antidiabetic effects of 2 species of genus Ganoderma, the red lingzhi (G. lucidum) and purple lingzhi (G. sinense) mushrooms. In Chinese medicinal practice, hot water and ethanol are used as solvents to extract samples. In this study, a total of 4 extracts (ethanol and hot water extracts from G. lucidum and G. sinense) were prepared for further assays. Hot water extracts presented much higher values for total phenolic content and ferric-reducing antioxidant power than the ethanol extracts. Ethanol (70%) extract of G. lucidum had the strongest α-glycosidase inhibitory capacity, but the lingzhi polysaccharides showed no inhibitory effect. It also had the largest amount of total ganoderic acids. The results indicated that ethanol extracts from both G. lucidum and G. sinense showed better antidiabetic effects than the hot water extracts. Ganoderic acids, rather than polysaccharides, may contribute the antidiabetic effects of both the Ganoderma species.

Promising anti-diabetes mellitus activity in rats of β-amyrin palmitate isolated from Hemidesmus indicus roots.

PubMed

Nair, S Ajikumaran; Sabulal, B; Radhika, J; Arunkumar, R; Subramoniam, A

2014-07-05

While evaluating the toxicity of the tuberous root extracts of Hemidesmus indicus, a traditional medicinal plant, the glucose lowering property of the root was observed by the investigators. Therefore, it was thought of interest to isolate the anti-hyperglycemic principle from the root and determine its utility to develop an anti-diabetes mellitus medicine. The active principle was isolated from H. indicus root extract by anti-hyperglycemic activity guided chromatographic techniques. Glucose tolerance test in rats was used to evaluate the anti-hyperglycenic property. Anti-diabetes mellitus property was evaluated in alloxan-induced diabetic rats as well as streptozotocin-induced (type-2 model) diabetic rats. The active principle was isolated and identified with spectral data as β-amyrin palmitate. Although it is a known compound, its presence in H. indicus is not known previously. It was observed for the first time that β-amyrin palmitate has remarkable anti-hyperglycemic activity in orally glucose loaded rats. Further, interestingly, it exhibited excellent anti-diabetes mellitus activity in both alloxan-diabetic and streptozotocin-diabetic rats at a very low concentration (50µg/kg body weight). One of the mechanisms of action of β-amyrin palmitate appears to be blocking the entry of glucose from the intestine. β-Amyrin palmitate is very promising to develop a medicine for diabetes for combination therapy and/or mono-therapy. Copyright © 2014 Elsevier B.V. All rights reserved.

Plants used as antidiabetics in popular medicine in Rio Grande do Sul, southern Brazil.

PubMed

Trojan-Rodrigues, M; Alves, T L S; Soares, G L G; Ritter, M R

2012-01-06

Plants are widely as antidiabetics. The study of these plants is essential because many of them may have undesirable effects, such as acute or chronic toxicity; or their use may even delay or discourage the adoption of the proper and effective treatment. The present study surveyed the plant species that are popularly used to treat diabetes mellitus in the state of Rio Grande do Sul in southern Brazil. Sixteen ethnobotanical surveys performed in the state were consulted, and the species used to treat diabetes were listed. For species cited in at least two of the studies, scientific data related to antidiabetic activity were searched in the ISI Knowledge database. The scientific binomial of each species was used as keywords, and data found in review papers were also included. A total of 81 species in 42 families were mentioned; the most important families were Asteraceae and Myrtaceae. Twenty eight species were cited at least twice as being used to treat diabetes in the state. For 11 of these, no scientific data regarding antidiabetic activity could be located. The species most frequently mentioned for use with diabetes were Syzygium cumini (Myrtaceae) and Bauhinia forficata (Fabaceae), in 12 studies each, followed by Sphagneticola trilobata (Asteraceae), in six studies; and Baccharis trimera (Asteraceae), Bidens pilosa (Asteraceae), Cynara scolymus (Asteraceae), and Leandra australis (Melastomataceae) in four studies each. Bauhinia forficata and Syzygium cumini have been studied in more detail for antidiabetic activity. A considerable number of plant species are traditionally used for the treatment of diabetes melitus in the Rio Grande do Sul State. The majority of those plants that have been studied for antidiabetic activity showed promising results, mainly for Bauhinia forficata and Syzygium cumini. However, for most of the plants mentioned, the studies are not sufficient to guarantee the efficacy and safety in the use of these plants in the treatment against diabetes. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Effects of culture medium compositions on antidiabetic activity and anticancer activity of marine endophitic bacteria isolated from sponge

NASA Astrophysics Data System (ADS)

Maryani, Faiza; Mulyani, Hani; Artanti, Nina; Udin, Linar Zalinar; Dewi, Rizna Triana; Hanafi, Muhammad; Murniasih, Tutik

2017-01-01

High diversity of Indonesia marine spesies and their ability in producing secondary metabolite that can be used as a drug candidate cause this fascinating topic need to explore. Most of marine organisms explored to discover drug is macroorganism whereas microorganism (such as Indonesia marine bacteria) is very limited. Therefore, in this report, antidiabetic and anticancer activity of Indonesia marine bacteria isolated from Sponges's extract have been studied. Bacteria strain 8.9 which are collection of Research Center for Oseanography, Indonesian Institute of Sciences were from Barrang Lompo Island, Makasar, Indonesia. Bacteria were cultured in different culture medium compositions (such as: different pH, source of glucose and water) for 48 hours on a shaker, then they were extracted with ethyl asetate. Extracts of bacteria were tested by DPPH method (antioxidant activity), alpha glucosidase inhibitory activity method (antidiabetic activity), and Alamar Blue assay (anticancer activity) at 200 ppm. According to result, extract of bacteria in pH 8.0 exhibited the greatest antioxidant (19.27% inhibition), antidiabetic (63.95% inhibition) and anticancer activity of T47D cell line (44.62% cell viability) compared to other extracts. However, effect of addition of sugar sources (such as: glucose, sucrose, and soluble starch) and effect of addition of water/sea water exhibited less influence on their bioactivities. In conclusion, Indonesia marine bacteria isolated from sponge have potential a source of bioactive compound in drug discovery field.

Antidiabetic Effects of Tea.

PubMed

Fu, Qiu-Yue; Li, Qing-Sheng; Lin, Xiao-Ming; Qiao, Ru-Ying; Yang, Rui; Li, Xu-Min; Dong, Zhan-Bo; Xiang, Li-Ping; Zheng, Xin-Qiang; Lu, Jian-Liang; Yuan, Cong-Bo; Ye, Jian-Hui; Liang, Yue-Rong

2017-05-20

Diabetes mellitus (DM) is a chronic endocrine disease resulted from insulin secretory defect or insulin resistance and it is a leading cause of death around the world. The care of DM patients consumes a huge budget due to the high frequency of consultations and long hospitalizations, making DM a serious threat to both human health and global economies. Tea contains abundant polyphenols and caffeine which showed antidiabetic activity, so the development of antidiabetic medications from tea and its extracts is increasingly receiving attention. However, the results claiming an association between tea consumption and reduced DM risk are inconsistent. The advances in the epidemiologic evidence and the underlying antidiabetic mechanisms of tea are reviewed in this paper. The inconsistent results and the possible causes behind them are also discussed.

Fishing for Nature's Hits: Establishment of the Zebrafish as a Model for Screening Antidiabetic Natural Products.

PubMed

Tabassum, Nadia; Tai, Hongmei; Jung, Da-Woon; Williams, Darren R

2015-01-01

Diabetes mellitus affects millions of people worldwide and significantly impacts their quality of life. Moreover, life threatening diseases, such as myocardial infarction, blindness, and renal disorders, increase the morbidity rate associated with diabetes. Various natural products from medicinal plants have shown potential as antidiabetes agents in cell-based screening systems. However, many of these potential "hits" fail in mammalian tests, due to issues such as poor pharmacokinetics and/or toxic side effects. To address this problem, the zebrafish (Danio rerio) model has been developed as a "bridge" to provide an experimentally convenient animal-based screening system to identify drug candidates that are active in vivo. In this review, we discuss the application of zebrafish to drug screening technologies for diabetes research. Specifically, the discovery of natural product-based antidiabetes compounds using zebrafish will be described. For example, it has recently been demonstrated that antidiabetic natural compounds can be identified in zebrafish using activity guided fractionation of crude plant extracts. Moreover, the development of fluorescent-tagged glucose bioprobes has allowed the screening of natural product-based modulators of glucose homeostasis in zebrafish. We hope that the discussion of these advances will illustrate the value and simplicity of establishing zebrafish-based assays for antidiabetic compounds in natural products-based laboratories.

Anti-diabetic activity of a mineraloid isolate, in vitro and in genetically diabetic mice.

PubMed

Deneau, Joel; Ahmed, Taufeeq; Blotsky, Roger; Bojanowski, Krzysztof

2011-01-01

Type II diabetes is a metabolic disease mediated through multiple molecular pathways. Here, we report anti-diabetic effect of a standardized isolate from a fossil material - a mineraloid leonardite - in in vitro tests and in genetically diabetic mice. The mineraloid isolate stimulated mitochondrial metabolism in human fibroblasts and this stimulation correlated with enhanced expression of genes coding for mitochondrial proteins such as ATP synthases and ribosomal protein precursors, as measured by DNA microarrays. In the diabetic animal model, consumption of the Totala isolate resulted in decreased weight gain, blood glucose, and glycated hemoglobin. To our best knowledge, this is the first description ever of a fossil material having anti-diabetic activity in pre-clinical models.

Characteristics and in vitro Anti-diabetic Properties of the Korean Rice Wine, Makgeolli Fermented with Laminaria japonica

PubMed Central

Choi, Jae-Suk; Seo, Hyo Ju; Lee, Yu-Ri; Kwon, Su-Jung; Moon, Sun Hwa; Park, Sun-Mee; Sohn, Jae Hak

2014-01-01

New in vitro anti-diabetes makgeolli was produced from rice by adding various quantities of Laminaria japonica, and the fermentation characteristics of the L. japonica makgeolli during the fermentation process were investigated. The contents of alcohol and reducing sugar, and viable count of yeast, of L. japonica makgeolli were not significantly changed when the proportion of L. japonica was increased. The total acid content decreased with an increase in L. japonica concentration; the pH and total bacterial cell count increased in proportion with the increase in L. japonica concentration. The L. japonica makgeolli contents of free sugars, such as fructose, glucose, and sucrose, and of organic acids, such as acetic acid, citric acid, succinic acid, and lactic acid, were altered during fermentation and showed various patterns. The effects of the quantity of L. japonica added on the acceptability and anti-diabetes activities of L. japonica makgeolli were also investigated. In a sensory evaluation, L. japonica makgeolli brewed by adding 2.5 or 5% L. japonica to the mash showed the best overall acceptability; the 12.5% L. japonica sample was least favored due to its seaweed flavor. L. japonica addition did not increase the peroxynitrite-scavenging activity of makgeolli. L. japonica makgeolli showed potent anti-diabetes activity, particularly that containing >7.5% L. japonica. Therefore, L. japonica makgeolli may represent a new functional makgeolli with anti-diabetes properties. PMID:25054108

QSAR studies in the discovery of novel type-II diabetic therapies.

PubMed

Abuhammad, Areej; Taha, Mutasem O

2016-01-01

Type-II diabetes mellitus (T2DM) is a complex chronic disease that represents a major therapeutic challenge. Despite extensive efforts in T2DM drug development, therapies remain unsatisfactory. Currently, there are many novel and important antidiabetic drug targets under investigation by many research groups worldwide. One of the main challenges to develop effective orally active hypoglycemic agents is off-target effects. Computational tools have impacted drug discovery at many levels. One of the earliest methods is quantitative structure-activity relationship (QSAR) studies. QSAR strategies help medicinal chemists understand the relationship between hypoglycemic activity and molecular properties. Hence, QSAR may hold promise in guiding the synthesis of specifically designed novel ligands that demonstrate high potency and target selectivity. This review aims to provide an overview of the QSAR strategies used to model antidiabetic agents. In particular, this review focuses on drug targets that raised recent scientific interest and/or led to successful antidiabetic agents in the market. Special emphasis has been made on studies that led to the identification of novel antidiabetic scaffolds. Computer-aided molecular design and discovery techniques like QSAR have a great potential in designing leads against complex diseases such as T2DM. Combined with other in silico techniques, QSAR can provide more useful and rational insights to facilitate the discovery of novel compounds. However, since T2DM is a complex disease that includes several faulty biological targets, multi-target QSAR studies are recommended in the future to achieve efficient antidiabetic therapies.

Antidiabetic and Antioxidant Activity of Scoparia dulcis Linn.

PubMed

Mishra, M R; Mishra, A; Pradhan, D K; Panda, A K; Behera, R K; Jha, S

2013-09-01

The hypoglycaemic activity of methanol extract of Scoparia dulcis was performed on both in vitro and in vivo models along with determination of total extractable polyphenol. Methanol extract of Scoparia dulcis contains 4.9% and water extract contains 3.2% of total extractable polyphenol. The antioxidant activity showed very promising result in both the tested methods that is 2,2-diphenyl-1-picrylhydrazyl and ferric ion reducing capacity. The antioxidant activity is directly correlated to the antidiabetic potential of drug. The two enzymes (amylase and glycosidase) found in intestine are responsible for the increasing postprandial glucose in body. In vitro model was performed on these enzymes and the results showed that methanol extract of Scoparia dulcis was effective to check the postprandial glucose level. The in vivo hypoglycaemic activity of methanol extract of Scoparia dulcis was performed on streptozotocin-induced diabetes mellitus showed significant inhibition of blood glucose level as compared to control and similar to that of standard glibenclamide. The overall data potentiates the traditional value of Scoparia dulcis as an antidiabetic drug.

Evaluation of Antioxidant, Antidiabetic and Anticholinesterase Activities of Smallanthus sonchifolius Landraces and Correlation with Their Phytochemical Profiles

PubMed Central

Russo, Daniela; Valentão, Patrícia; Andrade, Paula B.; Fernandez, Eloy C.; Milella, Luigi

2015-01-01

The present study aimed to investigate the phytochemical profile of leaf methanol extracts of fourteen Smallanthus sonchifolius (yacon) landraces and their antioxidant, anticholinesterase and antidiabetic activities that could lead to the finding of more effective agents for the treatment and management of Alzheimer’s disease and diabetes. For this purpose, antioxidant activity was assessed using different tests: ferric reducing ability power (FRAP), 2,2-diphenyl-1-picryl hydrazyl (DPPH), nitric oxide (˙NO) and superoxide (O2˙−) scavenging and lipid peroxidation inhibition assays. Anticholinesterase activity was investigated by quantifying the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities, whereas antidiabetic activity was investigated by α-amylase and α-glucosidase inhibition tests. To understand the contribution of metabolites, phytochemical screening was also performed by high performance liquid chromatography-diode array detector (HPLC-DAD) system. Among all, methanol extract of PER09, PER04 and ECU44 landraces exhibited the highest relative antioxidant capacity index (RACI). ECU44 was found to be rich in 4,5-di-O-caffeoylquinic acid (CQA) and 3,5-di-O-CQA and displayed a good α-amylase and α-glucosidase inhibition, showing the lowest IC50 values. Flavonoids, instead, seem to be involved in the AChE and BChE inhibition. The results of this study revealed that the bioactive compound content differences could be determinant for the medicinal properties of this plant especially for antioxidant and antidiabetic activities. PMID:26263984

Evaluation of Antioxidant, Antidiabetic and Anticholinesterase Activities of Smallanthus sonchifolius Landraces and Correlation with Their Phytochemical Profiles.

PubMed

Russo, Daniela; Valentão, Patrícia; Andrade, Paula B; Fernandez, Eloy C; Milella, Luigi

2015-07-31

The present study aimed to investigate the phytochemical profile of leaf methanol extracts of fourteen Smallanthus sonchifolius (yacon) landraces and their antioxidant, anticholinesterase and antidiabetic activities that could lead to the finding of more effective agents for the treatment and management of Alzheimer's disease and diabetes. For this purpose, antioxidant activity was assessed using different tests: ferric reducing ability power (FRAP), 2,2-diphenyl-1-picryl hydrazyl (DPPH), nitric oxide (˙NO) and superoxide (O2˙-) scavenging and lipid peroxidation inhibition assays. Anticholinesterase activity was investigated by quantifying the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities, whereas antidiabetic activity was investigated by α-amylase and α-glucosidase inhibition tests. To understand the contribution of metabolites, phytochemical screening was also performed by high performance liquid chromatography-diode array detector (HPLC-DAD) system. Among all, methanol extract of PER09, PER04 and ECU44 landraces exhibited the highest relative antioxidant capacity index (RACI). ECU44 was found to be rich in 4,5-di-O-caffeoylquinic acid (CQA) and 3,5-di-O-CQA and displayed a good α-amylase and α-glucosidase inhibition, showing the lowest IC50 values. Flavonoids, instead, seem to be involved in the AChE and BChE inhibition. The results of this study revealed that the bioactive compound content differences could be determinant for the medicinal properties of this plant especially for antioxidant and antidiabetic activities.

Antidiabetic Properties, Bioactive Constituents, and Other Therapeutic Effects of Scoparia dulcis.

PubMed

Pamunuwa, Geethi; Karunaratne, D Nedra; Waisundara, Viduranga Y

2016-01-01

This review discusses the antidiabetic activities of Scoparia dulcis as well as its antioxidant and anti-inflammatory properties in relation to the diabetes and its complications. Ethnomedical applications of the herb have been identified as treatment for jaundice, stomach problems, skin disease, fever, and kidney stones, reproductory issues, and piles. Evidence has been demonstrated through scientific studies as to the antidiabetic effects of crude extracts of S. dulcis as well as its bioactive constituents. The primary mechanisms of action of antidiabetic activity of the plant and its bioactive constituents are through α-glucosidase inhibition, curbing of PPAR-γ and increased secretion of insulin. Scoparic acid A, scoparic acid D, scutellarein, apigenin, luteolin, coixol, and glutinol are some of the compounds which have been identified as responsible for these mechanisms of action. S. dulcis has also been shown to exhibit analgesic, antimalarial, hepatoprotective, sedative, hypnotic, antiulcer, antisickling, and antimicrobial activities. Given this evidence, it may be concluded that S. dulcis could be promoted among the masses as an alternative and complementary therapy for diabetes, provided further scientific studies on the toxicological and pharmacological aspects are carried out through either in vivo or clinical means.

Antidiabetic Properties, Bioactive Constituents, and Other Therapeutic Effects of Scoparia dulcis

PubMed Central

Karunaratne, D. Nedra

2016-01-01

This review discusses the antidiabetic activities of Scoparia dulcis as well as its antioxidant and anti-inflammatory properties in relation to the diabetes and its complications. Ethnomedical applications of the herb have been identified as treatment for jaundice, stomach problems, skin disease, fever, and kidney stones, reproductory issues, and piles. Evidence has been demonstrated through scientific studies as to the antidiabetic effects of crude extracts of S. dulcis as well as its bioactive constituents. The primary mechanisms of action of antidiabetic activity of the plant and its bioactive constituents are through α-glucosidase inhibition, curbing of PPAR-γ and increased secretion of insulin. Scoparic acid A, scoparic acid D, scutellarein, apigenin, luteolin, coixol, and glutinol are some of the compounds which have been identified as responsible for these mechanisms of action. S. dulcis has also been shown to exhibit analgesic, antimalarial, hepatoprotective, sedative, hypnotic, antiulcer, antisickling, and antimicrobial activities. Given this evidence, it may be concluded that S. dulcis could be promoted among the masses as an alternative and complementary therapy for diabetes, provided further scientific studies on the toxicological and pharmacological aspects are carried out through either in vivo or clinical means. PMID:27594892

Antidiabetic Activity of Polyherbal Formulation in Streptozotocin – Nicotinamide Induced Diabetic Wistar Rats

PubMed Central

Petchi, Rajendran Ramesh; Vijaya, Chockalingam; Parasuraman, Subramani

2014-01-01

Glycosmis pentaphylla, Tridax procumbens, and Mangifera indica are well-known plants available throughout India and they are commonly used for the treatment of various diseases including diabetes mellitus. The antidiabetic activity of the individual plant parts is well known, but the synergistic or combined effects are unclear. The concept of polyherbalism has been highlighted in Sharangdhar Samhita, an Ayurvedic literature dating back to 1300 AD. Polyherbal formulations enhance the therapeutic action and reduce the concentrations of single herbs, thereby reducing adverse events. The aim of the present study is to formulate a polyherbal formulation and evaluate its antidiabetic potential in animals. The polyherbal formulation was formulated using the ethanol extracts of the stem bark of G. pentaphylla, whole plant of T. procumbens, and leaves of M. indica. The polyherbal formulation contains the ethanol extracts of G. pentaphylla, T. procumbens, and M. indica in the ratio of 2:2:1. The quality of the finished product was evaluated as per the World Health Organization's guidelines for the quality control of herbal materials. The quality testing parameters of the polyherbal formulation were within the limits. Fingerprint analysis of the polyherbal formulation showed effective separation at 366 nm, and it revealed that the active compound present in the polyherbal formulation and the active compounds present in all the three extracts were the same. The acute toxicity studies of the polyherbal formulation did not show any toxic symptoms in doses up to 2000 mg/kg over 14 days. The oral antidiabetic activity of the polyherbal formulation (250 and 500 mg/kg) was screened against streptozotocin (50 mg/kg; i.p.) + nicotinamide (120 mg/kg; i.p.) induced diabetes mellitus in rats. The investigational drug was administered for 21 consecutive days, and the effect of the polyherbal formulation on blood glucose levels was studied at regular intervals. At the end of the study, the blood samples were collected from all the animals for biochemical estimation, and the animals were sacrificed and the liver and pancreatic tissues were collected for histopathologic analysis. Polyherbal formulation showed significant antidiabetic activity at 250 and 500 mg/kg, respectively, and this effect was comparable with that of glibenclamide. The antidiabetic activity of polyherbal formulation is supported by biochemical and histopathologic analysis. PMID:24860734

Antidiabetic activity of polyherbal formulation in streptozotocin - nicotinamide induced diabetic wistar rats.

PubMed

Petchi, Rajendran Ramesh; Vijaya, Chockalingam; Parasuraman, Subramani

2014-04-01

Glycosmis pentaphylla, Tridax procumbens, and Mangifera indica are well-known plants available throughout India and they are commonly used for the treatment of various diseases including diabetes mellitus. The antidiabetic activity of the individual plant parts is well known, but the synergistic or combined effects are unclear. The concept of polyherbalism has been highlighted in Sharangdhar Samhita, an Ayurvedic literature dating back to 1300 AD. Polyherbal formulations enhance the therapeutic action and reduce the concentrations of single herbs, thereby reducing adverse events. The aim of the present study is to formulate a polyherbal formulation and evaluate its antidiabetic potential in animals. The polyherbal formulation was formulated using the ethanol extracts of the stem bark of G. pentaphylla, whole plant of T. procumbens, and leaves of M. indica. The polyherbal formulation contains the ethanol extracts of G. pentaphylla, T. procumbens, and M. indica in the ratio of 2:2:1. The quality of the finished product was evaluated as per the World Health Organization's guidelines for the quality control of herbal materials. The quality testing parameters of the polyherbal formulation were within the limits. Fingerprint analysis of the polyherbal formulation showed effective separation at 366 nm, and it revealed that the active compound present in the polyherbal formulation and the active compounds present in all the three extracts were the same. The acute toxicity studies of the polyherbal formulation did not show any toxic symptoms in doses up to 2000 mg/kg over 14 days. The oral antidiabetic activity of the polyherbal formulation (250 and 500 mg/kg) was screened against streptozotocin (50 mg/kg; i.p.) + nicotinamide (120 mg/kg; i.p.) induced diabetes mellitus in rats. The investigational drug was administered for 21 consecutive days, and the effect of the polyherbal formulation on blood glucose levels was studied at regular intervals. At the end of the study, the blood samples were collected from all the animals for biochemical estimation, and the animals were sacrificed and the liver and pancreatic tissues were collected for histopathologic analysis. Polyherbal formulation showed significant antidiabetic activity at 250 and 500 mg/kg, respectively, and this effect was comparable with that of glibenclamide. The antidiabetic activity of polyherbal formulation is supported by biochemical and histopathologic analysis.

Pterocarpus santalinus L. Regulated Ultraviolet B Irradiation-induced Procollagen Reduction and Matrix Metalloproteinases Expression Through Activation of TGF-β/Smad and Inhibition of the MAPK/AP-1 Pathway in Normal Human Dermal Fibroblasts.

PubMed

Gao, Wei; Lin, Pei; Hwang, Eunson; Wang, Yushuai; Yan, Zhengfei; Ngo, Hien T T; Yi, Tae-Hoo

2018-01-01

Ultraviolet light-induced reactive oxygen species (ROS) damage human skin and prematurely cause aging. A growing body of research is focusing on considering plants and plant-derived compounds as antiphotoaging therapeutic material. Pterocarpus santalinus L., as an Indian traditional medicine, possesses antidiabetic, anti-inflammatory and antioxidative effects. Here, we studied the antiphotoaging effects of ethanolic extract of P. santalinus L. heartwood (EPS) on ultraviolet radiation B (UVB)-irradiated normal human dermal fibroblasts (NHDFs). Results showed that EPS significantly inhibited the upregulation of matrix metalloproteinases and IL-6 caused by UVB irradiation, and suppressed UVB-induced phosphorylation of extracellular signal-regulated kinase, Jun N-terminal kinase and p38, as well as the activation of AP-1 transcription factors. Further study indicated that UVB-induced production of MMP-1 and IL-6 could be inhibited by PD 98059 (an ERK inhibitor) and SP600125 (A JNK inhibitor), implied that EPS inhibited UVB-induced MMP-1 and IL-6 secretion by inactivating MAPK signaling pathway. In addition, EPS possessed an excellent antioxidant activity, which could increase cytoprotective antioxidants such as HO-1, NQ-O1 expression by facilitating the nuclear accumulation of Nrf2. Treatment of NHDFs with EPS also recovered UVB-induced procollagen type I reduction by activating TGF-β/Smad pathway. These findings demonstrated that EPS had a potential effect against UVB-induced skin photoaging. © 2017 The American Society of Photobiology.

Antifertility Effect of Bougainvillea spectabilis or Paper Flower

PubMed Central

Ghogar, Anisa; Jiraungkoorskul, Wannee

2017-01-01

Bougainvillea spectabilis (Family: Nyctaginaceae), commonly referred to as Great Bougainvillea or Paper Flower, is one of the traditional medicinal plants with potential antifertility activity. The aqueous extract and decoction of this plant have been used as fertility control among the tribal people in many countries. Furthermore, it has been shown to possess anticancer, antidiabetic, antihepatotoxic, anti-inflammatory, antihyperlipidemic, antimicrobial, antioxidant, and antiulcer properties. Its phytoconstituents such as alkaloids, essential oils, flavonoids, glycosides, oxalates, phenolics, phlobotannins, quinones, saponins, tannins, and terpenoids were reported as the basis of its efficacious therapeutic properties. The other important constituents which contribute to the remedial properties are bougainvinones, pinitol, quercetagetin, quercetin, and terpinolene. Published information on the antifertility property of B. spectabilis was gathered by the use of different database platforms including Google Scholar, ScienceDirect, PubMed, SciFinder, and Scopus. These database platforms were used to provide an up-to-date review on its importance. PMID:28503048

Solubility enhancement and delivery systems of curcumin a herbal medicine: a review.

PubMed

Hani, Umme; Shivakumar, H G

2014-01-01

Curcumin diferuloylmethane is a main yellow bioactive component of turmeric, possess wide spectrum of biological actions. It was found to have anti-inflammatory, antioxidant, anticarcinogenic, antimutagenic, anticoagulant, antifertility, antidiabetic, antibacterial, antifungal, antiprotozoal, antiviral, antifibrotic, antivenom, antiulcer, hypotensive and hypocholesteremic activities. However, the benefits are curtailed by its extremely poor aqueous solubility, which subsequently limits the bioavailability and therapeutic effects of curcumin. Nanotechnology is the available approach in solving these issues. Therapeutic efficacy of curcumin can be utilized effectively by doing improvement in formulation properties or delivery systems. Numerous attempts have been made to design a delivery system of curcumin. Currently, nanosuspensions, micelles, nanoparticles, nano-emulsions, etc. are used to improve the in vitro dissolution velocity and in vivo efficiency of curcumin. This review focuses on the methods to increase solubility of curcumin and various nanotechnologies based delivery systems and other delivery systems of curcumin.

A review on Insulin plant (Costus igneus Nak).

PubMed

Hegde, Prakash K; Rao, Harini A; Rao, Prasanna N

2014-01-01

Costus igneus Nak and Costus pictus D. Don, commonly known as Spiral flag, is a member of Costaceae and a newly introduced plant in India from South and Central America. It is a perennial, upright, spreading plant reaching about two feet tall, with spirally arranged leaves and attractive flowers. In southern India, it usually grows as an ornamental plant and its leaves are used as a dietary supplement in the treatment of diabetes mellitus. Recently, a number of researches have been carried out to evaluate the anti-diabetic potential of this plant. Besides, it has been proven to possess various pharmacological activities like hypolipidemic, diuretic, antioxidant, anti-microbial, anti-cancerous. Further, various phytochemical investigations reveal the presence of carbohydrates, triterpenoids, proteins, alkaloids, tannins, saponins, flavonoids, steroid, and appreciable amounts of trace elements. This work is an attempt to compile and explore the different pharmacological and phytochemical studies reported till date.

Bitter melon: a panacea for inflammation and cancer.

PubMed

Dandawate, Prasad R; Subramaniam, Dharmalingam; Padhye, Subhash B; Anant, Shrikant

2016-02-01

Nature is a rich source of medicinal plants and their products that are useful for treatment of various diseases and disorders. Momordica charantia, commonly known as bitter melon or bitter gourd, is one of such plants known for its biological activities used in traditional system of medicines. This plant is cultivated in all over the world, including tropical areas of Asia, Amazon, east Africa, and the Caribbean and used as a vegetable as well as folk medicine. All parts of the plant, including the fruit, are commonly consumed and cooked with different vegetables, stir-fried, stuffed or used in small quantities in soups or beans to give a slightly bitter flavor and taste. The plant is reported to possess anti-oxidant, anti-inflammatory, anti-cancer, anti-diabetic, anti-bacterial, anti-obesity, and immunomodulatory activities. The plant extract inhibits cancer cell growth by inducing apoptosis, cell cycle arrest, autophagy and inhibiting cancer stem cells. The plant is rich in bioactive chemical constituents like cucurbitane type triterpenoids, triterpene glycosides, phenolic acids, flavonoids, essential oils, saponins, fatty acids, and proteins. Some of the isolated compounds (Kuguacin J, Karaviloside XI, Kuguaglycoside C, Momordicoside Q-U, Charantin, α-eleostearic acid) and proteins (α-Momorcharin, RNase MC2, MAP30) possess potent biological activity. In the present review, we are summarizing the anti-oxidant, anti-inflammatory, and anti-cancer activities of Momordica charantia along with a short account of important chemical constituents, providing a basis for establishing detail biological activities of the plant and developing novel drug molecules based on the active chemical constituents. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Target guided isolation, in-vitro antidiabetic, antioxidant activity and molecular docking studies of some flavonoids from Albizzia Lebbeck Benth. bark.

PubMed

Ahmed, Danish; Kumar, Vikas; Sharma, Manju; Verma, Amita

2014-05-13

Albizzia Lebbeck Benth. is traditionally important plant and is reported to possess a variety of pharmacological actions. The present research exertion was undertaken to isolate and characterized the flavonoids from the extract of stem bark of Albizzia Lebbeck Benth. and to evaluate the efficacy of the isolated flavonoids on in-vitro models of type-II diabetes. Furthermore, the results of in-vitro experimentation inveterate by the molecular docking studies of the isolated flavonoids on α-glucosidase and α-amylase enzymes. Isolation of the flavonoids from the methanolic extract of stem bark of A. Lebbeck Benth was executed by the Silica gel (Si) column chromatography to yield different fractions. These fractions were then subjected to purification to obtain three important flavonoids. The isolated flavonoids were then structurally elucidated with the assist of 1H-NMR, 13C-NMR, and Mass spectroscopy. In-vitro experimentation was performed with evaluation of α-glucosidase, α-amylase and DPPH inhibition capacity. Molecular docking study was performed with GLIDE docking software. Three flavonoids, (1) 5-deoxyflavone (geraldone), (2) luteolin and (3) Isookanin were isolated from the EtOAc fraction of the methanolic extract of Albizzia lebbeck Benth bark. (ALD). All the compounds revealed to inhibit the α-glucosidase and α-amylase enzymes in in-vitro investigation correlating to reduce the plasma glucose level. Molecular docking study radically corroborates the binding affinity and inhibition of α-glucosidase and α-amylase enzymes. The present research exertion demonstrates the anti-diabetic and antioxidant activity of the important isolated flavonoids with inhibition of α-glucosidase, α-amylase and DPPH which is further supported by molecular docking analysis.

Target guided isolation, in-vitro antidiabetic, antioxidant activity and molecular docking studies of some flavonoids from Albizzia Lebbeck Benth. bark

PubMed Central

2014-01-01

Background Albizzia Lebbeck Benth. is traditionally important plant and is reported to possess a variety of pharmacological actions. The present research exertion was undertaken to isolate and characterized the flavonoids from the extract of stem bark of Albizzia Lebbeck Benth. and to evaluate the efficacy of the isolated flavonoids on in-vitro models of type-II diabetes. Furthermore, the results of in-vitro experimentation inveterate by the molecular docking studies of the isolated flavonoids on α-glucosidase and α-amylase enzymes. Methods Isolation of the flavonoids from the methanolic extract of stem bark of A. Lebbeck Benth was executed by the Silica gel (Si) column chromatography to yield different fractions. These fractions were then subjected to purification to obtain three important flavonoids. The isolated flavonoids were then structurally elucidated with the assist of 1H-NMR, 13C-NMR, and Mass spectroscopy. In-vitro experimentation was performed with evaluation of α-glucosidase, α-amylase and DPPH inhibition capacity. Molecular docking study was performed with GLIDE docking software. Results Three flavonoids, (1) 5-deoxyflavone (geraldone), (2) luteolin and (3) Isookanin were isolated from the EtOAc fraction of the methanolic extract of Albizzia lebbeck Benth bark. (ALD). All the compounds revealed to inhibit the α-glucosidase and α-amylase enzymes in in-vitro investigation correlating to reduce the plasma glucose level. Molecular docking study radically corroborates the binding affinity and inhibition of α-glucosidase and α-amylase enzymes. Conclusion The present research exertion demonstrates the anti-diabetic and antioxidant activity of the important isolated flavonoids with inhibition of α-glucosidase, α-amylase and DPPH which is further supported by molecular docking analysis. PMID:24886138

Investigation of the Blood Glucose Lowering Potential of the Jamaican Momordica charantia (Cerasee) Fruit in Sprague-Dawley Rats

PubMed Central

Burnett, A; McKoy, M-L; Singh, P

2015-01-01

ABSTRACT The Momordica charantia (MC) fruit has been documented to possess antidiabetic properties. However, these studies were not without controversy surrounding the blood glucose-lowering ability and the mechanism of action in diabetes therapy. In an effort to evaluate such claims in the Jamaican MC species known as cerasee, aqueous extracts of the unripe fruit were studied in normal and diabetic rats. Normal male Sprague-Dawley rats were divided into groups (n = 6) orally administered distilled water, 10% dimethyl sulfoxide (DMSO) solution, the aqueous extract (400 mg/kg body weight) and glibenclamide (15 mg/kg body weight), respectively prior to assessment of fasting blood glucose (FBG) concentration. The oral glucose tolerance test (OGTT) was conducted in normoglycaemic rats orally administered distilled water, 10% DMSO solution, glibenclamide (15 mg/kg body weight) or aqueous extracts of the fruit (200 and 400 mg/kg body weight). Blood glucose concentration was also monitored in streptozotocin-induced diabetic rats administered the aqueous extract (250 mg/kg body weight) or water vehicle after an overnight fast. The aqueous extracts showed no hypoglycaemic or antidiabetic activity. However, the administration of the aqueous extracts (200 and 400 mg/kg body weight) resulted in significant improvement in glucose tolerance of glucose-primed normoglycaemic rats during the OGTT. These data suggest that the glucose-lowering mechanism of the Jamaican MC fruit species likely involves altered glucose absorption across the gastrointestinal tract. PMID:26624580

An invertebrate hyperglycemic model for the identification of anti-diabetic drugs.

PubMed

Matsumoto, Yasuhiko; Sumiya, Eriko; Sugita, Takuya; Sekimizu, Kazuhisa

2011-03-30

The number of individuals diagnosed with type 2 diabetes mellitus, which is caused by insulin resistance and/or abnormal insulin secretion, is increasing worldwide, creating a strong demand for the development of more effective anti-diabetic drugs. However, animal-based screening for anti-diabetic compounds requires sacrifice of a large number of diabetic animals, which presents issues in terms of animal welfare. Here, we established a method for evaluating the anti-diabetic effects of compounds using an invertebrate animal, the silkworm, Bombyx mori. Sugar levels in silkworm hemolymph increased immediately after feeding silkworms a high glucose-containing diet, resulting in impaired growth. Human insulin and 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), an AMP-activated protein kinase (AMPK) activator, decreased the hemolymph sugar levels of the hyperglycemic silkworms and restored growth. Treatment of the isolated fat body with human insulin in an in vitro culture system increased total sugar in the fat body and stimulated Akt phosphorylation. These responses were inhibited by wortmannin, an inhibitor of phosphoinositide 3 kinase. Moreover, AICAR stimulated AMPK phosphorylation in the silkworm fat body. Administration of aminoguanidine, a Maillard reaction inhibitor, repressed the accumulation of Maillard reaction products (advanced glycation end-products; AGEs) in the hyperglycemic silkworms and restored growth, suggesting that the growth defect of hyperglycemic silkworms is caused by AGE accumulation in the hemolymph. Furthermore, we identified galactose as a hypoglycemic compound in jiou, an herbal medicine for diabetes, by monitoring its hypoglycemic activity in hyperglycemic silkworms. These results suggest that the hyperglycemic silkworm model is useful for identifying anti-diabetic drugs that show therapeutic effects in mammals.

Antidiabetic activity of Pongamia pinnata leaf extracts in alloxan-induced diabetic rats

PubMed Central

Sikarwar, Mukesh S.; Patil, M.B.

2010-01-01

The antidiabetic activity of Pongamia pinnata ( Family: Leguminosae) leaf extracts was investigated in alloxan-induced diabetic albino rats. A comparison was made between the action of different extracts of P. pinnata and a known antidiabetic drug glibenclamide (600 μg/kg b. wt.). An oral glucose tolerance test (OGTT) was also performed in experimental diabetic rats. The petroleum ether, chloroform, alcohol and aqueous extracts of P. pinnata were obtained by simple maceration method and were subjected to standardization using pharmacognostical and phytochemical screening methods. Dose selection was made on the basis of acute oral toxicity study (50-5000 mg/kg b. w.) as per OECD guidelines. P. pinnata ethanolic extract (PPEE) and aqueous extract (PPAE) showed significant (P < 0.001) antidiabetic activity. In alloxan-induced model, blood glucose levels of these extracts on 7th day of the study were 155.83 ± 11.211mg/dl (PPEE) and 132.00 ± 4.955mg/dl (PPAE) in comparison of diabetic control (413.50 ± 4.752mg/dl) and chloroform extract (210.83 ± 14.912mg/dl). In glucose loaded rats, PPEE exhibited glucose level of 164.50 ± 6.350mg/dl after 30 min and 156.50 ± 4.089mg/dl after 90 min, whereas the levels in PPAE treated animals were 176 ± 3.724mg/dl after 30 min and 110.33 ± 6.687mg/dl after 90 min. These extracts also prevented body weight loss in diabetic rats. The drug has the potential to act as an antidiabetic drug. PMID:21455444

Antidiabetic phytoconstituents and their mode of action on metabolic pathways

PubMed Central

Bharti, Sudhanshu Kumar; Krishnan, Supriya; Kumar, Ashwini

2018-01-01

Diabetes Mellitus, characterized by persistent hyperglycaemia, is a heterogeneous group of disorders of multiple aetiologies. It affects the human body at multiple organ levels thus making it difficult to follow a particular line of the treatment protocol and requires a multimodal approach. The increasing medical burden on patients with diabetes-related complications results in an enormous economic burden, which could severely impair global economic growth in the near future. This shows that today’s healthcare system has conventionally been poorly equipped towards confronting the mounting impact of diabetes on a global scale and demands an urgent need for newer and better options. The overall challenge of this field of diabetes treatment is to identify the individualized factors that can lead to improved glycaemic control. Plants are traditionally used worldwide as remedies for diabetes healing. They synthesize a diverse array of biologically active compounds having antidiabetic properties. This review is an endeavour to document the present armamentarium of antidiabetic herbal drug discovery and developments, highlighting mechanism-based antidiabetic properties of over 300 different phytoconstituents of various chemical categories from about 100 different plants modulating different metabolic pathways such as glycolysis, Krebs cycle, gluconeogenesis, glycogen synthesis and degradation, cholesterol synthesis, carbohydrate metabolism as well as peroxisome proliferator activated receptor activation, dipeptidyl peptidase inhibition and free radical scavenging action. The aim is to provide a rich reservoir of pharmacologically established antidiabetic phytoconstituents with specific references to the novel, cost-effective interventions, which might be of relevance to other low-income and middle-income countries of the world. PMID:29492244

Antidiabetic and antihiperlipidemic effect of Andrographis paniculata (Burm. f.) Nees and andrographolide in high-fructose-fat-fed rats

PubMed Central

Nugroho, Agung Endro; Andrie, Mohamad; Warditiani, Ni Kadek; Siswanto, Eka; Pramono, Suwidjiyo; Lukitaningsih, Endang

2012-01-01

Objectives: Andrographis paniculata (Burm. f.) Nees originates from India and grows widely in many areas in Southeast Asian countries. Andrographis paniculata (Burm. f.) Nees has shown an antidiabetic effect in type 1 DM rats. The present study investigates the purified extract of the plant and its active compound andrographolide for antidiabetic and antihyperlipidemic effects in high-fructose-fat-fed rats, a model of type 2 DM rats. Materials and Methods: Hyperglycemia in rats was induced by high-fructose-fat diet containing 36% fructose, 15% lard, and 5% egg yolks in 0.36 g/200 gb.wt. 55 days. The rats were treated with the extract or test compound on the 50th day. Antidiabetic activity was measured by estimating mainly the pre– and postprandial blood glucose levels and other parameters such as cholesterol, LDL, triglyceride, and body weight. Results: The purified extract and andrographolide significantly (P<0.05) decreased the levels of blood glucose, triglyceride, and LDL compared to controls. However, no changes were observed in serum cholesterol and rat body weight. Metformin also showed similar effects on these parameters. Conclusions: Andrographis paniculata (Burm. f.) Nees or its active compound andrographolide showed hypoglycemic and hypolipidemic effects in high-fat-fructose-fed rat. PMID:22701250

Studies on the Antidiabetic Activities of Cordyceps militaris Extract in Diet-Streptozotocin-Induced Diabetic Sprague-Dawley Rats

PubMed Central

Dong, Yuan; Jing, Tianjiao; Meng, Qingfan; Liu, Chungang; Hu, Shuang; Ma, Yihang; Liu, Yan; Lu, Jiahui; Cheng, Yingkun; Teng, Lirong

2014-01-01

Due to substantial morbidity and high complications, diabetes mellitus is considered as the third “killer” in the world. A search for alternative antidiabetic drugs from herbs or fungi is highly demanded. Our present study aims to investigate the antidiabetic activities of Cordyceps militaris on diet-streptozotocin-induced type 2 diabetes mellitus in rats. Diabetic rats were orally administered with water extract or alcohol extract at 0.05 g/kg and 2 g/kg for 3 weeks, and then, the factors levels related to blood glucose, lipid, free radicals, and even nephropathy were determined. Pathological alterations on liver and kidney were examined. Data showed that, similar to metformin, Cordyceps militaris extracts displayed a significant reduction in blood glucose levels by promoting glucose metabolism and strongly suppressed total cholesterol and triglycerides concentration in serum. Cordyceps militaris extracts exhibit antioxidative effects indicated by normalized superoxide dismutase and glutathione peroxidase levels. The inhibitory effects on blood urea nitrogen, creatinine, uric acid, and protein revealed the protection of Cordyceps militaris extracts against diabetic nephropathy, which was confirmed by pathological morphology reversion. Collectively, Cordyceps militaris extract, a safe pharmaceutical agent, presents excellent antidiabetic and antinephropathic activities and thus has great potential as a new source for diabetes treatment. PMID:24738047

Cinnamic acid exerts anti-diabetic activity by improving glucose tolerance in vivo and by stimulating insulin secretion in vitro.

PubMed

Hafizur, Rahman M; Hameed, Abdul; Shukrana, Mishkat; Raza, Sayed Ali; Chishti, Sidra; Kabir, Nurul; Siddiqui, Rehan A

2015-02-15

Although the anti-diabetic activity of cinnamic acid, a pure compound from cinnamon, has been reported but its mechanism(s) is not yet clear. The present study was designed to explore the possible mechanism(s) of anti-diabetic activity of cinnamic acid in in vitro and in vivo non-obese type 2 diabetic rats. Non-obese type 2 diabetes was developed by injecting 90 mg/kg streptozotocin in 2-day-old Wistar pups. Cinnamic acid and cinnamaldehyde were administered orally to diabetic rats for assessing acute blood glucose lowering effect and improvement of glucose tolerance. Additionally, insulin secretory activity of cinnamic acid and cinnamaldehyde was evaluated in isolated mice islets. Cinnamic acid, but not cinnamaldehyde, decreased blood glucose levels in diabetic rats in a time- and dose-dependent manner. Oral administration of cinnamic acid with 5 and 10 mg/kg doses to diabetic rats improved glucose tolerance in a dose-dependent manner. The improvement by 10 mg/kg cinnamic acid was comparable to that of standard drug glibenclamide (5 mg/kg). Further in vitro studies showed that cinnamaldehyde has little or no effect on glucose-stimulated insulin secretion; however, cinnamic acid significantly enhanced glucose-stimulated insulin secretion in isolated islets. In conclusion, it can be said that cinnamic acid exerts anti-diabetic activity by improving glucose tolerance in vivo and stimulating insulin secretion in vitro. Copyright © 2015 Elsevier GmbH. All rights reserved.

Cameroonian Medicinal Plants: Pharmacology and Derived Natural Products

PubMed Central

Kuete, Victor; Efferth, Thomas

2010-01-01

Many developing countries including Cameroon have mortality patterns that reflect high levels of infectious diseases and the risk of death during pregnancy and childbirth, in addition to cancers, cardiovascular diseases and chronic respiratory diseases that account for most deaths in the developed world. Several medicinal plants are used traditionally for their treatment. In this review, plants used in Cameroonian traditional medicine with evidence for the activities of their crude extracts and/or derived products have been discussed. A considerable number of plant extracts and isolated compounds possess significant antimicrobial, anti-parasitic including antimalarial, anti-proliferative, anti-inflammatory, anti-diabetes, and antioxidant effects. Most of the biologically active compounds belong to terpenoids, phenolics, and alkaloids. Terpenoids from Cameroonian plants showed best activities as anti-parasitic, but rather poor antimicrobial effects. The best antimicrobial, anti-proliferative, and antioxidant compounds were phenolics. In conclusion, many medicinal plants traditionally used in Cameroon to treat various ailments displayed good activities in vitro. This explains the endeavor of Cameroonian research institutes in drug discovery from indigenous medicinal plants. However, much work is still to be done to standardize methodologies and to study the mechanisms of action of isolated natural products. PMID:21833168

Antidiabetic and Antioxidant Activity of Scoparia dulcis Linn.

PubMed Central

Mishra, M. R.; Mishra, A.; Pradhan, D. K.; Panda, A. K.; Behera, R. K.; Jha, S.

2013-01-01

The hypoglycaemic activity of methanol extract of Scoparia dulcis was performed on both in vitro and in vivo models along with determination of total extractable polyphenol. Methanol extract of Scoparia dulcis contains 4.9% and water extract contains 3.2% of total extractable polyphenol. The antioxidant activity showed very promising result in both the tested methods that is 2,2-diphenyl-1-picrylhydrazyl and ferric ion reducing capacity. The antioxidant activity is directly correlated to the antidiabetic potential of drug. The two enzymes (amylase and glycosidase) found in intestine are responsible for the increasing postprandial glucose in body. In vitro model was performed on these enzymes and the results showed that methanol extract of Scoparia dulcis was effective to check the postprandial glucose level. The in vivo hypoglycaemic activity of methanol extract of Scoparia dulcis was performed on streptozotocin-induced diabetes mellitus showed significant inhibition of blood glucose level as compared to control and similar to that of standard glibenclamide. The overall data potentiates the traditional value of Scoparia dulcis as an antidiabetic drug. PMID:24403665

Anti-Diabetic Effects of Dung Beetle Glycosaminoglycan on db Mice and Gene Expression Profiling.

PubMed

Ahn, Mi Young; Kim, Ban Ji; Yoon, Hyung Joo; Hwang, Jae Sam; Park, Kun-Koo

2018-04-01

Anti-diabetes activity of Catharsius molossus (Ca, a type of dung beetle) glycosaminoglycan (G) was evaluated to reduce glucose, creatinine kinase, triglyceride and free fatty acid levels in db mice. Diabetic mice in six groups were administrated intraperitoneally: Db heterozygous (Normal), Db homozygous (CON), Heuchys sanguinea glycosaminoglycan (HEG, 5 mg/kg), dung beetle glycosaminoglycan (CaG, 5 mg/kg), bumblebee ( Bombus ignitus ) queen glycosaminoglycan (IQG, 5 mg/kg) and metformin (10 mg/kg), for 1 month. Biochemical analyses in the serum were evaluated to determine their anti-diabetic and anti-inflammatory actions in db mice after 1 month treatment with HEG, CaG or IQG treatments. Blood glucose level was decreased by treatment with CaG. CaG produced significant anti-diabetic actions by inhiting creatinine kinase and alkaline phosphatase levels. As diabetic parameters, serum glucose level, total cholesterol and triglyceride were significantly decreased in CaG5-treated group compared to the controls. Dung beetle glycosaminoglycan, compared to the control, could be a potential therapeutic agent with anti-diabetic activity in diabetic mice. CaG5-treated group, compared to the control, showed the up-regulation of 48 genes including mitochondrial yen coded tRNA lysine (mt-TK), cytochrome P450, family 8/2, subfamily b, polypeptide 1 (Cyp8b1), and down-regulation of 79 genes including S100 calcium binding protein A9 (S100a9) and immunoglobulin kappa chain complex (Igk), and 3-hydroxy-3-methylglutaryl-CoenzymeAsynthase1 (Hmgcs1). Moreover, mitochondrial thymidine kinase (mt-TK), was up-regulated, and calgranulin A (S100a9) were down-regulated by CaG5 treatment, indicating a potential therapeutic use for anti-diabetic agent.

New Findings on Biological Actions and Clinical Applications of Royal Jelly: A Review.

PubMed

Khazaei, Mozafar; Ansarian, Atefe; Ghanbari, Elham

2017-10-13

Royal jelly (RJ) is a natural bee product with great potential for use in medicine. The chemical composition of RJ indicates the presence of various bioactive substances including 10-hydroxydecanoic acid and 24-methylenecholesterol. In addition, a number of biological and pharmacological activities of RJ have been documented. The aim of this study was to review the biological and medical effects of RJ. The search was conducted in articles from electronic and scientific literature databases such as Pub Med, Science Direct, Scopus, Medline, and ISI Web of Science published from 1990 to 2017 using keywords of pharmacological, biological, and clinical effects and royal jelly. Data were chosen after the primary survey of all abstracts and selected full articles. Comparison among related data was done by the authors. Literature has shown that RJ possesses many beneficial effects on biological systems. For example, the therapeutic uses of RJ have been reported in several diseases such as hypercholesterolemia, diabetes, hypertension, and cancers. It was also found to possess neurotrophic, hypotensive, immunomodulatory, antimicrobial, antioxidant, antidiabetic, antihypercholesterolemic, antitumor, and anti-inflammatory effects. Owing to the broad spectrum of biological effects and valuable clinical trials, evaluating the beneficial pharmaceutical effects of RJ in animal and human models seems to be important.

Effect of novel water soluble curcumin derivative on experimental type- 1 diabetes mellitus (short term study)

PubMed Central

2012-01-01

Background Diabetes mellitus type 1 is an autoimmune disorder caused by lymphocytic infiltration and beta cells destruction. Curcumin has been identified as a potent inducer of heme-oxygenase-1 (HO-1), a redoxsensitive inducible protein that provides protection against various forms of stress. A novel water soluble curcumin derivative (NCD) has been developed to overcome low in vivo bioavailability of curcumin. The aim of the present work is to evaluate the anti diabetic effects of the “NCD” and its effects on diabetes-induced ROS generation and lipid peroxidation in experimental type- 1 diabetes mellitus. We also examine whether the up regulation of HO-1 accompanied by increased HO activity mediates these antidiabetic and anti oxidant actions. Materials and methods Rats were divided into control group, control group receiving curcumin derivative, diabetic group, diabetic group receiving curcumin derivative and diabetic group receiving curcumin derivative and HO inhibitor ZnPP. Type-1 diabetes was induced by intraperitoneal injection of streptozotocin. Curcumin derivative was given orally for 45 days. At the planned sacrification time (after 45 days), fasting blood samples were withdrawn for estimation of plasma glucose, plasma insulin and lipid profile . Animals were sacrificed; pancreas, aorta and liver were excised for the heme oxygenase - 1 expression, activity and malondialdehyde estimation. Results NCD supplementation to diabetic rats significantly lowered the plasma glucose by 27.5% and increased plasma insulin by 66.67%. On the other hand, the mean plasma glucose level in the control group showed no significant difference compared to the control group receiving the oral NCD whereas, NCD supplementation to the control rats significantly increased the plasma insulin by 47.13% compared to the control. NCD decreased total cholesterol, triglycerides, LDL cholesterol and increased HDL cholesterol levels. Also, it decreased lipid peroxides (malondialdehyde) in the pancreas, aorta and liver. Conclusion The (NCD) by its small dose possesses antidiabetic actions and that heme oxygenase induction seems to play an important role in its anti-diabetic effects. NCD also improves the lipid profile and oxidative status directly, proved by decreasing lipid peroxides (malondialdehyde) in pancreas, liver & aorta. The new water soluble curcumin derivative still retains the essential potencies of natural curcumin. PMID:22762693

The development of Terminalia chebula Retz. (Combretaceae) in clinical research

PubMed Central

Bag, Anwesa; Bhattacharyya, Subir Kumar; Chattopadhyay, Rabi Ranjan

2013-01-01

Medicinal plants are part and parcel of human society to combat diseases from the dawn of civilization. Terminalia chebula Retz. (Fam. Combretaceae), is called the ‘King of Medicine’ in Tibet and is always listed at the top of the list of ‘Ayurvedic Materia Medica’ because of its extraordinary power of healing. The whole plant possesses high medicinal value and traditionally used for the treatment of various ailments for human beings. Some of the folklore people used this plant in the treatment of asthma, sore throat, vomiting, hiccough, diarrhea, dysentery, bleeding piles, ulcers, gout, heart and bladder diseases. The plant has been demonstrated to possess multiple pharmacological and medicinal activities, such as antioxidant, antimicrobial, antidiabetic, hepatoprotective, anti-inflammatory, antimutagenic, antiproliferative, radioprotective, cardioprotective, antiarthritic, anticaries, gastrointestinal motility and wound healing activity. But no systematic updated information on the therapeutic effectiveness of Terminalia chebula, a popular herbal remedy in India and South-East Asia has so far been reported. This review highlights an updated information particularly on the phytochemistry and various pharmacological and medicinal properties of Terminalia chebula Retz. and some of its isolated compounds, along with their safety evaluation. This may provide incentive for proper evaluation of the plant as medicinal agent against the human diseases and also to bridge the lacunae in the existing literature and future scope which may offer immense opportunity for researchers engaged in validation of the traditional claims and development of safe and effective botanical medicine. PMID:23620847

The development of Terminalia chebula Retz. (Combretaceae) in clinical research.

PubMed

Bag, Anwesa; Bhattacharyya, Subir Kumar; Chattopadhyay, Rabi Ranjan

2013-03-01

Medicinal plants are part and parcel of human society to combat diseases from the dawn of civilization. Terminalia chebula Retz. (Fam. Combretaceae), is called the 'King of Medicine' in Tibet and is always listed at the top of the list of 'Ayurvedic Materia Medica' because of its extraordinary power of healing. The whole plant possesses high medicinal value and traditionally used for the treatment of various ailments for human beings. Some of the folklore people used this plant in the treatment of asthma, sore throat, vomiting, hiccough, diarrhea, dysentery, bleeding piles, ulcers, gout, heart and bladder diseases. The plant has been demonstrated to possess multiple pharmacological and medicinal activities, such as antioxidant, antimicrobial, antidiabetic, hepatoprotective, anti-inflammatory, antimutagenic, antiproliferative, radioprotective, cardioprotective, antiarthritic, anticaries, gastrointestinal motility and wound healing activity. But no systematic updated information on the therapeutic effectiveness of Terminalia chebula, a popular herbal remedy in India and South-East Asia has so far been reported. This review highlights an updated information particularly on the phytochemistry and various pharmacological and medicinal properties of Terminalia chebula Retz. and some of its isolated compounds, along with their safety evaluation. This may provide incentive for proper evaluation of the plant as medicinal agent against the human diseases and also to bridge the lacunae in the existing literature and future scope which may offer immense opportunity for researchers engaged in validation of the traditional claims and development of safe and effective botanical medicine.

Evaluation of α-Glucosidase Inhibitory Effect of 50% Ethanolic Standardized Extract of Orthosiphon stamineus Benth in Normal and Streptozotocin-Induced Diabetic Rats

PubMed Central

Mohamed, Elsnoussi Ali; Ang, Lee Fung; Asmawi, Mohd. Zaini

2015-01-01

In the present study, a 50% ethanolic extract of Orthosiphon stamineus was tested for its α-glucosidase inhibitory activity. In vivo assays of the extract (containing 1.02%, 3.76%, and 3.03% of 3′hydroxy-5,6,7,4′-tetramethoxyflavone, sinensetin, and eupatorin, resp.) showed that it possessed an inhibitory activity against α-glucosidase in normal rats loaded with starch and sucrose. The results showed that 1000 mg/kg of the 50% ethanolic extract of O. stamineus significantly (P < 0.05) decreased the plasma glucose levels of the experimental animals in a manner resembling the effect of acarbose. In streptozotocin-induced diabetic rats, only the group treated with 1000 mg/kg of the extract showed significantly (P < 0.05) lower plasma glucose levels after starch loading. Hence, α-glucosidase inhibition might be one of the mechanisms by which O. stamineus extract exerts its antidiabetic effect. Furthermore, our findings indicated that the 50% ethanolic extract of O. stamineus can be considered as a potential agent for the management of diabetes mellitus. PMID:26649063

Evaluation of α-Glucosidase Inhibitory Effect of 50% Ethanolic Standardized Extract of Orthosiphon stamineus Benth in Normal and Streptozotocin-Induced Diabetic Rats.

PubMed

Mohamed, Elsnoussi Ali; Ahmad, Mariam; Ang, Lee Fung; Asmawi, Mohd Zaini; Yam, Mun Fei

2015-01-01

In the present study, a 50% ethanolic extract of Orthosiphon stamineus was tested for its α-glucosidase inhibitory activity. In vivo assays of the extract (containing 1.02%, 3.76%, and 3.03% of 3'hydroxy-5,6,7,4'-tetramethoxyflavone, sinensetin, and eupatorin, resp.) showed that it possessed an inhibitory activity against α-glucosidase in normal rats loaded with starch and sucrose. The results showed that 1000 mg/kg of the 50% ethanolic extract of O. stamineus significantly (P < 0.05) decreased the plasma glucose levels of the experimental animals in a manner resembling the effect of acarbose. In streptozotocin-induced diabetic rats, only the group treated with 1000 mg/kg of the extract showed significantly (P < 0.05) lower plasma glucose levels after starch loading. Hence, α-glucosidase inhibition might be one of the mechanisms by which O. stamineus extract exerts its antidiabetic effect. Furthermore, our findings indicated that the 50% ethanolic extract of O. stamineus can be considered as a potential agent for the management of diabetes mellitus.

Alpha-Glucosidase Enzyme Biosensor for the Electrochemical Measurement of Antidiabetic Potential of Medicinal Plants

NASA Astrophysics Data System (ADS)

Mohiuddin, M.; Arbain, D.; Islam, A. K. M. Shafiqul; Ahmad, M. S.; Ahmad, M. N.

2016-02-01

A biosensor for measuring the antidiabetic potential of medicinal plants was developed by covalent immobilization of α-glucosidase (AG) enzyme onto amine-functionalized multi-walled carbon nanotubes (MWCNTs-NH2). The immobilized enzyme was entrapped in freeze-thawed polyvinyl alcohol (PVA) together with p-nitrophenyl-α- d-glucopyranoside (PNPG) on the screen-printed carbon electrode at low pH to prevent the premature reaction between PNPG and AG enzyme. The enzymatic reaction within the biosensor is inhibited by bioactive compounds in the medicinal plant extracts. The capability of medicinal plants to inhibit the AG enzyme on the electrode correlates to the potential of the medicinal plants to inhibit the production of glucose from the carbohydrate in the human body. Thus, the inhibition indicates the antidiabetic potential of the medicinal plants. The performance of the biosensor was evaluated to measure the antidiabetic potential of three medicinal plants such as Tebengau ( Ehretis laevis), Cemumar ( Micromelum pubescens), and Kedondong ( Spondias dulcis) and acarbose (commercial antidiabetic drug) via cyclic voltammetry, amperometry, and spectrophotometry. The cyclic voltammetry (CV) response for the inhibition of the AG enzyme activity by Tebengau plant extracts showed a linear relation in the range from 0.423-8.29 μA, and the inhibition detection limit was 0.253 μA. The biosensor exhibited good sensitivity (0.422 μA/mg Tebengau plant extracts) and rapid response (22 s). The biosensor retains approximately 82.16 % of its initial activity even after 30 days of storage at 4 °C.

Economic impact of compliance to treatment with antidiabetes medication in type 2 diabetes mellitus: a review paper.

PubMed

Breitscheidel, L; Stamenitis, S; Dippel, F-W; Schöffski, O

2010-03-01

Suboptimal compliance and failure to persist with antidiabetes therapies are of potential economic significance. The present research aims to describe the impact of poor compliance and persistence with antidiabetes medications on the cost of healthcare or its components for patients with type 2 diabetes mellitus (T2DM). Literature search was conducted in PubMed for relevant articles published in the period between 1 January 2000 and 30 April 2009. Thus, it is possible that relevant articles not listed in PubMed, but available in other databases are not included in the current review. Studies describing economic consequence of compliance and/or persistence with pharmaceutical antidiabetes treatment were identified. The variability in the studies reviewed was high, making it extremely difficult to make a comparison between them. Of 449 articles corresponding to the primary search algorithm, 12 studies (all conducted in USA) fulfilled the inclusion criteria regarding the economic impact of compliance and/or persistence with treatment on the overall cost of T2DM care or its components. Compliance was assessed via medication possession ratio (MPR) in ten studies, where it ranged from 0.52 to 0.93 depending on regimen. Persistence was assessed in one study. Mean total annual costs per T2DM patient varied between the studies, ranging from $4570 to $17338. In seven studies, medication compliance was inversely associated with total healthcare costs, while in four other studies inverse associations between medication compliance and hospitalisation costs were reported. In one study increased adherence did not change overall healthcare costs. Improved compliance may lead to reductions of the total healthcare costs in T2DM, Further research is needed in countries other than the US to assess impact of compliance and persistence to pharmacotherapy on T2DM costs in country-specific settings.

Diabetes mellitus: An overview on its pharmacological aspects and reported medicinal plants having antidiabetic activity

PubMed Central

Patel, DK; Kumar, R; Laloo, D; Hemalatha, S

2012-01-01

Diabetes mellitus is not a single disease but is a group of metabolic disorders affecting a huge number of population in the world. It is mainly characterized by chronic hyperglycemia, resulting from defects in insulin secretion or insulin action. It is predicated that the number of diabetes person in the world could reach upto 366 million by the year 2030. Even though the cases of diabetes are increasing day by day, except insulin and oral hypoglycemic drugs no other way of treatment has been successfully developed so far. Thus, the objective of the present review is to provide an insight over the pathophysiological and etiological aspects of diabetes mellitus along with the remedies available for this metabolic disorder. The review also contains brief idea about diabetes mellitus and the experimental screening model with their relevant mechanism and significance mainly used nowadays. Alloxan and streptozotocin are mainly used for evaluating the antidiabetic activity of a particular drug. This review contain list of medicinal plants which have been tested for their antidiabetic activity in the alloxan induced diabetic rat model. From the available data in the literature, it was found that plant having antidiabetic activity is mainly due to the presence of the secondary metabolite. Thus, the information provided in this review will help the researchers for the development of an alternative methods rather than insulin and oral hypoglycemic agents for the treatment of diabetes mellitus, which will minimize the complication associated with the diabetes and related disorder. PMID:23569941

Antihyperglycemic effect of crude extracts of some Egyptian plants and algae.

PubMed

AbouZid, Sameh Fekry; Ahmed, Osama Mohamed; Ahmed, Rasha Rashad; Mahmoud, Ayman; Abdella, Ehab; Ashour, Mohamed Badr

2014-03-01

Diabetes mellitus is a major global health problem. Various plant extracts have proven antidiabetic activity and are considered as promising substitution for antidiabetic drugs. The antihyperglycemic effect of 16 plants and 4 algae, commonly used in Egypt for the treatment of diabetes mellitus, was investigated. A diabetes model was induced by intraperitoneal injection of nicotinamide (120 mg/kg body weight [b.wt.]), then streptozotocin (200 mg/kg b.wt.) after 15 min. Hydroethanolic extracts (80%) of the plants and algae under investigation were prepared. The extracts were orally administered to nicotinamide-streptozotocin-induced diabetic mice by a gastric tube at doses 10 or 50 mg/kg b.wt. for 1 week. The antidiabetic activity was assessed by detection of serum glucose concentrations at the fasting state and after 2 h of oral glucose loading (4.2 mg/kg b.wt.). Extracts prepared from Cassia acutifolia, Fraxinus ornus, Salix aegyptiaca, Cichorium intybus, and Eucalyptus globulus showed the highest antihyperglycemic activity among the tested plants. Extracts prepared from Sonchus oleraceus, Bougainvillea spectabilis (leaves), Plantago psyllium (seeds), Morus nigra (leaves), and Serena repens (fruits) were found to have antihyperglycemic potentials. Extracts prepared from Caulerpa lentillifera and Spirulina versicolor showed the most potent antihyperglycemic activity among the tested algae. However, some of the tested plants have insulinotropic effects, all assessed algae have not. Identification of lead compounds from these plants and algae for novel antidiabetic drug development is recommended.

Antioxidant and antidiabetic properties of tartary buckwheat rice flavonoids after in vitro digestion*

PubMed Central

Bao, Tao; Wang, Ye; Li, Yu-ting; Gowd, Vemana; Niu, Xin-he; Yang, Hai-ying; Chen, Li-shui; Chen, Wei; Sun, Chong-de

2016-01-01

Oxidative stress and diabetes have a tendency to alter protein, lipid, and DNA moieties. One of the strategic methods used to reduce diabetes-associated oxidative stress is to inhibit the carbohydrate-digesting enzymes, thereby decreasing gastrointestinal glucose production. Plant-derived natural antioxidant molecules are considered a therapeutic tool in the treatment of oxidative stress and diabetes. The objective of this study was to identify tartary buckwheat rice flavonoids and evaluate the effect of in vitro digestion on their antioxidant and antidiabetic properties. High performance liquid chromatography (HPLC) analysis indicated the presence of rutin as a major component and quercitrin as a minor component of both digested and non-digested flavonoids. Both extracts showed a significant antioxidant capacity, but digested flavonoids showed reduced activity compared to non-digested. There were some decreases of the antioxidant activities (2,2'-azino-bis-(3-ethylbenzthiazoline-6-sulfonic acid) diammonium salt (ABTS), 2,2-diphenyl-1-picrylhydrazy (DPPH) radical, and ferric reducing antioxidant power (FRAP)) of digested tartary buckwheat rice flavonoids compared with non-digested. Flavonoids from both groups significantly inhibited reactive oxygen species (ROS) production and α-glucosidase activity. Both digested and non-digested flavonoids markedly increased glucose consumption and glycogen content in HepG2 cells. Tartary buckwheat rice flavonoids showed appreciable antioxidant and antidiabetic properties, even after digestion. Tartary buckwheat rice appears to be a promising functional food with potent antioxidant and antidiabetic properties. PMID:27921399

DFT predictions, synthesis, stoichiometric structures and anti-diabetic activity of Cu (II) and Fe (III) complexes of quercetin, morin, and primuletin

NASA Astrophysics Data System (ADS)

Jabeen, Erum; Janjua, Naveed Kausar; Ahmed, Safeer; Murtaza, Iram; Ali, Tahir; Masood, Nosheen; Rizvi, Aysha Sarfraz; Murtaza, Gulam

2017-12-01

The current study is aimed at the synthesis of Cu (II) and Fe (III) complexes of three flavonoids {morin (mor), quercetin (quer) and primuletin (prim)} and characterization through UV-Vis spectroscopy, cyclic voltammetry, FTIR, and thermal analysis. Structure prediction through DFT calculation was supported by experimental data. Benesi-Hildebrand equation was modified to function for 1:2 Cu-flavonoid and 1:3 Fe-flavonoid complexes. DFT predictions revealed that out of poly chelation sites present in morin and quercetin, 3-OH site was utilized as preferable chelation site while primuletin chelated through 5-OH position. In-vivo trials revealed the complexes to have better anti-diabetic potential than respective flavonoid. Fls/M-Fls proved as antagonistic to Alloxan induced diabetes and also retained anti-diabetic activity even in the presence of (2-hydroxypropyl)-β-cyclodextrin (HPβCD).

Evaluation of antioxidative and antidiabetic activity of bark of holarrhena pubescens wall.

PubMed

Bhusal, Anup; Jamarkattel, Nirmala; Shrestha, Aasmin; Lamsal, Nisha Kiran; Shakya, Sangam; Rajbhandari, Sneha

2014-09-01

The objectives of the study are to screen out various phytochemicals and to evaluate the antioxidant and antidiabetic potential of the stem bark of Holarrhena pubescens Wall (Holarrhena antidysenterica). The antioxidant activity was determined by the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity where ascorbic acid was taken as positive control. The antioxidant property was later exploited and the methanolic extract of plant was tested for antihyperglycemic activity in glucose overloaded hyperglycemic mice. The extract was tested for its hypoglycemic activity at two-dose levels, 250 and 500 mg/kg respectively where Glipizide 5 mg/kg was taken as standard reference drug. All results are presented as mean ± SD (Standard Deviation). Significant differences between experimental groups were determined by Student's t-test. The methanolic and water extract showed strong antioxidant activity with inhibition of more than 90% DPPH free radicals at the concentration of 100μg/mL. The hypoglycemic activity of methanolic extract on glucose tolerance test were significant (p <0.05) for the effects of 500 mg/kg after 120 min of treatment and (p <0.01) for 250 mg/kg of extract after half hour of treatment compared to control. The presence of flavonoides, phenolic compounds suggested that they may be partially responsible for antioxidant and antidiabetic activity.

Melatonin as a Pleiotropic Molecule with Therapeutic Potential for Type 2 Diabetes and Cancer.

PubMed

Wojcik, Marzena; Krawczyk, Michal; Wojcik, Pawel; Cypryk, Katarzyna; Wozniak, Lucyna Alicja

2017-11-20

The incidence of both type 2 diabetes (T2DM) and cancer is increasing worldwide, making these diseases a global health problem along with increasing healthcare expenditures. The current therapeutic approaches for treating these multifactorial diseases are far from satisfactory. As increasing evidence shows beneficial effects of melatonin (MLT) on typical pathological changes occurring during the development of T2DM and cancer, the present review focuses on molecular aspects of antidiabetic and anticancer activities of MLT and, moreover, discusses several future directions of research regarding MLT application as potential therapeutic agent. Critical literature analysis in PubMed central combined with personal expertise. Numerous in vitro and in vivo studies have revealed that MLT possesses a number of antidiabetic health benefits by diminishing hyperglycemia, insulin resistance, oxidative stress, and inflammation through modulating various intracellular signaling pathways or other targets involved in the pathophysiology of this disease. Mounting evidence also indicates that MLT exhibits multi-targeted anticancer effects in numerous human malignancies, mainly resulting from its ability to modulate several signal transduction pathways associated with cell survival, proliferation, and apoptosis. Furthermore, beneficial synergistic action of MLT with chemotherapy and radiotherapy has also been observed. Importantly, no adverse outcomes have been found from the clinical use of MLT, which highlights its therapeutic usefulness, either alone or in combination with other conventional therapies, in cancer treatment. The findings described in this review suggest that MLT may confer potential benefits to human health, particularly in respect to T2DM and cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Tangeretin inhibits high glucose-induced extracellular matrix accumulation in human glomerular mesangial cells.

PubMed

Chen, Fang; Ma, Yali; Sun, Zhiqiang; Zhu, Xiaoguang

2018-06-01

Tangeretin (5, 6, 7, 8, 4'-pentamethoxyflavone), a natural compound extracted from citrus plants, has been shown to possess a variety of pharmacological activities, including anti-oxidant, anti-tumor, cytostatic and anti-diabetic properties. However, the role of tangeretin in diabetic nephropathy (DN) has not yet been investigated. This study was undertaken to elucidate the effects of tangeretin on high glucose (HG)-induced oxidative stress and extracellular matrix (ECM) accumulation in human glomerular mesangial cells (MCs) and explore the underlying mechanisms. Our results showed that tangeretin significantly inhibited HG-induced the proliferation of MCs. In addition, tangeretin dramatically reduced the levels of reactive oxygen species (ROS) and malondialdhyde (MDA), and induced SOD activity, as well as inhibited the expression of fibronectin (FN) and collagen IV in HG-stimulated MCs. Furthermore, tangeretin efficiently prevented the activation of ERK signaling pathway in HG-stimulated MCs. Taken together, these data indicated that tangeretin inhibits HG-induced cell proliferation, oxidative stress and ECM expression in glomerular MCs, at least in part, through the inactivation of ERK signaling pathway. Therefore, tangeretin may be a potential agent in the treatment of DN. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Insulinotrophic and insulin-like effects of a high molecular weight aqueous extract of Pterocarpus marsupium Roxb. hardwood.

PubMed

Mohankumar, Suresh K; O'Shea, Tim; McFarlane, James R

2012-05-07

Pterocarpus marsupium Roxb. (PM) is an Ayurvedic traditional medicine well known for its antidiabetic potential. To fractionate the antidiabetic constituent(s) of the aqueous of extract of PM hardwood (PME). Bio-assay methods including, insulin secretion from mouse pancreas and glucose uptake by mouse skeletal muscle, were used to determine and fractionate the antidiabetic activity of PME. Results obtained from the in vitro experiments were then verified by examining the effect of PME on glucose clearance in normoglycemic, non-diabetic sheep in vivo. Exposure of mouse pancreatic and muscle tissues to PME stimulated the insulin secretion and glucose uptake, respectively, in a concentration-dependent manner. PME-mediated muscle glucose uptake was not potentiated in the presence of insulin indicating that PME acts via pathways which are utilized by insulin. Bio-assay-guided fractionation of PME yielded a high molecular weight fraction which had potent antidiabetic properties in vitro, and in in vivo. Our findings, we believe for the first time, provide novel insights for the antidiabetic constituents of PM and demonstrate that a high molecular weight constituent(s) of PM has potent insulinotrophic and insulin-like properties. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

A combination of (+)-catechin and (-)-epicatechin underlies the in vitro adipogenic action of Labrador tea (Rhododendron groenlandicum), an antidiabetic medicinal plant of the Eastern James Bay Cree pharmacopeia.

PubMed

Eid, Hoda M; Ouchfoun, Meriem; Saleem, Ammar; Guerrero-Analco, Jose A; Walshe-Roussel, Brendan; Musallam, Lina; Rapinski, Michel; Cuerrier, Alain; Martineau, Louis C; Arnason, John T; Haddad, Pierre S

2016-02-03

Rhododendron groenlandicum (Oeder) Kron & Judd (Labrador tea) was identified as an antidiabetic plant through an ethnobotanical study carried out with the close collaboration of Cree nations of northern Quebec in Canada. In a previous study the plant showed glitazone-like activity in a 3T3-L1 adipogenesis bioassay. The current study sought to identify the active compounds responsible for this potential antidiabetic activity using bioassay guided fractionation based upon an in vitro assay that measures the increase of triglycerides content in 3T3-L1 adipocyte. Isolation and identification of the crude extract's active constituents was carried out. The 80% ethanol extract was fractionated using silica gel column chromatography. Preparative HPLC was then used to isolate the constituents. The identity of the isolated compounds was confirmed by UV and mass spectrometry. Nine chemically distinct fractions were obtained and the adipogenic activity was found in fraction 5 (RGE-5). Quercetins, (+)-catechin and (-)-epicatechin were detected and isolated from this fraction. While (+)-catechin and (-)-epicatechin stimulated adipogenesis (238±26% and 187±21% relative to vehicle control respectively) at concentrations equivalent to their concentrations in the active fraction RGE-5, none afforded biological activity similar to RGE-5 or the plant's crude extract when used alone. When cells were incubated with a mixture of the two compounds, the adipogenic activity was close to that of the crude extract (280.7±27.8 vs 311± 30%). Results demonstrate that the mixture of (+)-catechin and (-)-epicatechin is responsible for the adipogenic activity of Labrador tea. This brings further evidence for the antidiabetic potential of R. groenlandicum and provides new opportunities to profile active principles in biological fluids or in traditional preparations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Bioactivities and Health Benefits of Mushrooms Mainly from China.

PubMed

Zhang, Jiao-Jiao; Li, Ya; Zhou, Tong; Xu, Dong-Ping; Zhang, Pei; Li, Sha; Li, Hua-Bin

2016-07-20

Many mushrooms have been used as foods and medicines for a long time. Mushrooms contain polyphenols, polysaccharides, vitamins and minerals. Studies show that mushrooms possess various bioactivities, such as antioxidant, anti-inflammatory, anticancer, immunomodulatory, antimicrobial, hepatoprotective, and antidiabetic properties, therefore, mushrooms have attracted increasing attention in recent years, and could be developed into functional food or medicines for prevention and treatment of several chronic diseases, such as cancer, cardiovascular diseases, diabetes mellitus and neurodegenerative diseases. The present review summarizes the bioactivities and health benefits of mushrooms, and could be useful for full utilization of mushrooms.

Red ginseng powder fermented with probiotics exerts antidiabetic effects in the streptozotocin-induced mouse diabetes model.

PubMed

Jang, Sun-Hee; Park, Jisang; Kim, Sae-Hae; Choi, Kyung-Min; Ko, Eun-Sil; Cha, Jeong-Dan; Lee, Young-Ran; Jang, Hyonseok; Jang, Yong-Suk

2017-12-01

Red ginseng (heat-processed Panax ginseng) is a well-known alternative medicine with pharmacological antidiabetic activity. It exerts pharmacological effects through the transformation of saponin into metabolites by the intestinal microbiota. Given that intestinal conditions and intestinal microflora vary among individuals, the pharmacological effects of orally administered red ginseng likely may vary among individuals. To overcome this variation and produce homogeneously effective red ginseng, we evaluated the antidiabetic effects of probiotic-fermented red ginseng in a mouse model. The antidiabetic efficacy of orally administered probiotic-fermented red ginseng was assessed in ICR mice after induction of diabetes using streptozotocin (170 mg/kg body weight). Samples were given orally for 8 weeks, and indicators involved in diabetic disorders such as body weight change, water intake, blood glucose, glucose tolerance and various biochemical parameters were determined. Oral administration of probiotic-fermented red ginseng significantly decreased the level of blood glucose of about 62.5% in the fasting state and induced a significant increase in glucose tolerance of about 10.2% compared to the control diabetic mice. Additionally, various indicators of diabetes and biochemical data (e.g., blood glycosylated haemoglobin level, serum concentrations of insulin, and α-amylase activity) showed a significant improvement in the diabetic conditions of the mice treated with probiotic-fermented red ginseng in comparison with those of control diabetic mice. Our results demonstrate the antidiabetic effects of probiotic-fermented red ginseng in the streptozotocin-induced mouse diabetes model and suggest that probiotic-fermented red ginseng may be a uniformly effective red ginseng product.

Trivaric acid, a new inhibitor of PTP1b with potent beneficial effect on diabetes.

PubMed

Sun, Wenlong; Zhang, Bowei; Zheng, Haizhou; Zhuang, Chunlin; Li, Xia; Lu, Xinhua; Quan, Chunshan; Dong, Yuesheng; Zheng, Zhihui; Xiu, Zhilong

2017-01-15

To screen a potential PTP1b inhibitor from the microbial origin-based compound library and to investigate the potential anti-diabetic effects of the inhibitor in vivo and determine its primary anti-diabetic mechanism in vitro and in silico. PTP1b inhibitory activity was measured using recombination protein as the enzyme and p-NPP as the substrate. The binding of the inhibitor to PTP1b was analysed by docking in silico and confirmed by ITC experiments. The intracellular signalling pathway was detected by Western blot analysis in HepG2 cells. The anti-diabetic effects were evaluated using a diabetic mice model in vivo. Among 545 microbial origin-based pure compounds tested, trivaric acid, a tridepside, was selected as a PTP1B inhibitor exhibiting strong inhibitory activity with an IC 50 of 173nM. Docking and ITC studies showed that trivaric acid was able to spontaneously bind to PTP1b and may inhibit PTP1b by blocking the catalytic domain of the phosphatase. Trivaric acid also enhanced the ability of insulin to stimulate the IR/IRS/Akt/GLUT2 pathway and increase the glucose consumption in HepG2 cells. In diabetic mice, trivaric acid that had been encapsulated into Eudrgit L100-5.5 showed significant anti-diabetic effects, improving insulin resistance, leptin resistance and lipid profile and weight control at doses of 5mg/kg and 50mg/kg. Trivaric acid is a potential lead compound in the search for anti-diabetic agents targeting PTP1b. Copyright © 2016 Elsevier Inc. All rights reserved.

Alpha-Glucosidase Enzyme Biosensor for the Electrochemical Measurement of Antidiabetic Potential of Medicinal Plants.

PubMed

Mohiuddin, M; Arbain, D; Islam, A K M Shafiqul; Ahmad, M S; Ahmad, M N

2016-12-01

A biosensor for measuring the antidiabetic potential of medicinal plants was developed by covalent immobilization of α-glucosidase (AG) enzyme onto amine-functionalized multi-walled carbon nanotubes (MWCNTs-NH2). The immobilized enzyme was entrapped in freeze-thawed polyvinyl alcohol (PVA) together with p-nitrophenyl-α-D-glucopyranoside (PNPG) on the screen-printed carbon electrode at low pH to prevent the premature reaction between PNPG and AG enzyme. The enzymatic reaction within the biosensor is inhibited by bioactive compounds in the medicinal plant extracts. The capability of medicinal plants to inhibit the AG enzyme on the electrode correlates to the potential of the medicinal plants to inhibit the production of glucose from the carbohydrate in the human body. Thus, the inhibition indicates the antidiabetic potential of the medicinal plants. The performance of the biosensor was evaluated to measure the antidiabetic potential of three medicinal plants such as Tebengau (Ehretis laevis), Cemumar (Micromelum pubescens), and Kedondong (Spondias dulcis) and acarbose (commercial antidiabetic drug) via cyclic voltammetry, amperometry, and spectrophotometry. The cyclic voltammetry (CV) response for the inhibition of the AG enzyme activity by Tebengau plant extracts showed a linear relation in the range from 0.423-8.29 μA, and the inhibition detection limit was 0.253 μA. The biosensor exhibited good sensitivity (0.422 μA/mg Tebengau plant extracts) and rapid response (22 s). The biosensor retains approximately 82.16 % of its initial activity even after 30 days of storage at 4 °C.

Comparison of microwave-assisted and conventional extraction of mangiferin from mango (Mangifera indica L.) leaves.

PubMed

Zou, Tangbin; Wu, Hongfu; Li, Huawen; Jia, Qing; Song, Gang

2013-10-01

Mangiferin is the main bioactive component in mango leaves, which possesses anti-inflammatory, antioxidative, antidiabetic, immunomodulatory, and antitumor activities. In the present study, a microwave-assisted extraction method was developed for the extraction of mangiferin from mango leaves. Some parameters such as ethanol concentration, liquid-to-solid ratio, microwave power, and extraction time were optimized by single-factor experiments and response surface methodology. The optimal extraction conditions were 45% ethanol, liquid-to-solid ratio of 30:1 (mL/g), and extraction time of 123 s under microwave irradiation of 474 W. Under optimal conditions, the yield of mangiferin was 36.10 ± 0.72 mg/g, significantly higher than that of conventional extraction. The results obtained are beneficial for the full utilization of mango leaves and also indicate that microwave-assisted extraction is a very useful method for extracting mangiferin from plant materials. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Phytochemical Constituents, Health Benefits, and Industrial Applications of Grape Seeds: A Mini-Review

PubMed Central

Zhang, Hongxia

2017-01-01

Grapes are one of the most widely grown fruits and have been used for winemaking since the ancient Greek and Roman civilizations. Grape seeds are rich in proanthocyanidins which have been shown to possess potent free radical scavenging activity. Grape seeds are a complex matrix containing 40% fiber, 16% oil, 11% proteins, and 7% complex phenols such as tannins. Grape seeds are rich sources of flavonoids and contain monomers, dimers, trimers, oligomers, and polymers. The monomeric compounds includes (+)-catechins, (−)-epicatechin, and (−)-epicatechin-3-O-gallate. Studies have reported that grape seeds exhibit a broad spectrum of pharmacological properties against oxidative stress. Their potential health benefits include protection against oxidative damage, and anti-diabetic, anti-cholesterol, and anti-platelet functions. Recognition of such health benefits of proanthocyanidins has led to the use of grape seeds as a dietary supplement by the consumers. This paper summarizes the studies of the phytochemical compounds, pharmacological properties, and industrial applications of grape seeds. PMID:28914789

Synthesis of berberine loaded polymeric nanoparticles by central composite design

NASA Astrophysics Data System (ADS)

Mehra, Meenakshi; Sheorain, Jyoti; Kumari, Santosh

2016-04-01

Berberine is an isoquinoline alkaloid which is extracted from bark and roots of Berberis vulgaris plant. It has been used in ayurvedic medicine as it possess antimicrobial, antidiabetic, anticancer, antioxidant properties etc. But poor solubility of berberine leads to poor stability and bioavailability in medical formulations decreasing its efficacy. Hence nanoformulations of berberine can help in removing the limiting factors of alkaloid enhancing its utilization in pharmaceutical industry. Sodium alginate polymer was used to encapsulate berberine within nanoparticles by emulsion solvent evaporation method using tween 80 as a surfactant. Two factors and three level in central composite design was used to study the formulation. The optimized formulation (1% v/v of Tween 80 and 0.01% w/v of sodium alginate) of polymeric nanoparticles was taken for further evaluations. The size of synthesized nanoparticles was found to be 71.18 nm by particle size analysis (PSA). The berberine loaded polymeric nanoparticles showed better antibacterial activity compared to aqueous solution of berberine by well diffusion assay.

Antidiabetic activity of flower buds of Michelia champaca Linn

PubMed Central

Jarald, E. Edwin; Joshi, S.B.; Jain, D.C.

2008-01-01

Objective: To identify the antihyperglycemic activity of various extracts, petroleum ether (60-80°), chloroform, acetone, ethanol, aqueous and crude aqueous, of the flower buds of Michelia champaca, and to identify the antidiabetic activity of active antihyperglycemic extract. Materials and Methods: Plant extracts were tested for antihyperglycemic activity in glucose overloaded hyperglycemic rats. The effective antihyperglycemic extract was tested for its hypoglycemic activity at two-dose levels, 200 and 400 mg/kg respectively. To confirm its utility in the higher model, the effective extract of M. champaca was subjected to antidiabetic study in alloxan induced diabetic model at two dose levels, 200 and 400 mg/kg respectively. The biochemical parameters, glucose, urea, creatinine, serum cholesterol, serum triglyceride, high density lipoprotein, low density lipoprotein, hemoglobin and glycosylated hemoglobin were also assessed in the experimental animals. Results: The ethanolic extract of M. champaca exhibited significant antihyperglycemic activity but did not produce hypoglycemia in fasted normal rats. Apart from this extract, the crude aqueous and petroleum ether extracts were found active only at the end of the first hour. Treatment of diabetic rats with ethanolic extract of this plant restored the elevated biochemical parameters significantly (P<0.05) (P<0.01) and the activity was found dose dependent. Conclusion: This study supports the traditional claim and the ethanolic extract of this plant could be added in traditional preparations for the ailment of various diabetes-associated complications. PMID:21279181

Antidiabetic effect of Sida cordata in alloxan induced diabetic rats.

PubMed

Shah, Naseer Ali; Khan, Muhammad Rashid

2014-01-01

Medicinal plants are efficient ameliorator of oxidative stress associated with diabetes mellitus. In this study, ethyl acetate fraction (SCEE) of Sida cordata was investigated for scientific validation of its folk use in diabetes. Antidiabetic effect of SCEE was confirmed by antihyperglycemic activity in normal glucose loaded and diabetic glucose loaded animals as well as normal off feed animals. Confirmation of antidiabetic activity and toxicity ameliorative role of S. cordata was investigated in a chronic multiple dose treatment study of fifteen days. A single dose of alloxan (120 mg/kg) produced a decrease in insulin level, hyperglycemia, elevated total lipids, triglycerides, and cholesterol and decreased the high-density lipoproteins. Concurrent with these changes, there was an increase in the concentration of lipid peroxidation (TBARS), H2O2, and nitrite in pancreas, liver, and testis. This oxidative stress was related to a decrease in glutathione content (GSH) and antioxidant enzymes. Administration of SCEE for 15 days after diabetes induction ameliorated hyperglycemia, restored lipid profile, blunted the increase in TBARS, H2O2, and nitrite content, and stimulated the GSH production in the organs of alloxan-treated rats. We suggested that SCEE could be used as antidiabetic component in case of diabetes mellitus. This may be related to its antioxidative properties.

Utilization of Fishery Processing By-Product Squid Pens for α-Glucosidase Inhibitors Production by Paenibacillus sp.

PubMed

Nguyen, Van Bon; Nguyen, Anh Dzung; Wang, San-Lang

2017-08-30

The supernatants (the solution part received after centrifugation) of squid pens fermented by four species of Paenibacillus showed potent inhibitory activity against α-glucosidases derived from yeast (79-98%) and rats (76-83%). The inhibition of acarbose-a commercial antidiabetic drug, used against yeast and rat α-glucosidases-was tested for comparison; it showed inhibitory activity of 64% and 88%, respectively. Other chitinolytic or proteolytic enzyme-producing bacterial strains were also used to ferment squid pens, but no inhibition activity was detected from the supernatants. Paenibacillus sp. TKU042, the most active α-glucosidase inhibitor (aGI)-producing strain, was selected to determine the optimal cultivation parameters. This bacterium achieved the highest aGI productivity (527 µg/mL) when 1% squid pens were used as the sole carbon/nitrogen source with a medium volume of 130 mL (initial pH 6.85) in a 250 mL flask (48% of air head space), at 30 °C for 3-4 d. The aGI productivity increased 3.1-fold after optimization of the culture conditions. Some valuable characteristics of Paenibacillus aGIs were also studied, including pH and thermal stability and specific inhibitory activity. These microbial aGIs showed efficient inhibition against α-glucosidases from rat, yeast, and bacteria, but weak inhibition against rice α-glucosidase with IC 50 values of 362, 252, 189, and 773 µg/mL, respectively. In particular, these aGIs showed highly stable activity over a large pH (2-13) and temperature range (40-100 °C). Various techniques, including: Diaoin, Octadecylsilane opened columns, and preparative HPLC coupled with testing bioactivity resulted in isolating a main active compound; this major inhibitor was identified as homogentisic acid (HGA). Notably, HGA was confirmed as a new inhibitor, a non-sugar-based aGI, and as possessing stronger activity than acarbose with IC 50, and maximum inhibition values of 220 μg/mL, 95%, and 1510 μg/mL, 65%, respectively. These results suggest that squid pens, an abundant and low-cost fishery processing by-product, constitute a viable source for the production of antidiabetic materials via fermentation by strains of Paenibacillus . This fermented product shows promising applications in diabetes or diabetes related to obesity treatment due to their stability, potent bioactivity, and efficient inhibition against mammalian enzymes.

Phytochemical distribution in hull and cotyledon of adzuki bean (Vigna angularis L.) and mung bean (Vigna radiate L.), and their contribution to antioxidant, anti-inflammatory and anti-diabetic activities.

PubMed

Luo, Jiaqiang; Cai, Weixi; Wu, Tong; Xu, Baojun

2016-06-15

Total saponin content, total phenolics content, total flavonoids content, condensed tannin content in hull, cotyledon and whole grain of both adzuki bean and mung bean were determined by colorimetric methods. Vitexin and isovitexin contents in mung bean were determined by HPLC. Antioxidant effects were evaluated with DPPH scavenging activity and ferric reducing antioxidant power assay. In vitro anti-inflammatory and anti-diabetic effects of beans were evaluated by protease and aldose reductase inhibitory assays, respectively. The results indicated that the bean hulls were the most abundant in phytochemicals and largely contributed antioxidant activities, anti-inflammatory effects and anti-diabetic effects of whole grains. The result showed that mung bean hull was the most abundant with vitexin at 37.43 mg/g and isovitexin at 47.18 mg/g, respectively. Most of the phytochemicals and bioactivities were most predominantly contributed by the bean hulls with exception for condensed tannin of mung bean; which was more abundant in the cotyledon than its hull. Copyright © 2016 Elsevier Ltd. All rights reserved.

Antidiabetic compounds from Sarracenia purpurea used traditionally by the Eeyou Istchee Cree First Nation.

PubMed

Muhammad, Asim; Guerrero-Analco, Jose A; Martineau, Louis C; Musallam, Lina; Madiraju, Padma; Nachar, Abir; Saleem, Ammar; Haddad, Pierre S; Arnason, John T

2012-07-27

Through ethnobotanical surveys, the CIHR Team in Aboriginal Antidiabetic Medicines identified 17 boreal forest plants stemming from the pharmacopeia of the Cree First Nations of Eeyou Istchee (James Bay region of Northern Quebec) that were used traditionally against diabetes symptoms. The leaves of Sarracenia purpurea (pitcher plant), one of the identified Cree plants, exhibited marked antidiabetic activity in vitro by stimulating glucose uptake in C2C12 mouse muscle cells and by reducing glucose production in H4IIE rat liver cells. Fractionation guided by glucose uptake in C2C12 cells resulted in the isolation of 11 compounds from this plant extract, including a new phenolic glycoside, flavonoid glycosides, and iridoids. Compounds 6 (isorhamnetin-3-O-glucoside), 8 [kaempferol-3-O-(6″-caffeoylglucoside], and 11 (quercetin-3-O-galactoside) potentiated glucose uptake in vitro, which suggests they represent active principles of S. purpurea (EC(50) values of 18.5, 13.8, and 60.5 μM, respectively). This is the first report of potentiation of glucose uptake by compounds 6 and 8, while compound 11 (isolated from Vaccinium vitis) was previously shown to enhance glucose uptake. Treatment of H4IIE liver cells with the new compound 1, 6'-O-caffeoylgoodyeroside, decreased hepatic glucose production by reducing glucose-6-phosphatase enzymatic activity (IC(50) = 13.6 μM), which would contribute to lowering glycemia and to the antidiabetic potential of S. purpurea.

Pistacia lentiscus Oleoresin: Virtual Screening and Identification of Masticadienonic and Isomasticadienonic Acids as Inhibitors of 11β-Hydroxysteroid Dehydrogenase 1.

PubMed

Vuorinen, Anna; Seibert, Julia; Papageorgiou, Vassilios P; Rollinger, Judith M; Odermatt, Alex; Schuster, Daniela; Assimopoulou, Andreana N

2015-04-01

In traditional medicine, the oleoresinous gum of Pistacia lentiscus var. chia, so-called mastic gum, has been used to treat multiple conditions such as coughs, sore throats, eczema, dyslipidemia, and diabetes. Mastic gum is rich in triterpenes, which have been postulated to exert antidiabetic effects and improve lipid metabolism. In fact, there is evidence of oleanonic acid, a constituent of mastic gum, acting as a peroxisome proliferator-activated receptor γ agonist, and mastic gum being antidiabetic in mice in vivo. Despite these findings, the exact antidiabetic mechanism of mastic gum remains unknown. Glucocorticoids play a key role in regulating glucose and fatty acid metabolism, and inhibition of 11β-hydroxysteroid dehydrogenase 1 that converts inactive cortisone to active cortisol has been proposed as a promising approach to combat metabolic disturbances including diabetes. In this study, a pharmacophore-based virtual screening was applied to filter a natural product database for possible 11β-hydroxysteroid dehydrogenase 1 inhibitors. The hit list analysis was especially focused on the triterpenoids present in Pistacia species. Multiple triterpenoids, such as masticadienonic acid and isomasticadienonic acid, main constituents of mastic gum, were identified. Indeed, masticadienonic acid and isomasticadienonic acid selectively inhibited 11β-hydroxysteroid dehydrogenase 1 over 11β-hydroxysteroid dehydrogenase 2 at low micromolar concentrations. These findings suggest that inhibition of 11β-hydroxysteroid dehydrogenase 1 contributes to the antidiabetic activity of mastic gum. Georg Thieme Verlag KG Stuttgart · New York.

Evaluation of Antioxidative and Antidiabetic Activity of Bark of Holarrhena Pubescens Wall

PubMed Central

Jamarkattel, Nirmala; Shrestha, Aasmin; Lamsal, Nisha Kiran; Shakya, Sangam; Rajbhandari, Sneha

2014-01-01

Objective: The objectives of the study are to screen out various phytochemicals and to evaluate the antioxidant and antidiabetic potential of the stem bark of Holarrhena pubescens Wall (Holarrhena antidysenterica). Materials and Methods: The antioxidant activity was determined by the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging activity where ascorbic acid was taken as positive control. The antioxidant property was later exploited and the methanolic extract of plant was tested for antihyperglycemic activity in glucose overloaded hyperglycemic mice. The extract was tested for its hypoglycemic activity at two-dose levels, 250 and 500 mg/kg respectively where Glipizide 5 mg/kg was taken as standard reference drug. All results are presented as mean ± SD (Standard Deviation). Significant differences between experimental groups were determined by Student’s t-test. Results: The methanolic and water extract showed strong antioxidant activity with inhibition of more than 90% DPPH free radicals at the concentration of 100μg/mL. The hypoglycemic activity of methanolic extract on glucose tolerance test were significant (p <0.05) for the effects of 500 mg/kg after 120 min of treatment and (p <0.01) for 250 mg/kg of extract after half hour of treatment compared to control. Conclusion: The presence of flavonoides, phenolic compounds suggested that they may be partially responsible for antioxidant and antidiabetic activity. PMID:25386454

The therapeutic journey of benzimidazoles: a review.

PubMed

Bansal, Yogita; Silakari, Om

2012-11-01

Presence of benzimidazole nucleus in numerous categories of therapeutic agents such as antimicrobials, antivirals, antiparasites, anticancer, anti-inflammatory, antioxidants, proton pump inhibitors, antihypertensives, anticoagulants, immunomodulators, hormone modulators, CNS stimulants as well as depressants, lipid level modulators, antidiabetics, etc. has made it an indispensable anchor for development of new therapeutic agents. Varied substitutents around the benzimidazole nucleus have provided a wide spectrum of biological activities. Importance of this nucleus in some activities like, Angiotensin I (AT(1)) receptor antagonism and proton-pump inhibition is reviewed separately in literature. Even some very short reviews on biological importance of this nucleus are also known in literature. However, owing to fast development of new drugs possessing benzimidazole nucleus many research reports are generated in short span of time. So, there is a need to couple the latest information with the earlier information to understand the current status of benzimidazole nucleus in medicinal chemistry research. In the present review, various derivatives of benzimidazole with different pharmacological activities are described on the basis of substitution pattern around the nucleus with an aim to help medicinal chemists for developing an SAR on benzimidazole derived compounds for each activity. This discussion will further help in the development of novel benzimidazole compounds. Copyright © 2012 Elsevier Ltd. All rights reserved.

Plantago maxima leaves extract inhibits adipogenic action of a high-fat diet in female Wistar rats.

PubMed

Tinkov, Alexey A; Nemereshina, Olga N; Popova, Elizaveta V; Polyakova, Valentina S; Gritsenko, Viktor A; Nikonorov, Alexandr A

2014-04-01

The primary objective of this study is to investigate the content of biologically active compounds producing an antioxidant effect in Plantago maxima and their influence on main mechanisms of dietary obesity development. Biologically active compounds in P. maxima were tested using paper chromatography. In in vivo experiment, high-fat-fed Wistar rats obtained P. maxima water extract for 3 months. Morphometric parameters, weight gain, serum adipokines, and cytokines, as well as oxidative stress biomarkers in rats’ tissues were evaluated. Gut microflora was also examined. Plantago maxima leaves used in the experiment contained significant amount of flavonoids, iridoids, phenol carboxylic acids, and tannins and ascorbic acid. Our in vivo experiment data demonstrate that P. maxima water extract prevents excessive adiposity in a diet-induced model. P. maxima consumption reduced serum leptin (twofold), macrophage chemoattractant protein-1 (sevenfold), tumornecrosis factor-α (25%), and interleukine-6 (26%) levels. P. maxima water extract decreased adipose tissue oxidative stress biomarkers in rats fed a high-fat diet. In addition, increased bacterial growth in the diet-induced obesity model was reversed by the P. maxima extract treatment. Plantago maxima water extract possessed antiadipogenic, antidiabetic, antiinflammatory, antioxidant activity, and normalized gut microflora in a rat model of diet-induced excessive adiposity due to a high content of biologically active compounds.

A review of the pharmacological effects of Arctium lappa (burdock).

PubMed

Chan, Yuk-Shing; Cheng, Long-Ni; Wu, Jian-Hong; Chan, Enoch; Kwan, Yiu-Wa; Lee, Simon Ming-Yuen; Leung, George Pak-Heng; Yu, Peter Hoi-Fu; Chan, Shun-Wan

2011-10-01

Arctium lappa, commonly known as burdock, is being promoted/recommended as a healthy and nutritive food in Chinese societies. Burdock has been used therapeutically in Europe, North America and Asia for hundreds of years. The roots, seeds and leaves of burdock have been investigated in view of its popular uses in traditional Chinese medicine (TCM). In this review, the reported therapeutic effects of the active compounds present in the different botanical parts of burdock are summarized. In the root, the active ingredients have been found to "detoxify" blood in terms of TCM and promote blood circulation to the skin surface, improving the skin quality/texture and curing skin diseases like eczema. Antioxidants and antidiabetic compounds have also been found in the root. In the seeds, some active compounds possess anti-inflammatory effects and potent inhibitory effects on the growth of tumors such as pancreatic carcinoma. In the leaf extract, the active compounds isolated can inhibit the growth of micro-organisms in the oral cavity. The medicinal uses of burdock in treating chronic diseases such as cancers, diabetes and AIDS have been reported. However, it is also essential to be aware of the side effects of burdock including contact dermatitis and other allergic/inflammatory responses that might be evoked by burdock.

Black Cumin (Nigella sativa) and Its Active Constituent, Thymoquinone: An Overview on the Analgesic and Anti-inflammatory Effects.

PubMed

Amin, Bahareh; Hosseinzadeh, Hossein

2016-01-01

For many centuries, seeds of Nigella sativa (black cumin), a dicotyledon of the Ranunculaceae family, have been used as a seasoning spice and food additive in the Middle East and Mediterranean areas. Traditionally, the plant is used for asthma, hypertension, diabetes, inflammation, cough, bronchitis, headache, eczema, fever, dizziness, and gastrointestinal disturbances. The literature regarding the biological activities of seeds of this plant is extensive, citing bronchodilative, anti-inflammatory, antinociceptive, antibacterial, hypotensive, hypolipidemic, cytotoxic, antidiabetic, and hepatoprotective effects. The active ingredients of N. sativa are mainly concentrated in the fixed or essential oil of seeds, which are responsible for most health benefits. This review will provide all updated reported activities of this plant with an emphasis on the antinociceptive and anti-inflammatory effects. Results of various studies have demonstrated that the oil, extracts, and their active ingredients, in particular, thymoquinone, possess antinociceptive and anti-inflammatory effects, supporting the common folk perception of N. Sativa as a potent analgesic and anti-inflammatory agent. Many protective properties are attributed to reproducible radical scavenging activity as well as an interaction with numerous molecular targets involved in inflammation, including proinflammatory enzymes and cytokines. However, there is a need for further investigations to find out the precise mechanisms responsible for the antinociceptive and anti-inflammatory effects of this plant and its active constituents. Georg Thieme Verlag KG Stuttgart · New York.

[The vanadium compounds: chemistry, synthesis, insulinomimetic properties].

PubMed

Fedorova, E V; Buriakina, A V; Vorob'eva, N M; Baranova, N I

2014-01-01

The review considers the biological role of vanadium, its participation in various processes in humans and other mammals, and the anti-diabetic effect of its compounds. Vanadium salts have persistent hypoglycemic and antihyperlipidemic effects and reduce the probability of secondary complications in animals with experimental diabetes. The review contains a detailed description of all major synthesized vanadium complexes having antidiabetic activity. Currently, vanadium complexes with organic ligands are more effective and safer than the inorganic salts. Despite the proven efficacy of these compounds as the anti-diabetic agents in animal models, only one organic complex of vanadium is currently under the second phase of clinical trials. All of the considered data suggest that vanadium compound are a new promising class of drugs in modern pharmacotherapy of diabetes.

Effects of commonly used antidiabetic drugs on antioxidant enzymes and liver function test markers in type 2 diabetes mellitus subjects - pilot study.

PubMed

Ghadge, A; Harke, S; Khadke, S; Diwan, A; Pankaj, M; Kulkarni, O; Ranjekar, P; Harsulkar, A; Kuvalekar, A A

2015-09-01

The present study analyzed the effects of antidiabetic drugs on antioxidant enzymes and liver function test (LFT) markers and their association with homeostatic model assessment of insulin resistance (HOMA-IR) in type 2 diabetic subjects. We assessed healthy and diabetic subjects (100 each). Diabetic subjects were divided based on treatment with only metformin, metformin in combination with other antidiabetic drugs and insulin in combination with other antidiabetic drugs. LFT markers, antioxidant status and HOMA-IR were assessed in the subjects. Superoxide dismutase activity was higher (p<0.01) while catalase activity was lower (p<0.01) in the diabetic subjects as compared to controls. Serum glutamate-pyruvate transaminase (SGPT) (p<0.01) and bilirubin (p<0.05) levels were higher in diabetic male subjects while urea (p<0.05) levels were lower and SGPT (p<0.01) levels were higher in diabetic female subjects. In male subjects consuming only metformin, a positive association between HOMA-IR and insulin (p<0.05) was seen. A positive association between HOMA-IR and glucose (p<0.01), insulin (p<0.01), SOD (p<0.01) and SGPT (p<0.05) was seen in males receiving metformin with other drugs. Interestingly, the female subjects on metformin displayed a positive association between HOMA-IR and insulin (p<0.05) only. A positive association of HOMA-IR with glucose (p<0.01) and insulin (p<0.05) was seen in females on metformin in combination with other anti-diabetic drugs. The alterations in the antioxidant enzyme activities and liver function tests are dependent upon the gender and glycemic status of subjects while the variations in correlations of HOMA-IR with antioxidant enzymes, liver function tests and inflammatory markers are dependent on type of treatments. © Georg Thieme Verlag KG Stuttgart · New York.

Antidiabetic Evaluation of Momordica charantia L Fruit Extracts

PubMed Central

Tahira, S; Hussain, F

2014-01-01

To investigate hypoglycaemic, hypolipidaemic and pancreatic beta cell regeneration activities of Momordica charantia L fruits (MC). Alloxan-induced diabetic rabbits were treated with methanolic and ethanolic MC extract. Effects of plant extracts and the drug glibenclamide on serum glucose, lipid profile and pancreatic beta cell were determined after two weeks of treatment. Serum glucose and lipid profiles were assayed by kit methods. Pancreatic tissue histopathology was performed to study pancreatic beta cell regeneration. Momordica charantia extracts produced significant hypoglycaemic effects (p < 0.05). Hypolipidaemic activity of MC was negligible. Momordica charantia supplementations were unable to normalize glucose and lipid profiles. Glibenclamide, a standard drug, not only lowered hyperglycaemia and hyperlipidaemia but also restored the normal levels. Regeneration of pancreatic beta cells by MC extracts was minimal, with fractional improvement produced by glibenclamide. The most significant finding of the present study was a 28% reduction in hyperglycaemia by MC ethanol extracts. To determine reliable antidiabetic potentials of MC, identification of the relevant antidiabetic components and underlying mechanisms is warranted. PMID:25429471

Binding Energy calculation of GSK-3 protein of Human against some anti-diabetic compounds of Momordica charantia linn (Bitter melon)

PubMed Central

Hazarika, Ridip; Parida, Pratap; Neog, Bijoy; Yadav, Raj Narain Singh

2012-01-01

Diabetes is one of the major life threatening diseases worldwide. It creates major health problems in urban India. Glycogen Synthase Kinase-3 (GSK-3) protein of human is known for phosphorylating and inactivating glycogen synthase which also acts as a negative regulator in the hormonal control of glucose homeostasis. In traditional medicine, Momordica charantia is used as antidiabetic plant because of its hypoglycemic effect. Hence to block the active site of the GSK-3 protein three anti-diabetic compounds namely, charantin, momordenol & momordicilin were taken from Momordica charantia for docking study and calculation of binding energy. The aim of present investigation is to find the binding energy of three major insulin-like active compounds against glycogen synthase kinase-3 (GSK-3), one of the key proteins involved in carbohydrate metabolism, with the help of molecular docking using ExomeTM Horizon suite. The study recorded minimum binding energy by momordicilin in comparison to the others. PMID:22493531

Binding Energy calculation of GSK-3 protein of Human against some anti-diabetic compounds of Momordica charantia linn (Bitter melon).

PubMed

Hazarika, Ridip; Parida, Pratap; Neog, Bijoy; Yadav, Raj Narain Singh

2012-01-01

Diabetes is one of the major life threatening diseases worldwide. It creates major health problems in urban India. Glycogen Synthase Kinase-3 (GSK-3) protein of human is known for phosphorylating and inactivating glycogen synthase which also acts as a negative regulator in the hormonal control of glucose homeostasis. In traditional medicine, Momordica charantia is used as antidiabetic plant because of its hypoglycemic effect. Hence to block the active site of the GSK-3 protein three anti-diabetic compounds namely, charantin, momordenol & momordicilin were taken from Momordica charantia for docking study and calculation of binding energy. The aim of present investigation is to find the binding energy of three major insulin-like active compounds against glycogen synthase kinase-3 (GSK-3), one of the key proteins involved in carbohydrate metabolism, with the help of molecular docking using ExomeTM Horizon suite. The study recorded minimum binding energy by momordicilin in comparison to the others.

Antioxidant and antidiabetic properties of condensed tannins in acetonic extract of selected raw and processed indigenous food ingredients from Kenya.

PubMed

Kunyanga, Catherine Nkirote; Imungi, Jasper Kathenya; Okoth, Michael; Momanyi, Clare; Biesalski, Han Konrad; Vadivel, Vellingiri

2011-05-01

Recently, tannins have received considerable attention as health-promoting component in various plant foods and several studies have reported on its nutraceutical properties. However, no study has established the role of condensed tannins in indigenous foods of Kenya. Therefore, this study was designed to evaluate the antioxidant activity (DPPH and FRAP) and antidiabetic effects (α-amylase and α-glucosidase inhibition activities) of condensed tannins in some selected raw and traditionally processed indigenous cereals, legumes, oil seeds, and vegetables. The condensed tannin content of the grains and vegetables ranged between 2.55 and 4.35 g/100 g DM and 1.53 and 5.73 g/100 g DM, respectively. The scavenging effect of acetonic extract on DPPH radical ranged from 77% to 90% while the reducing power was found to be 31 to 574 mmol Fe(II)/g DM in all the investigated food ingredients. The condensed tannin extracts of the analyzed samples showed promising antidiabetic effects with potential α-amylase and α-glucosidase inhibition activities of 23% to 44% and 58% to 88%, respectively. Condensed tannins extracted from the amaranth grain, finger millet, field bean, sunflower seeds, drumstick, and amaranth leaves exerted significantly higher antioxidant and antidiabetic activities than other food ingredients. Among the traditional processing methods, roasting of grains and cooking of vegetables were found to be more suitable mild treatments for preserving the tannin compound and its functional properties as opposed to soaking + cooking and blanching treatments. The identified elite sources of optimally processed indigenous food ingredients with promising results could be used as health-promoting ingredients through formulation of therapeutic diets. © 2011 Institute of Food Technologists®

A Comparison of Food-grade Folium mori (桑葉 Sāng Yè) Extract and 1-Deoxynojirimycin for Glycemic Control and Renal Function in Streptozotocin-induced Diabetic Rats

PubMed Central

Huang, Shiang-Suo; Yan, Yi-Hui; Ko, Chien-Hui; Chen, Ke-Ming; Lee, Shih-Chieh; Liu, Cheng-Tzu

2014-01-01

Folium mori (桑葉 Sāng Yè, leaf of Morus alba L.; FM) is known to possess hypoglycemic effects, and 1-deoxynojirimycin (1-DNJ) has been proposed as an important functional compound in FM. However, the hypoglycemic activity of purified 1-DNJ has been rarely studied. It is also not known how FM and 1-DNJ affect the development of DM nephropathy. This study compared the antidiabetic effect of a commercial FM product with that of purified 1-DNJ in streptozotocin-induced diabetic rats. Seven days after induction, the diabetic rats were gavaged with FM (1, 3, 10, and 30 mg/kg/day), 1-DNJ (30 mg/kg/day), or vehicle (distilled deionized water; 2 ml/kg/day) for 7 days. All doses of FM ameliorated fasting and post-prandial blood glucose concomitantly with an increase in peripheral and pancreatic levels of insulin and improved homeostasis model assessment (HOMA-IR) in diabetic rats in a dose-dependent manner. Increased thiobarbituric acid reactive substances (TBARS) and nitrate/nitrite levels in the kidney, liver, and muscle of diabetic rats were reversed by all doses of FM. The renal function of the diabetic rats was normalized by all doses of FM, while blood pressure changes were reversed by FM at doses of 3 mg/kg and above. Moreover, most of the above-mentioned parameters were improved by FM at doses of 3 mg/kg and above to a similar extent as that of 1-DNJ. The results showed superior antidiabetic potential of the commercial FM product for glycemic control and protection against the development of diabetic nephropathy. PMID:25161921

New amides from seeds of Silybum marianum with potential antioxidant and antidiabetic activities.

PubMed

Qin, Ning-Bo; Jia, Cui-Cui; Xu, Jun; Li, Da-Hong; Xu, Fan-Xing; Bai, Jiao; Li, Zhan-Lin; Hua, Hui-Ming

2017-06-01

Two new amide compounds, mariamides A and B (1-2), were obtained together with fourteen known compounds from the seeds of milk thistle (Silybum marianum). Their structures were established on the basis of extensive 1D and 2D NMR analyses, as well as HR-ESI-MS data. Most of the compounds showed significant antioxidant activities than positive control in ABTS and FRAP assays. However, only amide compounds 1-4 showed moderate DPPH radical scavenging activity and compounds 7 and 16 showed the most potent activity against DPPH. Most of the compounds showed moderate to stronger α-glucosidase inhibitory activities. Nevertheless, only flavonoids showed strong PTP1B inhibitory activities. These results indicate a use of milk thistle seed extracts as promising antioxidant and antidiabetic agents. Copyright © 2017 Elsevier B.V. All rights reserved.

Anti-Diabetic Activity and Metabolic Changes Induced by Andrographis paniculata Plant Extract in Obese Diabetic Rats.

PubMed

Akhtar, Muhammad Tayyab; Bin Mohd Sarib, Mohamad Syakir; Ismail, Intan Safinar; Abas, Faridah; Ismail, Amin; Lajis, Nordin Hj; Shaari, Khozirah

2016-08-09

Andrographis paniculata is an annual herb and widely cultivated in Southeast Asian countries for its medicinal use. In recent investigations, A. paniculata was found to be effective against Type 1 diabetes mellitus (Type 1 DM). Here, we used a non-genetic out-bred Sprague-Dawley rat model to test the antidiabetic activity of A. paniculata against Type 2 diabetes mellitus (Type 2 DM). Proton Nuclear Magnetic Resonance (¹H-NMR) spectroscopy in combination with multivariate data analyses was used to evaluate the A. paniculata and metformin induced metabolic effects on the obese and obese-diabetic (obdb) rat models. Compared to the normal rats, high levels of creatinine, lactate, and allantoin were found in the urine of obese rats, whereas, obese-diabetic rats were marked by high glucose, choline and taurine levels, and low lactate, formate, creatinine, citrate, 2-oxoglutarate, succinate, dimethylamine, acetoacetate, acetate, allantoin and hippurate levels. Treatment of A. paniculata leaf water extract was found to be quite effective in restoring the disturbed metabolic profile of obdb rats back towards normal conditions. Thisstudy shows the anti-diabetic potential of A. paniculata plant extract and strengthens the idea of using this plant against the diabetes. Further classical genetic methods and state of the art molecular techniques could provide insights into the molecular mechanisms involved in the pathogenesis of diabetes mellitus and anti-diabetic effects of A. paniculata water extract.

Piracetam Facilitates the Anti-Amnesic but not Anti-Diabetic Activity of Metformin in Experimentally Induced Type-2 Diabetic Encephalopathic Rats.

PubMed

Pandey, Shruti; Garabadu, Debapriya

2017-07-01

Piracetam exhibits anti-amnesic activity in several animal models of dementia. However, its anti-amnesic potential has yet to be evaluated in type-2 diabetes mellitus (T2DM)-induced encephalopathy. Therefore, in the present study, piracetam (25, 50 and 100 mg/kg) was screened for anti-amnesic and anti-diabetic activity in T2DM-induced encephalopathic male rats. Subsequently, anti-amnesic and anti-diabetic activities were evaluated for piracetam, metformin and their combination in T2DM-induced encephalopathic animals. Rats received streptozotocin (45 mg/kg) and nicotinamide (110 mg/kg) injections on day-1 (D-1) of the experimental schedule and were kept undisturbed for 35 days to exhibit T2DM-induced encephalopathy. All drug treatments were continued from D-7 to D-35 in both experiments. Piracetam (100 mg/kg) attenuated loss in learning and memory in terms of increase in escape latency on D-4 (D-34) and decrease in time spent in the target quadrant on D-5 (D-35) of Morris water maze test protocol, and spatial memory in terms of reduced spontaneous alternation behavior in Y-maze test of encephalopathic rats. Additionally, piracetam attenuated altered levels of fasting plasma glucose and insulin, HOMA-IR and HOMA-B in encephalopathic animals, comparatively lesser than metformin. In the next experiment, combination of piracetam and metformin exhibited better anti-amnesic but not anti-diabetic activity than respective monotherapies in encephalopathic rats. Further, the combination attenuated reduced acetylcholine level and increased acetylcholinesterase activity, increased glycogen synthase kinase-3β level and decreased brain-derived neurotropic factor level in hippocampus and pre-frontal cortex of encephalopathic animals. Thus, piracetam could be used as an adjuvant to metformin in the management of dementia in T2DM-induced encephalopathy.

Effects of Germinated Brown Rice and Its Bioactive Compounds on the Expression of the Peroxisome Proliferator-Activated Receptor Gamma Gene

PubMed Central

Imam, Mustapha Umar; Ismail, Maznah; Ithnin, Hairuszah; Tubesha, Zaki; Omar, Abdul Rahman

2013-01-01

Dysregulated metabolism is implicated in obesity and other disease conditions like type 2 diabetes mellitus and cardiovascular diseases, which are linked to abnormalities of peroxisome proliferator-activated receptor gamma (PPARγ). PPARγ has been the focus of much research aimed at managing these diseases. Also, germinated brown rice (GBR) is known to possess antidiabetic, antiobesity and hypocholesterolemic effects. We hypothesized that GBR bioactive compounds may mediate some of the improvements in metabolic indices through PPARγ modulation. Cultured HEP-G2 cells were treated with 50 ppm and 100 ppm of extracts from GBR (GABA, ASG and oryzanol) after determination of cell viabilities using MTT assays. Results showed that all extracts upregulated the expression of the PPARγ. However, combination of all three extracts showed downregulation of the gene, suggesting that, in combination, the effects of these bioactives differ from their individual effects likely mediated through competitive inhibition of the gene. Upregulation of the gene may have therapeutic potential in diabetes mellitus and cardiovascular diseases, while its downregulation likely contributes to GBR’s antiobesity effects. These potentials are worth studying further. PMID:23389305

Antidiabetic effects of Momordica charantia (bitter melon) and its medicinal potency

PubMed Central

Joseph, Baby; Jini, D

2013-01-01

Diabetes mellitus is among the most common disorder in developed and developing countries, and the disease is increasing rapidly in most parts of the world. It has been estimated that up to one-third of patients with diabetes mellitus use some form of complementary and alternative medicine. One plant that has received the most attention for its anti-diabetic properties is bitter melon, Momordica charantia (M. charantia), commonly referred to as bitter gourd, karela and balsam pear. Its fruit is also used for the treatment of diabetes and related conditions amongst the indigenous populations of Asia, South America, India and East Africa. Abundant pre-clinical studies have documented in the anti-diabetic and hypoglycaemic effects of M. charantia through various postulated mechanisms. However, clinical trial data with human subjects are limited and flawed by poor study design and low statistical power. The present review is an attempt to highlight the antidiabetic activity as well as phytochemical and pharmacological reports on M. charantia and calls for better-designed clinical trials to further elucidate its possible therapeutic effects on diabetes.

In vitro evaluation of anti-diabetic activity and cytotoxicity of chemically analysed Ocimum basilicum extracts.

PubMed

Kadan, Sleman; Saad, Bashar; Sasson, Yoel; Zaid, Hilal

2016-04-01

The aim of this study was to evaluate the role of glucose transporter-4 (GLUT4) in the anti-diabetic effects of methanol, hexane and dichloromethane extracts of the aerial parts of Ocimum basilicum (OB) and to analyze their phytochemical composition. Phytochemical analysis of the three extracts by GC/MS using the silylation derivatization technique revealed 53 compounds, 17 of them were found for the first time in OB. Cytotoxic and anti-diabetic properties of the extracts were evaluated using L6-GLUT4myc muscle cells stably expressing myc epitope at the exofacial loop (GLUT4). No cytotoxic effects were observed in treated cells up to 0.25 mg/ml extract as measured with MTT and LDH-leakage assays. GLUT4 translocation to the plasma membrane was elevated by 3.5 and 7 folds (-/+ insulin) after treatment with OB extracts for 20 h. Our findings suggest that the observed anti-diabetic properties of OB extracts are possibly mediated in part through one or more of the 17 new identified compound. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Glucokinase and glucokinase regulatory proteins as molecular targets for novel antidiabetic drugs].

PubMed

Rubtsov, P M; Igudin, E L; Tiulpakov, A N

2015-01-01

The impairment of glucose homeostasis leads to hyperglycemia and type-2 diabetes mellitus. Glucokinase (GK), an enzyme that catalyzes the conversion of glucose to glucose-6-phosphate in pancreatic ß-cells, liver hepatocytes, specific hypothalamic neurons, and intestine enterocytes, is a key regulator of glucose homeostasis. In hepatocytes, GK controls the glucose uptake and glycogen synthesis and inhibits the glucose synthesis via the gluconeogenesis pathway. Glucokinase regulatory protein (GKRP) synthesized in hepatocytes acts as an endogenous GK inhibitor. During fasting, GKRP binds GK, inactivates it, and transports it into the cell nucleus, thus isolating it from the hepatocyte carbohydrate metabolism. In the beginning of the 2000s, the research was mainly focused on the development and trials of the small molecule GK activators as potential antidiabetic glucose-lowering drugs. However, the use of such substances increased the risk of hypoglycemia, and clinical studies of most synthetic GK activators are currently discontinued. Allosteric inhibitors of the GK-GKRP interaction are coming as alternative agents increasing the GK activity that can substitute GKA. In this review, we discuss the recent advances and the current state of art in the development of potential antidiabetic drugs targeted to GK as a key regulator of glucose homeostasis.

Synthesis, pharmacological evaluation and molecular docking studies of pyrimidinedione based DPP-4 inhibitors as antidiabetic agents

NASA Astrophysics Data System (ADS)

Jha, Vibhu; Bhadoriya, Kamlendra Singh

2018-04-01

Dipeptidyl peptidase-4 (DPP-4) inhibitors are a class of newly developed antidiabetic drugs that bock DPP-4. DPP-4 is responsible for degradation of incretins harmones such as GLP-1 (Glucagon like Peptide) and GIP (Gastric inhibitory polypeptide) that maintain blood-glucose level. Pyrimidinedione based compounds were designed and synthesized for DPP-4 inhibitory activity. These heterocycles were designed by taking Alogliptin as a reference DPP-4 inhibitors and synthesized as N-methylated and N-benzylated pyrimidinediones. These compounds were subjected to DPP-4 assay, five out of nine synthesized compounds have shown in vitro DPP-4 inhibitory activity in significant range. Further, molecular docking studies of these compounds were performed on DPP-4 subunit and compared with natural DPP-4 inhibitors like Flavone, Resveratrol, Quercetin, Diprotin A. Docking studies have led to the conclusion that there are some identical amino acid interactions as Tyr 666 and Tyr 662, seen in both synthesized compounds and natural DPP-4 inhibitors. This study completely gives a good scope for further derivatisation and optimization of synthesized compounds to get clinical candidate as DPP-4 inhibitor for antidiabetic activity.

A site-specific PEGylated analog of exendin-4 with improved pharmacokinetics and pharmacodynamics in vivo.

PubMed

Gao, Mingming; Jin, Yuhao; Tong, Yue; Tian, Hong; Gao, Xiangdong; Yao, Wenbing

2012-11-01

Our aim was to improve the in vivo pharmacokinetics and pharmacodynamics of exendin-4 by using site-specific PEGylation. We designed the PEGylated peptide based on its structure and activity relationship and prepared the conjugate by two steps of chromatographic purification. After obtained the conjugate we confirmed its glucose-lowering activity in normal mice and determined its half-life in SD rats. Then we evaluated its anti-diabetic activity in a multiple low-dose Streptozocin (STZ)-induced diabetic mice model. With the process established in this study the product conjugate was obtained with a yield of over 60% and purity of above 99%. The conjugate maintained its original conformation after modification. In SD rats its half-life was prolonged to 27.12 ± 5.75 h which was 17.61-fold longer than that of the natural exendin-4 for which the half-life was only 1.54 ± 0.47 h. Its anti-diabetic activity was significantly improved in the diabetic mice. Compare with native exendin-4, the C-terminal site-specific PEGylated analog of exendin-4 obtained in this study has an improved pharmacokinetics and pharmacodynamics in vivo and could be regarded as a potential candidate for the future development of anti-diabetic drugs. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

Evaluation of Sedative and Hypnotic Activity of Ethanolic Extract of Scoparia dulcis Linn.

PubMed Central

Moniruzzaman, Md.; Atikur Rahman, Md.; Ferdous, Afia

2015-01-01

Scoparia dulcis Linn. (SD) is a perennial herb that has been well studied for its antioxidant, anti-inflammatory, antidiabetic, and hepatoprotective effects. However, scientific information on SD regarding the neuropharmacological effect is limited. This study evaluated the sedative and hypnotic effect of the ethanolic extract of whole plants of Scoparia dulcis (EESD). For this purpose, the whole plants of S. dulcis were extracted with ethanol following maceration process and tested for the presence of phytochemical constituents. The sedative and hypnotic activity were then investigated using hole cross, open field, hole-board, rota-rod, and thiopental sodium-induced sleeping time determination tests in mice at the doses of 50, 100, and 200 mg/kg of EESD. Diazepam at the dose of 1 mg/kg was used as a reference drug in all the experiments. We found that EESD produced a significant dose-dependent inhibition of locomotor activity of mice both in hole cross and open field tests (P < 0.05). Besides, it also decreased rota-rod performances and the number of head dips in hole-board test. Furthermore, EESD significantly decreased the induction time to sleep and prolonged the duration of sleeping, induced by thiopental sodium. Taken together, our study suggests that EESD may possess sedative principles with potent hypnotic properties. PMID:25861372

Evaluation of Sedative and Hypnotic Activity of Ethanolic Extract of Scoparia dulcis Linn.

PubMed

Moniruzzaman, Md; Atikur Rahman, Md; Ferdous, Afia

2015-01-01

Scoparia dulcis Linn. (SD) is a perennial herb that has been well studied for its antioxidant, anti-inflammatory, antidiabetic, and hepatoprotective effects. However, scientific information on SD regarding the neuropharmacological effect is limited. This study evaluated the sedative and hypnotic effect of the ethanolic extract of whole plants of Scoparia dulcis (EESD). For this purpose, the whole plants of S. dulcis were extracted with ethanol following maceration process and tested for the presence of phytochemical constituents. The sedative and hypnotic activity were then investigated using hole cross, open field, hole-board, rota-rod, and thiopental sodium-induced sleeping time determination tests in mice at the doses of 50, 100, and 200 mg/kg of EESD. Diazepam at the dose of 1 mg/kg was used as a reference drug in all the experiments. We found that EESD produced a significant dose-dependent inhibition of locomotor activity of mice both in hole cross and open field tests (P < 0.05). Besides, it also decreased rota-rod performances and the number of head dips in hole-board test. Furthermore, EESD significantly decreased the induction time to sleep and prolonged the duration of sleeping, induced by thiopental sodium. Taken together, our study suggests that EESD may possess sedative principles with potent hypnotic properties.

Oxindole: A chemical prism carrying plethora of therapeutic benefits.

PubMed

Kaur, Maninder; Singh, Manjinder; Chadha, Navriti; Silakari, Om

2016-11-10

Oxindole has emerged as a valuable scaffold in medicinal chemistry possessing diverse range of pharmacological activities. Its value has further been increased by its natural occurrence as alkaloids in variety of plants. It was first extracted from the cat claw's plant Uncaria tomentosa found in the Amazon rainforest and other tropical areas of South and Central America. Traditionally as well as present emerging therapeutic potential of oxindole nucleus has captured the interest of medicinal chemists to synthesize novel oxindole derivatives. In the present review the authors have integrated its chemistry and synthetic strategies developed after 1945. Also the information of naturally occurring oxindole alkaloids has been incorporated. The detailed pharmacological activities including anti-cancer, anti-HIV, antidiabetic, antibacterial, antioxidant, kinase inhibitory, AChE inhibitory, anti-leishmanial, β3 adrenergic receptor agonistic, phosphatase inhibitory, analgesic, spermicidal, vasopressin antagonists, progesterone antagonists, neuroprotection, and NMDA blocker activities of oxindole derivatives alongwith their SAR has also been discussed in detail. Additionally, information regarding the oxindole derivatives in clinical trials has been incorporated. Thus, this review will provide insights for the synthetic as well as medicinal chemist for the designing and synthesis of novel oxindole derivatives with novel improved range of pharmacological implications. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

A dimeric urea of the bisabolene sesquiterpene from the Okinawan marine sponge Axinyssa sp. inhibits protein tyrosine phosphatase 1B activity in Huh-7 human hepatoma cells.

PubMed

Abdjul, Delfly B; Kanno, Syu-Ichi; Yamazaki, Hiroyuki; Ukai, Kazuyo; Namikoshi, Michio

2016-01-15

Protein tyrosine phosphatase 1B (PTP1B) plays an important role as a negative regulator of the insulin and leptin signaling pathways. Therefore, this enzyme is regarded as an attractive therapeutic target for the treatment of type 2 diabetes and obesity. Our screening program for PTP1B inhibitors led to the isolation of four sesquiterpenes and sterol: N,N'-bis[(6R,7S)-7-amino-7,8-dihydro-α-bisabolen-7-yl]urea (1), (6R,7S)-7-amino-7,8-dihydro-α-bisabolene (2), (1R,6S,7S,10S)-10-isothiocyanato-4-amorphene (3), axinisothiocyanate J (4), and axinysterol (5) from the marine sponge Axinyssa sp. collected at Iriomote Island. Of these, compound 1 was the most potent inhibitor of PTP1B activity (IC50=1.9μM) without cytotoxicity at 50μM in two human cancer cell lines, hepatoma Huh-7 and bladder carcinoma EJ-1 cells. Compound 1 also moderately enhanced the insulin-stimulated phosphorylation levels of Akt in Huh-7 cells. Therefore, compound 1 has potential as a new type of anti-diabetic drug candidate possessing PTP1B inhibitory activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Phytochemical and Pharmacological Profiles of Three Fagopyrum Buckwheats

PubMed Central

Jing, Rui; Li, Hua-Qiang; Hu, Chang-Ling; Jiang, Yi-Ping; Qin, Lu-Ping; Zheng, Cheng-Jian

2016-01-01

The genus Fagopyrum (Polygonaceae), currently comprising 15 species of plants, includes three important buckwheat species: Fagopyrum esculentum (F. esculentum) Moench. (common buckwheat), Fagopyrum tataricum (F. tataricum) (L.) Gaertn. (tartary buckwheat) and Fagopyrum dibotrys (F. dibotrys) (D. Don) Hara. (perennial buckwheat), which have been well explored due to their long tradition of both edible and medicinal use. This review aimed to present an up-to-date and comprehensive analysis of the phytochemistry and pharmacology of the three Fagopyrum buckwheats. In addition, the scope for future research was also discussed. All available references included in this paper were compiled from major databases, such as MEDLINE, Pubmed, Scholar, Elsevier, Springer, Wiley and CNKI. A total of 106 compounds isolated from three Fagopyrum buckwheats can be mainly divided into six classes: flavonoids, phenolics, fagopyritols, triterpenoids, steroids and fatty acids. Flavonoids and phenolic compounds were considered to be the major active components. Considerable pharmacological experiments both in vitro and in vivo have validated that Fagopyrum buckwheats possess antitumor, anti-oxidant, anti-inflammatory, hepatoprotective, anti-diabetic activities, etc. All reported data lead us to conclude that Fagopyrum buckwheats have convincing medicinal potential. However, further research is needed to explore its bioactive constituents, the relationship to their structural activities and the molecular mechanisms of action. PMID:27104519

Antiobesity effects and improvement of insulin sensitivity by 1-deoxynojirimycin in animal models.

PubMed

Kong, Won-Ho; Oh, Seung-Hoon; Ahn, You-Ran; Kim, Kwang-Won; Kim, Jin-Hoon; Seo, Soo-Won

2008-04-23

The alpha-glucosidase inhibitor 1-deoxynojirimycin (DNJ) is one of the simplest naturally occurring carbohydrate mimics, with promising biological activity in vivo. Although there is considerable interest in the pharmacological effects of DNJ, the antidiabetic effects of DNJ in type 2 diabetes mellitus have received little attention. In this work, DNJ was isolated from the silkworm (Bombyx mori), and its antidiabetic effects were evaluated in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an established animal model of human type 2 diabetes mellitus, and in control Long-Evans Tokushima Otsuka (LETO) rats. DNJ treatment showed significant antidiabetic effects in OLETF rats, with significant improvements in fasting blood glucose levels and glucose tolerance and, especially, increased insulin sensitivity. Furthermore, there was significant loss of body weight in both groups. DNJ also showed significant antihyperglycemic effects in streptozotocin- and high-fat-diet-induced hyperglycemic rats. Its efficacy and dose profiles were better than those of acarbose, a typical alpha-glucosidase inhibitor in clinical use. Furthermore, a substantial fraction of DNJ was absorbed into the bloodstream within a few minutes of oral administration. DNJ was also detected in the urine. These findings suggest that its postprandial hypoglycemic effect in the gastrointestinal tract is a possible but insufficient mechanism of action underlying the antidiabetic effects of DNJ. Its antiobesity effect and improvement of insulin sensitivity are other possible antidiabetic effects of DNJ.

In vitro studies to assess the antidiabetic, antiperoxidative, and radical scavenging potential of Stereospermum colais.

PubMed

Rani, M Priya; Padmakumari, K P

2012-10-01

Stereospermum colais (Buch.-Ham. ex Dillw.) Mabberley (Bignoniaceae), which has traditional medicinal properties, is distributed all over deciduous forests. In spite of its many uses, the antidiabetic, antiperoxidative and radical scavenging activities of this species have not been assessed, and its chemical composition is scarcely known. Antidiabetic, antiperoxidation, xanthine oxidase (XO) inhibition, and radical scavenging activities of acetone and methanol extracts of Stereospermum colais roots were investigated. Protective effects of Stereospermum colais root extract in stabilizing sunflower oil was also examined. The protective effect of acetone (ASC) and methanol (MSC) extracts of Stereospermum colais root for the potential inhibition of α-glucosidase and α-amylase enzymes were studied by in vitro method. Glycation inhibitory activity was also studied to inhibit the production of glycated end products. Compared with acarbose, ASC showed a strong inhibitory activity against α-glucosidase (IC(50) 61.21 µg/mL) and a moderate inhibitory activity against α-amylase (IC(50) 681.08 µg/mL). Glycation inhibitory activity of Stereospermum colais root extracts by using an in vitro glucose-bovine serum albumin (BSA) assay was also done and compared with standard gallic acid. ASC also shows high XO inhibition potential, free radical scavenging activities, and low p-anisidine value indicates the high medicinal potency of Stereospermum colais root. These results suggest that the extract of Stereospermum colais may be interesting for incorporation in pharmaceutical preparations for human health, since it can suppress hyperglycaemia, and or as food additives due to its antiradical efficiency.

Metal based biologically active compounds: Design, synthesis, DNA binding and antidiabetic activity of 6-methyl-3-formyl chromone derived hydrazones and their metal (II) complexes.

PubMed

Philip, Jessica Elizabeth; Shahid, Muhammad; Prathapachandra Kurup, M R; Velayudhan, Mohanan Puzhavoorparambil

2017-10-01

Two chromone hydrazone ligands HL 1 and HL 2 were synthesized and characterized by elemental analyses, IR, 1 H NMR & 13 C NMR, electronic absorption and mass spectra. The reactions of the chromone hydrazones with transition metals such as Ni, Cu, and Zn (II) salts of acetate afforded mononuclear metal complexes. Characterization and structure elucidation of the prepared chromone hydrazone metal (II) complexes were done by elemental, IR, electronic, EPR spectra and thermo gravimetric analyses as well as conductivity and magnetic susceptibility measurements. The spectroscopic data showed that the ligand acts as a mono basic bidentate with coordination sites are azomethine nitrogen and hydrazonic oxygen, and they exhibited distorted geometry. The biological studies involved antidiabetic activity i.e. enzyme inhibition of α-amylase and α-glucosidase, Calf Thymus - DNA (CT-DNA) interaction and molecular docking. Potential capacity of synthesized compounds to inhibit the α-amylase and α-glucosidase activity was assayed whereas DNA interaction studies were carried out with the help UV-Vis absorption titration and viscosity method. The docking studies of chromone hydrazones show that they are minor groove binders. Complexes were found to be good DNA - intercalates. Chromone hydrazones and its transition metal complexes have shown comparable antidiabetic activity with a standard drug acarbose. Copyright © 2017 Elsevier B.V. All rights reserved.

The fatty acid-rich fraction of Eruca sativa (rocket salad) leaf extract exerts antidiabetic effects in cultured skeletal muscle, adipocytes and liver cells.

PubMed

Hetta, Mona H; Owis, Asmaa I; Haddad, Pierre S; Eid, Hoda M

2017-12-01

Eruca sativa Mill. (Brassicaceae), commonly known as rocket salad, is a popular leafy-green vegetable with many health benefits. To evaluate the antidiabetic activities of this plant in major insulin-responsive tissues. Five E. sativa leaf extracts of varying polarity were prepared (aqueous extract, 70% and 95% ethanol extracts, the n-hexane-soluble fraction of the 95% ethanol extract (ES3) and the defatted 95% ethanol extract). Eruca sativa extracts were investigated through a variety of cell-based in vitro bioassays for antidiabetic activities in C2C12 skeletal muscle cells, H4IIE hepatocytes and 3T3-L1 adipocytes. Guided by the results of these bioassays, ES3 was fractionated into the saponifiable (SM) and the unspaonifiable (USM) fractions. Glucose uptake was measured using [ 3 H]-deoxy-glucose, while the effects on hepatic glucose-6-phosphatase (G6Pase) and adipogenesis were assessed using Wako AutoKit Glucose and AdipoRed assays, respectively. ES3 and its SM fraction significantly stimulated glucose uptake with EC 50 values of 8.0 and 5.8 μg/mL, respectively. Both extracts significantly inhibited G6Pase activity (IC 50 values of 4.8 and 9.3 μg/mL, respectively). Moreover, ES3 and SM showed significant adipogenic activities with EC 50 of 4.3 and 6.1 μg/mL, respectively. Fatty acid content of SM was identified by GC-MS. trans-Vaccenic and palmitoleic acids were the major unsaturated fatty acids, while palmitic and azelaic acids were the main saturated fatty acids. These findings indicate that ES3 and its fatty acid-rich fraction exhibit antidiabetic activities in insulin-responsive cell lines and may hence prove useful for the treatment of type 2 diabetes.

Evidence based study of antidiabetic potential of C. maxima seeds - In vivo.

PubMed

Kushawaha, Devesh Kumar; Yadav, Manjulika; Chatterji, Sanjukta; Srivastava, Amrita Kumari; Watal, Geeta

2017-10-01

In vitro antidiabetic efficacy of Cucurbita maxima seed extract (CMSE) has already been studied in our previous findings. Thus, in order to validate these findings in biological system, in vivo antidiabetic activity of aqueous extract was investigated in normal as well as diabetic experimental models. Variable doses of extract were administered orally to normal and STZ induced mild diabetic rats during fasting blood glucose (FBG) and glucose tolerance test (GTT) studies. In order to determine the extract's antidiabetic potential long-term FBG and post prandial glucose (PPG) studies were also carried out. Most effective dose of 200 mg kg -1 of CMSE decreases the blood glucose level (BGL) in normal rats by 29.02% at 6 h during FBG studies and 23.23% at 3 h during GTT. However, the maximum reduction observed in BGL of mild diabetic rats during GTT the same interval of time was 26.15%. Moreover, in case of severely diabetic rats a significant reduction of 39.33% was observed in FBG levels whereas, in case of positive control, rats treated with 2.5 mg kg -1 of glipizide, a fall of 42.9% in FBG levels was observed after 28 days. Results of PPG level also showed a fall of 33.20% in severely diabetic rats as compared to the positive control showing a fall of 44.2% at the end of the 28 days. Thus, the present study validate the hypoglycemic and antidiabetic effect of CMSE and hence this extract could be explored further for developing as a novel antidiabetic agent.

Alpha-amylase Inhibition and Antioxidant Activity of Marine Green Algae and its Possible Role in Diabetes Management.

PubMed

Unnikrishnan, P S; Suthindhiran, K; Jayasri, M A

2015-10-01

In the continuing search for safe and efficient antidiabetic drug, marine algae become important source which provide several compounds of immense therapeutic potential. Alpha-amylase, alpha-glucosidase inhibitors, and antioxidant compounds are known to manage diabetes and have received much attention recently. In the present study, four green algae (Chaetomorpha aerea, Enteromorpha intestinalis, Chlorodesmis, and Cladophora rupestris) were chosen to evaluate alpha-amylase, alpha-glucosidase inhibitory, and antioxidant activity in vitro. The phytochemical constituents of all the extracts were qualitatively determined. Antidiabetic activity was evaluated by inhibitory potential of extracts against alpha-amylase and alpha-glucosidase by spectrophotometric assays. Antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl, hydrogen peroxide (H2O2), and nitric oxide scavenging assay. Gas chromatography-mass spectrometry (GC-MS) analysis was carried out to determine the major compound responsible for its antidiabetic action. Among the various extracts screened, chloroform extract of C. aerea (IC50 - 408.9 μg/ml) and methanol extract of Chlorodesmis (IC50 - 147.6 μg/ml) showed effective inhibition against alpha-amylase. The extracts were also evaluated for alpha-glucosidase inhibition, and no observed activity was found. Methanol extract of C. rupestris showed notable free radical scavenging activity (IC50 - 666.3 μg/ml), followed by H2O2 (34%) and nitric oxide (49%). Further, chemical profiling by GC-MS revealed the presence of major bioactive compounds. Phenol, 2,4-bis (1,1-dimethylethyl) and z, z-6,28-heptatriactontadien-2-one were predominantly found in the methanol extract of C. rupestris and chloroform extract of C. aerea. Our results demonstrate that the selected algae exhibit notable alpha-amylase inhibition and antioxidant activity. Therefore, characterization of active compounds and its in vivo assays will be noteworthy. Four green algae were chosen to evaluate alpha-amylase, alpha-glucosidase inhibitory, and antioxidant activity in vitro C. aerea and Chlorodesmis showed significant inhibition against alpha-amylase, and C. rupestris showed notable free radical scavenging activityNo observed activity was found against alpha-glucosidaseGC-MS analysis of the active extracts reveals the presence of major compounds which gives an insight on the antidiabetic and antioxidant activity of these algae. Abbreviations used: DPPH: 2,2-diphenyl-1-picrylhydrazyl, BHT: Butylated hydroxytoluene, GC-MS: Gas chromatography-mass spectrometry.

Alpha-amylase Inhibition and Antioxidant Activity of Marine Green Algae and its Possible Role in Diabetes Management

PubMed Central

Unnikrishnan, P. S.; Suthindhiran, K.; Jayasri, M. A.

2015-01-01

Aim: In the continuing search for safe and efficient antidiabetic drug, marine algae become important source which provide several compounds of immense therapeutic potential. Alpha-amylase, alpha-glucosidase inhibitors, and antioxidant compounds are known to manage diabetes and have received much attention recently. In the present study, four green algae (Chaetomorpha aerea, Enteromorpha intestinalis, Chlorodesmis, and Cladophora rupestris) were chosen to evaluate alpha-amylase, alpha-glucosidase inhibitory, and antioxidant activity in vitro. Materials and Methods: The phytochemical constituents of all the extracts were qualitatively determined. Antidiabetic activity was evaluated by inhibitory potential of extracts against alpha-amylase and alpha-glucosidase by spectrophotometric assays. Antioxidant activity was determined by 2,2-diphenyl-1-picrylhydrazyl, hydrogen peroxide (H2O2), and nitric oxide scavenging assay. Gas chromatography-mass spectrometry (GC-MS) analysis was carried out to determine the major compound responsible for its antidiabetic action. Results: Among the various extracts screened, chloroform extract of C. aerea (IC50 − 408.9 μg/ml) and methanol extract of Chlorodesmis (IC50 − 147.6 μg/ml) showed effective inhibition against alpha-amylase. The extracts were also evaluated for alpha-glucosidase inhibition, and no observed activity was found. Methanol extract of C. rupestris showed notable free radical scavenging activity (IC50 – 666.3 μg/ml), followed by H2O2 (34%) and nitric oxide (49%). Further, chemical profiling by GC-MS revealed the presence of major bioactive compounds. Phenol, 2,4-bis (1,1-dimethylethyl) and z, z-6,28-heptatriactontadien-2-one were predominantly found in the methanol extract of C. rupestris and chloroform extract of C. aerea. Conclusion: Our results demonstrate that the selected algae exhibit notable alpha-amylase inhibition and antioxidant activity. Therefore, characterization of active compounds and its in vivo assays will be noteworthy. SUMMARY Four green algae were chosen to evaluate alpha-amylase, alpha-glucosidase inhibitory, and antioxidant activity in vitro C. aerea and Chlorodesmis showed significant inhibition against alpha-amylase, and C. rupestris showed notable free radical scavenging activityNo observed activity was found against alpha-glucosidaseGC-MS analysis of the active extracts reveals the presence of major compounds which gives an insight on the antidiabetic and antioxidant activity of these algae. Abbreviations used: DPPH: 2,2-diphenyl-1-picrylhydrazyl, BHT: Butylated hydroxytoluene, GC-MS: Gas chromatography-mass spectrometry. PMID:27013787

A pharmacological appraisal of medicinal plants with antidiabetic potential

PubMed Central

Khan, Vasim; Najmi, Abul Kalam; Akhtar, Mohd.; Aqil, Mohd.; Mujeeb, Mohd.; Pillai, K. K.

2012-01-01

Diabetes mellitus is a complicated metabolic disorder that has gravely troubled the human health and quality of life. Conventional agents are being used to control diabetes along with lifestyle management. However, they are not entirely effective and no one has ever been reported to have fully recovered from diabetes. Numerous medicinal plants have been used for the management of diabetes mellitus in various traditional systems of medicine worldwide as they are a great source of biological constituents and many of them are known to be effective against diabetes. Medicinal plants with antihyperglycemic activities are being more desired, owing to lesser side-effects and low cost. This review focuses on the various plants that have been reported to be effective in diabetes. A record of various medicinal plants with their established antidiabetic and other health benefits has been reported. These include Allium sativa, Eugenia jambolana, Panax ginseng, Gymnema sylvestre, Momrodica charantia, Ocimum sanctum, Phyllanthus amarus, Pterocarpus marsupium, Trigonella foenum graecum and Tinospora cordifolia. All of them have shown a certain degree of antidiabetic activity by different mechanisms of action. PMID:22368396

Chalcones and their therapeutic targets for the management of diabetes: structural and pharmacological perspectives.

PubMed

Mahapatra, Debarshi Kar; Asati, Vivek; Bharti, Sanjay Kumar

2015-03-06

Diabetes Mellitus (DM) is the fastest growing metabolic disorder affecting about 387 million people across the globe and is estimated to affect 592 million people by year 2030. The search for newer anti-diabetic agents is the foremost need to control the accelerating diabetic population. Several natural and (semi) synthetic chalcones deserve the credit of being potential candidates that act by modulating the therapeutic targets PPAR-γ, DPP-4, α-glucosidase, PTP1B, aldose reductase, and stimulate insulin secretion and tissue sensitivity. In this review, a comprehensive study (from January 1977 to October 2014) of anti-diabetic chalcones, their molecular targets, structure activity relationships (SARs), mechanism of actions (MOAs) and patents have been described. The compounds which showed promising activity and have a well-defined MOAs, SARs must be considered as prototype for the design and development of potential anti-diabetic agents. They should be evaluated critically at all clinical stages to ensure their therapeutic and toxicological profile to meet the demand of diabetics. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Polyphenols and Glycemic Control

PubMed Central

Kim, Yoona; Keogh, Jennifer B.; Clifton, Peter M.

2016-01-01

Growing evidence from animal studies supports the anti-diabetic properties of some dietary polyphenols, suggesting that dietary polyphenols could be one dietary therapy for the prevention and management of Type 2 diabetes. This review aims to address the potential mechanisms of action of dietary polyphenols in the regulation of glucose homeostasis and insulin sensitivity based on in vitro and in vivo studies, and to provide a comprehensive overview of the anti-diabetic effects of commonly consumed dietary polyphenols including polyphenol-rich mixed diets, tea and coffee, chocolate and cocoa, cinnamon, grape, pomegranate, red wine, berries and olive oil, with a focus on human clinical trials. Dietary polyphenols may inhibit α-amylase and α-glucosidase, inhibit glucose absorption in the intestine by sodium-dependent glucose transporter 1 (SGLT1), stimulate insulin secretion and reduce hepatic glucose output. Polyphenols may also enhance insulin-dependent glucose uptake, activate 5′ adenosine monophosphate-activated protein kinase (AMPK), modify the microbiome and have anti-inflammatory effects. However, human epidemiological and intervention studies have shown inconsistent results. Further intervention studies are essential to clarify the conflicting findings and confirm or refute the anti-diabetic effects of dietary polyphenols. PMID:26742071

Antioxidant and Inhibitory Effects of Saponin Extracts from Dianthus basuticus Burtt Davy on Key Enzymes Implicated in Type 2 Diabetes In vitro.

PubMed

Nafiu, Mikhail Olugbemiro; Ashafa, Anofi Omotayo Tom

2017-01-01

Dianthus basuticus is a plant of South African origin with various acclaimed pharmaceutical potentials. This study explored the antioxidant and antidiabetic activities of saponin extract from D. basuticus in vitro . Antioxidant activity of saponin was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (*NO)-free radical scavenging activity while antidiabetic potentials were measured by the α-amylase and α-glucosidase inhibitory activities of the saponin extract. The results showed that the saponin extract, compared with quercetin, displayed better DPPH (IC 50 = 6.95 mg/ml) and NO (IC 50 = 3.31 mg/ml) radical scavenging capabilities. Similarly, the saponin extracts elicited stronger α-glucosidase (IC 50 = 3.80 mg/ml) and moderate α-amylase (IC 50 = 4.18 mg/ml) inhibitory activities as compared to acarbose. Saponin exhibited a competitive mode of inhibition on α-amylase with same maximum velocity (Vmax) of 0.0093 mM/min for saponin compared with control 0.0095 mM/min and different the Michaelis constant (Km) values of 2.6 × 10 -6 mM and 2.1 × 10 -5 mM, respectively, while for α-glucosidase, the inhibition was uncompetitive, Vmax of 0.027 mM/min compared with control 0.039 mM/min and Km values of 1.02 × 10 -6 mM and 1.38 × 10 -6 mM, respectively. The gas chromatography-mass spectrometric analysis revealed the presence of bioactive like β- and α-amyrin, 3-O-methyl-D-glucose, methyl commate, and olean-12-en-3-beta-ol. Overall, the data suggested that the saponin extract from D. basuticus has potentials as natural antioxidants and antidiabetics. Saponin extract from Dianthus basuticus displayed promising antidiabetic and antioxidant activitySaponin competitively and uncompetitively inhibited a-amylase and a-glucosidase, respectivelyThe stronger inhibition of α-glucosidase and moderate inhibition of α-amylase by saponin extract from D. basuticus is promising good antidiabetes compared with existing drugs with associated side effects. Abbreviations used: DPPH: 2,2-diphenyl-1-picrylhydrazyl, Km: The Michaelis constant, Vmax: Maximum velocity, ROS: Reactive oxygen species, NIDDM: Non-insulin-dependent diabetes mellitus, UFS: University of the Free State, GC-MS: Gas chromatography-mass spectrometric, MS: Mass spectrometry, NIST: National Institute of Standards and Technology, DNS: 3,5-dinitrosalicylic acid, NO: Nitric oxide, RNS: Reactive nitrogen species, PNPG: p-Nitrophenyl-α-D-glucopyranoside.

Antioxidant and Inhibitory Effects of Saponin Extracts from Dianthus basuticus Burtt Davy on Key Enzymes Implicated in Type 2 Diabetes In vitro

PubMed Central

Nafiu, Mikhail Olugbemiro; Ashafa, Anofi Omotayo Tom

2017-01-01

Context: Dianthus basuticus is a plant of South African origin with various acclaimed pharmaceutical potentials. Aims: This study explored the antioxidant and antidiabetic activities of saponin extract from D. basuticus in vitro. Materials and Methods: Antioxidant activity of saponin was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (*NO)-free radical scavenging activity while antidiabetic potentials were measured by the α-amylase and α-glucosidase inhibitory activities of the saponin extract. Results: The results showed that the saponin extract, compared with quercetin, displayed better DPPH (IC50 = 6.95 mg/ml) and NO (IC50 = 3.31 mg/ml) radical scavenging capabilities. Similarly, the saponin extracts elicited stronger α-glucosidase (IC50 = 3.80 mg/ml) and moderate α-amylase (IC50 = 4.18 mg/ml) inhibitory activities as compared to acarbose. Saponin exhibited a competitive mode of inhibition on α-amylase with same maximum velocity (Vmax) of 0.0093 mM/min for saponin compared with control 0.0095 mM/min and different the Michaelis constant (Km) values of 2.6 × 10-6 mM and 2.1 × 10-5 mM, respectively, while for α-glucosidase, the inhibition was uncompetitive, Vmax of 0.027 mM/min compared with control 0.039 mM/min and Km values of 1.02 × 10-6 mM and 1.38 × 10-6 mM, respectively. The gas chromatography-mass spectrometric analysis revealed the presence of bioactive like β- and α-amyrin, 3-O-methyl-D-glucose, methyl commate, and olean-12-en-3-beta-ol. Conclusion: Overall, the data suggested that the saponin extract from D. basuticus has potentials as natural antioxidants and antidiabetics. SUMMARY Saponin extract from Dianthus basuticus displayed promising antidiabetic and antioxidant activitySaponin competitively and uncompetitively inhibited a-amylase and a-glucosidase, respectivelyThe stronger inhibition of α-glucosidase and moderate inhibition of α-amylase by saponin extract from D. basuticus is promising good antidiabetes compared with existing drugs with associated side effects. Abbreviations used: DPPH: 2,2-diphenyl-1-picrylhydrazyl, Km: The Michaelis constant, Vmax: Maximum velocity, ROS: Reactive oxygen species, NIDDM: Non-insulin-dependent diabetes mellitus, UFS: University of the Free State, GC-MS: Gas chromatography-mass spectrometric, MS: Mass spectrometry, NIST: National Institute of Standards and Technology, DNS: 3,5-dinitrosalicylic acid, NO: Nitric oxide, RNS: Reactive nitrogen species, PNPG: p-Nitrophenyl-α-D-glucopyranoside. PMID:29200716

Increase in the free radical scavenging capability of bitter gourd by a heat-drying process.

PubMed

Wei, Lu; Shaoyun, Wang; Shutao, Liu; Jianwu, Zhou; Lijing, Ke; Pingfan, Rao

2013-12-01

Bitter gourd (Momordica charantia Linn.) is widely regarded as one of the best remedy foods for diabetes. The positive effect of bitter gourd on diabetes has been attributed in part to the remarkable free radical scavenging activity of its boiled water extract from sun-dried fruits. It is well known that a heat process significantly influences the antioxidant activity of fresh fruits. However, the heat drying processes of bitter gourd have not been studied so far. Here, we show that the free radical scavenging capability of bitter gourd extract significantly increases after the heat drying process, while the content of flavonoids and phenols, which are generally regarded as the main antioxidant components in bitter gourd, remain unaffected. Furthermore, the content of free amino acids and the total reducing sugar were found to decrease with increasing browning index, indicating the progression of the Maillard reaction, products of which are known to possess significant antioxidant activity. Therefore, it suggests that Maillard reaction products may be the main contributors to the increase in antioxidant capability. Finally, the bitter gourd extract with the higher antioxidant activity, was shown to manifest a corresponding higher proliferation activity on NIT-1 beta-cells. These results suggest that controllable conditions in the heat-drying processing of fresh bitter gourd fruit is of significance for enhancing the total free radical scavenging capacity, beta-cell proliferation activity and possibly the anti-diabetic activity of this fruit.

Metabolomics Study of Type 2 Diabetes Mellitus and the AntiDiabetic Effect of Berberine in Zucker Diabetic Fatty Rats Using Uplc-ESI-Hdms.

PubMed

Dong, Yu; Chen, Yi-Tao; Yang, Yuan-Xiao; Zhou, Xiao-Jie; Dai, Shi-Jie; Tong, Jun-Feng; Shou, Dan; Li, Changyu

2016-05-01

The present study aimed to evaluate the pathogenesis of type 2 diabetes mellitus (T2DM) and the anti-diabetic effect of berberine in Zucker diabetic fatty (ZDF) rats. A urinary metabolomics analysis was performed with ultra-performance liquid chromatography/electrospray ionization synapt high-definition mass spectrometry. Pattern recognition approaches were integrated to discover differentiating metabolites. We identified 29 ions (13 in negative mode and 16 in positive mode) as 'differentiating metabolites' with this metabolomic approach. A functional pathway analysis revealed that the alterations were mainly associated with glyoxylate and dicarboxylate metabolism, pentose and glucuronate interconversions and sphingolipid metabolism. These results indicated that the dysfunctions of glycometabolism and lipometabolism are involved in the pathological process of T2DM. Berberine could decrease the serum levels of glycosylated hemoglobin, total cholesterol and triglyceride and increase the secretion of insulin. The urinary metabolomics analysis showed that berberine could reduce the concentrations of citric acid, tetrahydrocortisol, ribothymidine and sphinganine to a near-normal state. These results suggested that the anti-diabetic effect of berberine occurred mainly via its regulation of glycometabolism and lipometabolism and activation of adenosine 5'-monophosphate-activated protein kinase. Our work not only provides a better understanding of the anti-diabetic effect of berberine in ZDF rats but also supplies a useful database for further study in humans and for investigating the pharmacological actions of drugs. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

In Vitro and In Vivo Antidiabetic Evaluation of Selected Culinary-Medicinal Mushrooms (Agaricomycetes).

PubMed

Singh, Varinder; Bedi, Gurleen Kaur; Shri, Richa

2017-01-01

Management of type 2 diabetes by delaying or preventing glucose absorption using natural products is gaining significant attention. Edible mushrooms are well documented for their nutritional and medicinal properties. This investigation was designed to evaluate the antidiabetic activity of aqueous extracts of selected culinary-medicinal mushrooms, namely, Pleurotus ostreatus, Calocybe indica, and Volvariella volvacea, using in vitro models (α-amylase inhibition assay, glucose uptake by yeast cells, and glucose adsorption capacity). The most active extract was subsequently examined in vivo using the oral starch tolerance test in mice. All prepared extracts showed dose-dependent inhibition of α-amylase and an increase in glucose transport across yeast cells. C. indica extract was the most active α-amylase inhibitor (half-maximal inhibitory concentration, 18.07 ± 0.75 mg/mL) and exhibited maximum glucose uptake by yeast cells (77.53 ± 0.97% at 35 mg/mL). All extracts demonstrated weak glucose adsorption ability. The positive in vitro tests for C. indica paved the way for in vivo studies. C. indica extract (200 and 400 mg/kg) significantly (P < 0.05) reduced postprandial blood glucose peaks in mice challenged with starch. The extract (400 mg/kg) and acarbose normalized blood glucose levels at 180 minutes, when they were statistically similar to values in normal mice. Thus, it may be concluded that the antidiabetic effect of C. indica is mediated by inhibition of starch metabolism (α-amylase inhibition), increased glucose uptake by peripheral cells (promotion of glucose uptake by yeast cells), and mild entrapment (adsorption) of glucose. Hence, C. indica can be developed as antidiabetic drug after detailed pharmacological studies.

Synthesis, spectroscopic characterization, DFT optimization and biological activities of Schiff bases and their metal (II) complexes

NASA Astrophysics Data System (ADS)

Rauf, Abdur; Shah, Afzal; Munawar, Khurram Shahzad; Khan, Abdul Aziz; Abbasi, Rashda; Yameen, Muhammad Arfat; Khan, Asad Muhammad; Khan, Abdur Rahman; Qureshi, Irfan Zia; Kraatz, Heinz-Bernhard; Zia-ur-Rehman

2017-10-01

A Novel Schiff base, 3-(((4-chlorophenyl)imino)methyl)benzene-1,2-diol (HL1) was successfully synthesized along with a structurally similar Schiff base 3-(((4-bromophenyl)imino)methyl)benzene-1,2-diol (HL2). Both the Schiff bases were used to synthesize their zinc (II) and cobalt (II) complexes. These compounds were characterized by FTIR, 1H NMR, 13C NMR and elemental analysis. Metal complexes were confirmed by TGA. Crystals of Schiff bases were also characterized by X-ray analysis and experimental parameters were found in line with the theoretical parameters. Quantum mechanical approach was also used to fine useful structural parameters and to ensure the geometry of metal complexes. The photometric behaviors of all the synthesized compounds were investigated in a wide pH range using BR buffers. The appearance of isosbestic points indicated the existence of Schiff bases in more than one isomeric form. Moreover, these compounds were screened for enzyme inhibition; antibacterial, cytotoxic and in vivo antidiabetic activities and compounds were found active against one or other activity. Results indicate that ZnL22 is a good inhibitor of alkaline phosphatase enzyme and possess highest potential against diabetes, blood cholesterol level and cancer cells. This effort just provides preliminary data for some biological properties. Further investigations are required to precisely determine mechanistic pathways of their use towards drug development.

Antidiabetic effects of Justicia spicigera Schltdl (Acanthaceae).

PubMed

Ortiz-Andrade, Rolffy; Cabañas-Wuan, Angel; Arana-Argáez, Víctor E; Alonso-Castro, Angel Josabad; Zapata-Bustos, Rocio; Salazar-Olivo, Luis A; Domínguez, Fabiola; Chávez, Marco; Carranza-Álvarez, Candy; García-Carrancá, Alejandro

2012-09-28

Justicia spicigera is a plant species used for the Teenak (Huesteca Potosina) and Mayan (Yucatan peninsula) indigenous for the empirical treatment of diabetes, infections and as stimulant. To evaluate the cytotoxicity, antioxidant and antidiabetic properties of J. spicigera. The effects of ethanolic extracts of J. spicigera (JSE) on the glucose uptake in insulin-sensitive and insulin-resistant murine 3T3-F442A and human subcutaneous adipocytes was evaluated. The antioxidant activities of the extract of JSE was determined by ABTS and DPPH methods. Additionally, it was evaluated the antidiabetic properties of JSE on T2DM model. JSE stimulated 2-NBDG uptake by insulin-sensitive and insulin-resistant human and murine adipocytes in a concentration-dependent manner with higher potency than rosiglitazone 1mM. JSE showed antioxidant effects in vitro and induced glucose lowering effects in normoglycemic and STZ-induced diabetic rats. The antidiabetic effects of administration of J. spicigera are related to the stimulation of glucose uptake in both insulin-sensitive and insulin-resistant murine and human adipocytes and this evidence justify its empirical use in Traditional Medicine. In addition, J. spicigera exerts glucose lowering effects in normoglycemic and STZ-induced diabetic rats. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The Interaction of Anti-diabetic α-Glucosidase Inhibitors and Gut Bacteria α-Glucosidase.

PubMed

Tan, Kemin; Tesar, Christine; Wilton, Rosemarie; Jedrzejczak, Robert P; Joachimiak, Andrzej

2018-05-15

Carbohydrate hydrolyzing α-glucosidases are commonly found in microorganisms present in the human intestine microbiome. We have previously reported crystal structures of an α-glucosidase from the human gut bacterium Blaubia (Ruminococcus) obeum (Ro-αG1) and its substrate preference/specificity switch. This novel member of the GH31 family is a structural homolog of human intestinal maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI) with a highly conserved active site that is predicted to be common in Ro-αG1 homologs among other species that colonize the human gut. In this report, we present structures of Ro-αG1 in complex with the anti-diabetic α-glucosidase inhibitors voglibose, miglitol and acarbose and supporting binding data. The in vitro binding of these anti-diabetic drugs to Ro-αG1 suggests the potential for unintended in vivo cross-reaction of the α-glucosidase inhibitors to bacterial α-glucosidases that are present in gut microorganism communities. Moreover, analysis of these drug-bound enzyme structures could benefit further anti-diabetic drug development. This article is protected by copyright. All rights reserved. © 2018 The Protein Society.

Production of Gymnemic Acid from Cell Suspension Cultures of Gymnema sylvestre.

PubMed

Nagella, Praveen; Dandin, Vijayalaxmi S; Murthy, Hosakatte Niranjana

2016-01-01

Gymnema sylvestre R. Br. is a popular herbal medicine. It has been used in ayurvedic system of medicine for thousands of years. It is popularly called as "Gur-mar" for its distinctive property of temporarily destroying the taste of sweetness and is used in the treatment of diabetes. The leaves of gymnema possess antidiabetic, antimicrobial, anti-hypercholesterolemic, anti-sweetener, anti-inflammatory, and hepatoprotective properties and have traditional uses in the treatment of asthma, eye complaints, and snake bite. The leaves contain triterpene saponins such as gymnemic acid which is an active ingredient of Gymnema. Since the cultivation of G. sylvestre is a very slow process and the content of gymnemic acid depends on the environmental factors, cell suspension culture is sought as an alternative means for the production of Gymnema biomass and to enhance the gymnemic acid content. In this chapter, the methods employed for the induction of callus and subsequent establishment of cell suspension cultures for the production of biomass and analysis of gymnemic acid using high performance liquid chromatography are described.

Beneficial effects of mangiferin isolated from Salacia chinensis on biochemical and hematological parameters in rats with streptozotocin-induced diabetes.

PubMed

Sellamuthu, Periyar Selvam; Arulselvan, Palanisamy; Fakurazi, Sharida; Kandasamy, Murugesan

2014-01-01

Salacia chinensis L. is a traditional Southeast Asian herbal medicine and used in the treatment of diabetes. To investigate the antidiabetic properties of mangiferin from Salacia chinensis and its beneficial effect on toxicological and hematological parameters in streptozotocin induced diabetic rats. Mangiferin was orally treated with the dose of 40 mg/kg body weight/day for 30 days to diabetic rats. Biochemical (blood glucose, uric acid, urea and creatinine), toxicological (AST, ALT and ALP) and hematological parameters (red and white blood cells) and their functional indices were evaluated in diabetic treated groups with mangiferin and glibenclamide. Mangiferin treated diabetic rats significantly (p<0.05) lowered the level of blood glucose, in addition, altered the levels of biochemical parameters including urea, uric acid, and creatinine. Toxicological parameters including AST, ALT and ALP were also significantly reduced after treatment with mangiferin in diabetic rats. Similarly, the levels of red blood, white blood cells and their functional indices were significantly improved through the administration of mangiferin. Thus, our results indicate that mangiferin present in S. chinensis possesses antidiabetic properties and nontoxic nature against chemically induced diabetic rats. Further experimental investigations are warrant to make use of its relevant therapeutic effect to substantiate its ethno-medicinal usage.

Non-coding RNAs and Berberine: A new mechanism of its anti-diabetic activities.

PubMed

Chang, Wenguang

2017-01-15

Type 2 Diabetes (T2D) is a metabolic disease with high mortality and morbidity. Non-coding RNAs, including small and long non-coding RNAs, are a novel class of functional RNA molecules that regulate multiple biological functions through diverse mechanisms. Studies in the last decade have demonstrated that non-coding RNAs may represent compelling therapeutic targets and play important roles in regulating the course of insulin resistance and T2D. Berberine, a plant-based alkaloid, has shown promise as an anti-hyperglycaemic, anti-hyperlipidaemic agent against T2D. Previous studies have primarily focused on a diverse array of efficacy end points of berberine in the pathogenesis of metabolic syndromes and inflammation or oxidative stress. Currently, an increasing number of studies have revealed the importance of non-coding RNAs as regulators of the anti-diabetic effects of berberine. The regulation of non-coding RNAs has been associated with several therapeutic actions of berberine in T2D progression. Thus, this review summarizes the anti-diabetic mechanisms of berberine by focusing on its role in regulating non-coding RNA, thus demonstrating that berberine exerts global anti-diabetic effects by targeting non-coding RNAs and that these effects involve several miRNAs, lncRNAs and multiple signal pathways, which may enhance the current understanding of the anti-diabetic mechanism actions of berberine and provide new pathological targets for the development of berberine-related drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

Assessment of antidiabetic activity and acute toxicity of leaf extracts from Physalis peruviana L. in guinea-pig

PubMed Central

Kasali, Félicien Mushagalusa; Kadima, Justin Ntokamunda; Mpiana, Pius Tshimankinda; Ngbolua, Koto-te-Nyiwa; Tshibangu, Damien Sha-Tshibey

2013-01-01

Objective To verify the antidiabetic activity of leaf extracts from Physalis peruviana L. popularly used in the Eastern part of the Democratic Republic of the Congo and to point out the possible toxicity. Method Aqueous decoctions prepared from dried leaves powder were administrated to guinea pigs at the dose range of 100 mg/kg to 3.2 g/kg of body weight. The hypoglycemic activity was evaluated by glucose tolerance test, loading animals with glucose 4 g/kg and measuring blood glucose concentrations at various times. The effect was compared to the control and glibenclamide as antidiabetic reference drug. Acute toxicity was evaluated by recording mortality rate, changes on blood biomarkers and damage caused to vital organs. Results At a dose of 100 mg/kg, the aqueous extract induced a significant reduction of peak concentration at 30 min after glucose loading as compared with control or reference (P<0.05). At doses greater than 400 mg, some alterations on blood, kidney and liver markers were observed. Upper 800 mg/kg, mortality was observed with LD50 estimated at about 1 280 mg/kg. At the autopsy, vital organs were in haemorrhage and swelling state. Conclusion The crude aqueous extracts from the leaves of Physalis peruviana L. present hypoglycemic activity in animal model, but at high doses the plant may cause severe intoxication.

A Network Pharmacology Approach to Determine Active Compounds and Action Mechanisms of Ge-Gen-Qin-Lian Decoction for Treatment of Type 2 Diabetes

PubMed Central

Li, Huiying; Zhao, Linhua; Zhang, Bo; Jiang, Yuyu; Wang, Xu; Guo, Yun; Liu, Hongxing; Li, Shao; Tong, Xiaolin

2014-01-01

Traditional Chinese medicine (TCM) herbal formulae can be valuable therapeutic strategies and drug discovery resources. However, the active ingredients and action mechanisms of most TCM formulae remain unclear. Therefore, the identification of potent ingredients and their actions is a major challenge in TCM research. In this study, we used a network pharmacology approach we previously developed to help determine the potential antidiabetic ingredients from the traditional Ge-Gen-Qin-Lian decoction (GGQLD) formula. We predicted the target profiles of all available GGQLD ingredients to infer the active ingredients by clustering the target profile of ingredients with FDA-approved antidiabetic drugs. We also applied network target analysis to evaluate the links between herbal ingredients and pharmacological actions to help explain the action mechanisms of GGQLD. According to the predicted results, we confirmed that a novel antidiabetic ingredient from Puerariae Lobatae radix (Ge-Gen), 4-Hydroxymephenytoin, increased the insulin secretion in RIN-5F cells and improved insulin resistance in 3T3-L1 adipocytes. The network pharmacology strategy used here provided a powerful means for identifying bioactive ingredients and mechanisms of action for TCM herbal formulae, including Ge-Gen-Qin-Lian decoction. PMID:24527048

Diverse mechanisms of antidiabetic effects of the different procyanidin oligomer types of two different cinnamon species on db/db mice.

PubMed

Chen, Liang; Sun, Peng; Wang, Ting; Chen, Kaixian; Jia, Qi; Wang, Heyao; Li, Yiming

2012-09-12

The procyanidin oligomers are thought to be responsible for the antidiabetic activity of cinnamon. To investigate the hypoglycemic effects of different procyanidin oligomer types, the procyanidin oligomer-rich extracts were prepared from two different cinnamon species. Using high-performance liquid chromatography with purified procyanidin oligomers as reference compounds, we found that the Cinnamomum cassia extract (CC-E) and Cinnamomum tamala extract (CT-E) were rich in B- and A-type procyanidin oligomers, respectively. In the experiment, 8-week-old diabetic (db/db) mice were gavaged with CC-E and CT-E (both 200 mg/kg per day) for 4 weeks. Both CC-E and CT-E exhibited antidiabetic effects. Moreover, histopathological studies of the pancreas, liver, and adipose tissue showed that CC-E promoted lipid accumulation in the adipose tissue and liver, whereas CT-E mainly improved the insulin concentration in the blood and pancreas.

An overview on antidiabetic medicinal plants having insulin mimetic property

PubMed Central

Patel, DK; Prasad, SK; Kumar, R; Hemalatha, S

2012-01-01

Diabetes mellitus is one of the common metabolic disorders acquiring around 2.8% of the world's population and is anticipated to cross 5.4% by the year 2025. Since long back herbal medicines have been the highly esteemed source of medicine therefore, they have become a growing part of modern, high-tech medicine. In view of the above aspects the present review provides profiles of plants (65 species) with hypoglycaemic properties, available through literature source from various database with proper categorization according to the parts used, mode of reduction in blood glucose (insulinomimetic or insulin secretagogues activity) and active phytoconstituents having insulin mimetics activity. From the review it was suggested that, plant showing hypoglycemic potential mainly belongs to the family Leguminoseae, Lamiaceae, Liliaceae, Cucurbitaceae, Asteraceae, Moraceae, Rosaceae and Araliaceae. The most active plants are Allium sativum, Gymnema sylvestre, Citrullus colocynthis, Trigonella foenum greacum, Momordica charantia and Ficus bengalensis. The review describes some new bioactive drugs and isolated compounds from plants such as roseoside, epigallocatechin gallate, beta-pyrazol-1-ylalanine, cinchonain Ib, leucocyandin 3-O-beta-d-galactosyl cellobioside, leucopelargonidin-3- O-alpha-L rhamnoside, glycyrrhetinic acid, dehydrotrametenolic acid, strictinin, isostrictinin, pedunculagin, epicatechin and christinin-A showing significant insulinomimetic and antidiabetic activity with more efficacy than conventional hypoglycaemic agents. Thus, from the review majorly, the antidiabetic activity of medicinal plants is attributed to the presence of polyphenols, flavonoids, terpenoids, coumarins and other constituents which show reduction in blood glucose levels. The review also discusses the management aspect of diabetes mellitus using these plants and their active principles. PMID:23569923

Rapid Screening for α-Glucosidase Inhibitors from Gymnema sylvestre by Affinity Ultrafiltration–HPLC-MS

PubMed Central

Chen, Guilin; Guo, Mingquan

2017-01-01

Gymnema sylvestre R. Br. (Asclepiadaceae) has been known to posses potential anti-diabetic activity, and the gymnemic acids were reported as the main bioactive components in this plant species. However, the specific components responsible for the hypoglycemic effect still remain unknown. In the present study, the in vitro study revealed that the extract of G. sylvestre exhibited significant inhibitory activity against α-glucosidase with IC50 at 68.70 ± 1.22 μg/mL compared to acarbose (positive control) at 59.03 ± 2.30 μg/mL, which further indicated the potential anti-diabetic activity. To this end, a method based on affinity ultrafiltration coupled with liquid chromatography mass spectrometry (UF-HPLC-MS) was established to rapidly screen and identify the α-glucosidase inhibitors from G. sylvestre. In this way, 9 compounds with higher enrichment factors (EFs) were identified according to their MS/MS spectra. Finally, the structure-activity relationships revealed that glycosylation could decrease the potential antisweet activity of sapogenins, and other components except gymnemic acids in G. sylvestre could also be good α-glucosidase inhibitors due to their synergistic effects. Taken together, the proposed method combing α-glucosidase and UF-HPLC-MS presents high efficiency for rapidly screening and identifying potential inhibitors of α-glucosidase from complex natural products, and could be further explored as a valuable high-throughput screening (HTS) platform in the early anti-diabetic drug discovery stage. PMID:28496409

Rapid Screening for α-Glucosidase Inhibitors from Gymnema sylvestre by Affinity Ultrafiltration-HPLC-MS.

PubMed

Chen, Guilin; Guo, Mingquan

2017-01-01

Gymnema sylvestre R. Br. (Asclepiadaceae) has been known to posses potential anti-diabetic activity, and the gymnemic acids were reported as the main bioactive components in this plant species. However, the specific components responsible for the hypoglycemic effect still remain unknown. In the present study, the in vitro study revealed that the extract of G. sylvestre exhibited significant inhibitory activity against α-glucosidase with IC 50 at 68.70 ± 1.22 μg/mL compared to acarbose (positive control) at 59.03 ± 2.30 μg/mL, which further indicated the potential anti-diabetic activity. To this end, a method based on affinity ultrafiltration coupled with liquid chromatography mass spectrometry (UF-HPLC-MS) was established to rapidly screen and identify the α-glucosidase inhibitors from G. sylvestre . In this way, 9 compounds with higher enrichment factors (EFs) were identified according to their MS/MS spectra. Finally, the structure-activity relationships revealed that glycosylation could decrease the potential antisweet activity of sapogenins, and other components except gymnemic acids in G. sylvestre could also be good α-glucosidase inhibitors due to their synergistic effects. Taken together, the proposed method combing α-glucosidase and UF-HPLC-MS presents high efficiency for rapidly screening and identifying potential inhibitors of α-glucosidase from complex natural products, and could be further explored as a valuable high-throughput screening (HTS) platform in the early anti-diabetic drug discovery stage.

Mahanine enhances the glucose-lowering mechanisms in skeletal muscle and adipocyte cells.

PubMed

Nooron, Nattakarn; Athipornchai, Anan; Suksamrarn, Apichart; Chiabchalard, Anchalee

2017-12-09

Insulin resistance is a major defect underlying type 2 diabetes development. Skeletal muscle tissue and adipocyte tissue are the major sites of postprandial glucose disposal, and enhancing glucose uptake into this tissue may decrease insulin resistance in type 2 diabetes patients. Mahanine (3,11-dihydro-3,5-dimethyl-3-(4-methyl-3-pentenyl)pyrano[3,2-a]carbazol-9-ol) has been reported to be a major bioactive carbazole alkaloid that has many biological activities including antitumor, anti-inflammatory, antioxidant and anti-diabetic activities. However, the molecular mechanism and signaling pathways mediating the anti-diabetic effects of mahanine require further investigation. Therefore, the aim of this study was to investigate the effects of mahanine, a carbazole alkaloid from Murraya koenigii, on glucose uptake and glucose transporter 4 (GLUT4) translocation in skeletal muscle and adipocyte cells. Mahanine treatment promoted a dose dependent increased in glucose uptake in L6 myotubes and adipocyte cells via activation of the Akt signaling pathway. Mahanine induced Akt-activation was reversed by co-treatment with wortmannin, an Akt inhibitor. Moreover, it was found that mahanine significantly enhanced GLUT4 translocation to the plasma membrane in L6 myotubes. These results suggest that increased activation of the Akt signaling pathway lead to increased plasma membrane GLUT4 content and increased glucose uptake. These data strongly suggest that mahanine has anti-diabetic potential for treating diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

Antihyperglycemic effect of the traditional Chinese scutellaria-coptis herb couple and its main components in streptozotocin-induced diabetic rats.

PubMed

Liu, Sheng-Zi; Deng, Yuan-Xiong; Chen, Bo; Zhang, Xiao-Jie; Shi, Qun-Zhi; Qiu, Xi-Min

2013-01-30

Scutellaria-coptis herb couple (SC) is the main herb couple in many traditional Chinese compound formulas used for the treatment of diabetes mellitus, which has been used to treat diabetes mellitus for thousands of years in China. In this study we provide experimental evidence for the clinical use of SC in the treatment of diabetes mellitus. To confirm the anti-diabetic effect of SC extract and its main components, and to explore its mechanism from the effect on intestinal disaccharidases by in vivo and in vitro experiment. SC extract was prepared and the main components (namely berberine and baicalin) contained in the extract were assayed with high performance liquid chromatography (HPLC). And diabetic model rats were induced by intraperitoneal injection of streptozotocin (STZ). After grouped randomly, diabetic rats were administered SC extract, berberine, baicalin, berberine+baicalin, acarbose and vehicle for 33d, respectively. Body weight, food intake, urine volume, urine sugars, fasting plasma glucose and fasting plasma insulin were monitored to evaluate the antidiabetic effects on diabetic rats. Intestinal mucosa homogenate was prepared and the activities of intestinal disaccharidases were assayed. Moreover, oral sucrose tolerance test (OSTT) was performed and the inhibitory effects of SC extract and its main components (berberine and baicalin) on the maltase and sucrase in vitro was evaluated. After the treatment of SC extract and its main components, the body weight and the fasting plasma insulin level were found to be increased while food intake, urine volume, urine sugars and fasting plasma were decreased. OSTT showed that SC extract and its main components could lower the postprandial plasma glucose level of diabetic rats. Furthermore, SC extract and its main components could inhibit the activities of intestinal disaccharidases in diabetic rats, whereas only SC extract and berberine could inhibit the activity of maltase in vitro. According to our present findings, scutellaria-coptis herb couple (SC) possessed potent anti-hyperglycemic effect on STZ-induced diabetic rats. And SC extract and its main components exerted anti-hyperglycemic effect partly via inhibiting the increased activities of intestinal disaccharidases and elevating the level of plasma insulin in diabetic rats induced by STZ. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Enzyme inhibitory and radical scavenging effects of some antidiabetic plants of Turkey.

PubMed

Orhan, Nilüfer; Hoçbaç, Sanem; Orhan, Didem Deliorman; Asian, Mustafa; Ergun, Fatma

2014-06-01

Ethnopharmacological field surveys demonstrated that many plants, such as Gentiana olivieri, Helichrysum graveolens, Helichrysum plicatum ssp. plicatum, Juniperus oxycedrus ssp. oxycedrus, Juniperus communis var. saxatilis, Viscum album (ssp. album, ssp. austriacum), are used as traditional medicine for diabetes in different regions of Anatolia. The present study was designed to evaluate the in vitro antidiabetic effects of some selected plants, tested in animal models recently. α-glucosidase and α-amylase enzyme inhibitory effects of the plant extracts were investigated and Acarbose was used as a reference drug. Additionally, radical scavenging capacities were determined using 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) ABTS radical cation scavenging assay and total phenolic content of the extracts were evaluated using Folin Ciocalteu method. H. graveolens ethanol extract exhibited the highest inhibitory activity (55.7 % ± 2.2) on α-amylase enzyme. Additionally, J. oxycedrus hydro-alcoholic leaf extract had potent α-amylase inhibitory effect, while the hydro-alcoholic extract of J. communis fruit showed the highest α-glucosidase inhibitory activity (IC50: 4.4 μg/ml). Results indicated that, antidiabetic effect of hydro-alcoholic extracts of H. graveolens capitulums, J. communis fruit and J. oxycedrus leaf might arise from inhibition of digestive enzymes.

Harnessing the medicinal properties of Andrographis paniculata for diseases and beyond: a review of its phytochemistry and pharmacology

PubMed Central

Okhuarobo, Agbonlahor; Falodun, Joyce Ehizogie; Erharuyi, Osayemwenre; Imieje, Vincent; Falodun, Abiodun; Langer, Peter

2014-01-01

Andrographis paniculata Wall (family Acanthaceae) is one of the most popular medicinal plants used traditionally for the treatment of array of diseases such as cancer, diabetes, high blood pressure, ulcer, leprosy, bronchitis, skin diseases, flatulence, colic, influenza, dysentery, dyspepsia and malaria for centuries in Asia, America and Africa continents. It possesses several photochemical constituents with unique and interesting biological properties. This review describes the past and present state of research on Andrographis paniculata with respect to the medicinal usage, phytochemistry, pharmacological activities, toxicity profile and therapeutic usage, in order to bridge the gap requiring future research opportunities. This review is based on literature study on scientific journals and books from library and electronic sources. Diterpenes, flavonoids, xanthones, noriridoides and other miscellaneous compounds have been isolated from the plant. Extract and pure compounds of the plant have been reported for their anti-microbial, cytotoxicity, anti-protozoan, anti-inflammatory, anti-oxidant, immunostimulant, anti-diabetic, anti-infective, anti-angiogenic, hepato-renal protective, sex hormone/sexual function modulation, liver enzymes modulation insecticidal and toxicity activities. The results of numerous toxicity evaluations of extracts and metabolites isolated from this plant did not show any significant acute toxicity in experimental animals. Detailed and more comprehensive toxicity profile on mammalian tissues and organs is needed in future studies.

Development of an Injectable Slow-Release Metformin Formulation and Evaluation of Its Potential Antitumor Effects.

PubMed

Baldassari, Sara; Solari, Agnese; Zuccari, Guendalina; Drava, Giuliana; Pastorino, Sara; Fucile, Carmen; Marini, Valeria; Daga, Antonio; Pattarozzi, Alessandra; Ratto, Alessandra; Ferrari, Angelo; Mattioli, Francesca; Barbieri, Federica; Caviglioli, Gabriele; Florio, Tullio

2018-03-02

Metformin is an antidiabetic drug which possesses antiproliferative activity in cancer cells when administered at high doses, due to its unfavorable pharmacokinetics. The aim of this work was to develop a pharmacological tool for the release of metformin in proximity of the tumor, allowing high local concentrations, and to demonstrate the in vivo antitumor efficacy after a prolonged metformin exposition. A 1.2% w/w metformin thermoresponsive parenteral formulation based on poloxamers P407 and P124, injectable at room temperature and undergoing a sol-gel transition at body temperature, has been developed and optimized for rheological, thermal and release control properties; the formulation is easily scalable, and proved to be stable during a 1-month storage at 5 °C. Using NOD/SCID mice pseudo-orthotopically grafted with MDA-MB-231/luc + human breast cancer cells, we report that multiple administrations of 100 mg of the optimized metformin formulation close to the tumor site cause tissue accumulation of the drug at levels significantly higher than those observed in plasma, and enough to exert antiproliferative and pro-apoptotic activities. Our results demonstrate that this formulation is endowed with good stability, tolerability, thermal and rheological properties, representing a novel tool to be pursued in further investigations for adjuvant cancer treatment.

Fucaceae: A Source of Bioactive Phlorotannins

PubMed Central

Catarino, Marcelo D.; Silva, Artur M. S.; Cardoso, Susana M.

2017-01-01

Fucaceae is the most dominant algae family along the intertidal areas of the Northern Hemisphere shorelines, being part of human customs for centuries with applications as a food source either for humans or animals, in agriculture and as remedies in folk medicine. These macroalgae are endowed with several phytochemicals of great industrial interest from which phlorotannins, a class of marine-exclusive polyphenols, have gathered much attention during the last few years due to their numerous possible therapeutic properties. These compounds are very abundant in brown seaweeds such as Fucaceae and have been demonstrated to possess numerous health-promoting properties, including antioxidant effects through scavenging of reactive oxygen species (ROS) or enhancement of intracellular antioxidant defenses, antidiabetic properties through their acarbose-like activity, stimulation of adipocytes glucose uptake and protection of β-pancreatic cells against high-glucose oxidative stress; anti-inflammatory effects through inhibition of several pro-inflammatory mediators; antitumor properties by activation of apoptosis on cancerous cells and metastasis inhibition, among others. These multiple health properties render phlorotannins great potential for application in numerous therapeutical approaches. This review addresses the major contribution of phlototannins for the biological effects that have been described for seaweeds from Fucaceae. In addition, the bioavailability of this group of phenolic compounds is discussed. PMID:28635652

GPR40 partial agonists and AgoPAMs: Differentiating effects on glucose and hormonal secretions in the rodent

PubMed Central

Pachanski, Michele J.; Kirkland, Melissa E.; Kosinski, Daniel T.; Mane, Joel; Cheewatrakoolpong, Boonlert; Xue, Jiyan; Szeto, Daphne; Forrest, Gail; Miller, Corin; Bunzel, Michelle; Plummer, Christopher W.; Chobanian, Harry R.; Miller, Michael W.; Souza, Sarah; Thomas-Fowlkes, Brande S.; Ogawa, Aimie M.; Weinglass, Adam B.; Di Salvo, Jerry; Li, Xiaoyan; Feng, Yue; Tatosian, Daniel A.; Howard, Andrew D.; Colletti, Steven L.

2017-01-01

GPR40 agonists are effective antidiabetic agents believed to lower glucose through direct effects on the beta cell to increase glucose stimulated insulin secretion. However, not all GPR40 agonists are the same. Partial agonists lower glucose through direct effects on the pancreas, whereas GPR40 AgoPAMs may incorporate additional therapeutic effects through increases in insulinotrophic incretins secreted by the gut. Here we describe how GPR40 AgoPAMs stimulate both insulin and incretin secretion in vivo over time in diabetic GK rats. We also describe effects of AgoPAMs in vivo to lower glucose and body weight beyond what is seen with partial GPR40 agonists in both the acute and chronic setting. Further comparisons of the glucose lowering profile of AgoPAMs suggest these compounds may possess greater glucose control even in the presence of elevated glucagon secretion, an unexpected feature observed with both acute and chronic treatment with AgoPAMs. Together these studies highlight the complexity of GPR40 pharmacology and the potential additional benefits AgoPAMs may possess above partial agonists for the diabetic patient. PMID:29053717

Chrysin Induces Antidiabetic, Antidyslipidemic and Anti-Inflammatory Effects in Athymic Nude Diabetic Mice.

PubMed

Ramírez-Espinosa, Juan José; Saldaña-Ríos, Johann; García-Jiménez, Sara; Villalobos-Molina, Rafael; Ávila-Villarreal, Gabriela; Rodríguez-Ocampo, Angélica Nallelhy; Bernal-Fernández, Germán; Estrada-Soto, Samuel

2017-12-28

Extensive knowledge of diabetes and its complications is helpful to find new drugs for proper treatment to stop degenerative changes derived from this disease. In this context, chrysin (5,7-dihydroxyflavone) is a natural product that occurs in a variety of flowers and fruits with anti-inflammatory and antidiabetic effects, among others. Thus, a diabetic model in athymic nude mice was developed and used to establish the ability of chrysin to decrease the secretion of pro-inflammatory cytokines. Also, it was determined the acute (50 mg/kg) and sub-acute (50 mg/kg/day/10 days) antidiabetic and antihyperlipidemic activities after the period of time treatment. Results indicate that chrysin has significant acute antihyperglycemic and antidiabetic effects in nude diabetic mice ( p < 0.05). Moreover, triglyceride blood levels were reduced and IL-1β and TNF-α were diminished after 10 days' treatment compared with control group ( p < 0.05). In conclusion, it was found that chrysin could produce similar effects as metformin, a drug used for the treatment of diabetes, since both test samples decreased glucose and triglycerides levels, they impaired the generation of pro-inflammatory cytokines involved in the development of diabetes and its consequences, such as atherosclerosis and other cardiovascular diseases.

α-Glucosidase inhibitory effect of resveratrol and piceatannol.

PubMed

Zhang, Albert J; Rimando, Agnes M; Mizuno, Cassia S; Mathews, Suresh T

2017-09-01

Dietary polyphenols have been shown to inhibit α-glucosidase, an enzyme target of some antidiabetic drugs. Resveratrol, a polyphenol found in grapes and wine, has been reported to inhibit the activity of yeast α-glucosidase. This triggered our interest to synthesize analogs and determine their effect on mammalian α-glucosidase activity. Using either sucrose or maltose as substrate resveratrol, piceatannol and 3'-hydroxypterostilbene showed strong inhibition of mammalian α-glucosidase activity; pinostilbene, cis-desoxyrhapontigenin and trans-desoxyrhapontigenin had moderate inhibition. Compared to acarbose (IC 50 3-13 μg/ml), piceatannol and resveratrol inhibited mammalian α-glucosidase to a lesser extent (IC 50 14-84 and 111-120 μg/ml, respectively). 3'-Hydroxypterostilbene (IC 50 105-302 μg/ml) was 23-35-fold less potent than acarbose. We investigated the effect of piceatannol and resveratrol on postprandial blood glucose response in high-fat-fed C57Bl/6 mice. Animals administered resveratrol (30 mg/kg body weight [BW]) or piceatannol (14 mg/kg BW) 60 min prior to sucrose or starch loading had a delayed absorption of carbohydrates, resulting in significant lowering of postprandial blood glucose concentrations, similar to the antidiabetic drug acarbose, while no significant effect was observed with the glucose-loaded animals. Our studies demonstrate that the dietary polyphenols resveratrol and piceatannol lower postprandial hyperglycemia and indicate that inhibition of intestinal α-glucosidase activity may be a potential mechanism contributing to their antidiabetic property. Copyright © 2017 Elsevier Inc. All rights reserved.

The Action of Antidiabetic Plants of the Canadian James Bay Cree Traditional Pharmacopeia on Key Enzymes of Hepatic Glucose Homeostasis

PubMed Central

Nachar, Abir; Vallerand, Diane; Musallam, Lina; Lavoie, Louis; Arnason, John; Haddad, Pierre S.

2013-01-01

We determined the capacity of putative antidiabetic plants used by the Eastern James Bay Cree (Canada) to modulate key enzymes of gluconeogenesis and glycogen synthesis and key regulating kinases. Glucose-6-phosphatase (G6Pase) and glycogen synthase (GS) activities were assessed in cultured hepatocytes treated with crude extracts of seventeen plant species. Phosphorylation of AMP-dependent protein kinase (AMPK), Akt, and Glycogen synthase kinase-3 (GSK-3) were probed by Western blot. Seven of the seventeen plant extracts significantly decreased G6Pase activity, Abies balsamea and Picea glauca, exerting an effect similar to insulin. This action involved both Akt and AMPK phosphorylation. On the other hand, several plant extracts activated GS, Larix laricina and A. balsamea, far exceeding the action of insulin. We also found a significant correlation between GS stimulation and GSK-3 phosphorylation induced by plant extract treatments. In summary, three Cree plants stand out for marked effects on hepatic glucose homeostasis. P. glauca affects glucose production whereas L. laricina rather acts on glucose storage. However, A. balsamea has the most promising profile, simultaneously and powerfully reducing G6Pase and stimulating GS. Our studies thus confirm that the reduction of hepatic glucose production likely contributes to the therapeutic potential of several antidiabetic Cree traditional medicines. PMID:23864882

Antidiabetic activity of the mangrove species Ceriops decandra in alloxan-induced diabetic rats.

PubMed

Nabeel, Mannalamkunnath Alikunhi; Kathiresan, Kandasamy; Manivannan, Subramanian

2010-06-01

Diabetes is a series of disorders characterized by increased fasting and postprandial glucose concentration and insulin deficiency and/or decreased insulin action. Although there are a number of commercially available drugs for the treatment of diabetes, their long-term use may cause unwanted side effects. Consequently, many studies are underway to find natural remedies that can effectively reduce the intensity of diabetes. The aim of the present study was to evaluate the antidiabetic activity of the mangrove species Ceriops decandra. The effects of daily oral administration of an ethanolic extract from the leaves of C. decandra (30, 60, 120 mg/kg) for 30 days on blood glucose, hemoglobin (Hb), HbA1c, liver glycogen and some carbohydrate metabolic enzymes were evaluated in normal and alloxan-induced diabetic rats. The effects of these extracts were compared with the effect of 30-days treatment with 0.1 mg/kg, p.o., glibenclamide, a commercially available drug commonly used in the treatment of diabetes. Oral administration of 120 mg/kg extract modulated all the parameters evaluated to levels seen in control rats. The effects of 120 mg/kg extract were comparable to those of glibenclamide. The extract of the mangrove plant C. decandra exhibited promising antidiabetic activity and could be considered for further evaluation in clinical studies and drug development. © 2010 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.

Antidiabetic and renoprotective effects of Cladophora glomerata Kützing extract in experimental type 2 diabetic rats: a potential nutraceutical product for diabetic nephropathy.

PubMed

Srimaroeng, Chutima; Ontawong, Atcharaporn; Saowakon, Naruwan; Vivithanaporn, Pornpun; Pongchaidecha, Anchalee; Amornlerdpison, Doungporn; Soodvilai, Sunhapas; Chatsudthipong, Varanuj

2015-01-01

Cladophora glomerata extract (CGE) has been shown to exhibit antigastric ulcer, anti-inflammatory, analgesic, hypotensive, and antioxidant activities. The present study investigated antidiabetic and renoprotective effects of CGE in type 2 diabetes mellitus (T2DM) rats. The rats were induced by high-fat diet and streptozotocin and supplemented daily with 1 g/kg BW of CGE for 12 weeks. The renal transport function was assessed by the uptake of para-aminohippurate mediated organic anion transporters 1 (Oat1) and 3 (Oat3), using renal cortical slices. These two transporters were known to be upregulated by insulin and PKCζ while they were downregulated by PKCα activation. Compared to T2DM, CGE supplemented rats had significantly improved hyperglycaemia, hypertriglyceridemia, insulin resistance, and renal morphology. The baseline uptake of para-aminohippurate was not different among experimental groups and was correlated with Oat1 and 3 mRNA expressions. Nevertheless, while insulin-stimulated Oat1 and 3 functions in renal slices were blunted in T2DM rats, they were improved by CGE supplementation. The mechanism of CGE-restored insulin-stimulated Oat1 and 3 functions was clearly shown to be associated with upregulated PKCζ and downregulated PKCα expressions and activations. These findings indicate that CGE has antidiabetic effect and suggest it may prevent diabetic nephropathy through PKCs in a T2DM rat model.

Supervised walking groups to increase physical activity in type 2 diabetic patients.

PubMed

Negri, Carlo; Bacchi, Elisabetta; Morgante, Susanna; Soave, Diego; Marques, Alessandra; Menghini, Elisabetta; Muggeo, Michele; Bonora, Enzo; Moghetti, Paolo

2010-11-01

To evaluate the impact of an exercise program organized into supervised walking groups in subjects with type 2 diabetes. Fifty-nine diabetic subjects were randomized to a control group receiving standard lifestyle recommendations or an intervention group assigned to three supervised walking sessions per week and counseling. Changes in metabolic features, weight, 6-min walk test, prescription of antidiabetic medications, and overall physical activity were assessed. Functional capacity and overall physical activity were higher in the intervention group, whereas metabolic changes were not different between groups after 4 months. However, in subjects who attended at least 50% of scheduled walking sessions, changes in A1C and fasting glucose were greater than in control subjects. Discontinuation or reduction of antidiabetic drugs occurred in 33% of these patients versus 5% of control subjects (P<0.05). Supervised walking may be beneficial in diabetic subjects, but metabolic improvement requires adequate compliance.

Traditional uses, fermentation, phytochemistry and pharmacology of Phellinus linteus: A review.

PubMed

Chen, Hua; Tian, Ting; Miao, Hua; Zhao, Ying-Yong

2016-09-01

Medicinal mushroom Phellinus linteus ("Sanghuang" in Chinese, ) is a famous fungus which is widely used in China, Korea, and other Asian countries. As a traditional Chinese medicine with a 2000-year long history, medicinal applications of Phellinus linteus mainly include treating hemorrhage, hemostasis and diseases related to female menstruation according to Chinese clinical empirical practice. A number of studies reported Phellinus linteus possessed good therapeutic effects on various ailments including tumor, diabetes, inflammation, obesity, etc. The present paper comprehensively reviewed the traditional uses, fermentation, constituent and pharmacology of Phellinus linteus based on scientific literature as well as critical analysis of the research. This review aimed to provide latest information and new foundations and directions for further investigations on Phellinus linteus. All available information about Phellinus linteus was supplied by library database and electronic search (CNKI, Google Scholar, ScienceDirect, Web of Science, PubMed, etc.). Some local and ancient books as well as brilliant scholars were also important information resources. Improvement of fermentation techniques promoted the production of Phellinus linteus. Studies of constituents showed the main chemical composition of Phellinus linteus included polysaccharides, flavones, triterpenes, aromatic acids, amino acids, etc. and polysaccharides were found to account for the largest proportion. Pharmacological researches revealed Phellinus linteus possessed a variety of biological activities including anti-cancer, immuno-regulation, anti-diabetes, anti-oxidation and anti-inflammation. Based on these summarized information, this review was presented to provide helpful references and beneficial directions for future studies of Phellinus linteus. Copyright © 2016 Elsevier B.V. All rights reserved.

Catechin-loaded Eudragit microparticles for the management of diabetes: formulation, characterization and in vivo evaluation of antidiabetic efficacy.

PubMed

Meena, Kedar Prasad; Vijayakumar, Mahalingam Rajamanickam; Dwibedy, Priti S

2017-06-01

Catechin (CT) is natural molecule proved for antidiabetic activity. Clinical application of CT is highly restricted because of its low bioavailability and ineffectiveness in in vivo conditions. Therefore, the main objective of the present investigation was to formulate CT-loaded Eudragit RS 100 microparticles and evaluated for its potential against diabetes. CT microparticles showing highest entrapment efficiency of 92.3 ± 6.5% and higher percentage yield of 63.46 ± 4.3% was selected as optimised formulation. CT microparticles treated rats showed significantly lower blood glucose, cholesterol, LDL, free fatty acid and triglyceride concentrations in comparison to pristine CT-treated rats. The glucose and lipid profiles of microparticle formulation were akin to normal rats. Moreover, CT microparticles did not produce obesity even after 60 days which is a comment side effect of antidiabetic drugs. These results indicate that the CT microparticles can be applied as potential and safe carrier for the treatment of diabetes.

Important Aspects of Post-Prandial Antidiabetic Drug, Acarbose.

PubMed

Singla, Rajeev Kumar; Singh, Radha; Dubey, Ashok Kumar

2016-01-01

Acarbose, a well known and efficacious α-amylase and α-glucosidase inhibitor, is a postprandial acting antidiabetic drug. DNS-based α-amylase inhibitory assays showed that use of acarbose at concentrations above 125 µg/ml resulted in release of reducing sugar in the reaction, an unexpected observation. Objective of the present study was to design experimental strategies to address this unusual finding. Acarbose was found to be susceptible to thermo-lysis. Further, besides being an inhibitor, it could also be hydrolyzed by porcine pancreatic α-amylase, but had weaker affinity for α - amylase compared to starch. GRIP docking was done for the mechanistic analysis of the active site in the enzyme for substrate, inhibitor and, inhibitor's metabolite (K2). Interaction between acarbose and α-amylase involved significant hydrogen binding compared to that of starch, producing a stronger enzyme-inhibitor complex. Further, docking analysis led us to predict the site on α-amylase where the inhibitor (acarbose) bound more tightly, which possibly affected the binding and hydrolysis of starch exerting its effective anti-diabetic function.

Garlic as an anti-diabetic agent: recent progress and patent reviews.

PubMed

Padiya, Raju; Banerjee, Sanjay K

2013-08-01

This article reviews recent literature on the usage and relevance of garlic and its bioactive components in controlling diabetes and diabetes-associated pathologies; and also updates recent patents on the subject. Antidiabetic effect of garlic is well documented even in ancient medical literature. Garlic and its active ingredients have been extensively studied for their antidiabetic efficacies in either experimentally induced or genetic animal models of diabetes. Human studies are also available where hypoglycemic effect of garlic was reported. The beneficial effects of garlic are mainly attributed to the presence of volatile sulfur compounds like alliin, allicin, diallyl disulfide, diallyl trisulfide, diallyl sulfide, S-allyl cysteine, ajoene and allyl mercaptan. Garlic and garlic extracts have been shown to be effective in reducing insulin resistance. Therefore, considering the importance of garlic in controlling diabetic complications, several preparations and food processes containing garlic have been patented. This review discusses some of the recent progresses made in this field and consolidates the results.

Changes in Adenosine Deaminase Activity in Patients with Type 2 Diabetes Mellitus and Effect of DPP-4 Inhibitor Treatment on ADA Activity.

PubMed

Lee, Jae-Geun; Kang, Dong Gu; Yu, Jung Re; Kim, Youngree; Kim, Jinsoek; Koh, Gwanpyo; Lee, Daeho

2011-04-01

Dipeptidyl peptidase 4 (DPP-4, also known as CD26) binds with adenosine deaminase (ADA) to activate T lymphocytes. Here, we investigated whether ADA activity is specifically affected by treatment with DPP-4 inhibitor (DPP4I) compared with other anti-diabetic agents. Fasting ADA activity, in addition to various metabolic and biochemical parameters, were measured in 262 type 2 diabetes mellitus (T2DM) patients taking various anti-diabetic agents and in 46 non-diabetic control subjects. ADA activity was increased in T2DM patients compared with that in non-diabetic control subjects (mean±standard error, 23.1±0.6 U/L vs. 18.6±0.8 U/L; P<0.05). ADA activity was correlated with fasting plasma glucose (r=0.258, P<0.05), HbA1c (r=0.208, P<0.05), aspartate aminotransferase (r=0.325, P<0.05), and alanine aminotransferase (r=0.248, P<0.05). Compared with the well-controlled T2DM patients (HbA1c<7%), the poorly controlled group (HbA1c>9%) showed significantly increased ADA activity (21.1±0.8 U/L vs. 25.4±1.6 U/L; P<0.05). The effect of DPP4I on ADA activity in T2DM patients did not differ from those of other oral anti-diabetic agents or insulin. T2DM patients on metformin monotherapy showed a lower ADA activity (20.9±1.0 U/L vs. 28.1±2.8 U/L; P<0.05) compared with that of those on sulfonylurea monotherapy. Our results show that ADA activity is increased in T2DM patients compared to that in non-diabetic patients, is positively correlated with blood glucose level, and that DPP4I has no additional specific effect on ADA activity, except for a glycemic control- or HbA1c-dependent effect.

In vitro anti-diabetic effect and chemical component analysis of 29 essential oils products.

PubMed

Yen, Hsiu-Fang; Hsieh, Chi-Ting; Hsieh, Tusty-Jiuan; Chang, Fang-Rong; Wang, Chin-Kun

2015-03-01

Twenty-nine commercial essential oil (EO) products that were purchased from the Taiwan market, including three different company-made Melissa officinalis essential oils, were assayed on their glucose consumption activity and lipid accumulation activity on 3T3-L1 adipocytes. The EOs of M. officinalis were significantly active in both model assays. By contrast, EOs of peppermint, lavender, bergamot, cypress, niaouli nerolidol, geranium-rose, and revensara did not increase glucose consumption activity from media, but displayed inhibited lipid accumulation activity (65-90% of lipid accumulation vs. the control 100%). Because of the promising activity of M. officinalis EOs, three different products were collected and compared for their gas chromatography chemical profiles and bioactivity. The Western blot data suggest that the key factors of the adenosine monophosphate-activated protein kinase/acetyl-CoA carboxylase pathway can be mediated by M. officinalis EOs. Together with biodata, gas chromatography-mass spectrometry profiles suggested mixtures of citrals and minor compounds of M. officinalis EOs may play an important role on effect of antidiabetes. Copyright © 2014. Published by Elsevier B.V.

Berberine regulates AMP-activated protein kinase signaling pathways and inhibits colon tumorigenesis in mice

PubMed Central

Li, Weidong; Hua, Baojin; Saud, Shakir M.; Lin, Hongsheng; Hou, Wei; Matter, Matthias S.; Jia, Libin; Colburn, Nancy H.; Young, Matthew R.

2015-01-01

Colorectal cancer, a leading cause of cancer death, has been linked to inflammation and obesity. Berberine, an isoquinoline alkaloid, possesses anti-inflammatory, anti-diabetes and anti-tumor properties. In the azoxymethane initiated and dextran sulfate sodium (AOM/DSS) promoted colorectal carcinogenesis mouse model, berberine treated mice showed a 60% reduction in tumor number (P=0.009), a 48% reduction in tumors <2 mm, (P=0.05); 94% reduction in tumors 2-4 mm, (P=0.001) and 100% reduction in tumors >4 mm (P=0.02) compared to vehicle treated mice. Berberine also decreased AOM/DSS induced Ki-67 and COX-2 expression. In vitro analysis showed that in addition to its anti-proliferation activity, berberine also induced apoptosis in colorectal cancer cell lines. Berberine activated AMP-activated protein kinase (AMPK), a major regulator of metabolic pathways, and inhibited mammalian target of rapamycin (mTOR), a downstream target of AMPK. Furthermore, 4E-binding protein-1 and p70 ribosomal S6 kinases, downstream targets of mTOR, were down regulated by berberine treatment. Berberine did not affect Liver kinase B1 (LKB1) activity or the mitogen-activated protein kinase pathway. Berberine inhibited Nuclear Factor kappa-B (NF-κB) activity, reduced the expression of cyclin D1 and survivin, induced phosphorylation of p53 and increased caspase-3 cleavage in vitro. Berberine inhibition of mTOR activity and p53 phosphorylation was found to be AMPK dependent, while inhibition NF-κB was AMPK independent. In vivo, berberine also activated AMPK, inhibited mTOR and p65 phosphorylation and activated caspase-3 cleavage. Our data suggests that berberine suppresses colon epithelial proliferation and tumorigenesis via AMPK dependent inhibition of mTOR activity and AMPK independent inhibition of NF-κB. PMID:24838344

Isoquercetin ameliorates hyperglycemia and regulates key enzymes of glucose metabolism via insulin signaling pathway in streptozotocin-induced diabetic rats.

PubMed

Jayachandran, Muthukumaran; Zhang, Tongze; Ganesan, Kumar; Xu, Baojun; Chung, Stephen Sum Man

2018-06-15

Among the foremost common flavonoids within the human diet, quercetin glycosides possess neuroprotective, cardioprotective, anti-oxidative, chemopreventive, and anti-allergic properties. Isoquercetin is one such promising candidate with anti-diabetic potential. However, complete studies of its molecular action on insulin signaling pathway and carbohydrate metabolizing enzymes remain unclear. Hence, we have designed this study to accumulate the experimental evidence in support of anti-diabetic effects of isoquercetin. Male albino Wistar rats were divided into seven groups. Rats (Groups 3-7) were administered a single intraperitoneal injection of streptozotocin (STZ; 40 mg/kg b.w) to induce diabetes mellitus. As an extension, STZ rats received isoquercetin at three different doses (20, 40 and 80 mg/kg b.w), and Group 7 rats received glibenclamide (standard drug) (600 μg/kg b.w). The results showed that STZ exaggerated blood sugar, decreased insulin, altered metabolizing enzymes, and impaired the mRNA expression of insulin signaling genes and carbohydrate metabolizing enzyme genes. Supplementation with isoquercetin significantly normalized blood sugar levels, insulin and regulated the mRNA expression of insulin signaling genes and carbohydrate metabolizing enzyme genes. The results achieved with isoquercetin are similar to that of standard drug glibenclamide. The findings suggest isoquercetin could be a possible therapeutic agent for treating diabetes mellitus in the near future. Copyright © 2018 Elsevier B.V. All rights reserved.

Antidiabetic and antihyperlipidemic effects of an ethanolic extract of the whole plant of Tridax procumbens (Linn.) in streptozotocin-induced diabetic rats.

PubMed

Petchi, Ramesh R; Parasuraman, S; Vijaya, C

2013-09-01

To study the antidiabetic and antihyperlipidemic effects of an ethanolic extract of the whole plant of Tridax procumbens (Asteraceae) in streptozotocin-induced diabetic rats. The whole plant of T. procumbens was collected in different regions of Madurai districts, Tamil Nadu. The air dried whole plant of T. procumbens was extracted with ethanol (95%) in a Soxhlet apparatus for 72 h. Diabetes was induced in male Wistar rats by streptozotocin (50 mg/jk, i.p.) and nicotinamide (120 mg/kg, i.p) injection. The dry mass of the extract was used for preliminary phytochemical and pharmacological analysis. Diabetic rats were treated with glibenclamide (0.25 mg/kg, p.o.) or T. procumbens extract (250 and 500 mg/k, p.o.) for 21 consecutive days. The blood samples were collected at regular intervals to access hypoglycemic effect of an ethanolic extract of the whole plant of T. procumbens. At the end of the experiment, serum lipid profile and liver enzymes levels were analyzed for all the experimental animals and compared with diabetic control. The preliminary phytochemical analysis of an ethanolic extract of the whole plant of T. procumbens indicated the presence of alkaloids, tannins, flavonoids, saponins, and phenolic compounds. The ethanolic extract of the whole plant of T. procumbens at 250 and 500 mg/kg has significant antidiabetic and antihyperlipidemic activities. The diabetic control animals exhibited a significant decrease in body weight compared with control animals. T. procumbens inhibited streptozotocin-induced weight loss and significantly alter the lipid levels. The ethanolic extract of the whole plant of T. procumbens showed significant antidiabetic and antihyperlipidemic activities against streptozotocin-induced diabetes in rats.

Antidiabetic and antihyperlipidemic effects of an ethanolic extract of the whole plant of Tridax procumbens (Linn.) in streptozotocin-induced diabetic rats

PubMed Central

Petchi, Ramesh R.; Parasuraman, S.; Vijaya, C.

2013-01-01

Objective: To study the antidiabetic and antihyperlipidemic effects of an ethanolic extract of the whole plant of Tridax procumbens (Asteraceae) in streptozotocin-induced diabetic rats. Materials and Methods: The whole plant of T. procumbens was collected in different regions of Madurai districts, Tamil Nadu. The air dried whole plant of T. procumbens was extracted with ethanol (95%) in a Soxhlet apparatus for 72 h. Diabetes was induced in male Wistar rats by streptozotocin (50 mg/jk, i.p.) and nicotinamide (120 mg/kg, i.p) injection. The dry mass of the extract was used for preliminary phytochemical and pharmacological analysis. Diabetic rats were treated with glibenclamide (0.25 mg/kg, p.o.) or T. procumbens extract (250 and 500 mg/k, p.o.) for 21 consecutive days. The blood samples were collected at regular intervals to access hypoglycemic effect of an ethanolic extract of the whole plant of T. procumbens. At the end of the experiment, serum lipid profile and liver enzymes levels were analyzed for all the experimental animals and compared with diabetic control. Results: The preliminary phytochemical analysis of an ethanolic extract of the whole plant of T. procumbens indicated the presence of alkaloids, tannins, flavonoids, saponins, and phenolic compounds. The ethanolic extract of the whole plant of T. procumbens at 250 and 500 mg/kg has significant antidiabetic and antihyperlipidemic activities. The diabetic control animals exhibited a significant decrease in body weight compared with control animals. T. procumbens inhibited streptozotocin-induced weight loss and significantly alter the lipid levels. Conclusion: The ethanolic extract of the whole plant of T. procumbens showed significant antidiabetic and antihyperlipidemic activities against streptozotocin-induced diabetes in rats. PMID:24808679

Anti-diabetic properties of flavonoid compounds isolated from Hyphaene thebaica epicarp on alloxan induced diabetic rats

PubMed Central

Salib, Josline Y.; Michael, Helana N.; Eskande, Emad Fawzy

2013-01-01

Background: Diabetes mellitus, becoming the third killer of mankind after cancer and cardiovascular diseases, is one of the most challenging diseases facing health care professionals today. That is why; there has been a growing interest in the therapeutic use of natural products for diabetes, especially those derived from plants. Aim: To evaluate the anti-diabetic activity together with the accompanying biological effects of the fractions and the new natural compounds of Hyphaene thebaica (HT) epicarp. Materials and Methods: 500 g of coarsely powdered of (HT) fruits epicarp were extracted by acetone. The acetone crude extract was fractionated with methanol and ethyl acetate leaving a residual water-soluble fraction WF. The anti-diabetic effects of the WF and one of its compounds of the acetone extract of the (HT) epicarp were investigated in this study using 40 adult male rats. Results: Phytochemical investigation of active WF revealed the presence of ten different flavonoids, among which two new natural compounds luteolin 7-O-[6”-O-α-Lrhamnopyranosyl]-β-D-galactopyranoside 3 and chrysoeriol 7-O-β-D-galactopyranosyl(1→2)-α-L-arabinofuranoside 5 were isolated. Supplementation of the WF improved glucose and insulin tolerance and significantly lowered blood glycosylated hemoglobin levels. On the other hand, compound 5 significantly reduced AST and ALT levels of liver, respectively. Likewise, the kidney functions were improved for both WF and compound 5, whereby both urea and creatinine levels in serum were highly significant Conclusion: The results justify the use of WF and compound 5 of the (HT) epicarp as anti-diabetic agent, taking into consideration that the contents of WF were mainly flavonoids PMID:23598921

Antidiabetic drugs restore abnormal transport of amyloid-β across the blood-brain barrier and memory impairment in db/db mice.

PubMed

Chen, Fang; Dong, Rong Rong; Zhong, Kai Long; Ghosh, Arijit; Tang, Su Su; Long, Yan; Hu, Mei; Miao, Ming Xing; Liao, Jian Min; Sun, Hong Bing; Kong, Ling Yi; Hong, Hao

2016-02-01

Previous studies have shown significant changes in amyloid-β (Aβ) transport across the blood-brain barrier (BBB) under diabetic conditions with hypoinsulinemia, which is involved in diabetes-associated cognitive impairment. Present study employed db/db mice with hyperinsulinemia to investigate changes in Aβ transport across the BBB, hippocampal synaptic plasticity, and restorative effects of antidiabetic drugs. Our results showed that db/db mice exhibited similar changes in Aβ transport across the BBB to that of insulin-deficient mice. Chronic treatment of db/db mice with antidiabetic drugs such as metformin, glibenclamide and insulin glargine significantly decreased Aβ influx across the BBB determined by intra-arterial infusion of (125)I-Aβ(1-40), and expression of the receptor for advanced glycation end products (RAGE) participating in Aβ influx. Insulin glargine, but not, metformin or glibenclamide increased Aβ efflux across the BBB determined by stereotaxic intra-cerebral infusion of (125)I-Aβ(1-40), and expression of the low-density lipoprotein receptor related protein 1 (LRP1) participating in Aβ efflux. Moreover, treatment with these drugs significantly decreased hippocampal Aβ(1-40) or Aβ(1-42) and inhibited neuronal apoptosis. The drugs also ameliorated memory impairment confirmed by improved performance on behavioral tasks. However, insulin glargine or glibenclamide, but not metformin, restored hippocampal synaptic plasticity characterized by enhancing in vivo long-term potentiation (LTP). Further study found that these three drugs significantly restrained NF-κB, but only insulin glargine enhanced peroxisome proliferator-activated receptor γ (PPARγ) activity at the BBB in db/db mice. Our data indicate that the antidiabetic drugs can partially restore abnormal Aβ transport across the BBB and memory impairment under diabetic context. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characterization, antibacterial, antioxidant, antidiabetic, anti-inflammatory and antityrosinase activity of green synthesized silver nanoparticles using Calophyllum tomentosum leaves extract

NASA Astrophysics Data System (ADS)

Govindappa, M.; Hemashekhar, B.; Arthikala, Manoj-Kumar; Ravishankar Rai, V.; Ramachandra, Y. L.

2018-06-01

The current research study is to develop an easy and eco-friendly method for the synthesis of AgNPs using aqueous leaf extract of Calophyllum tomentosum (CtAgNPs) and evaluated the extract to know the effects of anti-bacterial, antioxidant, anti-diabetic, anti-inflammatory and anti-tyrosinase activity. Using UV-vis spectrophotometer, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDX) characterized the Calophyllum tomentosum mediated silver nanoparticles. The leaf extract of C. tomentosum yielded flavonoids, saponins, tannins, alkaloids, glycosides, phenols, terpenoids and coumarins. AgNPs formation was confirmed by UV-vis spectra at 438 nm. Crystalline structure with a face centered cubic (fcc) of AgNPs was observed in XRD. FTIR had shown that the phytochemicals were responsible for the reduction and capping material of silver nanoparticles. The size and shape of the AgNPs were determined using SEM. From EDX study analysed the strong absorption property of AgNPs. The CtAgNPs have showed significant antibacterial activity on multi drug resistance bacteria. The CtAgNPs had shown strong antioxidant (DPPH, H2O2 scavenging, nitric oxide scavenging power, reducing power) activities. The CtAgNPs had strongly inhibited the α-glucosidase and DPPIV compared to α-amylase. The CtAgNPs exhibited strong anti-inflammatory activity (albumin denaturation, membrane stabilization, heat haemolytic, protein inhibitory, lipoxygenase, xanthine oxidase) and tyrosinase inhibitory activity. To our best knowledge, this is the first attempt on the synthesis of silver nanoparticles using Calophyllum tomentosum leaves extract. Hence, to validate our results the in vivo studies at molecular level are needed to develop an antioxidant, anti-diabetic and anti-inflammatory agent.

Biospectroscopy for studying the influences of anti-diabetic metals (V, Cr, Mo, and W) to the insulin signaling pathway

NASA Astrophysics Data System (ADS)

Safitri, Anna; Levina, Aviva; Lee, Joonsup; Carter, Elizabeth A.; Lay, Peter A.

2017-03-01

The prevalence of diabetes, particularly with respect to type 2 diabetes, has reached epidemic proportions and continues to grow worldwide. One of the potential therapeutic targets in the treatment of type 2 diabetes involves the role of protein tyrosine phosphatases in the negative regulation of insulin signaling. The complexes of V(V/IV), Cr(III), W(VI), and Mo(VI), have all been proposed as possible drugs in the treatment of diabetes mellitus. Anti-diabetic activities of V(V/IV), Cr(III), Mo(VI), and W(VI) compounds are likely to be based on similar mechanisms, which involve phosphorylation/dephosphorylation reactions in the glucose uptake and metabolism. In order to clearly understand biological activities and phosphorylation/dephosphorylation reactions involved in anti-diabetic actions of Cr(III), V(V/IV), Mo(VI), and W(VI) complexes, the current research involves the use of cultured insulin-sensitive cells treated with these compounds. These reactions were investigated through vibrational spectroscopy. Protein phosphorylation/dephosphorylation induced conformational changes in secondary protein structure from α-helix to β-sheet, and these changes were detected by the IR spectra, which showed changes in the wavenumber and intensities of signals within the composite protein amide I band.

Enzyme inhibitory and radical scavenging effects of some antidiabetic plants of Turkey

PubMed Central

Orhan, Nilüfer; Hoçbaç, Sanem; Orhan, Didem Deliorman; Asian, Mustafa; Ergun, Fatma

2014-01-01

Objective(s): Ethnopharmacological field surveys demonstrated that many plants, such as Gentiana olivieri, Helichrysum graveolens, Helichrysum plicatum ssp. plicatum, Juniperus oxycedrus ssp. oxycedrus, Juniperus communis var. saxatilis, Viscum album (ssp. album, ssp. austriacum), are used as traditional medicine for diabetes in different regions of Anatolia. The present study was designed to evaluate the in vitro antidiabetic effects of some selected plants, tested in animal models recently. Materials and Methods: α-glucosidase and α-amylase enzyme inhibitory effects of the plant extracts were investigated and Acarbose was used as a reference drug. Additionally, radical scavenging capacities were determined using 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) ABTS radical cation scavenging assay and total phenolic content of the extracts were evaluated using Folin Ciocalteu method. Results: H. graveolens ethanol extract exhibited the highest inhibitory activity (55.7 % ± 2.2) on α-amylase enzyme. Additionally, J. oxycedrus hydro-alcoholic leaf extract had potent α-amylase inhibitory effect, while the hydro-alcoholic extract of J. communis fruit showed the highest α-glucosidase inhibitory activity (IC50: 4.4 μg/ml). Conclusion: Results indicated that, antidiabetic effect of hydro-alcoholic extracts of H. graveolens capitulums, J. communis fruit and J. oxycedrus leaf might arise from inhibition of digestive enzymes. PMID:25140204

Resource utilization with insulin pump therapy for type 2 diabetes mellitus.

PubMed

Lynch, Peter M; Riedel, Aylin Altan; Samant, Navendu; Fan, Ying; Peoples, Tim; Levinson, Jennifer; Lee, Scott W

2010-01-01

To evaluate the effects of switching from multiple daily injection (MDI) therapy to insulin pump therapy, also called continuous subcutaneous insulin infusion (CSII), on antidiabetic drug and healthcare resource utilization. This study was a retrospective analysis of administrative claims data from a large geographically diverse health plan in the United States from January 1, 2005, through April 30, 2008. Changes in antidiabetic drug use, antidiabetic drug switching and augmentation, and healthcare utilization during the baseline period and after CSII initiation were assessed using paired t test. There were 3649 possible subjects, of whom 943 met the criteria for analysis. The mean number of antidiabetic drugs used decreased by 46% after CSII initiation, and the mean reduction in antidiabetic drug utilization was 0.67; both were statistically significant. More than one-third of subjects who were taking antidiabetic drugs before CSII initiation discontinued oral therapy after CSII initiation. The number of subjects using multiple antidiabetic drugs significantly decreased after CSII initiation by 58%, and rates of switching or augmenting significantly decreased from 42% at baseline to 25% after CSII initiation.The rates of emergency department visits and inpatient admissions significantly decreased, and the rate of ambulatory visits significantly increased. CSII was associated with significant decreases in antidiabetic drug and healthcare resource utilization, contributing to stability of care. The evidence from this study indicates that CSII should be considered as an option for patients with type 2 diabetes mellitus who are using MDI and are experiencing a high degree of antidiabetic drug and healthcare resource utilization.

Stabilities and Biological Activities of Vanadium Drugs: What is the Nature of the Active Species?

PubMed

Levina, Aviva; Lay, Peter A

2017-07-18

Diverse biological activities of vanadium(V) drugs mainly arise from their abilities to inhibit phosphatase enzymes and to alter cell signaling. Initial interest focused on anti-diabetic activities but has shifted to anti-cancer and anti-parasitic drugs. V-based anti-diabetics are pro-drugs that release active components (e.g., H 2 VO 4 - ) in biological media. By contrast, V anti-cancer drugs are generally assumed to enter cells intact; however, speciation studies indicate that nearly all drugs are likely to react in cell culture media during in vitro assays and the same would apply in vivo. The biological activities are due to V V and/or V IV reaction products with cell culture media, or the release of ligands (e.g., aromatic diimines, 8-hydroxyquinolines or thiosemicarbazones) that bind to essential metal ions in the media. Careful consideration of the stability and speciation of V complexes in cell culture media and in biological fluids is essential to design targeted V-based anti-cancer therapies. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Berberine enhances antidiabetic effects and attenuates untoward effects of canagliflozin in streptozotocin-induced diabetic mice.

PubMed

Tian, Cai-Ming; Jiang, Xin; Ouyang, Xiao-Xi; Zhang, Ya-Ou; Xie, Wei-Dong

2016-07-01

The present study aimed at determining whether berberine can enhance the antidiabetic effects and alleviate the adverse effects of canagliflozin in diabetes mellitus. Streptozotocin-induced diabetic mice were introduced, and the combined effects of berberine and canagliflozin on glucose metabolism and kidney functions were investigated. Our results showed that berberine combined with canagliflozin (BC) increased reduction of fasting and postprandial blood glucose, diet, and water intake compared with berberine or canagliflozin alone. Interestingly, BC showed greater decrease in blood urea nitrogen and creatinine levels and lower total urine glucose excretion than canagliflozin alone. In addition, BC showed increased phosphorylated 5' AMP-activated protein kinase (pAMPK) expression and decreased tumor necrosis factor alpha (TNFα) levels in kidneys, compared with berberine or canagliflozin alone. These results indicated that BC was a stronger antidiabetic than berberine or canagliflozin alone with less negative side effects on the kidneys in the diabetic mice. The antidiabetic effect was likely to be mediated by synergically promoting the expression of pAMPK and reducing the expression of TNFα in kidneys. The present study represented the first report that canagliflozin combined with berberine was a promising treatment for diabetes mellitus. The exact underlying mechanisms of action should be investigated in future studies. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Plants used to treat diabetes in Sri Lankan Siddha Medicine - An ethnopharmacological review of historical and modern sources.

PubMed

Sathasivampillai, Saravanan V; Rajamanoharan, Pholtan R S; Munday, Michael; Heinrich, Michael

2017-02-23

In recent decades diabetes mellitus has become a considerable health problem in countries like Sri Lanka and results in an increasing economic burden hampering the social and economic development of these countries. About 60% to 70% of the rural population in Sri Lanka rely on indigenous medicinal systems as their main source for primary health care. Siddha (Tamil) Medicine is one of the four Sri Lankan traditional medicinal systems and it is practised mostly in the eastern and northern provinces of Sri Lanka where the majority of Tamils reside. The foundation of this study is a documentation of plant species recorded in historical and modern Sri Lankan Siddha Medical documents used to treat diabetes. Based on the systematic documentation and analysis of Siddha concepts about diabetes and its signs and preparations used to treat diabetes in Sri Lankan Siddha Medicine, the plant species included in these preparations (excluding globally or very widely used, very well studied species) were evaluated in terms of the current state-of-the-art about these species' pharmacology and effectiveness in order to lay a foundation for their further development. Historic and modern Sri Lankan university texts books in Tamil were used as sources for information on diabetes Siddha concepts and antidiabetic Sri Lankan Siddha Medicine preparations. Information on the known antidiabetic effects of extracts and compounds obtained from these species were used in order to assess the current state of the art of these species. Information of ingredients, preparation methods, amount of ingredients used, and dosages of 60 antidiabetic Sri Lankan Siddha Medicine preparations were obtained. Animal parts including marine organisms, inorganic substances, and plants are the three types of ingredients used. Overall 171 plant species in 73 families were documented. Senna auriculata (L.) Roxb. (Fabaceae) was identified as the most frequently cited species. Globally distributed and very well studied plants were excluded in the pharmacological and clinical literature review which includes 123 plant species. The majority (48%) of the plant species reviewed were studied up to in vivo level as the current maximum level of scientific evidence available. Followed by 41% of species have not been studied for antidiabetic activities or did not show antidiabetic activity. Moreover, 6% and 5% were studied up to in vitro and in clinical levels, respectively. The majority of the species were studied only in the models that represent type 1 diabetes. This is the first study systematically assessing the importance of preparations and plants used in antidiabetic Sri Lankan Siddha Medicine preparations. Antidiabetic plants are a crucial health care resource in Sri Lankan Siddha Medicine. This study also identified a wide range of methodological problems in the studies conducted so far. More and better type 2 diabetes models should be employed in future studies. This comprehensive review creates the basis for a more systematic study of these local resources. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

75 FR 79344 - Meeting of the Uniform Formulary Beneficiary Advisory Panel

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-20

... Director, TRICARE Management Activity, by the Pharmacy and Therapeutics Committee regarding the Uniform.... Scheduled Therapeutic Class Reviews (Comments will follow each agenda item). a. Non-Insulin Anti-Diabetic...

The potential role of GLUT4 transporters and insulin receptors in the hypoglycaemic activity of Ficus lutea acetone leaf extract.

PubMed

Olaokun, Oyinlola O; McGaw, Lyndy J; Awouafack, Maurice D; Eloff, Jacobus N; Naidoo, Vinny

2014-07-28

Some Ficus species have been used in traditional African medicine in the treatment of diabetes. The antidiabetic potential of certain species has been confirmed in vivo but the mechanism of activity remains uncertain. The aim was to investigate the hypoglycaemic potential of ten Ficus species focussing on glucose uptake, insulin secretion and the possible mechanism of hypoglycaemic activity. The dried and ground leaves of ten Ficus species were extracted with acetone. The dried acetone extract was reconstituted with DMSO to a concentration of 100 mg/ml which was then serially diluted and used to assay for glucose uptake in muscle, fat and liver cells, and insulin secretion in pancreatic cells. Only the F. lutea extract was able to modulate glucose metabolism. In comparison to insulin in the primary muscle cells, the glucose uptake ability of the extract was 33% as effective. In the hepatoma cell line, the extract was as effective as metformin in decreasing extracellular glucose concentration by approximately 20%. In the pancreatic insulin secretory assay, the extract was 4 times greater in its secretory activity than commercial glibenclamide. With F. lutea extract significantly increasing glucose uptake in the primary muscle cells, primary fat cells, C2C12 muscle and H-4-II-E liver cells, the extract may act by increasing the activity of cell surface glucose transporters. When the 3T3-L1 pre-adipocytes were compared to the primary muscle, primary fat and C2C12 cells, the differences in the former's ability to transport glucose into the cell may be due to the absence of the GLUT4 transporter, which on activation via the insulin receptor decreases extracellular glucose concentrations. Because the pre-adipocytes failed to show any active increase in glucose uptake, the present effect has to be linked to the absence of the GLUT4 transporter. Only F. lutea possessed substantial in vitro activity related to glucose metabolism. Based on the effect produced in the various cell types, F. lutea also appears to be a partial agonist/antagonist of the insulin cell membrane receptor. While the clinical effectiveness of F. lutea is not known, this plant species does possess the ability to modify glucose metabolism.

Tiny molecule, big power: Multi-target approach for curcumin in diabetic cardiomyopathy.

PubMed

Karuppagounder, Vengadeshprabhu; Arumugam, Somasundaram; Giridharan, Vijayasree V; Sreedhar, Remya; Bose, Rajendran J C; Vanama, Jyothi; Palaniyandi, Suresh S; Konishi, Tetsuya; Watanabe, Kenichi; Thandavarayan, Rajarajan A

2017-02-01

Diabetic cardiomyopathy (DCM) is described as impaired cardiac diastolic and systolic functions. Diabetes mellitus (DM), a related cardiovascular disease, has become one of the major causes of death in DM patients. Mortality in these diseases is 2 to 3 times higher than in non-DM patients with cardiovascular disease. The progression of DCM and the cellular and molecular perturbations associated with the pathogenesis are complex and multifactorial. Although considerable progress has been achieved, the molecular etiologies of DCM remain poorly understood. There is an expanding need for natural antidiabetic medicines that do not cause the side effects of modern drugs. Curcumin, a pleiotropic molecule, from Curcuma longa, is known to possess numerous impacts such as scavenging free radical, antioxidant, antitumor, and antiinflammatory activities. The reports from preclinical and clinical findings revealed that curcumin can reverse insulin resistance, hyperglycemia, obesity, and obesity-related metabolic diseases. The current review provides an updated overview of the possible molecular mechanism of DCM and multitarget approach of curcumin in alleviating DCM and diabetic complication. Additionally, we mentioned the approaches that are currently being implemented to improve the bioavailability of this promising natural product in diabetes therapeutics. Copyright © 2016 Elsevier Inc. All rights reserved.

In vitro studies on the hypoglycemic potential of Ficus racemosa stem bark.

PubMed

Ahmed, Faiyaz; Urooj, Asna

2010-02-01

Medicinal plants have been reported to play an important role in modulating glycemic responses and have preventive and therapeutic implications. Several mechanisms have been proposed for the antidiabetic effect of medicinal plants such as inhibition of carbohydrate-metabolizing enzymes, manipulation of glucose transporters, beta-cell regeneration and enhancing insulin-releasing activity. The present investigation evaluated the possible mechanism of action through which Ficus racemosa stem bark (Moraceae) exerts its hypoglycemic effect using suitable in vitro techniques. Ficus racemosa bark (FRB) exhibited significantly higher (P < or = 0.01) glucose-binding capacity than wheat bran (WB) and acarbose (ACB) consequently showed significantly higher (P < or = 0.01) retardation of glucose diffusion compared to WB and ACB. In case of amylolysis kinetics the liberation of glucose was greatly inhibited by FRB, as reflected by a significantly lower (P < or = 0.01) glucose diffusion rate in the system containing FRB compared to the control and acarbose. Furthermore, FRB significantly increased (P < or = 0.01) the rate of glucose transport across the yeast cell membrane and also in isolated rat hemi-diaphragm. The findings indicate F. racemosa bark to possess strong hypoglycemic effect and hence can be utilized as an adjunct in the management of diabetes mellitus.

Mature coconut water exhibits antidiabetic and antithrombotic potential via L-arginine-nitric oxide pathway in alloxan induced diabetic rats.

PubMed

Preetha, Prabhakaran Prabha; Devi, Vishalakshiamma Girija; Rajamohan, Thankappan

2015-11-01

The aims of the present study were to assess whether the antidiabetic activity of mature coconut water (MCW) is mediated through L-arginine-nitric oxide pathway in diabetic rats, and to study the effects of MCW on blood coagulation. Diabetes was induced in male Sprague-Dawley rats by injecting them with alloxan (150 mg/kg body weight). MCW (4 mL/100 g body weight) and L-arginine (7.5 mg/100 g body weight) was given orally for 45 days. L-NAME was given at a dose of 0.5 mg/kg body weight. Concentrations of blood glucose, plasma insulin, glycosylated hemoglobin (HbA1c), L-arginine, urine volume and urinary creatinine levels, activity of nitric oxide synthase (NOS), and arginase as well as the abnormalities in hemostasis and thrombosis were measured in all the experimental groups. Treatment with MCW and L-arginine reduced the concentration of blood glucose and HbA1c in diabetic rats. MCW and L-arginine treatment exhibited significant antithrombotic activity in diabetic rats, which was evident from the reduced levels of WBC, platelets, fibrin, and fibrinogen. MCW and L-arginine treatment prolonged the prothrombin time in diabetic rats and reduced the activity of Factor V. In addition to this, the activity of nitric oxide synthase, liver and plasma arginine content, and urinary nitrite were higher in MCW-treated diabetic rats whereas L-NAME treatment inhibited the beneficial effects induced by MCW and arginine. The results clearly indicate that L-arginine is a major factor responsible for the antidiabetic and antithrombotic potential of coconut water, and is mediated through the L-arginine-nitric oxide pathway.

Naphthalenemethyl ester derivative of dihydroxyhydrocinnamic acid, a component of cinnamon, increases glucose disposal by enhancing translocation of glucose transporter 4.

PubMed

Kim, W; Khil, L Y; Clark, R; Bok, S H; Kim, E E; Lee, S; Jun, H S; Yoon, J W

2006-10-01

Cinnamon extracts have anti-diabetic effects. Phenolic acids, including hydrocinnamic acids, were identified as major components of cinnamon extracts. Against this background we sought to develop a new anti-diabetic compound using derivatives of hydroxycinnamic acids purified from cinnamon. We purified hydroxycinnamic acids from cinnamon, synthesised a series of derivatives, and screened them for glucose transport activity in vitro. We then selected the compound with the highest glucose transport activity in epididymal adipocytes isolated from male Sprague-Dawley rats in vitro, tested it for glucose-lowering activity in vivo, and studied the mechanisms involved. A naphthalenemethyl ester of 3,4-dihydroxyhydrocinnamic acid (DHH105) showed the highest glucose transport activity in vitro. Treatment of streptozotocin-induced diabetic C57BL/6 mice and spontaneously diabetic ob/ob mice with DHH105 decreased blood glucose levels to near normoglycaemia. Further studies revealed that DHH105 increased the maximum speed of glucose transport and the translocation of glucose transporter 4 (GLUT4, now known as solute carrier family 2 [facilitated glucose transporter], member 4 [SLC2A4]) in adipocytes, resulting in increased glucose uptake. In addition, DHH105 enhanced phosphorylation of the insulin receptor-beta subunit and insulin receptor substrate-1 in adipocytes, both in vitro and in vivo. This resulted in the activation of phosphatidylinositol 3-kinase and Akt/protein kinase B, contributing to the translocation of GLUT4 to the plasma membrane. We conclude that DHH105 lowers blood glucose levels through the enhancement of glucose transport, mediated by an increase in insulin-receptor signalling. DHH105 may be a valuable candidate for a new anti-diabetic drug.

Synthesis, structural characterization, DFT studies and in-vitro antidiabetic activity of new mixed ligand oxovanadium(IV) complex with tridentate Schiff base

NASA Astrophysics Data System (ADS)

Patel, R. N.; Singh, Yogendra Pratap

2018-02-01

The mixed ligand oxovanadium(IV) complex [VO(L1)(L2)] [L1 = N'-[(Z)-phenyl(pyridin-2-yl)methylidene]benzohydrazide and L2 = Benzohydrazide] has been synthesized in aerobic condition. The complex was characterized by elemental analysis spectroscopic (UV-vis, IR, epr) and electrochemical methods. X-ray diffraction pattern was also used to characterize this complex, which has a distorted octahedral structure. Single crystal diffraction analysis reveals that Csbnd H⋯π (aryl/metal chelate rings) interactions contribute to the stabilization of the crystal structure in given dimension. The room temperature magnetic susceptibility data shows paramagnetic nature of the complex. The complex was also tested for in-vitro antidiabetic activity. Moderate α-glucosidase inhibition is shown by this complex, which may be considered as α-glucosidase inhibitors.

The anti-diabetic effects of ethanol extract from two variants of Artemisia princeps Pampanini in C57BL/KsJ-db/db mice.

PubMed

Jung, U J; Baek, N-I; Chung, H-G; Bang, M-H; Yoo, J-S; Jeong, T S; Lee, K-T; Kang, Y J; Lee, M K; Kim, H J; Yeo, J Y; Choi, M S

2007-10-01

The anti-diabetic effects of two variants of Artemisia princeps Pampanini, sajabalssuk (SB) and sajuarissuk (SS), were investigated in type 2 diabetic animal using their ethanol extracts. Male C57BL/KsJ-db/db (db/db) mice were divided into control, SB ethanol extract (SBE), SS ethanol extract (SSE), or rosiglitazone (RG) groups and their age-matched littermates (db/+) were used. Supplementation of the SBE (0.171 g/100g diet), SSE (0.154 g/100g diet), and RG (0.005 g/100g diet) improved glucose and insulin tolerance and significantly lowered blood glycosylated hemoglobin levels, as compared to the control group. Plasma insulin, C-peptide and glucagon levels in db/db mice were higher in the db/+ mice, however these values were significantly lowered by SBE, SSE or RG-supplement. Hepatic GK activity was significantly lower in the db/db mice than in the db/+ mice, while hepatic G6Pase activity was vice versa. Supplementation of SBE, SSE and RG reversed these hepatic glucose-regulating enzyme activities. In addition, SBE and SSE markedly increased the hepatic glycogen content and muscle ratio as compared to the control group, but they did not alter the food intake, body weight and plasma leptin level. The RG group, however, showed a significant increase in the food intake, body weight and plasma leptin. These results suggest that SBE and SSE exert an anti-diabetic effect in type 2 diabetic mice.

Antidiabetic and Renoprotective Effects of Cladophora glomerata Kützing Extract in Experimental Type 2 Diabetic Rats: A Potential Nutraceutical Product for Diabetic Nephropathy

PubMed Central

Srimaroeng, Chutima; Ontawong, Atcharaporn; Saowakon, Naruwan; Vivithanaporn, Pornpun; Pongchaidecha, Anchalee; Amornlerdpison, Doungporn; Soodvilai, Sunhapas; Chatsudthipong, Varanuj

2015-01-01

Cladophora glomerata extract (CGE) has been shown to exhibit antigastric ulcer, anti-inflammatory, analgesic, hypotensive, and antioxidant activities. The present study investigated antidiabetic and renoprotective effects of CGE in type 2 diabetes mellitus (T2DM) rats. The rats were induced by high-fat diet and streptozotocin and supplemented daily with 1 g/kg BW of CGE for 12 weeks. The renal transport function was assessed by the uptake of para-aminohippurate mediated organic anion transporters 1 (Oat1) and 3 (Oat3), using renal cortical slices. These two transporters were known to be upregulated by insulin and PKCζ while they were downregulated by PKCα activation. Compared to T2DM, CGE supplemented rats had significantly improved hyperglycaemia, hypertriglyceridemia, insulin resistance, and renal morphology. The baseline uptake of para-aminohippurate was not different among experimental groups and was correlated with Oat1 and 3 mRNA expressions. Nevertheless, while insulin-stimulated Oat1 and 3 functions in renal slices were blunted in T2DM rats, they were improved by CGE supplementation. The mechanism of CGE-restored insulin-stimulated Oat1 and 3 functions was clearly shown to be associated with upregulated PKCζ and downregulated PKCα expressions and activations. These findings indicate that CGE has antidiabetic effect and suggest it may prevent diabetic nephropathy through PKCs in a T2DM rat model. PMID:25883984

Evaluation of antihyperglycemic activity of Cocos nucifera Linn. on streptozotocin induced type 2 diabetic rats.

PubMed

Naskar, Sagar; Mazumder, Upal K; Pramanik, Goutam; Gupta, Malaya; Kumar, R B Suresh; Bala, Asis; Islam, Aminul

2011-12-08

The plant Cocos nucifera Linn. (Arecaceae) is commonly known as coconut. Traditionally the juice of the young spadix when fresh is used in diarrhea and diabetes. The objective of the present study was to investigate the effect of antidiabetic activity and effect on lipid profile as well as cardioprotective effect of hydro-methanol extract of Cocos nucifera (HECN) on streptozotocin (STZ)-induced diabetic rats. After 72 h of STZ (50 mg/kg, b.w. i.p.) administration, animals showing plasma sugar level more than 250 mg/dl were considered as diabetic rat. Fasting blood glucose (FBG) levels were measured on 0th (after 72 h of STZ), 5th, 10th, and 15th day. On the 15th day all the animals were sacrificed and the serum biochemical parameters and antioxidant enzyme status were measured. HECN treated animals showed a significant reduction in FBG level as compared with diabetic control group. Serum enzyme level (SGOT, SGPT, SALP), lipid peroxidation and antioxidant enzyme level such as CAT, GSH, SOD and cholesterol and triglycerides in the HECN treated groups were restored towards normal level as compared to diabetic control groups and the values were comparable with the standard groups (glibenclamide). Improvement in the FBG and the restoration of all other biomarker as well as enzymes indicates that HECN has very good antidiabetic activity with very low side effects and provides a scientific rationale for the use as an antidiabetic agent. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Dietary flavonoid aglycones and their glycosides: Which show better biological significance?

PubMed

Xiao, Jianbo

2017-06-13

The dietary flavonoids, especially their glycosides, are the most vital phytochemicals in diets and are of great general interest due to their diverse bioactivity. The natural flavonoids almost all exist as their O-glycoside or C-glycoside forms in plants. In this review, we summarized the existing knowledge on the different biological benefits and pharmacokinetic behaviors between flavonoid aglycones and their glycosides. Due to various conclusions from different flavonoid types and health/disease conditions, it is very difficult to draw general or universally applicable comments regarding the impact of glycosylation on the biological benefits of flavonoids. It seems as though O-glycosylation generally reduces the bioactivity of these compounds - this has been observed for diverse properties including antioxidant activity, antidiabetes activity, anti-inflammation activity, antibacterial, antifungal activity, antitumor activity, anticoagulant activity, antiplatelet activity, antidegranulating activity, antitrypanosomal activity, influenza virus neuraminidase inhibition, aldehyde oxidase inhibition, immunomodulatory, and antitubercular activity. However, O-glycosylation can enhance certain types of biological benefits including anti-HIV activity, tyrosinase inhibition, antirotavirus activity, antistress activity, antiobesity activity, anticholinesterase potential, antiadipogenic activity, and antiallergic activity. However, there is a lack of data for most flavonoids, and their structures vary widely. There is also a profound lack of data on the impact of C-glycosylation on flavonoid biological benefits, although it has been demonstrated that in at least some cases C-glycosylation has positive effects on properties that may be useful in human healthcare such as antioxidant and antidiabetes activity. Furthermore, there is a lack of in vivo data that would make it possible to make broad generalizations concerning the influence of glycosylation on the benefits of flavonoids for human health. It is possible that the effects of glycosylation on flavonoid bioactivity in vitro may differ from that seen in vivo. With in vivo (oral) treatment, flavonoid glycosides showed similar or even higher antidiabetes, anti-inflammatory, antidegranulating, antistress, and antiallergic activity than their flavonoid aglycones. Flavonoid glycosides keep higher plasma levels and have a longer mean residence time than those of aglycones. We should pay more attention to in vivo benefits of flavonoid glycosides, especially C-glycosides.

Real-world antidiabetic drug use and fracture risk in 12,277 patients with type 2 diabetes mellitus: a nested case-control study.

PubMed

Losada, E; Soldevila, B; Ali, M S; Martínez-Laguna, D; Nogués, X; Puig-Domingo, M; Díez-Pérez, A; Mauricio, D; Prieto-Alhambra, D

2018-06-02

We conducted a nested case-control study to study the association between antidiabetic treatments (alone or in combination) use and fracture risk among incident type 2 Diabetes mellitus patients. We found an increased risk of bone fracture with insulin therapy compared to metformin monotherapy. Patients with type 2 diabetes mellitus (T2DM) have an increased risk of fragility fractures, to which antidiabetic therapies may contribute. We aimed to characterize the risk of fracture associated with different antidiabetic treatments as usually prescribed to T2DM patients in actual practice conditions. A case-control study was nested within a cohort of incident T2DM patients registered in 2006-2012 in the Information System for Research Development in Primary Care (Catalan acronym, SIDIAP), a database which includes records for > 5.5 million patients in Catalonia (Spain). Each case (incident major osteoporotic fracture) was risk-set matched with up to five same-sex controls by calendar year of T2DM diagnosis and year of birth (± 10 years). Study exposure included previous use of all antidiabetic medications (alone or in combination), as dispensed in the 6 months before the index date, with metformin (MTF) monotherapy, the most commonly used drug, as a reference group (active comparator). Data on 12,277 T2DM patients (2049 cases and 10,228 controls) were analyzed. Insulin use was associated with increased fracture risk (adjusted OR 1.63 (95% CI 1.30-2.04)), as was the combination of MTF and sulfonylurea (SU) (adjusted OR 1.29 (1.07-1.56)), compared with MTF monotherapy. Sensitivity analyses suggest possible causality for insulin therapy but not for the MTF + SU combination association. No significant association was found with any other antidiabetic medications. Insulin monotherapy was associated with an increased fracture risk compared to MTF monotherapy in T2DM patients. Fracture risk should be taken into account when starting a glucose-lowering drug as part of T2DM treatment.

Therapeutic Potential of Genipin in Central Neurodegenerative Diseases.

PubMed

Li, Yanwei; Li, Lin; Hölscher, Christian

2016-10-01

Central neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), are one of the biggest health problems worldwide. Currently, there is no cure for these diseases. The Gardenia jasminoides fruit is a common herbal medicine in traditional Chinese medicine (TCM), and a variety of preparations are used as treatments for central nervous system (CNS) diseases. Pharmacokinetic studies suggest genipin is one of the main effective ingredients of G. jasminoides fruit extract (GFE). Accumulated research data show that genipin possesses a range of key pharmacological properties, such as anti-inflammatory, neuroprotective, neurogenic, antidiabetic, and antidepressant effects. Thus, genipin shows therapeutic potential for central neurodegenerative diseases. We review the pharmacological actions of genipin for the treatment of neurodegenerative diseases of the CNS. We also describe the potential mechanisms underlying these effects.

Sansevieria roxburghiana Schult. & Schult. F. (Family: Asparagaceae) Attenuates Type 2 Diabetes and Its Associated Cardiomyopathy.

PubMed

Bhattacharjee, Niloy; Khanra, Ritu; Dua, Tarun K; Das, Susmita; De, Bratati; Zia-Ul-Haq, M; De Feo, Vincenzo; Dewanjee, Saikat

2016-01-01

Sansevieria roxburghiana Schult. & Schult. F. (Family: Asparagaceae) rhizome has been claimed to possess antidiabetic activity in the ethno-medicinal literature in India. Therefore, present experiments were carried out to explore the protective role of edible (aqueous) extract of S. roxburghiana rhizome (SR) against experimentally induced type 2 diabetes mellitus (T2DM) and its associated cardiomyopathy in Wistar rats. SR was chemically characterized by GC-MS analysis. Antidiabetic activity of SR (50 and 100 mg/kg, orally) was measured in high fat diets (ad libitum) + low-single dose of streptozotocin (35 mg/kg, intraperitoneal) induced type 2 diabetic (T2D) rat. Fasting blood glucose level was measured at specific intermissions. Serum biochemical and inflammatory markers were estimated after sacrificing the animals. Besides, myocardial redox status, expressions of signal proteins (NF-κB and PKCs), histological and ultrastructural studies of heart were performed in the controls and SR treated T2D rats. Phytochemical screening of the crude extract revealed the presence of phenolic compounds, sugar alcohols, sterols, amino acids, saturated fatty acids within SR. T2D rats exhibited significantly (p < 0.01) higher fasting blood glucose level with respect to control. Alteration in serum lipid profile (p < 0.01) and increased levels of lactate dehydrogenase (p < 0.01) and creatine kinase (p < 0.01) in the sera revealed the occurrence of hyperlipidemia and cell destruction in T2D rats. T2DM caused significant (p < 0.05-0.01) alteration in the biochemical markers in the sera. T2DM altered the redox status (p < 0.05-0.01), decreased (p < 0.01) the intracellular NAD and ATP concentrations in the myocardial tissues of experimental rats. While investigating the molecular mechanism, activation PKC isoforms was observed in the selected tissues. T2D rats also exhibited an up-regulation in nuclear NF-κB (p65) in the cardiac tissues. So, oral administration of SR (50 and 500 mg/kg) could reduce hyperglycemia, hyperlipidemia, membrane disintegration, oxidative stress, vascular inflammation and prevented the activation of oxidative stress induced signaling cascades leading to cell death. Histological and ultra-structural studies of cardiac tissues supported the protective characteristics of SR. From the present findings it can be concluded that, SR could offer protection against T2DM and its associated cardio-toxicity via multiple mechanisms viz. hypoglycemic, antioxidant and anti-inflammatory actions.

Medicinal mushroom science: Current perspectives, advances, evidences, and challenges.

PubMed

Wasser, Solomon P

2014-01-01

The main target of the present review is to draw attention to the current perspectives, advances, evidences, challenges, and future development of medicinal mushroom science in the 21 st century. Medicinal mushrooms and fungi are thought to possess approximately 130 medicinal functions, including antitumor, immunomodulating, antioxidant, radical scavenging, cardiovascular, anti-hypercholesterolemic, antiviral, antibacterial, anti-parasitic, antifungal, detoxification, hepatoprotective, and antidiabetic effects. Many, if not all, higher Basidiomycetes mushrooms contain biologically active compounds in fruit bodies, cultured mycelium, and cultured broth. Special attention is paid to mushroom polysaccharides. The data on mushroom polysaccharides and different secondary metabolites are summarized for approximately 700 species of higher hetero- and homobasidiomycetes. Numerous bioactive polysaccharides or polysaccharide-protein complexes from the medicinal mushrooms described appear to enhance innate and cell-mediated immune responses, and exhibit antitumor activities in animals and humans. Whilst the mechanism of their antitumor actions is still not completely understood, stimulation and modulation of key host immune responses by these mushroom compounds appear central. Polysaccharides and low-molecular-weight secondary metabolites are particularly important due to their antitumor and immunostimulating properties. Several of the mushroom compounds have been subjected to Phase I, II, and III clinical trials, and are used extensively and successfully in Asia to treat various cancers and other diseases. Special attention is given to many important unsolved problems in the study of medicinal mushrooms.

Assessment of nutritional quality, glycaemic index, antidiabetic and sensory properties of plantain (Musa paradisiaca)-based functional dough meals.

PubMed

Famakin, Opeyemi; Fatoyinbo, Akindele; Ijarotimi, Oluwole Steve; Badejo, Adebanjo Ayobamidele; Fagbemi, Tayo Nathaniel

2016-11-01

Nutrition transition to high energy-dense foods has been implicated as the major causes of diet related diseases. Plantain-based dough meals supplemented with soybean cake and cassava fibre were developed by combining them in different proportions using response surface methodology. The flour blends were analyzed for the nutritional composition while the glycaemic index, antidiabetic potentials and protein digestibility of the dough meals were determined in wistar rats. The nutritional and essential amino acid contents of the flour blends were comparable to that of cerolina (a commercially available food product commonly recommended for diabetic patients). The rats fed with the formulated dough meals had lower glycaemic index and glycaemic load, and the blood glucose was significantly reduced compared to cerolina and metformin (a synthetic antidiabetic drug). All the plantain-based dough meals were comparable to cerolina and metformin in terms of nutritional quality and blood glycaemic control activities, respectively. Hence, the formulated plantain-based dough meals have potential to be used for the prevention and management of diabetes mellitus.

Antidiabetic activity of mefloquine via GLP-1 receptor modulation against STZ-NA-induced diabetes in albino wistar rats.

PubMed

Yadav, Rajnish Kumar; Rawat, Jitendra K; Gautam, Swetlana; Singh, Manjari; Kumar, Manish; Ansari, Mohd Nazam; Roy, Subhadeep; Saeedan, Abdulaziz S; Kaithwas, Gaurav

2018-05-01

Mefloquine was retrieved as a glucagon -like peptide-1 receptor agonist and, therefore, evaluated for its antidiabetic potential against non-insulin-dependent diabetes mellitus (NIDDM) in experimental animals. NIDDM was induced by single intraperitoneal injection of streptozotocin and nicotinamide (60 + 110 mg/kg) in albino wistar rats. The experimental animals were scrutinised for electrocardiographic (ECG) and heart rate variability (HRV) factors to study the autonomic dysfunction along with blood glucose, serum insulin, and liver glycogen levels for glycemic control. Simultaneously, antioxidant markers (TBARs, protein carbonyl, GSH, SOD, catalase) and inflammatory markers (COX, LOX, NO) were scrutinized as well. Oral administration of mefloquine normalised the heart rate with favourable regulation of time and frequency domain HRV parameters. Mefloquine restored the blood glucose, serum insulin, and liver glycogen levels favourably in diabetic rats. Treatment with mefloquine curtailed the antioxidant markers with favourable regulation of inflammatory signals. Mefloquine was also found to be less hepatotoxic in contrast to the standard metformin, providing an integrated advantage as an antidiabetic agent.

Anti-diabetic effect of pyroglutamic acid in type 2 diabetic Goto-Kakizaki rats and KK-Ay mice.

PubMed

Yoshinari, Orie; Igarashi, Kiharu

2011-10-01

With the rapidly increasing prevalence of type 2 diabetes mellitus (T2DM), specific dietary components with anti-diabetic efficacy could be one strategy with therapeutic potential. In the present study, the anti-diabetic effects of an amino acid, pyroglutamic acid (PA), found in vegetables and fruits were investigated in T2DM models using Goto-Kakizaki (GK) rats and KK-Ay mice by measuring glucose tolerance and other markers of diabetes. Moreover, the effect of PA on gene expression in GK rats was measured by DNA microarray analysis. Oral glucose tolerance and serum insulin levels were reduced by PA in both animal models. Serum and liver total cholesterol levels were also improved by PA. Expression of genes involved with gluconeogenesis and those involved with its related transcription factor were down-regulated by feeding PA. In KK-Ay mice, the glucokinase:glucose-6-phosphatase (G6Pase) activity ratio increased. From these results, it is suggested that dietary PA beneficially modifies glucose and lipid metabolism in diabetic animals, and can potentially contribute to the mitigation of T2DM.

The opposite effect of isotype-selective monoamine oxidase inhibitors on adipogenesis in human bone marrow mesenchymal stem cells.

PubMed

Byun, Youngjoo; Park, Jongho; Hong, Soo Hyun; Han, Mi Hwa; Park, Suzie; Jung, Hyo-Il; Noh, Minsoo

2013-06-01

Adiponectin production during adipocyte differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) can be used to evaluate the pharmacological activity of anti-diabetic drugs to improve insulin sensitivity. Monoamine oxidase (MAO) inhibitors such as phenelzine and pargyline inhibit adipogenesis in murine pre-adipocytes. In this study, however, we found that selective MAO-A inhibitors, moclobemide and Ro41-1049, and a selective MAO-B inhibitor, selegiline, promoted adiponectin production during adipocyte differentiation in hBM-MSCs, which suggested the anti-diabetic potential of these drugs. In contrast, non-selective MAO inhibitors, phenelzine and tranylcypromine, inhibited adipocyte differentiation of hBM-MSCs. Concomitant treatments of MAO-A and MAO-B selective inhibitors did not change the stimulatory effect on adiponectin production in hBM-MSCs. Taken together, the opposite effects of isotype-selective MAO inhibitors on adiponectin production during adipogenesis in hBM-MSCs may not be directly associated with the inhibitory effects of MAO, suggested that the structure of MAO inhibitors may contain a novel anti-diabetic pharmacophore. Copyright © 2013 Elsevier Ltd. All rights reserved.

Antidiabetic Activity of Aqueous Leaves Extract of Sesbania sesban (L) Merr. in Streptozotocin Induced Diabetic Rats

PubMed Central

Pandhare, Ramdas B.; Sangameswaran, B.; Mohite, Popat B.; Khanage, Shantaram G.

2011-01-01

The aqueous leaves extract of Sesbania sesban (L) Merr. (Family: Fabaceae) was evaluated for its antidiabetic potential on normal and streptozotocin (STZ)-induced diabetic rats. In the chronic model, the aqueous extract was administered to normal and STZ- induced diabetic rats at the doses of 250 and 500 mg/kg body weight (b.w.) p.o. per day for 30 days. The fasting Blood Glucose Levels (BGL), serum insulin level and biochemical data such as glycosylated hemoglobin, Total Cholesterol (TC), Triglycerides (TG), High Density Lipoproteins (HDL) and Low Density Lipoproteins (LDL) were evaluated and all were compared to that of the known anti-diabetic drug glibenclamide (0.25 mg/kg b.w.). The statistical data indicated significant increase in the body weight, liver glycogen, serum insulin and HDL levels and decrease in blood glucose, glycosylated hemoglobin, total cholesterol and serum triglycerides when compared with glibenclamide. Thus the aqueous leaves extract of Sesbania sesban had beneficial effects in reducing the elevated blood glucose level and lipid profile of STZ-induced diabetic rats. PMID:23407749

Anti-Diabetic Effects of Phenolic Extract from Rambutan Peels (Nephelium lappaceum) in High-Fat Diet and Streptozotocin-Induced Diabetic Mice

PubMed Central

Ma, Qingyu; Guo, Yan; Sun, Liping; Zhuang, Yongliang

2017-01-01

Recent studies have shown that rambutan peel phenolic (RPP) extract demonstrate high antioxidant and antiglycation activities in vitro and in vivo. This study further evaluated the anti-diabetic activity of RPP in a mouse model of Type II diabetes induced by streptozotocin combined with high-fat diet. Results showed that RPP increased the body weight and reduced the fasting blood glucose level of the diabetic mice. RPP significantly reduced the serum levels of total cholesterol, triglyceride, creatinine, and glycated serum protein in diabetic mice in a dose-dependent manner. Glycogen content in mice liver was recovered by RPP, which further increased the activity of superoxide dismutase and glutathione peroxidase and reduced lipid peroxidation in diabetic mice. Histological analysis showed that RPP effectively protected the tissue structure of the liver, kidney, and pancreas. In addition, RPP decreased the mesangial index and inhibited the expression of TGF-β in the kidney of diabetic mice. PMID:28933738

Anti-Diabetic Effects of Phenolic Extract from Rambutan Peels (Nephelium lappaceum) in High-Fat Diet and Streptozotocin-Induced Diabetic Mice.

PubMed

Ma, Qingyu; Guo, Yan; Sun, Liping; Zhuang, Yongliang

2017-07-26

Recent studies have shown that rambutan peel phenolic (RPP) extract demonstrate high antioxidant and antiglycation activities in vitro and in vivo. This study further evaluated the anti-diabetic activity of RPP in a mouse model of Type II diabetes induced by streptozotocin combined with high-fat diet. Results showed that RPP increased the body weight and reduced the fasting blood glucose level of the diabetic mice. RPP significantly reduced the serum levels of total cholesterol, triglyceride, creatinine, and glycated serum protein in diabetic mice in a dose-dependent manner. Glycogen content in mice liver was recovered by RPP, which further increased the activity of superoxide dismutase and glutathione peroxidase and reduced lipid peroxidation in diabetic mice. Histological analysis showed that RPP effectively protected the tissue structure of the liver, kidney, and pancreas. In addition, RPP decreased the mesangial index and inhibited the expression of TGF-β in the kidney of diabetic mice.

Marine Pharmacology in 2012-2013: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action.

PubMed

Mayer, Alejandro M S; Rodríguez, Abimael D; Taglialatela-Scafati, Orazio; Fusetani, Nobuhiro

2017-08-29

The peer-reviewed marine pharmacology literature from 2012 to 2013 was systematically reviewed, consistent with the 1998-2011 reviews of this series. Marine pharmacology research from 2012 to 2013, conducted by scientists from 42 countries in addition to the United States, reported findings on the preclinical pharmacology of 257 marine compounds. The preclinical pharmacology of compounds isolated from marine organisms revealed antibacterial, antifungal, antiprotozoal, antituberculosis, antiviral and anthelmitic pharmacological activities for 113 marine natural products. In addition, 75 marine compounds were reported to have antidiabetic and anti-inflammatory activities and affect the immune and nervous system. Finally, 69 marine compounds were shown to display miscellaneous mechanisms of action which could contribute to novel pharmacological classes. Thus, in 2012-2013, the preclinical marine natural product pharmacology pipeline provided novel pharmacology and lead compounds to the clinical marine pharmaceutical pipeline, and contributed significantly to potentially novel therapeutic approaches to several global disease categories.

Supervised Walking Groups to Increase Physical Activity in Type 2 Diabetic Patients

PubMed Central

Negri, Carlo; Bacchi, Elisabetta; Morgante, Susanna; Soave, Diego; Marques, Alessandra; Menghini, Elisabetta; Muggeo, Michele; Bonora, Enzo; Moghetti, Paolo

2010-01-01

OBJECTIVE To evaluate the impact of an exercise program organized into supervised walking groups in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS Fifty-nine diabetic subjects were randomized to a control group receiving standard lifestyle recommendations or an intervention group assigned to three supervised walking sessions per week and counseling. Changes in metabolic features, weight, 6-min walk test, prescription of antidiabetic medications, and overall physical activity were assessed. RESULTS Functional capacity and overall physical activity were higher in the intervention group, whereas metabolic changes were not different between groups after 4 months. However, in subjects who attended at least 50% of scheduled walking sessions, changes in A1C and fasting glucose were greater than in control subjects. Discontinuation or reduction of antidiabetic drugs occurred in 33% of these patients versus 5% of control subjects (P < 0.05). CONCLUSIONS Supervised walking may be beneficial in diabetic subjects, but metabolic improvement requires adequate compliance. PMID:20980426

Evidence of Immunosuppressive and Th2 Immune Polarizing Effects of Antidiabetic Momordica charantia Fruit Juice.

PubMed

Fachinan, Rufine; Fagninou, Adnette; Nekoua, Magloire Pandoua; Amoussa, Abdou Madjid; Adjagba, Marius; Lagnika, Latifou; Lalèyè, Anatole; Moutairou, Kabirou; Yessoufou, Akadiri

2017-01-01

The mechanism of action of the antidiabetic capacity of Momordica charantia is still under investigation. Here, we assessed phytochemical compositions, antioxidant activity, and effects of total and filtered fruit and leafy stem juices of Momordica charantia on human T cell proliferation and differentiation through quantification of Th1/Th2 cytokines. In the absence of stimulation, total fruit and leafy stem juices induced significant T cell proliferation. Under PHA stimulation, both juices potentiated plant-induced T cell proliferation. However, the filtered fruit and leafy stem juices significantly inhibited PHA-stimulated T cell proliferation, while neither juice influenced T cell proliferation. Moreover, total and filtered fruit juice increased IL-4 secretion, while total and filtered leafy stem juice enhanced IFN- γ production. Phytochemical screening revealed the presence of tannins, flavonoids, anthocyans, steroids, and triterpenoids in both juices. Alkaloids, quinone derivatives, cardenolides, and cyanogenic derivatives were undetectable. The saponins present in total juices were undetectable after filtration. Moreover, both juices had appreciable antioxidant capacity. Our study supports the type 1 antidiabetic effect of filtered fruit juice of M. charantia which may be related to its immunosuppressive and T-helper 2 cell inducing capacities. Due to their immune-stimulatory activities and their ability to increase T-helper 1 cell cytokines, total fruit and leafy stem juices may serve in the treatment of immunodeficiency and certain infections.

Evidence of Immunosuppressive and Th2 Immune Polarizing Effects of Antidiabetic Momordica charantia Fruit Juice

PubMed Central

Amoussa, Abdou Madjid; Adjagba, Marius; Lagnika, Latifou; Lalèyè, Anatole

2017-01-01

The mechanism of action of the antidiabetic capacity of Momordica charantia is still under investigation. Here, we assessed phytochemical compositions, antioxidant activity, and effects of total and filtered fruit and leafy stem juices of Momordica charantia on human T cell proliferation and differentiation through quantification of Th1/Th2 cytokines. In the absence of stimulation, total fruit and leafy stem juices induced significant T cell proliferation. Under PHA stimulation, both juices potentiated plant-induced T cell proliferation. However, the filtered fruit and leafy stem juices significantly inhibited PHA-stimulated T cell proliferation, while neither juice influenced T cell proliferation. Moreover, total and filtered fruit juice increased IL-4 secretion, while total and filtered leafy stem juice enhanced IFN-γ production. Phytochemical screening revealed the presence of tannins, flavonoids, anthocyans, steroids, and triterpenoids in both juices. Alkaloids, quinone derivatives, cardenolides, and cyanogenic derivatives were undetectable. The saponins present in total juices were undetectable after filtration. Moreover, both juices had appreciable antioxidant capacity. Our study supports the type 1 antidiabetic effect of filtered fruit juice of M. charantia which may be related to its immunosuppressive and T-helper 2 cell inducing capacities. Due to their immune-stimulatory activities and their ability to increase T-helper 1 cell cytokines, total fruit and leafy stem juices may serve in the treatment of immunodeficiency and certain infections. PMID:28812026

Evaluating the Effect of Ramadan Fasting on Muslim Patients with Diabetes in relation to Use of Medication and Lifestyle Patterns: A Prospective Study

PubMed Central

Siaw, Melanie Yee Lee; Chew, Daniel Ek Kwang; Dalan, Rinkoo; Abdul Shakoor, Shaikh Abdul Kader Kamaldeen; Othman, Noorani; Choo, Chor Hui; Shamsuri, Nur Hidayah; Abdul Karim, Siti Nurhana; Chan, Sui Yung; Lee, Joyce Yu-Chia

2014-01-01

Objectives. This study aimed to examine the effect of Ramadan fasting on HbA1c in Muslim patients with type 2 diabetes. The incidence of hypoglycemia and glycemic changes in relation to the adjustment of doses of antidiabetic agents, diet, and physical activity during Ramadan was also evaluated. Methods. This was a prospective study conducted in an outpatient endocrine clinic. A set of questionnaires was administered to Muslim patients with diabetes who fasted for ≥10 days. Those who were hospitalized for diabetic ketoacidosis or severe hypoglycemia a month prior to Ramadan or were given short-term corticosteroid therapy were excluded. The patients' responses and clinical outcomes from the clinic database were collected before, during, and after Ramadan. Results. A total of 153 participants completed the study. The mean HbA1c improved from 8.9% before Ramadan to 8.6% during Ramadan (P < 0.05). Although diet and physical activity did not contribute to changes in glycemia, a significant improvement in HbA1c was observed in patients who had adjustments made to their doses of antidiabetic agents during Ramadan (P < 0.001). In addition, their rate of hypoglycemia was minimal. Conclusions. Ramadan fasting appeared to improve glycemic control, especially in those whose doses of antidiabetic agents were adjusted during Ramadan. PMID:25435876

Cyanidin 3-glucoside attenuates obesity-associated insulin resistance and hepatic steatosis in high-fat diet-fed and db/db mice via the transcription factor FoxO1.

PubMed

Guo, Honghui; Xia, Min; Zou, Tangbin; Ling, Wenhua; Zhong, Ruimin; Zhang, Weiguo

2012-04-01

Obesity is a major risk factor for the development of type 2 diabetes, and both conditions are now recognized to possess significant inflammatory components underlying their pathophysiologies. Here, we hypothesized that cyanidin 3-glucoside (C3G), a typical anthocyanin reported to possess potent anti-inflammatory properties, would ameliorate obesity-associated inflammation and metabolic disorders, such as insulin resistance and hepatic steatosis in mouse models of diabesity. Male C57BL/6J obese mice fed a high-fat diet for 12 weeks and genetically diabetic db/db mice at an age of 6 weeks received dietary C3G supplementation (0.2%) for 5 weeks. We found that dietary C3G lowered fasting glucose levels and markedly improved the insulin sensitivity in both high-fat diet fed and db/db mice as compared with unsupplemented controls. White adipose tissue messenger RNA levels and serum concentrations of inflammatory cytokines (tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1) were reduced by C3G, as did macrophage infiltration in adipose tissue. Concomitantly, hepatic triglyceride content and steatosis were alleviated by C3G. Moreover, C3G treatment decreased c-Jun N-terminal kinase activation and promoted phosphorylation and nuclear exclusion of forkhead box O1 after refeeding. These findings clearly indicate that C3G has significant potency in antidiabetic effects by modulating the c-Jun N-terminal kinase/forkhead box O1 signaling pathway and the related inflammatory adipocytokines. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

Synthesis of 5-(ethylsulfonyl)-2-methoxyaniline: An important pharmacological fragment of VEGFR2 and other inhibitors

PubMed Central

Murár, Miroslav; Addová, Gabriela

2013-01-01

Summary Background: 5-(Ethylsulfonyl)-2-methoxyaniline (5) is part of the structure in 131 compounds possessing different biological activities. In most cases, they have antitumor properties (112 compounds). Other compounds are described as cardiovascular agents, ion-channel blockers, nervous-system blockers, anti-inflammatory agents, or antidiabetic, antiosteoporotic and hypolipemic species. Compound 5 is a precursor of different protein-kinase inhibitors or enzyme modulators (EGFR, PDGFR, ckit, CDK 2 and 4, MMPs 2, 3, 9 and 13, etc.). The structure of 5 represents a fragment for several powerful inhibitors of VEGFR2, a key angiogenic receptor. Antiangiogenic inhibitors slow down or stop new blood-vessel formation from pre-existing vasculature. Some antiangiogenic drugs inhibiting the VEGFR2 receptor are successfully used in clinics for the treatment of several types of tumours in synergy with chemotherapy (e.g., Nexavar® from Bayer, Sutent® from Pfizer and Votrient® from GlaxoSmithKline, approved by the FDA in 2005, 2006 and 2009, respectively). The structure of 5 is an important pharmacophoric fragment of potent VEGFR2 inhibitors (e.g., AAZ from PDB complex 1Y6A, enzymatic IC50 = 22 nM). Up to now, 25 VEGFR2 inhibitors possessing a fragment of 5 can be found in the literature. Despite the high significance of 5-(ethylsulfonyl)-2-methoxyaniline (5) its preparation has not yet been described. Results: Here we have developed a convenient synthesis of important polyheterosubstituted aniline 5 starting from commercially available 4-methoxybenzene-1-sulfonyl chloride (1) in four steps and 59% overall yield. The target 5-(ethylsulfonyl)-2-methoxyaniline (5) and its synthetic intermediates 2–4 together with a new compound 5-(ethylsulfonyl)-2-methoxy-1,3-dinitrobenzene (4a) have been precisely physicochemically characterised. PMID:23399884

Inhibition of key enzymes linked to type 2 diabetes by compounds isolated from Aframomum melegueta fruit.

PubMed

Mohammed, Aminu; Gbonjubola, Victoria Awolola; Koorbanally, Neil Anthony; Islam, Md Shahidul

2017-12-01

The use of Aframomum melegueta K. Schum. (Zingiberaceae) fruit for treatment of diabetes has recently been established in Nigeria. However, compounds responsible for the antidiabetic action have not been identified. The present study carried out the bioassay-guided isolation of possible bioactive compounds responsible for the antidiabetic action of A. melegueta fruit. The A. melegueta fruit was sequentially extracted using ethyl acetate (EtOAc), ethanol and water, and the most active extract (EtOAc) was subjected to column chromatography on a silica gel column using solvent gradient systems of hexane (HEX):EtOAc and EtOAc:MeOH and the isolation of compounds was guided by α-glycosidase and α-amylase inhibitory activities at various concentrations (30-240 μg/mL). According to the results, 3 arylalkanes, 6-paradol (1), 6-shogaol (2) and 6-gingerol (3) and a pentacyclic triterpene, oleanolic acid (4) were isolated from A. melegueta fruit. All the compounds exhibited inhibitory effects against α-amylase and α-glucosidase. 6-Gingerol (3) and oleanolic acid (4) showed higher inhibitory activity against α-amylase (IC 50 : 6-gingerol: 81.78 ± 7.79 μM; oleanolic acid: 91.72 ± 1.63 μM) and α-glucosidase (IC 50 : 6-gingerol: 21.55 ± 0.45 μM; oleanolic acid: 17.35 ± 0.88 μM) compared to the standard drug, acarbose and other isolated compounds. The kinetics of the enzyme action of the compounds showed a noncompetitive mode of inhibition. The data of this study suggest that the 6-gingerol (3) and oleanolic acid (4) showed higher α-amylase and α-glucosidase inhibitory action and therefore could be responsible for the antidiabetic activity of A. melegueta fruit.

β-Cell protection and antidiabetic activities of Crassocephalum crepidioides (Asteraceae) Benth. S. Moore extract against alloxan-induced oxidative stress via regulation of apoptosis and reactive oxygen species (ROS).

PubMed

Bahar, Entaz; Akter, Kazi-Marjahan; Lee, Geum-Hwa; Lee, Hwa-Young; Rashid, Harun-Or; Choi, Min-Kyung; Bhattarai, Kashi Raj; Hossain, Mir Mohammad Monir; Ara, Joushan; Mazumder, Kishor; Raihan, Obayed; Chae, Han-Jung; Yoon, Hyonok

2017-03-29

Medicinal plants are becoming more popular in the treatment of various diseases because of the adverse effects of the current therapy, especially antioxidant plant components such as phenols and flavonoids have a protective role against oxidative stress-induced degenerative diseases like diabetes. Thus, the purpose of this study was to investigate β-cell protection and antidiabetic activities of Crassocephalum crepidioides (Asteraceae) Benth. S. Moore. The in-vitro study was conducted by the pancreatic β-cell culture and α-amylase inhibition technique which includes two methods, namely starch-iodine method and 3,5-dinitrosalicylic acid (DNSA) method. On the other hand, the in-vivo study was performed by oral glucose tolerance test (OGTT) method and alloxan-induced diabetes method by using Wistar albino rat. At the end pancreatic specimens were removed and processed for histopathological study. The plant extract showed significant (*p < 0.05, **p < 0.01) effect on hyperglycemia as compared to standard (Gliclazide) in OGTT. The plant extract showed efficient protection activity of pancreatic β-cell from cell death in INS-1 cell line by significantly reduced (*p < 0.05, **p < 0.01) the levels alloxan-induced apoptosis and intracellular reactive oxygen species (ROS) accumulation. In addition, the plant extract showed a significant (*p < 0.05, **p < 0.01) effect on hyperglycemia by increases in percent of β-cells present in each islet (45% - 60%) compared to the diabetic group. The result showed that C. crepidioides had β-cell protection and antidiabetic activities in pancreatic β-cell culture and Wistar albino rat.

Antidiabetic Property of Symplocos cochinchinensis Is Mediated by Inhibition of Alpha Glucosidase and Enhanced Insulin Sensitivity

PubMed Central

Antu, Kalathookunnel Antony; Riya, Mariam Philip; Mishra, Arvind; Anilkumar, Karunakaran S.; Chandrakanth, Chandrasekharan K.; Tamrakar, Akhilesh K.; Srivastava, Arvind K.; Raghu, K. Gopalan

2014-01-01

The study is designed to find out the biochemical basis of antidiabetic property of Symplocos cochinchinensis (SC), the main ingredient of ‘Nisakathakadi’ an Ayurvedic decoction for diabetes. Since diabetes is a multifactorial disease, ethanolic extract of the bark (SCE) and its fractions (hexane, dichloromethane, ethyl acetate and 90% ethanol) were evaluated by in vitro methods against multiple targets relevant to diabetes such as the alpha glucosidase inhibition, glucose uptake, adipogenic potential, oxidative stress, pancreatic beta cell proliferation, inhibition of protein glycation, protein tyrosine phosphatase-1B (PTP-1B) and dipeptidyl peptidase-IV (DPP-IV). Among the extracts, SCE exhibited comparatively better activity like alpha glucosidase inhibition (IC50 value-82.07±2.10 µg/mL), insulin dependent glucose uptake (3 fold increase) in L6 myotubes, pancreatic beta cell regeneration in RIN-m5F (3.5 fold increase) and reduced triglyceride accumulation (22% decrease) in 3T3L1 cells, protection from hyperglycemia induced generation of reactive oxygen species in HepG2 cells (59.57% decrease) with moderate antiglycation and PTP-1B inhibition. Chemical characterization by HPLC revealed the superiority of SCE over other extracts due to presence and quantity of bioactives (beta-sitosterol, phloretin 2′glucoside, oleanolic acid) in addition to minerals like magnesium, calcium, potassium, sodium, zinc and manganese. So SCE has been subjected to oral sucrose tolerance test to evaluate its antihyperglycemic property in mild diabetic and diabetic animal models. SCE showed significant antihyperglycemic activity in in vivo diabetic models. We conclude that SC mediates the antidiabetic activity mainly via alpha glucosidase inhibition, improved insulin sensitivity, with moderate antiglycation and antioxidant activity. PMID:25184241

Traditional medicines used by Q'eqchi' Maya to treat diabetic symptoms and their antiglycation potential.

PubMed

Ferrier, J; Saleem, A; Carter Ramirez, A; Liu, R; Chen, Eric; Pesek, T; Cal, V; Balick, M; Arnason, J T

2018-06-21

Because of the recent increase in type 2 diabetes and the need for complementary treatments in remote communities in many parts of the world, we undertook a study of treatments for diabetic symptoms used by traditional Q'eqchi' Maya healers of Belize. We used quantitative ethnobotany to rank culturally important taxa and subsequent pharmacological and phytochemical studies to assess bioactivity. Antidiabetic plants identified in field interviews with traditional healers were ranked by syndromic importance value (SIV) based on 15 symptoms of diabetes.. Species ranked with high SIV were tested in an assay relevant to many diabetes complications, the advanced glycation endproduct (AGE) inhibition assay. Active principles were identified by phytochemical analysis and bioassay. We collected over 70 plant species having a promising SIV score. The plants represented a broad range of neotropical taxa. Selected Q'eqchi' antidiabetic plants with high SIV were collected in bulk and tested in the advanced glycation endproduct (AGE) inhibition assay. All plant extracts showed AGE inhibition and the half maximal inhibitory concentration (IC 50 ) ranged from 40.8 to 733µg/mL, while the most active species was Tynanthus guatemalensis Donn (Bignoniaceae). A linear regression showed a significant relationship between 1/ IC 50 and SIV. Phytochemical analysis revealed the presence of verbascoside, as a major component and active principle of the T guatemalensis which had an IC 50 = 5.1µg/mL, comparable to the positive control quercetin. The results reveal a rich botanical tradition of antidiabetic symptom treatments among the Q'eqchi'. Study of highly ranked plants revealed their activity in AGE inhibition correlated with SIV. T. guatemalensis was identified as a promising species for further evaluation and local use. Copyright © 2018. Published by Elsevier B.V.

Changes in Adenosine Deaminase Activity in Patients with Type 2 Diabetes Mellitus and Effect of DPP-4 Inhibitor Treatment on ADA Activity

PubMed Central

Lee, Jae-Geun; Kang, Dong Gu; Yu, Jung Re; Kim, Youngree; Kim, Jinsoek; Koh, Gwanpyo

2011-01-01

Background Dipeptidyl peptidase 4 (DPP-4, also known as CD26) binds with adenosine deaminase (ADA) to activate T lymphocytes. Here, we investigated whether ADA activity is specifically affected by treatment with DPP-4 inhibitor (DPP4I) compared with other anti-diabetic agents. Methods Fasting ADA activity, in addition to various metabolic and biochemical parameters, were measured in 262 type 2 diabetes mellitus (T2DM) patients taking various anti-diabetic agents and in 46 non-diabetic control subjects. Results ADA activity was increased in T2DM patients compared with that in non-diabetic control subjects (mean±standard error, 23.1±0.6 U/L vs. 18.6±0.8 U/L; P<0.05). ADA activity was correlated with fasting plasma glucose (r=0.258, P<0.05), HbA1c (r=0.208, P<0.05), aspartate aminotransferase (r=0.325, P<0.05), and alanine aminotransferase (r=0.248, P<0.05). Compared with the well-controlled T2DM patients (HbA1c<7%), the poorly controlled group (HbA1c>9%) showed significantly increased ADA activity (21.1±0.8 U/L vs. 25.4±1.6 U/L; P<0.05). The effect of DPP4I on ADA activity in T2DM patients did not differ from those of other oral anti-diabetic agents or insulin. T2DM patients on metformin monotherapy showed a lower ADA activity (20.9±1.0 U/L vs. 28.1±2.8 U/L; P<0.05) compared with that of those on sulfonylurea monotherapy. Conclusion Our results show that ADA activity is increased in T2DM patients compared to that in non-diabetic patients, is positively correlated with blood glucose level, and that DPP4I has no additional specific effect on ADA activity, except for a glycemic control- or HbA1c-dependent effect. PMID:21738897

The potential of cinnamon to reduce blood glucose levels in patients with type 2 diabetes and insulin resistance.

PubMed

Kirkham, S; Akilen, R; Sharma, S; Tsiami, A

2009-12-01

Cinnamon has a long history as an antidiabetic spice, but trials involving cinnamon supplementation have produced contrasting results. The aim of this review was to examine the results of randomized controlled clinical trials of cinnamon and evaluate the therapeutic potential amongst patients with diabetes and insulin-resistant patients, particularly the ability to reduce blood glucose levels and inhibit protein glycation. A systematic electronic literature search using the medical subject headings 'cinnamon' and 'blood glucose' was carried out to include randomized, placebo-controlled in vivo clinical trials using Cinnamomum verum or Cinnamomum cassia conducted between January 2003 and July 2008. Five type 2 diabetic and three non-diabetic studies (total N = 311) were eligible. Two of the diabetic studies illustrated significant fasting blood glucose (FBG) reductions of 18-29% and 10.3% (p < 0.05), supported by one non-diabetic trial reporting an 8.4% FBG reduction (p < 0.01) vs. placebo, and another illustrating significant reductions in glucose response using oral glucose tolerance tests (p < 0.05). Three diabetic studies reported no significant results. Whilst definitive conclusions cannot be drawn regarding the use of cinnamon as an antidiabetic therapy, it does possess antihyperglycaemic properties and potential to reduce postprandial blood glucose levels. Further research is required to confirm a possible correlation between baseline FBG and blood glucose reduction and to assess the potential to reduce pathogenic diabetic complications with cinnamon supplementation.

Drug-class-specific changes in the volume and cost of antidiabetic medications in Poland between 2012 and 2015.

PubMed

Śliwczyński, Andrzej; Brzozowska, Melania; Jacyna, Andrzej; Iltchev, Petre; Iwańczuk, Tymoteusz; Wierzba, Waldemar; Marczak, Michał; Orlewska, Katarzyna; Szymański, Piotr; Orlewska, Ewa

2017-01-01

to investigate the drug-class-specific changes in the volume and cost of antidiabetic medications in Poland in 2012-2015. This retrospective analysis was conducted based on the National Health Fund database covering an entire Polish population. The volume of antidiabetic medications is reported according to ATC/DDD methodology, costs-in current international dollars, based on purchasing power parity. During a 4-year observational period the number of patients, consumption of antidiabetic drugs and costs increased by 17%, 21% and 20%, respectively. Biguanides are the basic diabetes medication with a 39% market share. The insulin market is still dominated by human insulins, new antidiabetics (incretins, thiazolidinediones) are practically absent. Insulins had the largest share in diabetes medications expenditures (67% in 2015). The increase in antidiabetic medications costs over the analysed period of time was mainly caused by the increased use of insulin analogues. The observed tendencies correspond to the evidence-based HTA recommendations. The reimbursement status, the ratio of cost to clinical outcomes and data on the long-term safety have a deciding impact on how a drug is used.

Why Antidiabetic Vanadium Complexes are Not in the Pipeline of "Big Pharma" Drug Research? A Critical Review.

PubMed

Scior, Thomas; Guevara-Garcia, Jose Antonio; Do, Quoc-Tuan; Bernard, Philippe; Laufer, Stefan

2016-01-01

Public academic research sites, private institutions as well as small companies have made substantial contributions to the ongoing development of antidiabetic vanadium compounds. But why is this endeavor not echoed by the globally operating pharmaceutical companies, also known as "Big Pharma"? Intriguingly, today's clinical practice is in great need to improve or replace insulin treatment against Diabetes Mellitus (DM). Insulin is the mainstay therapeutically and economically. So, why do those companies develop potential antidiabetic drug candidates without vanadium (vanadium- free)? We gathered information about physicochemical and pharmacological properties of known vanadium-containing antidiabetic compounds from the specialized literature, and converted the data into explanations (arguments, the "pros and cons") about the underpinnings of antidiabetic vanadium. Some discoveries were embedded in chronological order while seminal reviews of the last decade about the Medicinal chemistry of vanadium and its history were also listed for further understanding. In particular, the concepts of so-called "noncomplexed or free" vanadium species (i.e. inorganic oxido-coordinated species) and "biogenic speciation" of antidiabetic vanadium complexes were found critical and subsequently documented in more details to answer the question.

Natural Prenylchalconaringenins and Prenylnaringenins as Antidiabetic Agents: α-Glucosidase and α-Amylase Inhibition and in Vivo Antihyperglycemic and Antihyperlipidemic Effects.

PubMed

Sun, Hua; Wang, Dong; Song, Xiaotong; Zhang, Yazhou; Ding, Weina; Peng, Xiaolin; Zhang, Xiaoting; Li, Yashan; Ma, Ying; Wang, Runling; Yu, Peng

2017-03-01

Inhibition of α-glucosidase and α-amylase decreases postprandial blood glucose levels and delays glucose absorption, making it a treatment strategy for type 2 diabetes. This study examined in vivo and in vitro antidiabetic activities of natural prenylchalconaringenins 1 and 2 and prenylnaringenins 3 and 4, found in hops and beer. 3'-Geranylchalconaringenin (2) competitively and irreversibly inhibited α-glucosidase (IC 50 = 1.08 μM) with activity 50-fold higher than that of acarbose (IC 50 = 51.30 μM) and showed moderate inhibitory activity against α-amylase (IC 50 = 20.46 μM). Docking analysis substantiated these findings. In addition, compound 2 suppressed the increase in postprandial blood glucose levels and serum levels of total cholesterol and triglycerides in streptozotocin-induced diabetic mice. Taken together, these results suggest that 2 has dual inhibitory activity against α-glucosidase and α-amylase and alleviates diabetic hyperglycemia and hyperlipidemia, making it a potential functional food ingredient and drug candidate for management of type 2 diabetes.

Amorfrutins are potent antidiabetic dietary natural products

PubMed Central

Weidner, Christopher; de Groot, Jens C.; Prasad, Aman; Freiwald, Anja; Quedenau, Claudia; Kliem, Magdalena; Witzke, Annabell; Kodelja, Vitam; Han, Chung-Ting; Giegold, Sascha; Baumann, Matthias; Klebl, Bert; Siems, Karsten; Müller-Kuhrt, Lutz; Schürmann, Annette; Schüler, Rita; Pfeiffer, Andreas F. H.; Schroeder, Frank C.; Büssow, Konrad; Sauer, Sascha

2012-01-01

Given worldwide increases in the incidence of obesity and type 2 diabetes, new strategies for preventing and treating metabolic diseases are needed. The nuclear receptor PPARγ (peroxisome proliferator-activated receptor gamma) plays a central role in lipid and glucose metabolism; however, current PPARγ-targeting drugs are characterized by undesirable side effects. Natural products from edible biomaterial provide a structurally diverse resource to alleviate complex disorders via tailored nutritional intervention. We identified a family of natural products, the amorfrutins, from edible parts of two legumes, Glycyrrhiza foetida and Amorpha fruticosa, as structurally new and powerful antidiabetics with unprecedented effects for a dietary molecule. Amorfrutins bind to and activate PPARγ, which results in selective gene expression and physiological profiles markedly different from activation by current synthetic PPARγ drugs. In diet-induced obese and db/db mice, amorfrutin treatment strongly improves insulin resistance and other metabolic and inflammatory parameters without concomitant increase of fat storage or other unwanted side effects such as hepatoxicity. These results show that selective PPARγ-activation by diet-derived ligands may constitute a promising approach to combat metabolic disease. PMID:22509006

In vivo biochemical and gene expression analyses of the antioxidant activities and hypocholesterolaemic properties of Tamarindus indica fruit pulp extract.

PubMed

Lim, Chor Yin; Mat Junit, Sarni; Abdulla, Mahmood Ameen; Abdul Aziz, Azlina

2013-01-01

Tamarindus indica (T. indica) is a medicinal plant with many biological activities including anti-diabetic, hypolipidaemic and anti-bacterial activities. A recent study demonstrated the hypolipidaemic effect of T. indica fruit pulp in hamsters. However, the biochemical and molecular mechanisms responsible for these effects have not been fully elucidated. Hence, the aims of this study were to evaluate the antioxidant activities and potential hypocholesterolaemic properties of T. indica, using in vitro and in vivo approaches. The in vitro study demonstrated that T. indica fruit pulp had significant amount of phenolic (244.9 ± 10.1 mg GAE/extract) and flavonoid (93.9 ± 2.6 mg RE/g extract) content and possessed antioxidant activities. In the in vivo study, hamsters fed with high-cholesterol diet for ten weeks showed elevated serum triglyceride, total cholesterol, HDL-C and LDL-C levels. Administration of T. indica fruit pulp to hypercholesterolaemic hamsters significantly lowered serum triglyceride, total cholesterol and LDL-C levels but had no effect on the HDL-C level. The lipid-lowering effect was accompanied with significant increase in the expression of Apo A1, Abcg5 and LDL receptor genes and significant decrease in the expression of HMG-CoA reductase and Mtp genes. Administration of T. indica fruit pulp to hypercholesterolaemic hamsters also protected against oxidative damage by increasing hepatic antioxidant enzymes, antioxidant activities and preventing hepatic lipid peroxidation. It is postulated that tamarind fruit pulp exerts its hypocholesterolaemic effect by increasing cholesterol efflux, enhancing LDL-C uptake and clearance, suppressing triglyceride accumulation and inhibiting cholesterol biosynthesis. T. indica fruit pulp has potential antioxidative effects and is potentially protective against diet-induced hypercholesterolaemia.

In Vivo Biochemical and Gene Expression Analyses of the Antioxidant Activities and Hypocholesterolaemic Properties of Tamarindus indica Fruit Pulp Extract

PubMed Central

Lim, Chor Yin; Mat Junit, Sarni; Abdulla, Mahmood Ameen; Abdul Aziz, Azlina

2013-01-01

Background Tamarindus indica (T. indica) is a medicinal plant with many biological activities including anti-diabetic, hypolipidaemic and anti-bacterial activities. A recent study demonstrated the hypolipidaemic effect of T. indica fruit pulp in hamsters. However, the biochemical and molecular mechanisms responsible for these effects have not been fully elucidated. Hence, the aims of this study were to evaluate the antioxidant activities and potential hypocholesterolaemic properties of T. indica, using in vitro and in vivo approaches. Methodology/Principal Findings The in vitro study demonstrated that T. indica fruit pulp had significant amount of phenolic (244.9±10.1 mg GAE/extract) and flavonoid (93.9±2.6 mg RE/g extract) content and possessed antioxidant activities. In the in vivo study, hamsters fed with high-cholesterol diet for ten weeks showed elevated serum triglyceride, total cholesterol, HDL-C and LDL-C levels. Administration of T. indica fruit pulp to hypercholesterolaemic hamsters significantly lowered serum triglyceride, total cholesterol and LDL-C levels but had no effect on the HDL-C level. The lipid-lowering effect was accompanied with significant increase in the expression of Apo A1, Abcg5 and LDL receptor genes and significant decrease in the expression of HMG-CoA reductase and Mtp genes. Administration of T. indica fruit pulp to hypercholesterolaemic hamsters also protected against oxidative damage by increasing hepatic antioxidant enzymes, antioxidant activities and preventing hepatic lipid peroxidation. Conclusion/Significance It is postulated that tamarind fruit pulp exerts its hypocholesterolaemic effect by increasing cholesterol efflux, enhancing LDL-C uptake and clearance, suppressing triglyceride accumulation and inhibiting cholesterol biosynthesis. T. indica fruit pulp has potential antioxidative effects and is potentially protective against diet-induced hypercholesterolaemia. PMID:23894592

Effects of antidiabetic drugs on the incidence of macrovascular complications and mortality in type 2 diabetes mellitus: a new perspective on sodium-glucose co-transporter 2 inhibitors.

PubMed

Rahelić, Dario; Javor, Eugen; Lucijanić, Tomo; Skelin, Marko

2017-02-01

Elevated hemoglobin A 1c (HbA 1c ) values correlate with microvascular and macrovascular complications. Thus, patients with type 2 diabetes mellitus (T2DM) are at an increased risk of developing macrovascular events. Treatment of T2DM should be based on a multifactorial approach because of its evidence regarding reduction of macrovascular complications and mortality in T2DM. It is well known that intensive glucose control reduces the risk of microvascular complications in T2DM, but the effects of antidiabetic drugs on macrovascular complications and mortality in T2DM are less clear. The results of recent trials have demonstrated clear evidence that empagliflozin and liraglutide reduce cardiovascular (CV) and all-cause mortality in T2DM, an effect that is absent in other members of antidiabetic drugs. Empagliflozin is a member of a novel class of antidiabetic drugs, the sodium-glucose co-transporter 2 (SGLT2) inhibitors. Two ongoing randomized clinical trials involving other SGLT2 inhibitors, canagliflozin and dapagliflozin, will provide additional evidence of the beneficial effects of SGLT2 inhibitors in T2DM population. The aim of this paper is to systematically present the latest evidence regarding the usage of antidiabetic drugs, and the reduction of macrovascular complications and mortality. A special emphasis is put on the novel class of antidiabetic drugs, of SGLT2 inhibitors. Key messages Macrovascular complications and mortality are best clinical trial endpoints for evaluating the efficacy of antidiabetic drugs. The first antidiabetic drug that demonstrated a reduction in mortality in the treatment of type 2 diabetes mellitus (T2DM) was empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor. SGLT2 inhibitors are novel class of antidiabetic drugs that play a promising role in the treatment of T2DM.

Review of antidiabetic fruits, vegetables, beverages, oils and spices commonly consumed in the diet.

PubMed

Beidokhti, Maliheh Najari; Jäger, Anna K

2017-04-06

Type 2 diabetes is the most common type of diabetes and its prevalence is rapidly increasing throughout the world. Modifications of lifestyle such as suitable diet and exercise programs along with pharmacotherapy and education of patients are beneficial therapies for patients with type 2 diabetes. The ethnopharmacological use of herbal medicines, many of them part of our diet as spices, vegetables and fruits, has been developed for the treatment of diabetes due to inexpensiveness, easy availability and few side effects. Our aim is to present a review for researchers who are interested in the biologically active dietary plants traditionally utilized in the treatment of diabetes. Information was obtained from a literature search of electronic databases such as Google Scholar, Pubmed, Sci Finder and Cochrane. Common and scientific name of the fruits, vegetables, beverages, oils and spices and the words 'antidiabetic', 'hypoglycemic', 'anti-hyperglycemic', 'type 2 diabetes' were used as keywords for search. Certain fruits and vegetables are functional foods and their consumption reduces the incidence of type 2 diabetes. Hypoglycemic effects of fruits and vegetables may be due to their inducing nature on pancreatic β-cells for insulin secretion, or bioactive compounds such as flavonoids, alkaloids and anthocyanins, which act as insulin-like molecules or insulin secretagogues. This write-up covers hypoglycemic, anti-hyperglycemic and anti-diabetic activities of some dietary fruits, vegetables, beverages, oils and spices and their active hypoglycemic constituents. Including such plant species in the diet might improve management of type 2 diabetes. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Antidiabetic activity of aqueous root extract of Ichnocarpus frutescens in streptozotocin-nicotinamide induced type-II diabetes in rats

PubMed Central

Barik, Rakesh; Jain, Sanjay; Qwatra, Deep; Joshi, Amit; Tripathi, Girraj Sharan; Goyal, Ravi

2008-01-01

Objective: To evaluate the antidiabetic activity of aqueous extract of roots of Ichnocarpus frutescens in streptozotocin-nicotinamide induced type-II diabetes in rats. Materials and Methods: Streptozotocin-nicotinamide induced type-II diabetic rats (n = 6) were administered aqueous root extract (250 and 500 mg/kg, p.o.) of Ichnocarpus frutescens or vehicle (gum acacia solution) or standard drug glibenclamide (0.25 mg/kg) for 15 days. Blood samples were collected by retro-orbital puncture and were analyzed for serum glucose on days 0, 5, 10, and 15 by using glucose oxidase-peroxidase reactive strips and a glucometer. For oral glucose tolerance test, glucose (2 g/kg, p.o.) was administered to nondiabetic control rats and the rats treated with glibenclamide (10 mg/kg, p.o.) and aqueous root extract of Ichnocarpus frutescens. The serum glucose levels were analyzed at 0, 30, 60, and 120 min after drug administration. The effect of the extract on the body weight of the diabetic rats was also observed. Results: The aqueous root extract of Ichnocarpus frutescens (250 and 500 mg/kg, p.o.) induced significant reduction (P < 0.05) of fasting blood glucose levels in streptozotocin-nicotinamide induced type-II diabetic rats on the 10th and 15th days. In the oral glucose tolerance test, the extract increased the glucose tolerance. It also brought about an increase in the body weight of diabetic rats. Conclusion: It is concluded that Ichnocarpus frutescens has significant antidiabetic activity as it lowers the fasting blood sugar level in diabetic rats and increases the glucose tolerance. PMID:21264156

Antidiabetic activity of aqueous root extract of Ichnocarpus frutescens in streptozotocin-nicotinamide induced type-II diabetes in rats.

PubMed

Barik, Rakesh; Jain, Sanjay; Qwatra, Deep; Joshi, Amit; Tripathi, Girraj Sharan; Goyal, Ravi

2008-01-01

To evaluate the antidiabetic activity of aqueous extract of roots of Ichnocarpus frutescens in streptozotocin-nicotinamide induced type-II diabetes in rats. Streptozotocin-nicotinamide induced type-II diabetic rats (n = 6) were administered aqueous root extract (250 and 500 mg/kg, p.o.) of Ichnocarpus frutescens or vehicle (gum acacia solution) or standard drug glibenclamide (0.25 mg/kg) for 15 days. Blood samples were collected by retro-orbital puncture and were analyzed for serum glucose on days 0, 5, 10, and 15 by using glucose oxidase-peroxidase reactive strips and a glucometer. For oral glucose tolerance test, glucose (2 g/kg, p.o.) was administered to nondiabetic control rats and the rats treated with glibenclamide (10 mg/kg, p.o.) and aqueous root extract of Ichnocarpus frutescens. The serum glucose levels were analyzed at 0, 30, 60, and 120 min after drug administration. The effect of the extract on the body weight of the diabetic rats was also observed. The aqueous root extract of Ichnocarpus frutescens (250 and 500 mg/kg, p.o.) induced significant reduction (P < 0.05) of fasting blood glucose levels in streptozotocin-nicotinamide induced type-II diabetic rats on the 10(th) and 15(th) days. In the oral glucose tolerance test, the extract increased the glucose tolerance. It also brought about an increase in the body weight of diabetic rats. It is concluded that Ichnocarpus frutescens has significant antidiabetic activity as it lowers the fasting blood sugar level in diabetic rats and increases the glucose tolerance.

In Vivo Evaluation of Anti Diabetic, Hypolipidemic, Antioxidative Activities of Saudi Date Seed Extract on Streptozotocin Induced Diabetic Rats.

PubMed

Hasan, Marghoob; Mohieldein, Abdelmarouf

2016-03-01

Phoenix dactylifera (date palm) is major fruit of gulf region. In folk medicine; dates have been traditionally use. The date seed is used as hypoglycaemic, expectorant, tonic, aphrodisiac, antidiarrheic and mouth hygiene. This study intended to evaluate the anti-diabetic, hypolipidaemic and antioxidative activities of date seed extract in diabetes-induced rats. Total of seven groups of rats, consisting of control rats and streptozotocin induced diabetic rats treated with aqueous seed extract in concentration of 100g/L in dosage of 10ml/day/rat. To evaluate the anti-diabetic property, glucose and weight was analysed weekly and at the end of eight week all rats were sacrificed. To evaluate the hypolipidaemic and antioxidative activities, serum cholesterol, triglyceride, malondialdehyde, superoxide dismutase, 8-hydroxy-2'-deoxyguanosine were estimated. Liver enzymes and kidney function tests were performed. Moreover to verify the glycaemic effect; glycated haemoglobin and serum insulin was performed. Aqueous seed extract in concentration of 100 gm/L in dosage of 10ml/day/rat brings a significant reduction of blood glucose levels in diabetic rats in comparison of control rats. There were significant differences in the investigated clinical chemistry and oxidative stress parameters between control and diabetic rats with both seed extract of Ajwa and Sukkari dates. Present study verifies the antidiabetic property, of aqueous seed extracts of two different varieties of dates namely Ajwa and Sukkari of Kingdom of Saudi on streptozotocin induced Diabetic rats. Prolong treatments with the extract restores the function of liver and kidney and balance the oxidative stress condition in diabetic treated rats.

A REVIEW ON SOME ANTIDIABETIC PLANTS OF INDIA

PubMed Central

Rai, M.K.

1995-01-01

The control over diabetes mellitus depends upon the availability of insulin. Various efforts have been made in the recent past to control / check it. There is an increasing demand to use the natural antidiabetic agents. The literature pertaining to antidiabetic herbs is scattered. The present article is a conglomeration of available indigenous literature. It gives an additional information of list of antidiabetic plants which have not been discussed by Nagarajan et al76 and Handa et al45. It also presents some common plants used in diabetes, and the future of hypoglycaemic herbal drugs. PMID:22556695

Nanostructured Lipid Carriers Loaded with Baicalin: An Efficient Carrier for Enhanced Antidiabetic Effects

PubMed Central

Shi, Feng; Wei, Zheng; Zhao, Yingying; Xu, Ximing

2016-01-01

Context: Recent studies have demonstrated that baicalin has antihyperglycemic effects by inhibiting lipid peroxidation. Baicalin is low hydrophilic and poorly absorbed after oral administration. Thus, a suitable formulation is highly desired to overcome the disadvantages of baicalin. Objective: The objective of this work was to prepare baicalin-loaded nanostructured lipid carriers (B-NLCs) for enhanced antidiabetic effects. Materials and Methods: B-NLCs were prepared by high-pressure homogenization method using Precirol as the solid lipid and Miglyol as the liquid lipid. The properties of the NLCs, such as particle size, zeta potential (ZP), and drug encapsulation efficiency (EE), were investigated. The morphology of NLCs was observed by transmission electron microscopy. In addition, drug release and antidiabetic activity were also studied. Results: The results revealed that B-NLCs particles were uniformly in the nanosize range and of spherical morphology with a mean size of 92 ± 3.1 nm, a ZP of −31.35 ± 3.08 mV, and an EE of 85.29 ± 3.42%. Baicalin was released from NLCs in a sustained manner. In addition, B-NLCs showed a significantly higher antidiabetic efficacy compared with baicalin. Conclusion: B-NLCs described in this study are well-suited for the delivery of baicalin. SUMMARY Currently, herbal medicines have attracted increasing attention as a complementary approach for type 2 diabetesBaicalin has antihyperglycemic effects by inhibiting lipid peroxidationA suitable formulation is highly desired to overcome the disadvantages (poor solubility and low bioavailability) of baicalinNanostructured lipid carriers could enhance the antidiabetic effects of baicalin. Abbreviations used: B-NLCs: Baicalin-Loaded Nanostructured Lipid Carriers, B-SUS: Baicalin Water Suspension, EE: Encapsulation Efficiency, FBG: Fasting Blood Glucose, HbAlc: Glycosylated Hemoglobin, HPLC: High-performance Liquid Chromatography; NLCs: Nanostructured Lipid Carriers, PI: Polydispersity Index, SD: Sprague-Dawley, SLNs: Solid lipid nanoparticles, STZ: Streptozotocin, TC: Total cholesterol, TEM: Transmission Electron Microscope, TG: Total Triglyceride, ZP: Zeta Potential. PMID:27601850

Nanostructured Lipid Carriers Loaded with Baicalin: An Efficient Carrier for Enhanced Antidiabetic Effects.

PubMed

Shi, Feng; Wei, Zheng; Zhao, Yingying; Xu, Ximing

2016-01-01

Recent studies have demonstrated that baicalin has antihyperglycemic effects by inhibiting lipid peroxidation. Baicalin is low hydrophilic and poorly absorbed after oral administration. Thus, a suitable formulation is highly desired to overcome the disadvantages of baicalin. The objective of this work was to prepare baicalin-loaded nanostructured lipid carriers (B-NLCs) for enhanced antidiabetic effects. B-NLCs were prepared by high-pressure homogenization method using Precirol as the solid lipid and Miglyol as the liquid lipid. The properties of the NLCs, such as particle size, zeta potential (ZP), and drug encapsulation efficiency (EE), were investigated. The morphology of NLCs was observed by transmission electron microscopy. In addition, drug release and antidiabetic activity were also studied. The results revealed that B-NLCs particles were uniformly in the nanosize range and of spherical morphology with a mean size of 92 ± 3.1 nm, a ZP of -31.35 ± 3.08 mV, and an EE of 85.29 ± 3.42%. Baicalin was released from NLCs in a sustained manner. In addition, B-NLCs showed a significantly higher antidiabetic efficacy compared with baicalin. B-NLCs described in this study are well-suited for the delivery of baicalin. Currently, herbal medicines have attracted increasing attention as a complementary approach for type 2 diabetesBaicalin has antihyperglycemic effects by inhibiting lipid peroxidationA suitable formulation is highly desired to overcome the disadvantages (poor solubility and low bioavailability) of baicalinNanostructured lipid carriers could enhance the antidiabetic effects of baicalin. Abbreviations used: B-NLCs: Baicalin-Loaded Nanostructured Lipid Carriers, B-SUS: Baicalin Water Suspension, EE: Encapsulation Efficiency, FBG: Fasting Blood Glucose, HbAlc: Glycosylated Hemoglobin, HPLC: High-performance Liquid Chromatography; NLCs: Nanostructured Lipid Carriers, PI: Polydispersity Index, SD: Sprague-Dawley, SLNs: Solid lipid nanoparticles, STZ: Streptozotocin, TC: Total cholesterol, TEM: Transmission Electron Microscope, TG: Total Triglyceride, ZP: Zeta Potential.

Sodium glucose co-transporter 2 (SGLT2) inhibitors: new among antidiabetic drugs.

PubMed

Opie, L H

2014-08-01

Type 2 diabetes is characterized by decreased insulin secretion and sensitivity. The available oral anti-diabetic drugs act on many different molecular sites. The most used of oral anti-diabetic agents is metformin that activates glucose transport vesicles to the cell surface. Others are: the sulphonylureas; agents acting on the incretin system; GLP-1 agonists; dipetidylpeptidase-4 inhibitors; meglinitide analogues; and the thiazolidinediones. Despite these many drugs acting by different mechanisms, glycaemic control often remains elusive. None of these drugs have a primary renal mechanism of action on the kidneys, where almost all glucose excreted is normally reabsorbed. That is where the inhibitors of glucose reuptake (sodium-glucose cotransporter 2, SGLT2) have a unique site of action. Promotion of urinary loss of glucose by SGLT2 inhibitors embodies a new principle of control in type 2 diabetes that has several advantages with some urogenital side-effects, both of which are evaluated in this review. Specific approvals include use as monotherapy, when diet and exercise alone do not provide adequate glycaemic control in patients for whom the use of metformin is considered inappropriate due to intolerance or contraindications, or as add-on therapy with other anti-hyperglycaemic medicinal products including insulin, when these together with diet and exercise, do not provide adequate glycemic control. The basic mechanisms are improved β-cell function and insulin sensitivity. When compared with sulphonylureas or other oral antidiabetic agents, SGLT2 inhibitors provide greater HbA1c reduction. Urogenital side-effects related to the enhanced glycosuria can be troublesome, yet seldom lead to discontinuation. On this background, studies are analysed that compare SGLT2 inhibitors with other oral antidiabetic agents. Their unique mode of action, unloading the excess glycaemic load, contrasts with other oral agents that all act to counter the effects of diabetic hyperglycaemia.

Antidiabetic activity and phytochemical screening of extracts of the leaves of Ajuga remota Benth on alloxan-induced diabetic mice.

PubMed

Tafesse, Tadesse Bekele; Hymete, Ariaya; Mekonnen, Yalemtsehay; Tadesse, Mekuria

2017-05-02

Ajuga remota Benth is traditionally used in Ethiopia for the management of diabetes mellitus. Since this claim has not been investigated scientifically, the aim of this study was to evaluate the antidiabetic effect and phytochemical screening of the aqueous and 70% ethanol extracts on alloxan-induced diabetic mice. After acute toxicity test, the Swiss albino mice were induced with alloxan to get experimental diabetes animals. The fasting mean blood glucose level before and after treatment for two weeks in normal, diabetic untreated and diabetic mice treated with aqueous and 70% ethanol extracts were performed. Data were statistically evaluated by using Statistical Package for the Social Sciences software version 20. P-value <0.05 was considered statistically significant. The medium lethal doses (LD 50 ) of both extracts were higher than 5000 mg/kg, indicating the extracts are not toxic under the observable condition. Aqueous extracts of A.remota (300 mg/kg and 500 mg/kg body weight) reduced elevated blood glucose levels by 27.83 ± 2.96% and 38.98 ± 0.67% (P < 0.0001), respectively while the 70% ethanol extract caused a reduction of 27.94 ± 1.92% (300 mg/kg) & 28.26 ± 1.82% (500 mg/kg). Treatment with the antidiabetic drug, Glibenclamide (10 mg/kg body weight) lowered blood glucose level by 51.06% (p < 0.05). Phytochemical screening of both extracts indicated the presence of phenolic compounds, flavonoids, saponins, tannins, and steroids, which might contribute to the antidiabetic activity. The extracts, however, did not contain alkaloids and anthraquinones. The aqueous extract (500 mg/kg) showed the highest percentage reduction in blood glucose levels and the ability of A. remota extracts in reducing blood glucose levels presumably due to the presence of antioxidant constituents such as flavonoids. The effect of the extract supported the traditional claim of the plant.

Comparative study of antidiabetic activity of Cajanus cajan and Tamarindus indica in alloxan-induced diabetic mice with a reference to in vitro antioxidant activity

PubMed Central

Nahar, Laizuman; Nasrin, Fatema; Zahan, Ronok; Haque, Anamul; Haque, Ekramul; Mosaddik, Ashik

2014-01-01

Background: Oxidative stress not only develops complications in diabetic (type 1 and type 2) but also contributes to beta cell destruction in type 2 diabetes in insulin resistance hyperglycemia. Glucose control plays an important role in the pro-oxidant/antioxidant balance. Some antidiabetic agents may by themselves have antioxidant properties independently of their role on glucose control. Objective: The present investigation draws a comparison of the protective antioxidant activity, total phenol content and the antihyperglycemic activity of the methanolic extract of Cajanus cajan root (MCC) and Tamarindus indica seeds (MTI). Materials and Methods: Antidiabetic potentials of the plant extracts were evaluated in alloxan-induced diabetic Swiss albino mice. The plant extracts at the doses of 200 and 400 mg/kg body weight was orally administered for glucose tolerance test during 1-hour study and hypoglycemic effect during 5-day study period in comparison with reference drug Metformin HCl (50 mg/kg). In vitro antioxidant potential of MCC and MTI was investigated by using 1, 1- diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity at 517 nm. Total phenolic content, total antioxidant capacity and reducing power activity was also assayed. Results: There was a significant decrease in fasting serum glucose level (P < 0.001), reduction in blood glucose level (P < 0.001) in 5-days study, observed in the alloxan-induced diabetic mice. The reduction efficacy of blood glucose level of both the extracts is proportional to their dose but MCC is more potent than MTI. Antioxidant study and quantification of phenolic compound of both the extracts revealed that they have high antioxidant capacity. Conclusion: These studies showed that MCC and MTI have both hypoglycemic and antioxidant potential but MCC is more potent than MTI. The present study suggests that both MCC and MTI could be used in managing oxidative stress. PMID:24761124

Quadruple high-resolution α-glucosidase/α-amylase/PTP1B/radical scavenging profiling combined with high-performance liquid chromatography-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance spectroscopy for identification of antidiabetic constituents in crude root bark of Morus alba L.

PubMed

Zhao, Yong; Kongstad, Kenneth Thermann; Jäger, Anna Katharina; Nielsen, John; Staerk, Dan

2018-06-29

In this paper, quadruple high-resolution α-glucosidase/α-amylase/PTP1B/radical scavenging profiling combined with HPLC-HRMS-SPE-NMR were used for studying the polypharmacological properties of crude root bark extract of Morus alba L. This species is used as an anti-diabetic principle in many traditional treatment systems around the world, and the crude ethyl acetate extract of M. alba root bark was found to inhibit α-glucosidase, α-amylase and protein-tyrosine phosphatase 1B (PTP1B) with IC 50 values of 1.70 ± 0.72, 5.16 ± 0.69, and 5.07 ± 0.68 μg/mL as well as showing radical scavenging activity equaling a TEAC value of (3.82 ± 0.14) × 10 4  mM per gram extract. Subsequent investigation of the crude extract using quadruple high-resolution α-glucosidase/α-amylase/PTP1B/radical scavenging profiling provided a quadruple biochromatogram that allowed direct correlation of the HPLC peaks with one or more of the tested bioactivities. This was used to target subsequent HPLC-HRMS-SPE-NMR analysis towards peaks representing bioactive analytes, and led to identification of a new Diels-Alder adduct named Moracenin E as well as a series of Diels-Alder adducts and isoprenylated flavonoids as potent α-glucosidase and α-amylase inhibitors with IC 50 values in the range of 0.60-27.15 μM and 1.22-69.38 μM, respectively. In addition, these compounds and two 2-arylbenzofurans were found to be potent PTP1B inhibitors with IC 50 values ranging from 4.04 to 21.67 μM. The high-resolution radical scavenging profile also revealed that almost all of the compounds possess radical scavenging activity. In conclusion the quadruple high-resolution profiling method presented here allowed a detailed profiling of individual constituents in crude root bark extract of M. alba, and the method provides a general tool for detailed mapping of bioactive constituents in polypharmacological herbal remedies. Copyright © 2018 Elsevier B.V. All rights reserved.

Recommendations on the effect of antidiabetic drugs in bone.

PubMed

Rozas-Moreno, Pedro; Reyes-García, Rebeca; Jódar-Gimeno, Esteban; Varsavsky, Mariela; Luque-Fernández, Inés; Cortés-Berdonces, María; Muñoz-Torres, Manuel

2017-03-01

To provide recommendations on the effect of antidiabetic drugs on bone fragility to help select the most adequate antidiabetic treatment, especially in diabetic patients with high risk of fracture. Members of the Bone Metabolism Working Group of the Spanish Society of Endocrinology. The GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) was used to establish both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed) using the following terms associated to the name of each antidiabetic drug: AND "osteoporosis", "fractures", "bone mineral density", "bone markers", "calciotropic hormones". Papers in English with publication date before 30 April 2016 were reviewed. Recommendations were jointly discussed by the Working Group. The document summaries the data on the potential effects of antidiabetic drugs on bone metabolism and fracture risk. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

Potent α-glucosidase and α-amylase inhibitory activities of standardized 50% ethanolic extracts and sinensetin from Orthosiphon stamineus Benth as anti-diabetic mechanism

PubMed Central

2012-01-01

Background In the present study, we tested a 50% ethanolic extract of Orthosiphon stamineus plants and its isolated bioactive compound with respect to their α-glucosidase and α-amylase inhibitory activities. Methods Bioactive flavonoid sinensetin was isolated from 50% ethanolic extract of Orthosiphon stamineus. The structure of this pure compound was determined on the NMR data and the α-glucosidase and α-amylase inhibitory activities of isolated sinensetin and 50% ethanolic extract of Orthosiphon stamineus were evaluated. Results In vitro studies of a 50% ethanolic extract of O. stamineus and the isolated sinensetin compound showed inhibitory activity on α-glucosidase (IC50: 4.63 and 0.66 mg/ml, respectively) and α-amylase (IC50: 36.70 mg/ml and 1.13 mg/ml, respectively). Inhibition of these enzymes provides a strong biochemical basis for the management of type 2 diabetes via the control of glucose absorption. Conclusion Alpha-glucosidase and α-amylase inhibition could the mechanisms through which the 50% ethanolic extract of O. stamineus and sinensetin exert their antidiabetic activity, indicating that it could have potential use in the management of non-insulin-dependent diabetes. PMID:23039079

The ingredients in Saengshik, a formulated health food, inhibited the activity of α-amylase and α-glucosidase as anti-diabetic function.

PubMed

Kim, Misook; Kim, Eunji; Kwak, Han Sub; Jeong, Yoonhwa

2014-10-01

We investigated total 26 ingredients of Saengshik which will be commercially produced as an anti-diabetic dietary supplement. Thirteen vegetables, nine cereals, three legumes and one seed were extracted with aqueous ethanol for 2 h at 60℃, and evaluated for their inhibitory effects against α-amylase and α-glucosidase and for total phenolic and flavonoid contents. All ingredients inhibited α-amylase activity except cabbage. Strong inhibitory activity of α-amylase was observed in leek, black rice, angelica and barley compared with acarbose as a positive control. Stronger inhibition of α-glucosidase activity was found in small water dropwort, radish leaves, sorghum and cabbage than acarbose. All Saengshik ingredients suppressed α-glucosidase activity in the range of 0.3-60.5%. Most ingredients contained total phenols which were in the range of 1.2-229.4 mg gallic acid equivalent/g dried extract. But, total phenolic contents were not observed in carrot, pumpkin and radish. All ingredients contained flavonoid in the range of 11.6-380.7 mg catechin equivalent/g dried extract. Our results demonstrate that Saengshik containing these ingredients would be an effective dietary supplement for diabetes.

Potent α-glucosidase and α-amylase inhibitory activities of standardized 50% ethanolic extracts and sinensetin from Orthosiphon stamineus Benth as anti-diabetic mechanism.

PubMed

Mohamed, Elsnoussi Ali Hussin; Siddiqui, Mohammad Jamshed Ahmad; Ang, Lee Fung; Sadikun, Amirin; Chan, Sue Hay; Tan, Soo Choon; Asmawi, Mohd Zaini; Yam, Mun Fei

2012-10-08

In the present study, we tested a 50% ethanolic extract of Orthosiphon stamineus plants and its isolated bioactive compound with respect to their α-glucosidase and α-amylase inhibitory activities. Bioactive flavonoid sinensetin was isolated from 50% ethanolic extract of Orthosiphon stamineus. The structure of this pure compound was determined on the NMR data and the α-glucosidase and α-amylase inhibitory activities of isolated sinensetin and 50% ethanolic extract of Orthosiphon stamineus were evaluated. In vitro studies of a 50% ethanolic extract of O. stamineus and the isolated sinensetin compound showed inhibitory activity on α-glucosidase (IC50: 4.63 and 0.66 mg/ml, respectively) and α-amylase (IC50: 36.70 mg/ml and 1.13 mg/ml, respectively). Inhibition of these enzymes provides a strong biochemical basis for the management of type 2 diabetes via the control of glucose absorption. Alpha-glucosidase and α-amylase inhibition could the mechanisms through which the 50% ethanolic extract of O. stamineus and sinensetin exert their antidiabetic activity, indicating that it could have potential use in the management of non-insulin-dependent diabetes.

N-hydroxycinnamide derivatives of osthole ameliorate hyperglycemia through activation of AMPK and p38 MAPK.

PubMed

Lee, Wei-Hwa; Wu, Hsueh-Hsia; Huang, Wei-Jan; Li, Yi-Ning; Lin, Ren-Jye; Lin, Shyr-Yi; Liang, Yu-Chih

2015-03-11

Our previous studies found that osthole markedly reduced blood glucose levels in both db/db and ob/ob mice. To improve the antidiabetic activity of osthole, a series of N-hydroxycinnamide derivatives of osthole were synthesized, and their hypoglycemia activities were examined in vitro and in vivo. Both N-hydroxycinnamide derivatives of osthole, OHC-4p and OHC-2m, had the greatest potential for activating AMPK and increasing glucose uptake by L6 skeletal muscle cells. In addition, OHC-4p and OHC-2m time- and dose-dependently increased phosphorylation levels of AMPK and p38 MAPK. The AMPK inhibitor, compound C, and the p38 MAPK inhibitor, SB203580, significantly reversed activation of AMPK and p38 MAPK, respectively, in OHC-4p- and OHC-2m-treated cells. Compound C and SB203580 also inhibited glucose uptake induced by OHC-4p and OHC-2m. Next, we found that OHC-4p and OHC-2m significantly increased glucose transporter 4 (GLUT4) translocation to plasma membranes and counteracted hyperglycemia in mice with streptozotocin-induced diabetes. These results suggest that activation of AMPK and p38 MAPK by OHC-4p and OHC-2m is associated with increased glucose uptake and GLUT4 translocation and subsequently led to amelioration of hyperglycemia. Therefore, OHC-4p and OHC-2m might have potential as antidiabetic agents for treating type 2 diabetes. Our previous studies found that osthole markedly reduced blood glucose levels in both db/db and ob/ob mice. To improve the antidiabetic activity of osthole, a series of N-hydroxycinnamide derivatives of osthole were synthesized, and their hypoglycemia activities were examined in vitro and in vivo. Both N-hydroxycinnamide derivatives of osthole, OHC-4p and OHC-2m, had the greatest potential for activating AMPK and increasing glucose uptake by L6 skeletal muscle cells. In addition, OHC-4p and OHC-2m time- and dose-dependently increased phosphorylation levels of AMPK and p38 MAPK. The AMPK inhibitor, compound C, and the p38 MAPK inhibitor, SB203580, significantly reversed activation of AMPK and p38 MAPK, respectively, in OHC-4p- and OHC-2m-treated cells. Compound C and SB203580 also inhibited glucose uptake induced by OHC-4p and OHC-2m. Next, we found that OHC-4p and OHC-2m significantly increased glucose transporter 4 (GLUT4) translocation to plasma membranes and counteracted hyperglycemia in mice with streptozotocin-induced diabetes. These results suggest that activation of AMPK and p38 MAPK by OHC-4p and OHC-2m is associated with increased glucose uptake and GLUT4 translocation and subsequently led to amelioration of hyperglycemia. Therefore, OHC-4p and OHC-2m might have potential as antidiabetic agents for treating type 2 diabetes.

Phytochemicals from Dodonaea viscosa and their antioxidant and anticholinesterase activities with structure-activity relationships.

PubMed

Muhammad, Akhtar; Tel-Çayan, Gülsen; Öztürk, Mehmet; Duru, Mehmet Emin; Nadeem, Said; Anis, Itrat; Ng, Seik Weng; Shah, Muhammad Raza

2016-09-01

Context Dodonaea viscosa (L.) Jacq (Sapindaceae) has been used in traditional medicine as antimalarial, antidiabetic and antibacterial agent, but further investigations are needed. Objective This study determines the antioxidant and anticholinesterase activities of six compounds (1-6) and two crystals (1A and 3A) isolated from D. viscosa, and discusses their structure-activity relationships. Materials and methods Antioxidant activity was evaluated using six complementary tests, i.e., β-carotene-linoleic acid; DPPH(•), ABTS(•+), superoxide scavenging, CUPRAC and metal chelating assays. Anticholinesterase activity was performed using the Elman method. Results Clerodane diterpenoids (1 and 2) and phenolics (3-6) - together with three crystals (1A, 3A and 7A) - were isolated from the aerial parts of D. viscosa. Compound 3A exhibited good antioxidant activity in DPPH (IC50: 27.44 ± 1.06 μM), superoxide (28.18 ± 1.35% inhibition at 100 μM) and CUPRAC (A0.5: 35.89 ± 0.09 μM) assays. Compound 5 (IC50: 11.02 ± 0.02 μM) indicated best activity in ABTS assay, and 6 (IC50: 14.30 ± 0.18 μM) in β-carotene-linoleic acid assay. Compounds 1 and 3 were also obtained in the crystal (1A and 3A) form. Both crystals showed antioxidant activity. Furthermore, crystal 3A was more active than 3 in all activity tests. Phenol 6 possessed moderate anticholinesterase activity against acetylcholinesterase and butyrylcholinesterase enzymes (IC50 values: 158.14 ± 1.65 and 111.60 ± 1.28 μM, respectively). Discussion and conclusion This is the first report on antioxidant and anticholinesterase activities of compounds 1, 2, 5, 6, 1A and 3A, and characterisation of 7A using XRD. Furthermore, the structure-activity relationships are also discussed in detail for the first time.

Why Antidiabetic Vanadium Complexes are Not in the Pipeline of “Big Pharma” Drug Research? A Critical Review

PubMed Central

Scior, Thomas; Guevara-Garcia, Jose Antonio; Do, Quoc-Tuan; Bernard, Philippe; Laufer, Stefan

2016-01-01

Public academic research sites, private institutions as well as small companies have made substantial contributions to the ongoing development of antidiabetic vanadium compounds. But why is this endeavor not echoed by the globally operating pharmaceutical companies, also known as “Big Pharma”? Intriguingly, today’s clinical practice is in great need to improve or replace insulin treatment against Diabetes Mellitus (DM). Insulin is the mainstay therapeutically and economically. So, why do those companies develop potential antidiabetic drug candidates without vanadium (vanadium-free)? We gathered information about physicochemical and pharmacological properties of known vanadium-containing antidiabetic compounds from the specialized literature, and converted the data into explanations (arguments, the “pros and cons”) about the underpinnings of antidiabetic vanadium. Some discoveries were embedded in chronological order while seminal reviews of the last decade about the Medicinal chemistry of vanadium and its history were also listed for further understanding. In particular, the concepts of so-called “noncomplexed or free” vanadium species (i.e. inorganic oxido-coordinated species) and “biogenic speciation” of antidiabetic vanadium complexes were found critical and subsequently documented in more details to answer the question. PMID:26997154

Traditional plants used for the treatment of diabetes mellitus in Sursagar constituency, Jodhpur, Rajasthan - An ethnomedicinal survey.

PubMed

Goyal, Manoj

2015-11-04

In Jodhpur, large number of people suffering with non-insulin dependent diabetes mellitus (type 2 diabetes). They are using medicinal plants along with modern medicine for the management of diabetes. The aim of this work is to document the anti-diabetic plants and determine the most relevant anti-diabetic plant species using the Disease Consensus Index. Ethnomedicinal survey was conducted for selection of anti-diabetic plant. Structured questionnaire was developed for calculation of Disease Consensus Index and administered to fifty Type 2 diabetic patients for recording their response. Twenty-one species of anti-diabetic plants were recorded, Momordica charantia (score: 0.71), Azadirachta indica (score: 0.64), Trigonella foenum-graecum (score: 0.63), Capparis decidua (score: 0.60), Withania coagulans (score: 0.54), Gymnema sylvestre (score: 0.52) and Syzygium cumini (score: 0.51) were the most significant anti-diabetic plants of the area of study, having DCI more than 0.5. Use of anti-diabetic plants is prevalent diabetic patients of the area. C. decidua, W. coagulans and G. sylvestre are recommend the further phytochemical and pharmacological investigation due to high DCI score and relatively unexplored status. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Phytochemicals, antioxidant, and anthelmintic activity of selected traditional wild edible plants of lower Assam.

PubMed

Swargiary, Ananta; Daimari, Abhijita; Daimari, Manita; Basumatary, Noymi; Narzary, Ezekiel

2016-01-01

Clerodendrum viscosum , Eryngium foetidum , Lippia javanica , and Murraya koenigii are one among the common wild edible plants in Northeast India which are also used as antidiabetic, stomach-ache relieving drugs, etc., The present study was aimed to reveal the phytochemical, antioxidant, and anthelmintic activity of the plants. The antioxidant capacity of methanolic extract of plants was studied by 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing antioxidant power, TBARS, and total antioxidant activity (TAA). Total phenolics, flavonoids, Vitamin C, carbohydrate, and protein are also estimated following standard protocols. Anthelmintic activity of the extracts has also been studied in vitro against trematode parasites. The result showed that the methanolic extracts of plants possess a substantial quantity of alkaloids, phenolics, flavonoids, proteins, carbohydrates, and Vitamin C. Phenolics, flavonoids, and Vitamin C contents were found higher in C. viscosum followed by M. koenigii , L. javanica , and E. foetidum . The in vitro antioxidant assays revealed substantial free radical scavenging property in all the plants. TAA increased in the order C. viscosum > M. koenigii > L. javanica > E. foetidum . Similarly, C. viscosum displayed a better antioxidant capacity with IC 50 values 29.74 ± 3.63 μg and 148.77 ± 18.38 μg for DPPH and thiobarbituric acid reactive species, respectively. In addition, the plant extracts also showed good anthelmintic activity against Paramphistomum sp. Time taken for paralysis and death were 0:56 ± 0:09 h and 1:35 ± 0:07 h for L. javanica at 50 mg/mL concentration. The study therefore suggests the importance of tested plants as a natural source of free radical scavenger and plausible veterinary uses.

Oral antidiabetic therapy in a large Italian sample: drug supply and compliance for different therapeutic regimens.

PubMed

Vittorino Gaddi, A; Benedetto, D; Capello, F; Di Pietro, C; Cinconze, E; Rossi, E; De Sando, V; Cevenini, M; D'Alò, G

2014-01-01

To define the main features of patients treated with oral antidiabetics, evaluating monotherapy (MT), loose-dose combination therapy (LDCT) and fixed-dose combination therapy (FDCT); to describe medication adherence to the different therapies; and to evaluate the differences in compliance with the prescribed therapy regimen among prevalent and incident patient cohorts. This study was a retrospective cohort analysis based on the ARNO database, a national record that tracks reimbursable prescription claims submitted from selected pharmacies to the Italian national health system. In total, 169,375 subjects, from an overall population of 4,040,624 were included in this study. The patients represented 12 different local health units. Each patient had at least one oral antidiabetic prescription claim (A10B ATC code). Patients were divided into four groups according to their treatment regimen during the recruitment period (1 January 2008-31 December 2008): MT, FDCT, LDCT and switching therapy. A timespan of 5 years was considered, from 4 years before to 1 year after the index date (i.e. date of the prescription selected in the recruitment period). A medication possession ratio (MPR) with a cut-off value of 80% was used to measure medication adherence. Descriptive statistics and multiple logistic regression were used to define the objectives, while P < 0.05 was considered to indicate significance. The median age of patients (n = 169,375, prevalence 4.2%) was 70 years [interquartile range (IQR) 17], and 49.1% were females. Considering the entire sample, the median MPRs for the treatment regimens were: MT, 0.73 (IQR 0.53; 43.9% compliant); FDCT, 1 (IQR 0.29, 68,5% compliant); and LDCT, 0.89 (IQR 0.33, 60.3% compliant). FDCT and LDCT were significantly correlated with MPR. Compliance was 48.9% in the prevalent patient cohort (i.e. patients prescribed oral antidiabetic therapy in both prerecruitment and recruitment periods); median MPRs for the treatment regimens were: MT, 0.73 (IQR 0.52); FDCT, 1 (IQR 0.28); and LDCT, 0.90 (IQR 0.32). Compliance was 43.0% in the incident patient cohort (i.e. patients who were first prescribed oral antidiabetic therapy in the recruitment period); median MPRs for the treatment regimens were: MT, 0.70 (IQR, 0.58); FDCT, 1 (IQR 0.34); and LDCT, 0.64 (IQR 0.39). Compliance was better for FDCT than the other therapeutic regimens in the study population. The same trend was observed in both the prevalent and incident patient cohorts. As type 2 diabetes is a chronic lifelong pathology, and multiple agents are often required to achieve glycaemic control, the preference for FDCT in the population, when clinically applicable, could be an effective strategy for functional administration of clinical outcome and sources. Evaluation of specific population fractions (age, sex, compliance, etc.) and specific agents or drug combinations could also be relevant in order to reach the healthcare objectives. Copyright © 2013 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Advance on the Flavonoid C-glycosides and Health Benefits.

PubMed

Xiao, Jianbo; Capanoglu, Esra; Jassbi, Amir Reza; Miron, Anca

2016-07-29

The dietary flavonoids, especially their glycosides, are the most vital phytochemicals in diets and are of great general interest due to their diverse bioactivity. Almost all natural flavonoids exist as their O-glycoside or C-glycoside forms in plants. The dietary flavonoid C-glycosides have received less attention than their corresponding O-glycosides. This review summarizes current knowledge regarding flavonoid C-glycosides and their influence on human health. Among the flavonoid C-glycosides, flavone C-glycosides, especially vitexin, isoorientin, orientin, isovitexin and their multiglycosides are more frequently mentioned than others. Flavonoid C-monoglycosides are poorly absorbed in human beings with very few metabolites in urine and blood and are deglycosylated and degraded by human intestinal bacteria in colon. However, flavonoid C-multiglycosides are absorbed unchanged in the intestine and distributed to other tissues. Flavonoid C-glycosides showed significant antioxidant activity, anticancer and antitumor activity, hepatoprotective activity, anti-inflammatory activity, anti-diabetes activity, antiviral activity, antibacterial and antifungal activity, and other biological effects. It looks like that the C-glycosylflavonoids in most cases showed higher antioxidant and anti-diabetes potential than their corresponding O-glycosylflavonoids and aglycones. However, there is a lack of in vivo data on the biological benefits of flavonoid C-glycosides. It is necessary to investigate more on how flavonoid C-glycosides prevent and handle the diseases.

Mechanisms for antidiabetic effect of gingerol in cultured cells and obese diabetic model mice.

PubMed

Son, Myoung Jin; Miura, Yutaka; Yagasaki, Kazumi

2015-08-01

There have been studies on health beneficial effects of ginger and its components. However, there still remain certain aspects that are not well defined in their anti-hyperglycemic effects. Our aims were to find evidence of possible mechanisms for antidiabetic action of [6]-gingerol, a pungent component of ginger, employing a rat skeletal muscle-derived cell line, a rat-derived pancreatic β-cell line, and type 2 diabetic model animals. The antidiabetic effect of [6]-gingerol was investigated through studies on glucose uptake in L6 myocytes and on pancreatic β-cell protective ability from reactive oxygen species (ROS) in RIN-5F cells. Its in vivo effect was also examined using obese diabetic db/db mice. [6]-Gingerol increased glucose uptake under insulin absent condition and induced 5' adenosine monophosphate-activated protein kinase phosphorylation in L6 myotubes. Promotion by [6]-gingerol of glucose transporter 4 (GLUT4) translocation to plasma membrane was visually demonstrated by immunocytochemistry in L6 myoblasts transfected with glut4 cDNA-coding vector. [6]-Gingerol suppressed advanced glycation end product-induced rise of ROS levels in RIN-5F pancreatic β-cells. [6]-Gingerol feeding suppressed the increases in fasting blood glucose levels and improved glucose intolerance in db/db mice. [6]-Gingerol regulated hepatic gene expression of enzymes related to glucose metabolism toward decreases in gluconeogenesis and glycogenolysis as well as an increase in glycogenesis, thereby contributing to reductions in hepatic glucose production and hence blood glucose concentrations. These in vitro and in vivo results strongly suggest that [6]-gingerol has antidiabetic potential through multiple mechanisms.

Glycogen synthase kinase 3: more than a namesake.

PubMed

Rayasam, Geetha Vani; Tulasi, Vamshi Krishna; Sodhi, Reena; Davis, Joseph Alex; Ray, Abhijit

2009-03-01

Glycogen synthase kinase 3 (GSK3), a constitutively acting multi-functional serine threonine kinase is involved in diverse physiological pathways ranging from metabolism, cell cycle, gene expression, development and oncogenesis to neuroprotection. These diverse multiple functions attributed to GSK3 can be explained by variety of substrates like glycogen synthase, tau protein and beta catenin that are phosphorylated leading to their inactivation. GSK3 has been implicated in various diseases such as diabetes, inflammation, cancer, Alzheimer's and bipolar disorder. GSK3 negatively regulates insulin-mediated glycogen synthesis and glucose homeostasis, and increased expression and activity of GSK3 has been reported in type II diabetics and obese animal models. Consequently, inhibitors of GSK3 have been demonstrated to have anti-diabetic effects in vitro and in animal models. However, inhibition of GSK3 poses a challenge as achieving selectivity of an over achieving kinase involved in various pathways with multiple substrates may lead to side effects and toxicity. The primary concern is developing inhibitors of GSK3 that are anti-diabetic but do not lead to up-regulation of oncogenes. The focus of this review is the recent advances and the challenges surrounding GSK3 as an anti-diabetic therapeutic target.

Anti-diabetic activity of methanolic extract of Alpinia galanga Linn. aerial parts in streptozotocin induced diabetic rats

PubMed Central

Verma, Ramesh Kumar; Mishra, Garima; Singh, Pradeep; Jha, Keshri K.; Khosa, Ratan L.

2015-01-01

Introduction: Alpinia galanga Linn. belongs to the family Zingiberaceae has been used as a traditional medicine in China for relieving stomach ache, treating cold, invigorating the circulatory systems, diabetes, and reducing swelling. Aim: To evaluate the antidiabetic activity of methanolic extract of A. galanga aerial parts on streptozotocin (STZ) induced diabetic rats. Materials and Methods: Diabetes was induced by single intraperitoneal injection of STZ at a dose of 60 mg/kg bodyweight. Test drug methanolic extract of A. galanga (200 and 400 mg/kg b.w.) and glibenclamide (10 mg/kg b.w.) as standard drug was administered orally for 21 consecutive days in STZ-induced diabetic rats. Fasting blood glucose level, serum lipid profiles, as well as initial and final changes in body weight were assessed along with histopathology. All the parameters were statistically analyzed by using one-way ANOVA followed by Bonferroni t-test. Results: Experimental findings showed significant dose dependent antidiabetic potential of methanolic extract in terms of reduction of fasting blood glucose level and various biochemical parameters in diabetic rats when compared with that of the diabetic control group, which might be due to the stimulatory effect of methanolic extracts on the regenerating β-cells and also on the surviving β-cells. Conclusion: Methanolic extract of aerial parts of A. galanga was effective in controlling blood glucose level and improve lipid profile in euglycemic as well as diabetic rats. PMID:26730146

Potential Dual Role of Eugenol in Inhibiting Advanced Glycation End Products in Diabetes: Proteomic and Mechanistic Insights

PubMed Central

Singh, Priyanka; Jayaramaiah, Ramesha H.; Agawane, Sachin B.; Vannuruswamy, Garikapati; Korwar, Arvind M.; Anand, Atul; Dhaygude, Vitthal S.; Shaikh, Mahemud L.; Joshi, Rakesh S.; Boppana, Ramanamurthy; Kulkarni, Mahesh J.; Thulasiram, Hirekodathakallu V.; Giri, Ashok P.

2016-01-01

Medicinally important genus Ocimum harbors a vast pool of chemically diverse metabolites. Current study aims at identifying anti-diabetic candidate compounds from Ocimum species. Major metabolites in O. kilimandscharicum, O. tenuiflorum, O. gratissimum were purified, characterized and evaluated for anti-glycation activity. In vitro inhibition of advanced glycation end products (AGEs) by eugenol was found to be highest. Preliminary biophysical analysis and blind docking studies to understand eugenol-albumin interaction indicated eugenol to possess strong binding affinity for surface exposed lysines. However, binding of eugenol to bovine serum albumin (BSA) did not result in significant change in secondary structure of protein. In vivo diabetic mice model studies with eugenol showed reduction in blood glucose levels by 38% likely due to inhibition of α-glucosidase while insulin and glycated hemoglobin levels remain unchanged. Western blotting using anti-AGE antibody and mass spectrometry detected notably fewer AGE modified peptides upon eugenol treatment both in vivo and in vitro. Histopathological examination revealed comparatively lesser lesions in eugenol-treated mice. Thus, we propose eugenol has dual mode of action in combating diabetes; it lowers blood glucose by inhibiting α-glucosidase and prevents AGE formation by binding to ε-amine group on lysine, protecting it from glycation, offering potential use in diabetic management. PMID:26739611

Pharmacological and Toxicological Profile of Harmane-β-Carboline Alkaloid: Friend or Foe.

PubMed

Khan, Haroon; Patel, Seema; Kamal, Mohammad A

2017-01-01

The plant secondary metabolites have an outstanding therapeutic potential and success over the years. In fact, it is the foundation of numerous clinically used drugs. Similarly, these is a general perception that these products are inherent safety. However, such products might have toxic/unwanted lethal effects therefore, along with biological relevance, toxicological evaluation is equally important for clinical applications. Therefore, harmane- β-carboline alkaloid was investigated for both therapeutic and toxicological potential. The literature related to the therapeutic/toxicological effects of the alkaloid was searched using various scientific data bases including Google, ScienceDirect, PubMed, SpringerLink, ASC. The peer reviewed articles were only selected. The harmane-β-carboline alkaloid has shown several pharmacological activities such as antianxiety, antidepressant, antiplatelet, antidiabetic, acetylcholinesterase and myeloperoxidase inhibition, antioxidant, antiparasitic, hypotensive, morphine withdrawal syndrome alleviation, and antinociceptive effects. On the other hand, it exhibited tremorogenic effect, for a symptom of Parkinson's disease. Adverse effect of the alkaloid on learning and memory have also been observed. All together, it is, concluded in this review that harmane elicited marked pharmacological effects but simultaneously, it possessed some serious side effects that could be the primary hurdle in the way of its clinical testing. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Potential Dual Role of Eugenol in Inhibiting Advanced Glycation End Products in Diabetes: Proteomic and Mechanistic Insights.

PubMed

Singh, Priyanka; Jayaramaiah, Ramesha H; Agawane, Sachin B; Vannuruswamy, Garikapati; Korwar, Arvind M; Anand, Atul; Dhaygude, Vitthal S; Shaikh, Mahemud L; Joshi, Rakesh S; Boppana, Ramanamurthy; Kulkarni, Mahesh J; Thulasiram, Hirekodathakallu V; Giri, Ashok P

2016-01-07

Medicinally important genus Ocimum harbors a vast pool of chemically diverse metabolites. Current study aims at identifying anti-diabetic candidate compounds from Ocimum species. Major metabolites in O. kilimandscharicum, O. tenuiflorum, O. gratissimum were purified, characterized and evaluated for anti-glycation activity. In vitro inhibition of advanced glycation end products (AGEs) by eugenol was found to be highest. Preliminary biophysical analysis and blind docking studies to understand eugenol-albumin interaction indicated eugenol to possess strong binding affinity for surface exposed lysines. However, binding of eugenol to bovine serum albumin (BSA) did not result in significant change in secondary structure of protein. In vivo diabetic mice model studies with eugenol showed reduction in blood glucose levels by 38% likely due to inhibition of α-glucosidase while insulin and glycated hemoglobin levels remain unchanged. Western blotting using anti-AGE antibody and mass spectrometry detected notably fewer AGE modified peptides upon eugenol treatment both in vivo and in vitro. Histopathological examination revealed comparatively lesser lesions in eugenol-treated mice. Thus, we propose eugenol has dual mode of action in combating diabetes; it lowers blood glucose by inhibiting α-glucosidase and prevents AGE formation by binding to ε-amine group on lysine, protecting it from glycation, offering potential use in diabetic management.

Structural characters and protecting β-cells of a polysaccharide from flowers of Inula japonica.

PubMed

Zhao, Chunzhi; Diao, Yulin; Wang, Changzhen; Qu, Wensheng; Zhao, Xiunan; Ma, Hao; Shan, Junjie; Sun, Guohui

2017-08-01

Our previous studies found that the crude polysaccharides (IJP) from flowers of Inula japonica exhibited significantly anti-diabetic activity in alloxan or MLD-STZ induced diabetic mice. In this study, we will trace an active polysaccharide from IJP and investigate its physico-chemical property and its protective mechanism on islet cell damage. The result showed that an active polysaccharide (IJP-B-1) was isolated from IJP, its molecular mass was 3.7×10 4 Da. IJP-B-1 was composed of rhamnose, arabinose, xylose, mannose, glucose, galactose and galactocuronic acid. Its major backbone structure was (1→3, 6)-linked-galactose and other branched residues. IJP-B-1 could protect pancreatic cells against STZ impairment at 50μg/mL and scavenge OH and O 2 radicals to decrease reactive oxygen generation in islet-cells in vitro. These results suggested that IJP-B-1 might be useful for protecting β-cells and against oxidative stress as an anti-diabetic candidate drug in future. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of Antioxidant, Anticholinesterase, and Antidiabetic Potential of Dry Leaves and Stems in Tamarix aphylla Growing Wild in Tunisia.

PubMed

Mahfoudhi, Adel; Grosso, Clara; Gonçalves, Rui F; Khelifi, Eltaief; Hammami, Saoussen; Achour, Sami; Trabelsi-Ayadi, Malika; Valentão, Patrícia; Andrade, Paula B; Mighri, Zine

2016-12-01

Tamarix aphylla (L.) Karst. has a wide geographic distribution and was employed in traditional medicine as astringent, anti-rheumatic and to treat fever. T. aphylla leaves and stems extracts were studied from both chemical and biological points of view to assess the antidiabetic, anticholinesterase and antioxidant potential of this species. The HPLC/Diode Array Detector (DAD) analysis showed the presence of 14 phenolic compounds (gallic, caffeic, p-coumaric, ferulic and ellagic acids, kaempferol, quercetin, quercetin 3-O-galactoside and six flavonol derivatives). This is the first study reporting a comparative study of the biological activities of different extracts from T. aphylla. High activities were obtained against DPPH radical, superoxide anion radical (O2∙-) and nitric oxide radical ( • NO) in a concentration-dependent manner, the most active extracts being the polar ones. T. aphylla also showed moderate protective effects against acetylcholinesterase, but no effects were observed against butyrylcholinesterase. Against α-glucosidase the MeOH extracts displayed IC 50 values from 8.41 to 24.81 μg/ml. © 2016 Wiley-VHCA AG, Zurich, Switzerland.

Marine Pharmacology in 2012–2013: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action †

PubMed Central

Mayer, Alejandro M. S.; Rodríguez, Abimael D.; Taglialatela-Scafati, Orazio; Fusetani, Nobuhiro

2017-01-01

The peer-reviewed marine pharmacology literature from 2012 to 2013 was systematically reviewed, consistent with the 1998–2011 reviews of this series. Marine pharmacology research from 2012 to 2013, conducted by scientists from 42 countries in addition to the United States, reported findings on the preclinical pharmacology of 257 marine compounds. The preclinical pharmacology of compounds isolated from marine organisms revealed antibacterial, antifungal, antiprotozoal, antituberculosis, antiviral and anthelmitic pharmacological activities for 113 marine natural products. In addition, 75 marine compounds were reported to have antidiabetic and anti-inflammatory activities and affect the immune and nervous system. Finally, 69 marine compounds were shown to display miscellaneous mechanisms of action which could contribute to novel pharmacological classes. Thus, in 2012–2013, the preclinical marine natural product pharmacology pipeline provided novel pharmacology and lead compounds to the clinical marine pharmaceutical pipeline, and contributed significantly to potentially novel therapeutic approaches to several global disease categories. PMID:28850074

In silico, in vitro and in vivo analyses of dipeptidyl peptidase IV inhibitory activity and the antidiabetic effect of sodium caseinate hydrolysate.

PubMed

Hsieh, Cheng-Hong; Wang, Tzu-Yuan; Hung, Chuan-Chuan; Jao, Chia-Ling; Hsieh, You-Liang; Wu, Si-Xian; Hsu, Kuo-Chiang

2016-02-01

The frequency (A), a novel in silico parameter, was developed by calculating the ratio of the number of truncated peptides with Xaa-proline and Xaa-alanine to all peptide fragments from a protein hydrolyzed with a specific protease. The highest in vitro DPP-IV inhibitory activity (72.7%) was observed in the hydrolysate of sodium caseinate by bromelain (Cas/BRO), and the constituent proteins of bovine casein also had relatively high A values (0.10-0.17) with BRO hydrolysis. 1CBR (the <1 kDa fraction of Cas/BRO) showed the greatest in vitro DPP-IV inhibitory activity of 77.5% and was used for in vivo test by high-fat diet-fed and low-dose streptozotocin-induced diabetic rats. The daily administration of 1CBR for 6 weeks was effective to improve glycaemic control in diabetic rats. The results indicate that the novel in silico method has the potential as a screening tool to predict dietary proteins to generate DPP-IV inhibitory and antidiabetic peptides.

Antidiabetic Activity from Gallic Acid Encapsulated Nanochitosan

NASA Astrophysics Data System (ADS)

Purbowatiningrum; Ngadiwiyana; Ismiyarto; Fachriyah, E.; Eviana, I.; Eldiana, O.; Amaliyah, N.; Sektianingrum, A. N.

2017-02-01

Diabetes mellitus (DM) has become a health problem in the world because it causes death. One of the phenolic compounds that have antidiabetic activity is gallic acid. However, the use of this compound still provides unsatisfactory results due to its degradation during the absorption process. The solution offered to solve the problem is by encapsulated it within chitosan nanoparticles that serve to protect the bioactive compound from degradation, increases of solubility and delivery of a bioactive compound to the target site by using freeze-drying technique. The result of chitosan nanoparticle’s Scanning Electron Microscopy (SEM) showed that chitosan nanoparticle’s size is uniform and it is smaller than chitosan. The value of encapsulation efficiency (EE) of gallic acid which encapsulated within chitosan nanoparticles is about 50.76%. Inhibition test result showed that gallic acid-chitosan nanoparticles at 50 ppm could inhibite α-glucosidase activity in 28.87% with 54.94 in IC50. So it can be concluded that gallic acid can be encapsulated in nanoparticles of chitosan and proved that it could inhibit α-glucosidase.

Chemical constituents of Swertia longifolia Boiss. with α-amylase inhibitory activity.

PubMed

Saeidnia, Soodabeh; Ara, Leila; Hajimehdipoor, Homa; Read, Roger W; Arshadi, Sattar; Nikan, Marjan

2016-01-01

α-Amylase inhibitors play a critical role in the control of diabetes and many of medicinal plants have been found to act as α-amylase inhibitors. Swertia genus, belonging to the family Gentianaceae, comprises different species most of which have been used in traditional medicine of several cultures as antidiabetic, anti-pyretic, analgesic, liver and gastrointestinal tonic. Swertia longifolia Boiss. is the only species of Swertia growing in Iran. In the present investigation, phytochemical study of S. longifolia was performed and α-amylase inhibitory effects of the plant fractions and purified compounds were determined. Aerial parts of the plant were extracted with hexane, chloroform, methanol and water, respectively. The components of the hexane and chloroform fractions were isolated by different chromatographic methods and their structures were determined by (1)H NMR and (13)C NMR data. α-Amylase inhibitory activity was determined by a colorimetric assay using 3,5-dinitro salysilic acid. During phytochemical examination, α-amyrin, β-amyrin and β-sitosterol were purified from the hexane fraction, while ursolic acid, daucosterol and swertiamarin were isolated from chloroform fraction. The results of the biochemical assay revealed α-amylase inhibitory activity of hexane, chloroform, methanol and water fractions, of which the chloroform and methanol fractions were more potent (IC50 16.8 and 18.1 mg/ml, respectively). Among examined compounds, daucosterol was found to be the most potent α-amylase inhibitor (57.5% in concentration 10 mg/ml). With regard to α-amylase inhibitory effects of the plant extracts, purified constituents, and antidiabetic application of the species of Swertia genus in traditional medicine of different countries, S. longifolia seems more appropriate species for further mechanistic antidiabetic evaluations.

Chemical constituents of Swertia longifolia Boiss. with α-amylase inhibitory activity

PubMed Central

Saeidnia, Soodabeh; Ara, Leila; Hajimehdipoor, Homa; Read, Roger W.; Arshadi, Sattar; Nikan, Marjan

2016-01-01

α-Amylase inhibitors play a critical role in the control of diabetes and many of medicinal plants have been found to act as α-amylase inhibitors. Swertia genus, belonging to the family Gentianaceae, comprises different species most of which have been used in traditional medicine of several cultures as antidiabetic, anti-pyretic, analgesic, liver and gastrointestinal tonic. Swertia longifolia Boiss. is the only species of Swertia growing in Iran. In the present investigation, phytochemical study of S. longifolia was performed and α-amylase inhibitory effects of the plant fractions and purified compounds were determined. Aerial parts of the plant were extracted with hexane, chloroform, methanol and water, respectively. The components of the hexane and chloroform fractions were isolated by different chromatographic methods and their structures were determined by 1H NMR and 13C NMR data. α-Amylase inhibitory activity was determined by a colorimetric assay using 3,5-dinitro salysilic acid. During phytochemical examination, α-amyrin, β-amyrin and β-sitosterol were purified from the hexane fraction, while ursolic acid, daucosterol and swertiamarin were isolated from chloroform fraction. The results of the biochemical assay revealed α-amylase inhibitory activity of hexane, chloroform, methanol and water fractions, of which the chloroform and methanol fractions were more potent (IC50 16.8 and 18.1 mg/ml, respectively). Among examined compounds, daucosterol was found to be the most potent α-amylase inhibitor (57.5% in concentration 10 mg/ml). With regard to α-amylase inhibitory effects of the plant extracts, purified constituents, and antidiabetic application of the species of Swertia genus in traditional medicine of different countries, S. longifolia seems more appropriate species for further mechanistic antidiabetic evaluations. PMID:27051429

Comparative hypoglycemic potentials and phytochemical profiles of 12 common leafy culinary vegetables consumed in Nsukka, Southeastern Nigeria.

PubMed

Aba, Patrick Emeka; Udechukwu, Ifeanyi Ronald

2018-04-11

Metabolic disease like diabetes mellitus is on the increase in developing countries due to lack of access to orthodox medicine owing to its high cost. Health benefits of culinary vegetables cannot be overemphasized. This study therefore aims to profile the hypoglycaemic potentials of 12 common leafy vegetables consumed in Nsukka, Southeastern Nigeria and advise diabetic patients accordingly. A total of 75 albino Wistar rats assigned to 15 groups of five rats per group were used for the study. Diabetes was induced in groups 1-14 rats by intraperitoneal injection of alloxan monohydrate (160 mg/kg), and rats in group 15 were not made diabetic. Groups 1-12 rats were treated with aqueous extracts of the vegetables (200 mg/kg), and group 13 rats received glibenclamide at 2 mg/kg and served as standard control. Rats in groups 14 and 15 received distilled water (10 mL/kg) to serve as negative and normal controls, respectively. The fasting blood glucose (FBG) values of the rats were determined 3, 6 and 24 h post-treatment. Phytochemical studies on the vegetables were also carried out. Results revealed that the hypoglycaemic activities of Gongronema latifolium, Pterocarpus santalinoides, Ocimum gratissimum, Pterocarpus mildbraedii and Vernonia amygdalina were comparable (p>0.05) to that obtained for glibenclamide (standard anti-diabetic drug) while Gnetum africanum and Piper guineense did not show significant hypoglycaemic activities. Phytochemicals such as flavonoids, alkaloids, tannins, saponins, glycosides, and terpenes were present in the vegetables. It was concluded that the vegetables possess hypoglycaemic activities at different capacities with G. latifolium being the most potent.

Investigation of repressive and enhancive effects of fruit extracts on the activity of glucose-6-phophatase.

PubMed

Zahoor, Muhammad; Jan, Muhammad Rasul; Naz, Sumaira

2016-11-01

Glucose-6-phosphatase is a key enzyme of glucose metabolic pathways. Deficiency of this enzyme leads to glycogen storage disease. This enzyme also plays a negative role in diabetes mellitus disorder in which the catalytic activity of this enzyme increases. Thus there is need for activators to enhance the activity of glucose-6-phosphatase in glycogen storage disease of type 1b while in diabetes mellitus repressors are needed to reduce its activity. Crude extracts of apricot, fig, mulberry and apple fruits were investigated for their repressive/enhancive effects on glucose-6-phosphatase in vivo. Albino mice were used as experimental animal. All the selected extracts showed depressive effects on glucose-6-phosphatase, which shows that all these extracts can be used as antidiabetic supplement of food. The inhibitory pattern was competitive one, which was evident from the effect of increasing dose from 1g/Kg body weight to 3g/Kg body weight for all the selected fruit extracts. However fig and apple fruit extracts showed high repressive effects for high doses as compared to apricot and mulberry fruit extracts. None of these selected fruit extracts showed enhancive effect on glucose-6-phosphatase activity. All these fruits or their extracts can be used as antidiabetic dietary supplement for diabetes mellitus.

Antihyperglycemic Activity of Houttuynia cordata Thunb. in Streptozotocin-Induced Diabetic Rats

PubMed Central

Kumar, Manish; Prasad, Satyendra K.; Krishnamurthy, Sairam; Hemalatha, Siva

2014-01-01

Present study is an attempt to investigate plausible mechanism involved behind antidiabetic activity of standardized Houttuynia cordata Thunb. extract in streptozotocin-induced diabetic rats. The plant is used as a medicinal salad for lowering blood sugar level in North-Eastern parts of India. Oral administration of extract at 200 and 400 mg/kg dose level daily for 21 days showed a significant (P < 0.05) decrease in fasting plasma glucose and also elevated insulin level in streptozotocin-induced diabetic rats. It also significantly reversed all the alterations in biochemical parameters, that is, total lipid profile, blood urea, creatinine, protein, and antioxidant enzymes in liver, pancreas, and adipose tissue of diabetic rats. Furthermore, we have demonstrated that the extract significantly reversed the expression patterns of various glucose homeostatic enzyme genes like GLUT-2, GLUT-4, and caspase-3 levels but did not show any significant effect on PPAR-γ protein expressions. Additionally, the extract positively regulated mitochondrial membrane potential and succinate dehydrogenase (SDH) activity in diabetic rats. The findings justified the antidiabetic effect of H. cordata which is attributed to an upregulation of GLUT-4 and potential antioxidant activity, which may play beneficial role in resolving complication associated with diabetes. PMID:24707284

Bioactivity-Guided Isolation of Potential Antidiabetic and Antihyperlipidemic Compounds from Trigonella stellata.

PubMed

Shams Eldin, Safa M; Radwan, Mohamed M; Wanas, Amira S; Habib, Abdel-Azim M; Kassem, Fahima F; Hammoda, Hala M; Khan, Shabana I; Klein, Michael L; Elokely, Khaled M; ElSohly, Mahmoud A

2018-05-25

The in vitro antidiabetic and antihyperlipidemic activities of an alcoholic extract of Trigonella stellata were evaluated in terms of the activation of PPAR α and PPAR γ in human hepatoma (HepG2) cells. The extract was investigated phytochemically, aiming at the isolation of the most active compounds to be used as a platform for drug discovery. Three new isoflavans, (3 S,4 R)-4,2',4'-trihydroxy)-7-methoxyisoflavan (1), (3 R,4 S)-4,2',4'-trihydroxy-7-methoxy-4'- O-β-d-glucopyranosylisoflavan (2), and (2 S,3 R,4 R)-4,2',4'-trihydroxy-2,7-dimethoxyisoflavan (3), were isolated and characterized along with the five known compounds p-hydroxybenzoic acid (4), 7,4'-dihydroxyflavone (5), dihydromelilotoside (6), quercetin-3,7- O-α-l-dirhamnoside (7), and soyasaponin I (8). The structures of 1-3 were elucidated using various spectroscopic techniques including HRESIMS and 1D and 2D NMR. The absolute stereochemistry of the new isoflavans (1-3) was determined using both experimental and calculated electronic circular dichroism as well as DP4 calculations. The isolated compounds were tested for their PPAR α and PPAR γ activation effects in HepG2 cells.

A Soxhlet Extract of Gongronema latifolium Retains Moderate Blood Glucose Lowering Effect and Produces Structural Recovery in the Pancreas of STZ-Induced Diabetic Rats

PubMed Central

Al-Hindi, Bassel; Yusoff, Nor A.; Atangwho, Item J.; Ahmad, Mariam; Asmawi, Mohd Z.; Yam, Mun F.

2016-01-01

Background: Gongronema latifolium Benth. (GL) possesses considerable glucose lowering effects able to be utilized on a large-scale. This paper investigates the effects of a Soxhlet extract on hyperglycemia, Langerhans islets and glucose uptake by abdominal muscles. Methods: Ethanol and a Soxhlet apparatus were used to obtain GL ethanolic Soxhlet extract (GLES). It was then administered to randomly-segregated male Sprague-Dawley, normal and STZ-induced diabetic rats, using oral gavage to evaluate blood glucose levels (BGLs), serum lipid profile, insulin levels and the pancreas post-treatment. Results: GLES significantly (p < 0.05) decreased BGLs of normal rats in glucose tolerance testing at a dose of 2 g/kg b.w. but failed to do so in diabetic rats undergoing acute 7-h treatment. Given twice-daily, 1 g/kg b.w. of GLES moderately controlled diabetic BGLs starting from day 10. After 14 days of treatment, 1 g/kg and 0.5 g/kg b.w. of GLES caused 44% and 50% respective increases in the average area of Langerhans islets compared to DC. Using isolated rat abdominal muscle, GLES was found to be a mild insulin-sensitizer. GC-MS analysis revealed the presence of the known glucose-lowering phytosterol, Sitostenone. Conclusion: Despite retaining moderate antidiabetic activity, Soxhlet extraction of Gongronema latifolium probably leads to the destruction of active heat-liable compounds. PMID:29083373

Bioconversion of marine carotenoids and their health functions

USDA-ARS?s Scientific Manuscript database

Fucoxanthin (FX), found in edible brown seaweeds, exhibits anti-obesity and anti-diabetic effects. In the body, FX is converted to fucoxanthinol (FXOH) and amarouciaxanthin A and accumulates in adipose tissue and other tissues. It was suggested that FXOH and amarouciaxanthin A were active metaboli...

In vitro callus and in vivo leaf extract of Gymnema sylvestre stimulate β-cells regeneration and anti-diabetic activity in Wistar rats.

PubMed

Ahmed, A Bakrudeen Ali; Rao, A S; Rao, M V

2010-11-01

A methanol extract of Gymnema sylvestre leaf and callus showed anti-diabetic activities through regenerating β-cells. Optimum callus was developed under stress conditions of blue light with 2,4-D (1.5 mg/l) and KN (0.5 mg/l), which induced maximum biomass of green compact callus at 45 days, as determined by growth curve analysis. Leaf and optimum callus extracts contains gymnemic acid, which was analyzed using TLC, HPTLC and HPLC methods. The research reported here deals with leaf and callus extracts of G. sylvestre, which significantly increase the weight of the whole body, liver, pancreas and liver glycogen content in alloxan-induced diabetic rats (Wistar rats). The gymnemic acid of leaf and callus extracts significantly increases the regeneration of β-cells in treated rats, when compared with the standard diabetic rats. It could have potential as a pharmaceutical drug for insulin-dependent diabetes mellitus (IDDM). Copyright © 2010 Elsevier GmbH. All rights reserved.

Supramolecular Cocrystals of Gliclazide: Synthesis, Characterization and Evaluation.

PubMed

Chadha, Renu; Rani, Dimpy; Goyal, Parnika

2017-03-01

To prepare the supramolecular cocrystals of gliclazide (GL, a BCS class II drug molecule) via mechanochemical route, with the goal of improving physicochemical and biopharmaceutical properties. Two cocrystals of GL with GRAS status coformers, sebacic acid (GL-SB; 1:1) and α-hydroxyacetic acid (GL-HA; 1:1) were screened out using liquid assisted grinding. The prepared cocrystals were characterized using thermal and analytical techniques followed by evaluation of antidiabetic activity and pharmacokinetic parameters. The generation of new, single and pure crystal forms was characterized by DSC and PXRD. The crystal structure determination from PXRD revealed the existence of both cocrystals in triclinic (P-1) crystal system. The hydrogen bonded network, determined by material studio was well supported by shifts in FTIR and SSNMR. Both the new solid forms displayed improved solubility, IDR, antidiabetic activity and pharmacokinetic parameters as compared to GL. The improvement in these physicochemical and biopharmaceutical properties corroborated the fact that the supramolecular cocrystallization may be useful in the development of pharmaceutical crystalline materials with interesting network and properties.

Pancreatoprotective effects of Geniotrigona thoracica stingless bee honey in streptozotocin-nicotinamide-induced male diabetic rats.

PubMed

Aziz, Muhammad Shakir Abdul; Giribabu, Nelli; Rao, Pasupuleti Visweswara; Salleh, Naguib

2017-05-01

Stingless bee honey (SLBH) has been claimed to possess multiple health benefits. Its anti-diabetic properties are however unknown. In this study, ability of SLBH from Geniotrigona thoracica stingless bee species in ameliorating pancreatic damage and in maintaining metabolic profiles were investigated in diabetic condition. SLBH at 1 and 2g/kg/b.w. was given orally to streptozotocin (STZ)-nicotinamide-induced male diabetic rats for 28days. Metabolic parameters (fasting blood glucose-FBG and lipid profiles-LP and serum insulin) were measured by biochemical assays. Distribution and expression level of insulin, oxidative stress marker i.e. catalase, inflammatory markers i.e. IKK-β, TNF-α, IL-1β and apoptosis marker i.e. caspase-9 in the pancreatic islets were identified and quantified respectively by immunohistochemistry. Levels of NF-κβ in pancreas were determined by enzyme-linked immunoassay (ELISA). SLBH administration to diabetic male rats prevented increase in FBG, total cholesterols (TC), triglyceride (TG) and low density lipoprotein (LDL) levels. However, high density lipoprotein (HDL) and serum insulin levels in diabetic rats receiving SLBH increased. Additionally, histopathological changes and expression level of oxidative stress, inflammation and apoptosis markers in pancreatic islets of diabetic rats decreased with increased expression level of insulin in the islets. LC-MS analysis revealed the presence of several compounds in SLBH that might be responsible for these effects. SLBH has great potential to be used as agent to protect the pancreas against damage and dysfunction where these could account for its anti-diabetic properties. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Medicinal properties of Peganum harmala L. in traditional Iranian medicine and modern phytotherapy: a review.

PubMed

Mina, Cheraghi Niroumand; Farzaei, Mohammad Hosein; Gholamreza, Amin

2015-02-01

To review the pharmacological activities of Peganum harmala L. (P. harmala, Nitrariaceae) in traditional Iranian medicine (TIM) and modern phytotherapy. Opinions of TIM and modern phytotherapy about safety and acceptable dosage of this plant are discussed. Various medical properties of P. harmala were collected from important TIM references and added to scientific reports derived from modern medical databases like PubMed, Scirus, ScienceDirect and Scopus. The main medicinal part of the plant is the seed. In TIM resources, this plant possesses various Pharmacological activities such as carminative, galactagogue, diuretic, emmenagogue, antithrombotic and analgesic. In modern phytotherapy, P. harmala demonstrated numerous medicinal effects including cardiovascular, neurologic, antimicrobial, insecticidal, antineoplasmic, antiproliferative, gastrointestinal and antidiabetic effects. Adverse events such as neuro-sensorial symptoms, visual hallucination, bradycardia, hypotension, agitation, tremors, ataxia, abortion and vomiting cause people to use this plant cautiously. P. harmala is contraindicated during pregnancy, due to its abortive and mutagenic activities. Because of increasing the expression of CYP1A2, 2C19, and 3A4 and inhibition of monoamine oxidase, the pharmacokinetic parameters of drugs which are mainly metabolized by these enzymes may be affected by P. harmala. The medicinal properties declared for this plant in TIM are compared with those showed in modern phytotherapy. Some of the TIM properties were confirmed in modern phytotherapy like emetic and analgesic activities and some have not been evaluated in modern phytotherapy such as its therapeutic effects on paralysis, epilepsy and numbness. Finally, the current review provides the evidence for other researchers to use TIM properties of P. harmala as an efficacious natural drug. Further preclinical and clinical studies for adequate evaluating safety and therapeutic efficacy are recommended.

A review of the use of Piper betel in oxidative stress disorders.

PubMed

Lee, C Y; Nurul Zaidah, A S; Nur Amalina, G; Muhammad Azree, Ema; Das, S; Zar, C T

2014-01-01

Increase in prevalence of disease related oxidative stress disorders have been on the rise in the entire world since the past decades. Significant positive effects with few antioxidant properties in the modern drugs pave for the alternative medicines in managing the disease. Piper betel (P. betel), a herb, is known to possess high anti-oxidant, anti-diabetic, anti-atherosclerosis, anti-hyperlipidemic, anti-cancer and neuroprotective property. This review focused on the effect of P. betel on diabetes mellitus, atherosclerosis and chronic kidney disease, Alzheimer's disease and breast cancer. P. betel proved to show positive effects with specific outcomes towards these diseases. Moreover, the promising effect of P. betel in vitro studies was also highlighted in the present review. It is believed that the findings obtained in this review will draw the attention of the medical professionals and general public towards P. betel and it will open the door for further detailed research.

Alpha-glucosidase inhibitory effect of resveratrol and piceatannol

USDA-ARS?s Scientific Manuscript database

Dietary polyphenols have been shown to inhibit a-glucosidase, an enzyme target of some anti-diabetic drugs. Resveratrol, a polyphenol found in grapes and wine, has been reported to inhibit the activity of yeast a-glucosidase. This triggered our interest to synthesize analogs and determine their ef...

Traditional management of diabetes in Pakistan: Ethnobotanical investigation from Traditional Health Practitioners.

PubMed

Yaseen, Ghulam; Ahmad, Mushtaq; Zafar, Muhammad; Sultana, Shazia; Kayani, Sadaf; Cetto, Adolfo Andrade; Shaheen, Shabnum

2015-11-04

The uses of anti-diabetic plants are well anchored in the traditional health care system of Pakistan. To the best of our knowledge, this is the first ethno-botanical study about the uses of plants for the treatment of diabetes. The aim of the study is to record indigenous knowledge on anti-diabetic plants from Traditional Health Practitioners (THPs) and diabetic patients. In addition, it is aimed to ascertain and validate the traditional uses of anti-diabetic plants by citing pharmacological activities and phytochemical constitutes from previously published literature. The ethno-medicinal data was documented during 14 field surveys, each comprising of 10 days, from 3 regions of Pakistan (Islamabad, Khyber Pukhtoonkhwa and Deserts of Sindh). In total, 113 THPs and 44 diabetic patients were interviewed using open-ended and semi-structured questionnaires. Quantitative indices, including Relative Frequency of Citation percentage (RFC %) and Disease Consensus Index (DCI) were calculated. The documented data is authenticated by comparing with 28 published articles on ethno-botanical aspects and many pharmacological studies. In total, 120 plant species belonging to 50 families were reported. The ethno-botanical results indicated that Moraceae (11 species); herb (56 reports) is dominant life form; the leaves (56 reports) are the most used plant part and decoction (24%) is the preferred mode of preparation. The quantitative analysis shows that RFC% ranges from 14 to 42 and DCI varies from 0.15 to 0.74. By comparing to previous studies, 64 species are reported new in traditional treatment of DM; 40 species are new to pharmacological evidence and 3 species are new to phytochemical studies. This study recoded the significant indigenous knowledge about anti-diabetic plants among the THPs and diabetic patients in Pakistan. This type of ethno-botanical knowledge on traditional use of anti-diabetic plants is an important step in designing detailed pharmacological and clinical trials for Diabetes Miletus treatment. It is recommended that further pharmacological and phytochemical analysis should be conducted on those species which lack previous references in literature and have highest Frequency of Citation (FC), Disease Consensus Index (DCI) and Relative Frequency of Citation percentage (RFC%). Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Evaluation of the anti-diabetic properties of Mucuna pruriens seed extract.

PubMed

Majekodunmi, Stephen O; Oyagbemi, Ademola A; Umukoro, Solomon; Odeku, Oluwatoyin A

2011-08-01

To explore the antidiabetic properties of Mucuna pruriens(M. pruriens). Diabetes was induced in Wistar rats by single intravenous injection of 120 mg/kg of alloxan monohydrate and different doses of the extract were administered to diabetic rats. The blood glucose level was determined using a glucometer and results were compared with normal and untreated diabetic rats. The acute toxicity was also determined in albino mice. Results showed that the administration of 5, 10, 20, 30, 40, 50, and 100 mg/kg of the crude ethanolic extract of M. pruriens seeds to alloxan-induced diabetic rats (plasma glucose > 450 mg/dL) resulted in 18.6%, 24.9%, 30.8%, 41.4%, 49.7%, 53.1% and 55.4% reduction, respectively in blood glucose level of the diabetic rats after 8h of treatment while the administration of glibenclamide (5 mg/kg/day) resulted in 59.7% reduction. Chronic administration of the extract resulted in a significant dose dependent reduction in the blood glucose level (P<0.001). It also showed that the antidiabetic activity of M. pruriens seeds resides in the methanolic and ethanolic fractions of the extract. Acute toxicity studies indicated that the extract was relatively safe at low doses, although some adverse reactions were observed at higher doses (8-32 mg/kg body weight), no death was recorded. Furthermore, oral administration of M. pruriens seed extract also significantly reduced the weight loss associated with diabetes. The study clearly supports the traditional use of M. pruriens for the treatment of diabetes and indicates that the plant could be a good source of potent antidiabetic drug. Copyright © 2011 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Antidiabetic and antihyperlipidemic effects of the stem of Musa sapientum Linn. in streptozotocin-induced diabetic rats.

PubMed

Dikshit, Piyush; Shukla, Kirtikar; Tyagi, Mool Kumar; Garg, Piyush; Gambhir, Jasvindar K; Shukla, Rimi

2012-12-01

Musa sapientum Linn. is a herbaceous plant of the Musaceae family. It has been used in India for the treatment of gastric ulcer, hypertension, diarrhea, dysentery, and diabetes. The antidiabetic effect of the fruit, root, and flower has been demonstrated. The aim of the present study was to assess the antidiabetic and antihyperlipidemic effects of the stem of M. sapientum Linn. Diabetes was induced in rats by streptozotocin injection (45 mg/kg, i.p.). Diabetic rats were treated for 2 weeks with different doses of lyophilized stem juice of M. sapientum Linn. (25, 50, and 100 mg/kg) to select the most effective dose. The effects of 4 weeks treatment with this dose (50 mg/kg) on fasting and postprandial plasma glucose (FPG, PPG) levels, body weight, lipid profile, HbA1c, insulin, liver enzymes (i.e. glucokinase, glucose-6-phosphatase and 3-hydroxy-3-methylglutaryl coenzyme A [HMG-CoA] reductase) and muscle and liver glycogen were evaluated. The most effective dose of lyophilized stem juice of M. sapientum Linn. was 50 mg/kg. Four weeks treatment with this dose resulted in significant decreases in FPG and PPG (P < 0.05). Serum insulin increased (P < 0.05) whereas HbA1c decreased (P < 0.05). Diabetes-induced changes to the lipid profile, muscle and liver glycogen, and enzyme activity (i.e. glucokinase, glucose-6-phosphatase, and HMG-CoA reductase) were restored near to normal levels (P < 0.05). Diabetic rats responded favorably to treatment with lyophilized stem juice of M. sapientum Linn., which exhibits antidiabetic and antihyperlipidemic effects. © 2012 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Micro-Environmental Signature of The Interactions between Druggable Target Protein, Dipeptidyl Peptidase-IV, and Anti-Diabetic Drugs.

PubMed

Chakraborty, Chiranjib; Mallick, Bidyut; Sharma, Ashish Ranjan; Sharma, Garima; Jagga, Supriya; Doss, C George Priya; Nam, Ju-Suk; Lee, Sang-Soo

2017-01-01

Druggability of a target protein depends on the interacting micro-environment between the target protein and drugs. Therefore, a precise knowledge of the interacting micro-environment between the target protein and drugs is requisite for drug discovery process. To understand such micro-environment, we performed in silico interaction analysis between a human target protein, Dipeptidyl Peptidase-IV (DPP-4), and three anti-diabetic drugs (saxagliptin, linagliptin and vildagliptin). During the theoretical and bioinformatics analysis of micro-environmental properties, we performed drug-likeness study, protein active site predictions, docking analysis and residual interactions with the protein-drug interface. Micro-environmental landscape properties were evaluated through various parameters such as binding energy, intermolecular energy, electrostatic energy, van der Waals'+H-bond+desolvo energy (E VHD ) and ligand efficiency (LE) using different in silico methods. For this study, we have used several servers and software, such as Molsoft prediction server, CASTp server, AutoDock software and LIGPLOT server. Through micro-environmental study, highest log P value was observed for linagliptin (1.07). Lowest binding energy was also observed for linagliptin with DPP-4 in the binding plot. We also identified the number of H-bonds and residues involved in the hydrophobic interactions between the DPP-4 and the anti-diabetic drugs. During interaction, two H-bonds and nine residues, two H-bonds and eleven residues as well as four H-bonds and nine residues were found between the saxagliptin, linagliptin as well as vildagliptin cases and DPP-4, respectively. Our in silico data obtained for drug-target interactions and micro-environmental signature demonstrates linagliptin as the most stable interacting drug among the tested anti-diabetic medicines.

Plasma-Induced Degradation of Quercetin Associated with the Enhancement of Biological Activities.

PubMed

Kim, Tae Hoon; Lee, Jaemin; Kim, Hyun-Joo; Jo, Cheorun

2017-08-16

Nonthermal plasma is a promising technology to improve the safety and to extend the shelf-life of various minimally processed foods. However, research on plasma-induced systemic degradation related to changes in chemical structure and biological activity is still very limited. In this study, the enhancement of biological activity and the mechanism of degradation of the most common type of flavonol, quercetin, induced by a dielectric barrier discharge (DBD) plasma were investigated. Quercetin is dissolved in methanol and exposed to nonthermal DBD plasma for 5, 10, 20, and 30 min. The quercetin treated with the plasma for 20 min showed rapidly increased α-glucosidase inhibitory and radical scavenging activities compared to those of parent quercetin. The structures of the degradation products 1-3 from the quercetin treated with the plasma for 20 min were isolated and characterized by interpretation of their spectroscopic data. Among the generated products, (±)-alphitonin (1) exhibited significantly improved antidiabetic and antioxidant properties compared to those of the parent quercetin. The antidiabetic and antioxidant properties were measured by α-glucosidase inhibition and 1,1-diphenyl-2-picrylhydrazyl radical scavenging assays. These results suggested that structural changes in quercetin induced by DBD plasma might be attributable to improving the biological activity.

Antidiabetic effect of gomisin N via activation of AMP-activated protein kinase.

PubMed

Jung, Dae Young; Kim, Ji-Hyun; Lee, Hoyoung; Jung, Myeong Ho

2017-12-16

Gomisin N (GN) is a lignan derived from Schisandra chinensis. AMP-activated kinase (AMPK) has gained attention as a therapeutic target for the treatment of metabolic syndrome. Previously, we reported that GN activated the AMPK pathway and ameliorated high-fat diet (HFD)-induced hepatic steatosis. In this study, we investigated the anti-diabetic effects of GN in C2C12 myotubes and HFD obese mice. GN enhanced the phosphorylation of AMPK/acetyl-CoA carboxylase (ACC) and Akt. In addition, GN promoted glucose uptake in C2C12 myotubes, which was accompanied by the translocation of glucose transporter 4 (GLUT4) to the plasma membrane. Treatment with compound C, an AMPK inhibitor, suppressed GN-mediated stimulation of glucose uptake. Furthermore, GN increased the expression of mitochondria biogenesis and fatty acid oxidation genes in C2C12 myotubes. In the in vivo study, administration of GN to HFD mice decreased the levels of fasting blood glucose and insulin, and improved glucose tolerance in HFD obese mice. GN administration rescued the decreased phosphorylation of AMPK and Akt and stimulated the expression of mitochondria biogenesis genes in the skeletal muscle of HFD mice. These findings suggested that GN exerted anti-hyperglycemic effects through AMPK activation. Copyright © 2017 Elsevier Inc. All rights reserved.

Something old, something new and something very old: drugs for treating type 2 diabetes.

PubMed

Kaiser, D; Oetjen, E

2014-06-01

Diabetes mellitus belongs to the most rapidly increasing diseases worldwide. Approximately 90-95% of these patients suffer from type 2 diabetes mellitus, which is characterized by peripheral insulin resistance and the progressive loss of beta-cell function and mass. Considering the complications of this chronic disease, a reliable anti-diabetic treatment is indispensable. An ideal oral anti-diabetic drug should not only correct glucose homeostasis but also preserve or even augment beta-cell function and mass, ameliorate the subclinical inflammation present under insulin-resistant conditions and prevent the macro- and microvascular consequences of diabetes in order to reduce the mortality. Despite the many anti-diabetic drugs already in use, there is an ongoing research for additional drugs, guided by different concepts of the pathogenesis of type 2 diabetes. This review will briefly summarize current oral anti-diabetic drugs. In addition, emerging strategies for the treatment of diabetes will be described, among them the inhibition of glucagon action and anti-inflammatory drugs. Their suitability as 'ideal anti-diabetic drugs' will be discussed. © 2014 The British Pharmacological Society.

Drug–drug Interaction between Pravastatin and Gemfibrozil (Antihyperlipidemic) with Gliclazide (Antidiabetic) in Rats

PubMed Central

Sultanpur, CM; Satyanarayana, S; Reddy, NS; Kumar, KE; Kumar, S

2010-01-01

Diabetes mellitus is a condition of increased blood glucose level in the body. Antihyperlipidemic drugs like statins and fibrates are widely used for prophylactic treatment in dyslipideamia and atherosclerosis. Diabetic dislipidemia exists with increased triglycerides, low HDL and high LDL levels. Hence, with oral hypoglycemic drugs, the addition of a lipid-lowering drug is necessary for controlling dislipidemia. In such a situation, there may be chances of drug–drug interactions between antidiabetic and antihyperlipidemic drugs. The present study is planned to evaluate the safety of gliclazide (antidiabetic) in the presence of pravastatin and gemfibrozil (antihyperlpidemic) in rats. Studies in normal and alloxan-induced diabetic rats were conducted with oral doses of gliclazide and their combination with pravastatin and gemfibrozil, with an adequate washout period in between the treatments. Blood samples were collected in rats by retroorbital puncture at 0, 1, 2, 3, 4, 6, 8, 10 and 12 h. All the blood samples were analyzed for glucose by GOD –POD. Gliclazide (½ TD) produced hypoglycemic activity in normal and diabetic rats, with peak activity at 2 and 8 h. Pravastatin (TD) + gemfibrozil (TD) combination treatment increased the hypoglycemic effect of gliclazide in normal rats or diabetic rats when administered together. The interaction observed due to inhibition of both the enzymes (CYP 450 2C9 and CYP 450 3A4) responsible for the metabolism of gliclazide showed increased half-life, which was seen in the present study. Because concomitant administration of gliclazide with provastatin and gemfibrozil in diabetes is associated with atherosclerosis, it should be contraindicated or used with caution. PMID:21264118

Glycogen synthase kinase 3: more than a namesake

PubMed Central

Rayasam, Geetha Vani; Tulasi, Vamshi Krishna; Sodhi, Reena; Davis, Joseph Alex; Ray, Abhijit

2009-01-01

Glycogen synthase kinase 3 (GSK3), a constitutively acting multi-functional serine threonine kinase is involved in diverse physiological pathways ranging from metabolism, cell cycle, gene expression, development and oncogenesis to neuroprotection. These diverse multiple functions attributed to GSK3 can be explained by variety of substrates like glycogen synthase, τ protein and β catenin that are phosphorylated leading to their inactivation. GSK3 has been implicated in various diseases such as diabetes, inflammation, cancer, Alzheimer's and bipolar disorder. GSK3 negatively regulates insulin-mediated glycogen synthesis and glucose homeostasis, and increased expression and activity of GSK3 has been reported in type II diabetics and obese animal models. Consequently, inhibitors of GSK3 have been demonstrated to have anti-diabetic effects in vitro and in animal models. However, inhibition of GSK3 poses a challenge as achieving selectivity of an over achieving kinase involved in various pathways with multiple substrates may lead to side effects and toxicity. The primary concern is developing inhibitors of GSK3 that are anti-diabetic but do not lead to up-regulation of oncogenes. The focus of this review is the recent advances and the challenges surrounding GSK3 as an anti-diabetic therapeutic target. British Journal of Pharmacology (2009) doi:10.1111/j.1476-5381.2008.00085.x PMID:19366350

Biological activity of Stevia rebaudiana Bertoni and their relationship to health.

PubMed

Ruiz-Ruiz, Jorge Carlos; Moguel-Ordoñez, Yolanda Beatriz; Segura-Campos, Maira Rubi

2017-08-13

The leaves of Stevia rebaudiana Bertoni has nutrients and phytochemicals, which make it an adequate source for the extraction and production of functional food ingredients. Preclinical and clinical studies suggest therapeutic and pharmacological applications for stevia and their extracts because they are not toxic and exhibit several biological activities. This review presents the biological activity of Stevia rebaudiana Bertoni and their relationship to antidiabetic, anticariogenic, antioxidant, hypotensive, antihypertensive, antimicrobial, anti-inflammatory and antitumor activities. Consumption and adverse effects were also reviewed.

An update on Ayurvedic herb Convolvulus pluricaulis Choisy

PubMed Central

Agarwa, Parul; Sharma, Bhawna; Fatima, Amreen; Jain, Sanjay Kumar

2014-01-01

Convolvulus pluricaulis Choisy (C. pluricaulis) is a perennial herb that seems like morning glory. All parts of the herb are known to possess therapeutic benefits. The plant is used locally in Indian and Chinese medicine to cure various diseases. It is used in Ayurvedic formulation for chronic cough, sleeplessness, epilepsy, hallucinations, anxiety etc. Based on the comprehensive review of plant profile, pharmacognosy, phytochemistry, pharmacological and toxicological data on the C. pluricaulis, there will be more opportunities for the future research and development on the herb C. pluricaulis. Information on the C. pluricaulis was collected via electronic search (using Pub Med, SciFinder, Google Scholar and Web of Science) and library search for articles published in peer-reviewed journals. Furthermore, information also was obtained from some local books on ethnopharmacology. This paper covers the literature, primarily pharmacological, from 1985 to the end of 2012. The C. pluricaulis is an important indigenous medicine, which has a long medicinal application for liver disease, epileptic disease, microbial disease, cytotoxic and viral diseases, central nervous system (CNS) disease in Ayurvedic medicine, traditional Chinese medicine and other indigenous medical systems. The isolated metabolites and crude extract have exhibited a wide of in vitro and in vivo pharmacological effect, including CNS depression, anxiolytic, tranquillizing, antidepressant, antistress, neurodegenerative, antiamnesic, antioxidant, hypolipidemic, immunomodulatory, analgesic, antifungal, antibacterial, antidiabetic, antiulcer, anticatatonic, and cardiovascular activity. A chemical study of this plant was then initiated, which led to the isolation of carbohydrats, proteins, alkaloids, fatty acids, steroids, coumarins, flavanoids, and glycosides as active chemicals that bring about its biological effects. A series of pharmacognostical studies of this plant show that it is a herb, its stem and leaves are hairy, more over it has two types of stomata, anisocytic and paracytic. A herb, C. pluricaulis has emerged as a good source of the traditional medicine for the treatment of liver disease, epileptic disease, microbial disease, cytotoxic and viral diseases, and CNS disease. Pharmacological results have validated the use of this species in traditional medicine. All the parts of the herb are known to possess therapeutic benefits. Expansion of research materials would provide more opportunities for the discovery of new bioactive principles from C. pluricaulis. PMID:25182446

Functional herbal food ingredients used in type 2 diabetes mellitus

PubMed Central

Perera, Pathirage Kamal; Li, Yunman

2012-01-01

From many reports it is clear that diabetes will be one of the major diseases in the coming years. As a result there is a rapidly increasing interest in searching new medicines, or even better searching prophylactic methods. Based on a large number of chemical and pharmacological research work, numerous bioactive compounds have been found in functional herbal food ingredients for diabetes. The present paper reviews functional herbal food ingredients with regards to their anti-diabetic active principles and pharmacological test results, which are commonly used in Asian culinary system and medical system and have demonstrated clinical or/and experimental anti-diabetic effectiveness. Our idea of reviewing this article is to give more attention to these functional food ingredients as targets medicinal foods in order to prevent or slow down the development of type 2 diabetes mellitus. PMID:22654403

Design, Synthesis and Pharmacological Evaluation of Novel Vanadium-Containing Complexes as Antidiabetic Agents

PubMed Central

Fedorova, Elena V.; Buryakina, Anna V.; Zakharov, Alexey V.; Filimonov, Dmitry A.; Lagunin, Alexey A.; Poroikov, Vladimir V.

2014-01-01

Based on the data about structure and antidiabetic activity of twenty seven vanadium and zinc coordination complexes collected from literature we developed QSAR models using the GUSAR program. These QSAR models were applied to 10 novel vanadium coordination complexes designed in silico in order to predict their hypoglycemic action. The five most promising substances with predicted potent hypoglycemic action were selected for chemical synthesis and pharmacological evaluation. The selected coordination vanadium complexes were synthesized and tested in vitro and in vivo for their hypoglycemic activities and acute rat toxicity. Estimation of acute rat toxicity of these five vanadium complexes was performed using a freely available web-resource (http://way2drug.com/GUSAR/acutoxpredict.html). It has shown that the selected compounds belong to the class of moderate toxic pharmaceutical agents, according to the scale of Hodge and Sterner. Comparison with the predicted data has demonstrated a reasonable correspondence between the experimental and predicted values of hypoglycemic activity and toxicity. Bis{tert-butyl[amino(imino)methyl]carbamato}oxovanadium (IV) and sodium(2,2′-Bipyridyl)oxo-diperoxovanadate(V) octahydrate were identified as the most potent hypoglycemic agents among the synthesized compounds. PMID:25057899

Antidiabetic effect of the α-lipoic acid γ-cyclodextrin complex.

PubMed

Naito, Yuki; Ikuta, Naoko; Nakata, Daisuke; Terao, Keiji; Matsumoto, Kinuyo; Kajiwara, Naemi; Okano, Ayaka; Yasui, Hiroyuki; Yoshikawa, Yutaka

2014-09-01

In recent years, the number of patients suffering from diabetes mellitus has been increasing worldwide. In particular, type 2 diabetes mellitus, a lifestyle-related disease, is recognized as a serious disease with various complications. Many types of pharmaceutics or specific health foods have been used for the management of diabetes mellitus. At the same time, the relationship between diabetes mellitus and α-lipoic acid has been recognized for many years. In this study, we found that the α-lipoic acid γ-cyclodextrin complex exhibited an HbA1c lowering effect for treating type 2 diabetes mellitus in animal models. Moreover, in this study, we investigated the activation of phosphorylation of AMP-activated protein kinase, which plays a role in cellular energy homeostasis, in the liver of KKA(y) mice by using α-lipoic acid and the α-lipoic acid γ-cyclodextrin complex. Our results show that the α-lipoic acid γ-cyclodextrin complex strongly induced the phosphorylation of AMP-activated protein kinase. Thus, we concluded that intake of the α-lipoic acid γ-cyclodextrin complex exerted an antidiabetic effect by suppressing the elevation of postprandial hyperglycemia as well as doing exercise.

Potential medicinal benefits of Cosmos caudatus (Ulam Raja): A scoping review

PubMed Central

Cheng, Shi-Hui; Barakatun-Nisak, Mohd Yusof; Anthony, Joseph; Ismail, Amin

2015-01-01

Cosmos caudatus is widely used as a traditional medicine in Southeast Asia. C. caudatus has been reported as a rich source of bioactive compounds such as ascorbic acid, quercetin, and chlorogenic acid. Studies have shown that C. caudatus exhibits high anti-oxidant capacity and various medicinal properties, including anti-diabetic activity, anti-hypertensive properties, anti-inflammatory responses, bone-protective effect, and anti-microbial activity. This review aims to present the potential medicinal benefits of C. caudatus from the available scientific literature. We searched PubMed and ScienceDirect database for articles published from 1995 to January 2015. Overall, 15 articles related to C. caudatus and its medicinal benefits are reviewed. All these studies demonstrated that C. caudatus is effective, having demonstrated its anti-diabetic, anti-hypertensive, anti-inflammatory, bone-protective, anti-microbial, and anti-fungal activity in both in vitro and animal studies. None of the studies showed any negative effect of C. caudatus related to medicinal use. Currently available evidence suggests that C. caudatus has beneficial effects such as reducing blood glucose, reducing blood pressure, promoting healthy bone formation, and demonstrating anti-inflammatory and anti-microbial properties. However, human clinical trial is warranted. PMID:26929767

Potential medicinal benefits of Cosmos caudatus (Ulam Raja): A scoping review.

PubMed

Cheng, Shi-Hui; Barakatun-Nisak, Mohd Yusof; Anthony, Joseph; Ismail, Amin

2015-10-01

Cosmos caudatus is widely used as a traditional medicine in Southeast Asia. C. caudatus has been reported as a rich source of bioactive compounds such as ascorbic acid, quercetin, and chlorogenic acid. Studies have shown that C. caudatus exhibits high anti-oxidant capacity and various medicinal properties, including anti-diabetic activity, anti-hypertensive properties, anti-inflammatory responses, bone-protective effect, and anti-microbial activity. This review aims to present the potential medicinal benefits of C. caudatus from the available scientific literature. We searched PubMed and ScienceDirect database for articles published from 1995 to January 2015. Overall, 15 articles related to C. caudatus and its medicinal benefits are reviewed. All these studies demonstrated that C. caudatus is effective, having demonstrated its anti-diabetic, anti-hypertensive, anti-inflammatory, bone-protective, anti-microbial, and anti-fungal activity in both in vitro and animal studies. None of the studies showed any negative effect of C. caudatus related to medicinal use. Currently available evidence suggests that C. caudatus has beneficial effects such as reducing blood glucose, reducing blood pressure, promoting healthy bone formation, and demonstrating anti-inflammatory and anti-microbial properties. However, human clinical trial is warranted.

Acute and subacute antidiabetic studies of ENP-9, a new 1,5-diarylpyrazole derivative.

PubMed

Hernández-Vázquez, Eduardo; Young-Peralta, Sandra; Cerón-Romero, Litzia; García-Jiménez, Sara; Estrada-Soto, Samuel

2018-05-17

To explore the antihyperglycaemic and antidiabetic effects and to determine the acute toxicity of 5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (ENP-9). The antihyperglycaemic effect of ENP-9 (50 mg/kg) was determined by oral glucose tolerance test (OGTT). Also, the acute (16, 50 and 160 mg/kg) and subacute (50 mg/kg/day for 10 days) antidiabetic effects of ENP-9 were determined. After subacute treatment, blood samples were analysed to determine glucose and lipid profiles. Also, an acute toxicity determination of ENP-9 was conducted followed the OECD recommendation. Molecular docking was performed using AutoDock 4.2.6 at human cannabinoid receptor 1 (PDB code 5TGZ). Acute Administration of ENP-9 showed significant antidiabetic effect and decreased the maximum OGTT peak, compared to the control group (P < 0.05). Moreover, the 10 days treatment induced a decrease in plasma glucose levels, being significant at the end of the experiments (P < 0.05); however, triacylglycerols and cholesterol were not modified. Finally, LD 50 of ENP-9 was estimated to be greater than 2000 mg/kg. Molecular docking suggests that ENP-9 may act as rimonabant does. ENP-9 showed significant antihyperglycaemic and antidiabetic properties and also was demonstrated to be safety in the studied doses, which might allow future studies for its potential development as antidiabetic agent. © 2018 Royal Pharmaceutical Society.

Honey - A Novel Antidiabetic Agent

PubMed Central

Erejuwa, Omotayo O.; Sulaiman, Siti A.; Wahab, Mohd S. Ab

2012-01-01

Diabetes mellitus remains a burden worldwide in spite of the availability of numerous antidiabetic drugs. Honey is a natural substance produced by bees from nectar. Several evidence-based health benefits have been ascribed to honey in the recent years. In this review article, we highlight findings which demonstrate the beneficial or potential effects of honey in the gastrointestinal tract (GIT), on the gut microbiota, in the liver, in the pancreas and how these effects could improve glycemic control and metabolic derangements. In healthy subjects or patients with impaired glucose tolerance or diabetes mellitus, various studies revealed that honey reduced blood glucose or was more tolerable than most common sugars or sweeteners. Pre-clinical studies provided more convincing evidence in support of honey as a potential antidiabetic agent than clinical studies did. The not-too-impressive clinical data could mainly be attributed to poor study designs or due to the fact that the clinical studies were preliminary. Based on the key constituents of honey, the possible mechanisms of action of antidiabetic effect of honey are proposed. The paper also highlights the potential impacts and future perspectives on the use of honey as an antidiabetic agent. It makes recommendations for further clinical studies on the potential antidiabetic effect of honey. This review provides insight on the potential use of honey, especially as a complementary agent, in the management of diabetes mellitus. Hence, it is very important to have well-designed, randomized controlled clinical trials that investigate the reproducibility (or otherwise) of these experimental data in diabetic human subjects. PMID:22811614

Insulin sensitizing and alpha-glucoamylase inhibitory action of sennosides, rheins and rhaponticin in Rhei Rhizoma.

PubMed

Choi, Soo Bong; Ko, Byoung Seob; Park, Seong Kyu; Jang, Jin Sun; Park, Sunmin

2006-01-25

Extracts from Rhei Rhizoma extracts (RR) have been reported to attenuate metabolic disorders such as diabetic nephropathy, hypercholesterolemia and platelet aggregation. With this study we investigated the anti-diabetic action of 70% ethanol RR extract in streptozotocin-induced diabetic mice, and determined the action mechanism of active compounds of RR in vitro. In the diabetic mice, serum glucose levels at fasting and post-prandial states and glucose area under the curve at modified oral glucose tolerance tests were lowered without altering serum insulin levels, indicating that RR contained potential anti-diabetic agents. The fractions fractionated from RR extracts by XAD-4 column revealed that 60%, 80% and 100% methanol fractions enhanced insulin sensitivity and inhibited alpha-glucoamylase activity. The major compounds of these fractions were sennosides, rhein and rhaponticin. Rhaponticin and rhein enhanced insulin-stimulated glucose uptake in 3T3-L1 adipocytes. Rhaponticin increased adipocytes with a differentiating effect similar to pioglitazone, but rhein and sennoside B decreased triglyceride accumulation. Sennoside A and B inhibited alpha-glucoamylase activity as much as acarbose. In conclusion, a crude extract of RR improves glucose intolerance by enhancing insulin-stimulated glucose uptake and decreasing carbohydrate digestion via inhibiting alpha-glucoamylase activity. Rhein and rhaponticin are potential candidates for hypoglycemic agents.

Anti-cancer, anti-diabetic and other pharmacologic and biological activities of penta-galloyl-glucose

PubMed Central

Zhang, Jinhui; Li, Li; Kim, Sung-Hoon; Hagerman, Ann E.; Lü, Junxuan

2010-01-01

1, 2, 3, 4, 6-penta-O-galloyl-β-D-glucose (PGG) is a polyphenolic compound highly enriched in a number of medicinal herbals. Several in vitro and a handful of in vivo studies have shown that PGG exhibits multiple biological activities which implicate a great potential for PGG in the therapy and prevention of several major diseases including cancer and diabetes. Chemically and functionally, PGG appears to be distinct from its constituent gallic acid or tea polyphenols. For anti-cancer activity, three published in vivo preclinical cancer model studies with PGG support promising efficacy to selectively inhibit malignancy without host toxicity. Potential mechanisms include anti-angiogenesis, anti-proliferative actions through inhibition of DNA replicative synthesis and S-phase arrest and also G1 arrest, induction of apoptosis, anti-inflammation and anti-oxidation. Putative molecular targets include p53, Stat3, Cox-2, VEGFR1, AP-1, SP-1, Nrf-2 and MMP-9. For anti-diabetic activity, PGG and analogues appear to improve glucose uptake. However, very little is known about the absorption, pharmacokinetics and metabolism of PGG, nor its toxicity profile. The lack of large quantity of highly pure PGG has been a bottleneck limiting in vivo validation of cancer preventive and therapeutic efficacies in clinically relevant models. PMID:19575286

Structure-Activity Relationships Based on 3D-QSAR CoMFA/CoMSIA and Design of Aryloxypropanol-Amine Agonists with Selectivity for the Human β3-Adrenergic Receptor and Anti-Obesity and Anti-Diabetic Profiles.

PubMed

Lorca, Marcos; Morales-Verdejo, Cesar; Vásquez-Velásquez, David; Andrades-Lagos, Juan; Campanini-Salinas, Javier; Soto-Delgado, Jorge; Recabarren-Gajardo, Gonzalo; Mella, Jaime

2018-05-16

The wide tissue distribution of the adrenergic β3 receptor makes it a potential target for the treatment of multiple pathologies such as diabetes, obesity, depression, overactive bladder (OAB), and cancer. Currently, there is only one drug on the market, mirabegron, approved for the treatment of OAB. In the present study, we have carried out an extensive structure-activity relationship analysis of a series of 41 aryloxypropanolamine compounds based on three-dimensional quantitative structure-activity relationship (3D-QSAR) techniques. This is the first combined comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) study in a series of selective aryloxypropanolamines displaying anti-diabetes and anti-obesity pharmacological profiles. The best CoMFA and CoMSIA models presented values of r ² ncv = 0.993 and 0.984 and values of r ² test = 0.865 and 0.918, respectively. The results obtained were subjected to extensive external validation ( q ², r ², r ² m , etc.) and a final series of compounds was designed and their biological activity was predicted (best pEC 50 = 8.561).

Anti-diabetic properties and phytochemistry of Momordica charantia L. (Cucurbitaceae).

PubMed

Raman, A; Lau, C

1996-03-01

Unripe fruit, seeds and aerial parts of Momordica charantia Linn. (Cucurbitaceae) have been used in various parts of the world to treat diabetes. Oral administration of the fruit juice or seed powder causes a reduction in fasting blood glucose and improves glucose tolerance in normal and diabetic animals and in humans. Animal and in vitro data support both insulin secretagogue and insulinomimetic activity of the fruit. However, enhanced insulin levels in vivo in response to its administration have not been observed. Although a wide range of compounds have been isolated from Momordica charantia, notably steroidal compounds and proteins, the orally active antidiabetic principle has not been adequately identified. A polypeptide, p-insulin, produces hypoglycaemic effects in humans and animals on subcutaneous injection, but oral activity is questionable. Other reported hypoglycaemic principles from Momordica charantia include the sterol glucoside mixture charantin (fruit) and the pyrimidine nucleoside vicine (seeds). However these are only effective at doses too high to account for all the activity of the plant extract. Principal toxicity of Momordica charantia in animals is to the liver and reproductive system. These effects have not been reported in humans despite widespread use of the fruit medicinally and as a vegetable. Copyright © 1996 Gustav Fischer Verlag · Struttgart · Jena · New York. Published by Elsevier GmbH.. All rights reserved.

Chemical Constituents Analysis and Antidiabetic Activity Validation of Four Fern Species from Taiwan

PubMed Central

Chen, Chen-Yu; Chiu, Fu-Yu; Lin, Yenshou; Huang, Wei-Jan; Hsieh, Po-Shiuan; Hsu, Feng-Lin

2015-01-01

Pterosins are abundant in ferns, and pterosin A was considered a novel activator of adenosine monophosphate-activated protein kinase, which is crucial for regulating blood glucose homeostasis. However, the distribution of pterosins in different species of ferns from various places in Taiwan is currently unclear. To address this question, the distribution of pterosins, glucose-uptake efficiency, and protective effects of pterosin A on β-cells were examined. Our results showed that three novel compounds, 13-chloro-spelosin 3-O-β-d-glucopyranoside (1), (3R)-Pterosin D 3-O-β-d-(3'-p-coumaroyl)-glucopyranoside (2), and (2R,3R)-Pterosin L 3-O-β-d-(3'-p-coumaroyl)-glucopyranoside (3), were isolated for the first time from four fern species (Ceratopteris thalictroides, Hypolepis punctata, Nephrolepis multiflora, and Pteridium revolutum) along with 27 known compounds. We also examined the distribution of these pterosin compounds in the mentioned fern species (except N. multiflora). Although all pterosin analogs exhibited the same effects in glucose uptake assays, pterosin A prevented cell death and reduced reactive oxygen species (ROS) production. This paper is the first report to provide new insights into the distribution of pterosins in ferns from Taiwan. The potential anti-diabetic activity of these novel phytocompounds warrants further functional studies. PMID:25622260

Synthesis of Thymoquinone derivatives and its activity analysis: In-silico approach

NASA Astrophysics Data System (ADS)

Ulfa, Siti Mariyah; Sholikhah, Shoimatus; Utomo, Edi Priyo

2017-03-01

Thymoquinone derivatives which synthesized in this research is bromoalkylquinones with alkyl chain consist of seven carbons (C7) and ten carbons (C10). The synthesis was carried out by oxidation of 2,3-dimethylhydroquinone followed by alkylation using reflux for 1.5 hours. The alkylation products were successfully characterized as 5-(7-bromoheptyl)-2,3-dimethyl-1,4-benzoquinone (C7) and 5-(10-bromodecyl)-2,3-dimethyl-1,4-benzoquinone (C10) in 31.93 and 16.89%, respectively. These compounds were fully characterized using FT-IR, 1H-NMR and 13C-NMR. Thus, the activity of C7 and C10 was analyzed by in silico approach with molecular docking using macromolecule model extracted from Protein Data Bank (PDB). Macromolecules used in this research is mitochondrial translocator protein (TSPO) as an antioxidant receptor, glycogen phosphorylase (GPA) as antidiabetic receptor and phosphatase tensin homolog (PTEN) as an anticancer agent. The result showed that C7 and C10 has a very good activity as antioxidant and antidiabetic agents with IC50 2.03 and 1.02 ppm (TSPO) and 16.98 and 14.88 ppm (GPA) compared with Thymoquinone. While the activity of C7 and C10 against PTEN gave the IC50 23.13 and 18.31 ppm showed a good candidate for an anticancer agent.

Antidiabetic activity of Ganoderma lucidum polysaccharides F31 down-regulated hepatic glucose regulatory enzymes in diabetic mice.

PubMed

Xiao, Chun; Wu, Qingping; Zhang, Jumei; Xie, Yizhen; Cai, Wen; Tan, Jianbin

2017-01-20

Ganoderma lucidum (Lin Zhi) has been used to treat diabetes in Chinese folk for centuries. Our laboratory previously demonstrated that Ganoderma lucidum polysaccharides (GLPs) had hypoglycemic effects in diabetic mice. Our aim was to identify the main bioactives in GLPs and corresponding mechanism of action. Four polysaccharide-enriched fraction were isolated from GLPs and the antidiabetic activities were evaluated by type 2 diabetic mice. Fasting serum glucose (FSG), fasting serum insulin (FSI) and epididymal fat/BW ratio were measured at the end of the experiment. In liver, the mRNA levels of hepatic glucose regulatory enzymes were determined by quantitative polymerase chain reaction (qPCR) and the protein levels of phospho-AMP-activated protein kinase (p-AMPK)/AMPK were determined by western blotting test. In epididymal fat tissue, the mRNA and protein levels GLUT4, resistin, fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC1) were determined by qPCR and immuno-histochemistry. The structure of polysaccharide F31 was obtained from GPC, FTIR NMR and GC-MS spectroscopy, RESULTS: F31 significantly decreased FSG (P<0.05), FSI and epididymal fat/BW ratio (P<0.01). In liver, F31 decreased the mRNA levels of hepatic glucose regulatory enzymes, and up-regulated the ratio of phospho-AMP-activated protein kinase (p-AMPK)/AMPK. In epididymal fat tissue, F31 increased the mRNA levels of GLUT4 but decreased fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC1) and resistin. Immuno-histochemistry results revealed F31 increased the protein levels of GLUT4 and decreased resistin. Data suggested that the main bioactives in GLPs was F31, which was determined to be a β-heteropolysaccharide with the weight-average molecular weight of 15.9kDa. The possible action mechanism of F31 may be associated with down-regulation of the hepatic glucose regulated enzyme mRNA levels via AMPK activation, improvement of insulin resistance and decrease of epididymal fat/BW ratio. These results strongly suggest that F31 has antidiabetic potential. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Novel Approach to Identify Potential Bioactive Plant Metabolites: Pharmacological and Metabolomics Analyses of Ethanol and Hot Water Extracts of Several Canadian Medicinal Plants of the Cree of Eeyou Istchee.

PubMed

Shang, Nan; Saleem, Ammar; Musallam, Lina; Walshe-Roussel, Brendan; Badawi, Alaa; Cuerrier, Alain; Arnason, John T; Haddad, Pierre S

2015-01-01

We evaluated and compared the antidiabetic potential and molecular mechanisms of 17 Cree plants' ethanol extracts (EE) and hot water extracts (HWE) on glucose homeostasis in vitro and used metabolomics to seek links with the content of specific phytochemicals. Several EE of medical plants stimulated muscle glucose uptake and inhibited hepatic G6Pase activity. Some HWE partially or completely lost these antidiabetic activities in comparison to EE. Only R. groenlandicum retained similar potential between EE and HWE in both assays. In C2C12 muscle cells, EE of R. groenlandicum, A. incana and S. purpurea stimulated glucose uptake by activating AMP-activated protein kinase (AMPK) pathway and increasing glucose transporter type 4 (GLUT4) expression. In comparison to EE, HWE of R. groenlandicum exhibited similar activities; HWE of A. incana completely lost its effect on all parameters; interestingly, HWE of S. purpurea activated insulin pathway instead of AMPK pathway to increase glucose uptake. In the liver, for a subset of 5 plants, HWE and EE activated AMPK pathway whereas the EE and HWE of S. purpurea and K. angustifolia also activated insulin pathways. Quercetin-3-O-galactoside and quercetin 3-O-α-L-arabinopyranoside, were successfully identified by discriminant analysis as biomarkers of HWE plant extracts that stimulate glucose uptake in vitro. More importantly, the latter compound was not identified by previous bioassay-guided fractionation.

Antidiabetic effects of Morus alba fruit polysaccharides on high-fat diet- and streptozotocin-induced type 2 diabetes in rats.

PubMed

Jiao, Yukun; Wang, Xueqian; Jiang, Xiang; Kong, Fansheng; Wang, Shumei; Yan, Chunyan

2017-03-06

Type 2 diabetes mellitus (T2DM) is becoming a serious threat to human health. The fruit of Morus alba L. is widely used as a traditional Chinese medicine for the treatment of DM, dizziness, tinnitus, insomnia, and premature graying, as well as to protect the liver and kidneys. Several studies have demonstrated that the aqueous extracts of the roots bark, leaves, and ramuli of mulberry, which are known to contain polyphenols and polysaccharides, have antihyperglycemic and antihyperlipidemic activities. The aim of the present study was to further investigate the active polysaccharides from M. alba fruit by evaluating the antidiabetic activities of different fractions on T2DM rats and elucidate the mechanism underlying these activities. Diabetic rats were treated with two fractions of M. alba fruit polysaccharides (MFP50 and MFP90). The disease models were induced by a high-fat diet and low dose injection of streptozotocin and were compared to normal rats and metformin-treated diabetic rats. After seven weeks, the fasting blood glucose (FBG), oral glucose tolerance test (OGTT), fasting serum insulin (FINS) levels, homeostasis model of assessment-insulin resistance (HOMA-IR), glycated serum protein (GSP), and serum alanine transaminase (ALT) levels, as well as serum lipid profiles and histopathological changes in the pancreas were measured. Next, the expressions of the insulin signaling pathway were measured by western blot analysis to elucidate the potential mechanism underlying these antidiabetic activities. After seven weeks of treatment, a significant reduction in the FBG levels, OGTT-area under the curve (OGTT-AUC), FINS, HOMA-IR, ALT, and triglyceride (TG) values of the MFP50 group was observed. On the other hand, in the MFP90 group, the FBG, OGTT-AUC, FINS, HOMA-IR, GSP, and TG levels were significantly reduced. The level of high-density lipoprotein cholesterol (HDL-c) and the proportion of HDL-c to total cholesterol (TC) significantly increased in the MFP50 group. Moreover, MFP50 and MFP90 induced repair of damaged pancreatic tissues of the diabetic rats. The hypoglycemic effect of MFP50 was more stable than MFP90, whereas the hypolipidemic effect of MFP90 was slightly better than MFP50. Moreover, the expression levels of InsR, IRS-2, Akt and GLUT4 in the MFP90 group significantly increased relative to that of the T2DM group. MFP50 and MFP90 have markedly antihyperglycemic and antihyperlipidemic effects and can clearly relieve diabetes symptoms in the T2DM rat model. The M. alba fruit polysaccharides may potentially be utilized as an effective treatment for T2DM. Further research into the structures of active M. alba fruit polysaccharides and their mechanisms in promoting antidiabetic effects are underway. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Opuntia ficus-indica seed attenuates hepatic steatosis and promotes M2 macrophage polarization in high-fat diet-fed mice.

PubMed

Kang, Jung-Woo; Shin, Jun-Kyu; Koh, Eun-Ji; Ryu, Hyojeong; Kim, Hyoung Ja; Lee, Sun-Mee

2016-04-01

Opuntia ficus-indica (L.) is a popular edible plant that possesses considerable nutritional value and exhibits diverse biological actions including anti-inflammatory and antidiabetic activities. In this study, we hypothesized that DWJ504, an extract of O ficus-indica seed, would ameliorate hepatic steatosis and inflammation by regulating hepatic de novo lipogenesis and macrophage polarization against experimental nonalcoholic steatohepatitis. Mice were fed a normal diet or a high-fat diet (HFD) for 10 weeks. DWJ504 (250, 500, and 1000 mg/kg) or vehicle (0.5% carboxymethyl cellulose) were orally administered for the last 4 weeks of the 10-week HFD feeding period. DWJ504 treatment remarkably attenuated HFD-induced increases in hepatic lipid content and hepatocellular damage. DWJ504 attenuated increases in sterol regulatory element-binding protein 1 and carbohydrate-responsive element-binding protein expression and a decrease in carnitine palmitoyltransferase 1A. Although DWJ504 augmented peroxisome proliferator-activated receptor α protein expression, it attenuated peroxisome proliferator-activated receptor γ expression. Moreover, DWJ504 promoted hepatic M2 macrophage polarization as indicated by attenuation of the M1 marker genes and enhancement of M2 marker genes. Finally, DWJ504 attenuated expression of toll-like receptor 4, nuclear factor κB, tumor necrosis factor α, interleukin 6, TIR-domain-containing adapter-inducing interferon β, and interferon β levels. Our results demonstrate that DWJ504 prevented intrahepatic lipid accumulation, induced M2 macrophage polarization, and suppressed the toll-like receptor 4-mediated inflammatory signaling pathway. Thus, DWJ504 has therapeutic potential in the prevention of nonalcoholic fatty liver disease. Copyright © 2016 Elsevier Inc. All rights reserved.

The soy-derived peptide Vglycin inhibits the growth of colon cancer cells in vitro and in vivo.

PubMed

Gao, Chang; Sun, Rui; Xie, Ya-Rong; Jiang, An-Li; Lin, Mei; Li, Min; Chen, Zheng-Wang; Zhang, Ping; Jin, Honglin; Feng, Jue-Ping

2017-05-01

Vglycin, a novel natural polypeptide isolated from pea seeds, possesses antidiabetic properties. Our previous studies have shown that Vglycin can induce the differentiation of human colon adenocarcinoma cells. We aimed to determine the anticancer activity of Vglycin against colon cancer cells and to elucidate related apoptosis-inducing mechanisms. Treatment with purified Vglycin significantly reduced growth, viability, and colony formation of CT-26, SW480, and NCL-H716 colon cancer cells in a dose-dependent manner while down-regulating the expression of proliferating cell nuclear antigen. Mouse xenograft studies showed a 38% inhibition of colon cancer growth in mice treated with Vglycin (20 mg/kg/day) at day 21. Furthermore, the potential mechanisms involved in Vglycin-induced cell apoptosis were examined using cell cycle studies, ultrastructural examination, as well as apoptosis-associated pathway analysis. The results showed that Vglycin significantly promoted apoptosis and G1/S phase cell cycle arrest. As revealed by Western blot, the expression of CDK2 and Cyclin D1 was down-regulated in all three Vglycin-treated colon cancer cells, indicating that the CDK2/Cyclin D1 cell cycle pathway involved in the initiation and progression of colon cancer. Moreover, the inhibition of Vglycin-induced cell proliferation in colon cancer cells was accompanied by alteration of the expression levels of the apoptosis-related proteins Bax, Bcl-2 and Mcl-1, and an increase of caspase-3 activity. Together, our results suggest that Vglycin may be another plant-derived peptide that suppresses colon cancer, supporting the continued investigation of Vglycin as therapeutic agent for colon cancer. Impact statement The antidiabetic properties and the capability of inducing differentiation of human colon adenocarcinoma cells of Vglycin have been reported in our previous studies. However, the anticancer potential of Vglycin on colon cancer cells and its possible related mechanisms were still unknown. In this study, we found that Vglycin could reduce growth, viability, and colony formation or colony size of CT-26, SW480, and NCL-H716 colon cancer cells. Moreover, Vglycin decreased tumor volume by 38% in xenograft mice transplanted with CT-26 cells. The mechanisms of these phenomena may be due to the down-regulated CDK2 and Cyclin D1, G1/S phase cell cycle arrest, and the dysregulated expression of Bax, Bcl-2, and Mcl-1. The findings highlight the anticancer potential of Vglycin against colon cancer cells, and suggest Vglycin may be another colon cancer potential suppressive component of plant-derived peptides.

Synthesis and biological evaluation of novel gigantol derivatives as potential agents in prevention of diabetic cataract

USDA-ARS?s Scientific Manuscript database

As a continuation of our efforts directed towards the development of natural anti-diabetic cataract agents, gigantol was isolated from Herba dendrobii and was found to inhibit both aldose reductase (AR) and inducible nitric oxide synthase (iNOS) activity, which play a significant role in the develop...

Protein tyrosine phosphatase 1B (PTP1B) inhibitors from Morinda citrifolia (Noni) and their insulin mimetic activity.

PubMed

Nguyen, Phi-Hung; Yang, Jun-Li; Uddin, Mohammad N; Park, So-Lim; Lim, Seong-Il; Jung, Da-Woon; Williams, Darren R; Oh, Won-Keun

2013-11-22

As part of our ongoing search for new antidiabetic agents from medicinal plants, we found that a methanol extract of Morinda citrifolia showed potential stimulatory effects on glucose uptake in 3T3-L1 adipocyte cells. Bioassay-guided fractionation of this active extract yielded two new lignans (1 and 2) and three new neolignans (9, 10, and 14), as well as 10 known compounds (3-8, 11-13, and 15). The absolute configurations of compounds 9, 10, and 14 were determined by ECD spectra analysis. Compounds 3, 6, 7, and 15 showed inhibitory effects on PTP1B enzyme with IC50 values of 21.86 ± 0.48, 15.01 ± 0.20, 16.82 ± 0.42, and 4.12 ± 0.09 μM, respectively. Furthermore, compounds 3, 6, 7, and 15 showed strong stimulatory effects on 2-NBDG uptake in 3T3-L1 adipocyte cells. This study indicated the potential of compounds 3, 6, 7, and 15 as lead molecules for antidiabetic agents.

Prevention of arthritis markers in experimental animal and inflammation signalling in macrophage by Karanjin isolated from Pongamia pinnata seed extract.

PubMed

Bose, Madhura; Chakraborty, Mousumi; Bhattacharya, Sourav; Mukherjee, Debarati; Mandal, Suvra; Mishra, Roshnara

2014-08-01

Karanjin, the furanoflavonoid reported to possess gastroprotective and anti-diabetic properties, was investigated against experimental arthritis and its molecular signalling in inflammation was explored in macrophages. Karanjin was isolated from hexane extract of Pongamia pinnata seeds and was evaluated on arthritis markers in adjuvant induced arthritis model (AIA) in two doses (per oral; 10 mg/kg/day and 20 mg/kg/day). Karanjin dose dependently reduced collagen and cartilage breakdown markers viz. urinary hydroxyproline and glucosamine, respectively, serum lysosomal enzymes responsible for articular cartilage damage, and major proinflammatory cytokine TNFα, secreted by macrophages involved in articular inflammation and destruction. Karanjin also prevented joint damage as evidenced from arthritis score, radiographic and histopathological analysis. To delineate the molecular target of Karanjin, in vitro study on LPS induced macrophages were performed at calibrated non toxic doses (4 µg/mL and 6 µg/mL). Karanjin reduced TNFα production and also showed potent inhibitory effect on nitric oxide and reactive oxygen species production which is generally induced by TNFα from activated macrophages. NF-κB, the key regulator of TNFα signalling during inflammation was significantly suppressed by Karanjin. Our study for the first time highlights the anti-inflammatory role of Karanjin in experimental arthritis model as well as on macrophage signalling, thereby depicting its probable mechanism of action. Copyright © 2014 John Wiley & Sons, Ltd.

Hydro-ethanolic extract of cashew tree (Anacardium occidentale) nut and its principal compound, anacardic acid, stimulate glucose uptake in C2C12 muscle cells.

PubMed

Tedong, Leonard; Madiraju, Padma; Martineau, Louis C; Vallerand, Diane; Arnason, John T; Desire, Dzeufiet D P; Lavoie, Louis; Kamtchouing, Pierre; Haddad, Pierre S

2010-12-01

Products of cashew tree (Anacardium occidentale) are used in traditional medicine for various ailments, including diabetes. The anti-diabetic properties of cashew plant parts were studied using differentiated C2C12 myoblasts (myotubes) and rat liver mitochondria. Hydroethanolic extract of cashew seed (CSE) and its active component, anacardic acid (AA), stimulated glucose transport into C2C12 myotubes in a concentration-dependent manner. Extracts of other parts (leaves, bark and apple) of cashew plant were inactive. Significant synergistic effect on glucose uptake with insulin was noticed at 100 μg/mL CSE. CSE and AA caused activation of adenosine monophosphate-activated protein kinase in C2C12 myotubes after 6 h of incubation. No significant effect was noticed on Akt and insulin receptor phosphorylation. Both CSE and AA exerted significant uncoupling of succinate-stimulated respiration in rat liver mitochondria. Activation of adenosine monophosphate-activated protein kinase by CSE and AA likely increases plasma membrane glucose transporters, resulting in elevated glucose uptake. In addition, the dysfunction of mitochondrial oxidative phosphorylation may enhance glycolysis and contribute to increased glucose uptake. These results collectively suggest that CSE may be a potential anti-diabetic nutraceutical. Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Diversity, bioactivities, and metabolic potentials of endophytic actinomycetes isolated from traditional medicinal plants in Sichuan, China.

PubMed

Qiu, Peng; Feng, Zhi-Xiang; Tian, Jie-Wei; Lei, Zu-Chao; Wang, Lei; Zeng, Zhi-Gang; Chu, Yi-Wen; Tian, Yong-Qiang

2015-12-01

The present study was designed to determine the taxonomic diversity and metabolic activity of the actinomycetes community, including 13 traditional medicinal plants collected in Sichuan province, China, using multiple approaches such as morphological and molecular identification methods, bioactivity assays, and PCR screening for genes involved in antibiotics biosynthesis. 119 endophytic actinomycetes were recovered; 80 representative strains were chosen for 16S rRNA gene partial sequence analyses, with 66 of them being affiliated to genus Streptomyces and the remaining 14 strains being rare actinomycetes. Antimicrobial tests showed that 12 (15%) of the 80 endophytic actinomycetes displayed inhibitory effects against at least one indicator pathogens, which were all assigned to the genus Streptomyces. In addition, 87.5% and 58.8% of the isolates showed anticancer and anti-diabetic activities, respectively. Meanwhile, the anticancer activities of the isolates negatively correlated with their anti-diabetic activities. Based on the results of PCR screening, five genes, PKS-I, PKS-II, NRPS, ANSA, and oxyB, were detected in 55.0%, 58.8%, 90.0%, 18.8% and 8.8% of the 80 actinomycetes, respectively. In conclusion, the PCR screening method employed in the present study was conducive for screening and selection of potential actinomycetes and predicting potential secondary metabolites, which could overcome the limitations of traditional activity screening models. Copyright © 2015 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Moringa olifeira Lam. Stimulates Activation of the Insulin-Dependent Akt Pathway. Antidiabetic Effect in a Diet-Induced Obesity (DIO) Mouse Model.

PubMed

Attakpa, E S; Sangaré, M M; Béhanzin, G J; Ategbo, J-M; Seri, B; Khan, N A

2017-01-01

We investigated the antidiabetic effect of Moringa olifeira Lam. in a diet-induced obesity (DIO) mouse model. Six mice were randomly selected as normal controls. Moringa olifeira Lam. leaf extract at a dose of 200, 400 or 600 mg/kg body weight, glibenclamide (Glib) at the dose of 10 mg/kg (positive control) and distilled water at 10 ml/kg (control group) were administered orally by gastric intubation, and each group consisted of six mice. Insulinsensitive tissues (liver, skeletal muscle) were collected to investigate antidiabetic effects and examine the plant's molecular mechanisms. Moringa olifeira Lam. leaf extract prevented weight gain. It also reduced blood glucose in DIO mice. Glib and Moringa olifeira Lam. leaf extract, 400 mg/kg, treatments restored insulin levels towards normal values (P < 0.05 versus diabetic control group). Western immunoblot analysis of different tissues, collected at the end of the study, demonstrated that Moringa olifeira Lam. stimulated activation of the insulin-dependent Akt pathway and increased the protein content of Glut 4 in skeletal muscle. The improvement of hepatic steatosis observed in DIO-treated mice was associated with a decrease in the hepatic content of SREBP-1, a transcription factor involved in de novo lipogenesis. The hepatic PPARα protein content in the plant extract- treated mice remained significantly higher than those of the control group (P < 0.05). In conclusion, this study provides the first evidence for direct action of Moringa olifeira Lam. on pancreatic β-cells, enhancing glucose-stimulated insulin secretion. This correlated with hypoglycaemic effects in diabetic mice associated with restored levels of plasma insulin.

Anti-diabetic activity of chromium picolinate and biotin in rats with type 2 diabetes induced by high-fat diet and streptozotocin.

PubMed

Sahin, Kazim; Tuzcu, Mehmet; Orhan, Cemal; Sahin, Nurhan; Kucuk, Osman; Ozercan, Ibrahim H; Juturu, Vijaya; Komorowski, James R

2013-07-28

The objective of the present study was to evaluate anti-diabetic effects of chromium picolinate (CrPic) and biotin supplementations in type 2 diabetic rats. The type 2 diabetic rat model was induced by high-fat diet (HFD) and low-dose streptozotocin. The rats were divided into five groups as follows: (1) non-diabetic rats fed a regular diet; (2) diabetic rats fed a HFD; (3) diabetic rats fed a HFD and supplemented with CrPic (80 μg/kg body weight (BW) per d); (4) diabetic rats fed a HFD and supplemented with biotin (300 μg/kg BW per d); (5) diabetic rats fed a HFD and supplemented with both CrPic and biotin. Circulating glucose, cortisol, total cholesterol, TAG, NEFA and malondialdehyde concentrations decreased (P< 0·05), but serum insulin concentrations increased (P< 0·05) in diabetic rats treated with biotin and CrPic, particularly with a combination of the supplements. Feeding a HFD to diabetic rats decreased PPAR-γ expression in adipose tissue and phosphorylated insulin receptor substrate 1 (p-IRS-1) expression of liver, kidney and muscle tissues, while the supplements increased (P< 0·001) PPAR-γ and p-IRS-1 expressions in relevant tissues. Expression of NF-κB in the liver and kidney was greater in diabetic rats fed a HFD, as compared with rats fed a regular diet (P< 0·01). The supplements decreased the expression of NF-κB in diabetic rats (P< 0·05). Results of the present study revealed that supplementing CrPic and biotin alone or in a combination exerts anti-diabetic activities, probably through modulation of PPAR-γ, IRS-1 and NF-κB proteins.

Navel orange peel hydroethanolic extract, naringin and naringenin have anti-diabetic potentials in type 2 diabetic rats.

PubMed

Ahmed, Osama M; Hassan, Mohamed A; Abdel-Twab, Sanaa M; Abdel Azeem, Manal N

2017-10-01

The therapy of Type 2 Diabetes Mellitus (T2DM) stays a challenging issue. During the last decade, there has been an interest in the expansion of anti-diabetic drugs especially those of natural sources. Thus, the aim of this study was to assess the anti-hyperglycemic and the anti-hyperlipidemic effects as well as the anti-oxidant activities of navel orange hydroethanolic extract and its constituting flavonoids naringin and naringenin on nicotineamide (NA)/streptozotocin (STZ)-induced type 2 diabetic rats. To induce T2DM, 16h-fasted rats were intraperitoneally injected with STZ at dose of 50mg/kg body weight (b. w.), 15min after the intraperitoneal administration of NA (120mg/kg b. w.). The NA/STZ-induced type 2 diabetic rats were orally treated with navel orange peel hydroethanolic extract, naringin and narengenin at dose level of 100mg/kg b. w./day for 4 weeks. The treatments with navel orange peel hydroethanolic extract, naringin and narengenin potentially alleviated the lowered serum insulin and C-peptide levels, the depleted liver glycogen content, the elevated liver glucose-6-phosphatase and glycogen phosphorylase activities, the deteriorated serum lipid profile, and the suppressed liver antioxidant defense system of NA/STZ-induced type 2 diabetic rats. The treatments also enhanced the mRNA expression of insulin receptor β-subunit, GLUT4 and adiponectin in adipose tissue of STZ/NA-induced type 2 diabetic rats. In conclusion, the navel orange peel hydroethanolic extract, naringin and naringenin have potent anti-diabetic effects in NA/STZ-induced type 2 diabetic rats via their insulinotropic effects and insulin improving action which in turn may be mediated through enhancing insulin receptor, GLUT4 and adiponectin expression in adipose tissue. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Validation of the Antidiabetic and Hypolipidemic Effects of Hawthorn by Assessment of Gluconeogenesis and Lipogenesis Related Genes and AMP-Activated Protein Kinase Phosphorylation.

PubMed

Shih, Chun-Ching; Lin, Cheng-Hsiu; Lin, Yih-Jiun; Wu, Jin-Bin

2013-01-01

Since with the increased use of antidiabetic and antihyperlipidemic effect of phytonutrients for daily supplement has gained considerable attention worldwide, we examine the effect and molecular mechanism of Crataegus pinnatifida Bge. var. major N.E. Br. (hawthorn) by quantifying the expression of hepatic gluconeogenesis and lipogenesis on diabetes and dyslipidemia in high-fat (HF)-fed C57BL/6J mice. Firstly, mice were divided randomly into two groups: the control (CON) group was fed with a low-fat diet, whereas the experimental group was fed a 45% HF diet for 8 weeks. Afterwards, the CON group was treated with vehicle, whereas the HF group was subdivided into five groups and was given orally hawthorn extract (including 0.2, 0.5, 1.0 g/kg/day extracts) or rosiglitazone (Rosi) or vehicle for 4 weeks afterward. Diabetic mice showed an increase in plasma glucose and insulin. Glucose lowering was comparable with Rosi-treated mice. This study demonstrated that hawthorn was effective in ameliorating the HF diet-induced hyperglycemia, hypertriglyceridemia and hypercholesterolaemia. Hawthorn extract significantly increases the hepatic protein contents of AMP-activated protein kinase (AMPK) phosphorylation and reduces expression of phosphenol pyruvate carboxykinase (PEPCK) and glucose production. Furthermore, hawthorn decreased in hepatic triacylglycerol and cholesterol synthesis (including sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), SREBP2). An increase in expressions of apoA-I gene and high-density lipoprotein cholesterol (HDL-C) was detected in HF-fed mice treated with high dose hawthorn. Our data suggest that hawthorn extract are capable of decreasing glucose production and triacylglycerol synthesis by inducing AMPK-phosphorylation and hawthorn is a candidate source of antidiabetic and antihyperlipidemic phytonutrients factors.

Validation of the Antidiabetic and Hypolipidemic Effects of Hawthorn by Assessment of Gluconeogenesis and Lipogenesis Related Genes and AMP-Activated Protein Kinase Phosphorylation

PubMed Central

Shih, Chun-Ching; Lin, Cheng-Hsiu; Lin, Yih-Jiun; Wu, Jin-Bin

2013-01-01

Since with the increased use of antidiabetic and antihyperlipidemic effect of phytonutrients for daily supplement has gained considerable attention worldwide, we examine the effect and molecular mechanism of Crataegus pinnatifida Bge. var. major N.E. Br. (hawthorn) by quantifying the expression of hepatic gluconeogenesis and lipogenesis on diabetes and dyslipidemia in high-fat (HF)-fed C57BL/6J mice. Firstly, mice were divided randomly into two groups: the control (CON) group was fed with a low-fat diet, whereas the experimental group was fed a 45% HF diet for 8 weeks. Afterwards, the CON group was treated with vehicle, whereas the HF group was subdivided into five groups and was given orally hawthorn extract (including 0.2, 0.5, 1.0 g/kg/day extracts) or rosiglitazone (Rosi) or vehicle for 4 weeks afterward. Diabetic mice showed an increase in plasma glucose and insulin. Glucose lowering was comparable with Rosi-treated mice. This study demonstrated that hawthorn was effective in ameliorating the HF diet-induced hyperglycemia, hypertriglyceridemia and hypercholesterolaemia. Hawthorn extract significantly increases the hepatic protein contents of AMP-activated protein kinase (AMPK) phosphorylation and reduces expression of phosphenol pyruvate carboxykinase (PEPCK) and glucose production. Furthermore, hawthorn decreased in hepatic triacylglycerol and cholesterol synthesis (including sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), SREBP2). An increase in expressions of apoA-I gene and high-density lipoprotein cholesterol (HDL-C) was detected in HF-fed mice treated with high dose hawthorn. Our data suggest that hawthorn extract are capable of decreasing glucose production and triacylglycerol synthesis by inducing AMPK-phosphorylation and hawthorn is a candidate source of antidiabetic and antihyperlipidemic phytonutrients factors. PMID:23690849

GC-MS analysis and screening of antidiabetic, antioxidant and hypolipidemic potential of Cinnamomum tamala oil in streptozotocin induced diabetes mellitus in rats

PubMed Central

2012-01-01

Aim of the study This study was made to investigate the antidiabetic, antioxidant and hypolipidemic potential of Cinnamomum tamala, (Buch.-Ham.) Nees & Eberm (Tejpat) oil (CTO) in streptozotocin (STZ) induced diabetes in rats along with evaluation of chemical constituents. Materials and methods The GC-MS (Gas chromatography–mass spectrometry) analysis of the oil showed 31 constituents of which cinnamaldehyde was found the major component (44.898%). CTO and cinnamaldehyde was orally administered to diabetic rats to study its effect in both acute and chronic antihyperglycemic models. The body weight, oral glucose tolerance test and biochemical parameters viz. glucose level, insulin level, liver glycogen content, glycosylated hemoglobin, total plasma cholesterol, triglyceride and antioxidant parameters were estimated for all treated groups and compared against diabetic control group. Results CTO (100 mg/kg and 200 mg/kg), cinnamaldehyde (20 mg/kg) and glibenclamide (0.6 mg/kg) in respective groups of diabetic animals administered for 28 days reduced the blood glucose level in streptozotocin induced diabetic rats. There was significant increase in body weight, liver glycogen content, plasma insulin level and decrease in the blood glucose, glycosylated hemoglobin and total plasma cholesterol in test groups as compared to control group. The results of CTO and cinnamaldehyde were found comparable with standard drug glibenclamide. In vitro antioxidant studies on CTO using various models showed significant antioxidant activity. In vivo antioxidant studies on STZ induced diabetic rats revealed decreased malondialdehyde (MDA) and increased reduced glutathione (GSH). Conclusion Thus the investigation results that CTO has significant antidiabetic, antioxidant and hypolipidemic activity. PMID:22882757

Formulation and evaluation of antihyperglycemic leaf extracts of Zizyphus spina-christi (L.) Willd.

PubMed

Nesseem, D I; Michel, C G; Sleem, A A; El-Alfy, T S

2009-02-01

This study deals with the formulation of antihyperglycemic leaf extracts of Zizyphus spina-christi (L.) Willd. A bioactivity guided fractionation of different leaf extracts [defatted ethanol 70% (a), butanol (b), ethanol 70% (c), ethyl acetate (d) and petroleum ether (e) extracts] revealed that extract (c) possessed the highest antihyperglycemic activity followed by (b) and (a). HPLC was adopted for standardization of the extract (c) based on evaluation of the major saponin christinin-A which was used as marker. The detection limit was 9.45 mg/ml for Christinin-A. Extracts (a), (b) and (c) were separately formulated in soft (S) and hard (H) gelatin capsules. Two different formulations (F1 and F2) were tried using different excipients suitable for oral drug delivery. Formula 1, used for soft gelatin capsules [(F1) Sa, Sb, Sc] Formula 2, used for hard gelatin capsules [(F2) - Ha, Hb, Hc]. The recovery rates of the samples of saponin were in the range 99.43-101.86% at 200, 800 microg/ml and 1200 microg/ml. Saponin release rates from different formulae were carried out using dissolution tester USP XXIV. The highest release was obtained from formulation Sc. The release of the extracts followed diffusion mechanism. The selected formula Sc exhibited highest anti-diabetic activity (P < 0.01) on acute and long-term administration and highest saponin release. This formula (Sc) contained poly-oxyethylene (20) cetyl ether (BC-20TX), PEG 400, PEG 6000, purified water, meglyol 810, ascorbic acid and 200 mg of extract (c).

Biotransformations of Antidiabetic Vanadium Prodrugs in Mammalian Cells and Cell Culture Media: A XANES Spectroscopic Study

PubMed Central

2016-01-01

The antidiabetic activities of vanadium(V) and -(IV) prodrugs are determined by their ability to release active species upon interactions with components of biological media. The first X-ray absorption spectroscopic study of the reactivity of typical vanadium (V) antidiabetics, vanadate ([VVO4]3–, A) and a vanadium(IV) bis(maltolato) complex (B), with mammalian cell cultures has been performed using HepG2 (human hepatoma), A549 (human lung carcinoma), and 3T3-L1 (mouse adipocytes and preadipocytes) cell lines, as well as the corresponding cell culture media. X-ray absorption near-edge structure data were analyzed using empirical correlations with a library of model vanadium(V), -(IV), and -(III) complexes. Both A and B ([V] = 1.0 mM) gradually converged into similar mixtures of predominantly five- and six-coordinate VV species (∼75% total V) in a cell culture medium within 24 h at 310 K. Speciation of V in intact HepG2 cells also changed with the incubation time (from ∼20% to ∼70% VIV of total V), but it was largely independent of the prodrug used (A or B) or of the predominant V oxidation state in the medium. Subcellular fractionation of A549 cells suggested that VV reduction to VIV occurred predominantly in the cytoplasm, while accumulation of VV in the nucleus was likely to have been facilitated by noncovalent bonding to histone proteins. The nuclear VV is likely to modulate the transcription process and to be ultimately related to cell death at high concentrations of V, which may be important in anticancer activities. Mature 3T3-L1 adipocytes (unlike for preadipocytes) showed a higher propensity to form VIV species, despite the prevalence of VV in the medium. The distinct V biochemistry in these cells is consistent with their crucial role in insulin-dependent glucose and fat metabolism and may also point to an endogenous role of V in adipocytes. PMID:25906315

An open-label drug-drug interaction study of the steady-state pharmacokinetics of topiramate and glyburide in patients with type 2 diabetes mellitus.

PubMed

Manitpisitkul, Prasarn; Curtin, Christopher R; Shalayda, Kevin; Wang, Shean-Sheng; Ford, Lisa; Heald, Donald L

2013-12-01

Topiramate is approved for epilepsy and migraine headache management and has potential antidiabetic activity. Because topiramate and antidiabetic drugs may be co-administered, the potential drug-drug interactions between topiramate and glyburide (glibenclamide), a commonly used sulfonylurea antidiabetic agent, was evaluated at steady state in patients with type 2 diabetes mellitus (T2DM). This was a single-center, open-label, phase I, drug interaction study of topiramate (150 mg/day) and glyburide (5 mg/day alone and concomitantly) in patients with T2DM. The study consisted of 14-day screening, 48-day open-label treatment, and a 7-day follow-up phase. Serial blood and urine were obtained and analyzed by liquid chromatography coupled mass spectrometry/mass spectrometry for topiramate, glyburide, and its active metabolites M1 (4-trans-hydroxy-glyburide) and M2 (3-cis-hydroxy-glyburide) concentrations. Pharmacokinetic parameters were estimated by model-independent methods. Changes in fasting plasma glucose from baseline and safety parameters were monitored throughout the study. Of 28 enrolled patients, 24 completed the study. Co-administration of topiramate resulted in a significant (p < 0.05) decrease in the glyburide area under the concentration-time curve (25 %) and maximum plasma concentration (22 %), and reduction in systemic exposure of M1 (13 %) and M2 (15 %). Renal clearance of M1 (13 %) and M2 (12 %) increased during treatment with topiramate. Steady-state pharmacokinetics of topiramate were unaffected by co-administration of glyburide. Co-administration of topiramate and glyburide was generally tolerable in patients with T2DM. Glyburide did not affect the pharmacokinetics of topiramate. Co-administration of topiramate decreased systemic exposure of glyburide and its active metabolites; combined treatment may require dosing adjustments of glyburide as per clinical judgment and glycemic control.

Antidiabetic therapies and male reproductive function: where do we stand?

PubMed

Tavares, R S; Escada-Rebelo, S; Silva, A F; Sousa, M I; Ramalho-Santos, J; Amaral, S

2018-01-01

Diabetes mellitus has been increasing at alarming rates in recent years, thus jeopardizing human health worldwide. Several antidiabetic drugs have been introduced in the market to manage glycemic levels, and proven effective in avoiding, minimizing or preventing the appearance or development of diabetes mellitus-related complications. However, and despite the established association between such pathology and male reproductive dysfunction, the influence of these therapeutic interventions on such topics have been scarcely explored. Importantly, this pathology may contribute toward the global decline in male fertility, giving the increasing preponderance of diabetes mellitus in young men at their reproductive age. Therefore, it is mandatory that the reproductive health of diabetic individuals is maintained during the antidiabetic treatment. With this in mind, we have gathered the available information and made a critical analysis regarding the effects of several antidiabetic drugs on male reproductive function. Unlike insulin, which has a clear and fundamental role on male reproductive function, the other antidiabetic therapies' effects at this level seem incoherent. In fact, studies are highly controversial possibly due to the different experimental study approaches, which, in our opinion, suggests caution when it comes to prescribing such drugs to young diabetic patients. Overall, much is still to be determined and further studies are needed to clarify the safety of these antidiabetic strategies on male reproductive system. Aspects such as the effects of insulin levels variations, consequent of insulin therapy, as well as what will be the impact of the side effect hypoglycemia, common to several therapeutic strategies discussed, on the male reproductive system are still to be addressed. © 2018 Society for Reproduction and Fertility.

Use of glucagon-like peptide-1 receptor agonists and bone fractures: a meta-analysis of randomized clinical trials.

PubMed

Mabilleau, Guillaume; Mieczkowska, Aleksandra; Chappard, Daniel

2014-05-01

Patients with type 2 diabetes mellitus (T2DM) are at a higher risk of bone fractures independent of the use of antidiabetic medications. Furthermore, antidiabetic medications could directly affect bone metabolism. Recently, the use of dipeptidyl peptidase-4 inhibitors has been associated with a lower rate of bone fracture. The aim of the present meta-analysis was to assess whether patients with T2DM treated with glucagon-like peptide-1 receptor agonists (GLP-1Ra) present a lower incidence of bone fracture compared with patients using other antidiabetic drugs. A search on Medline, Embase, and http://www.clinicaltrials.gov, as well as a manual search for randomized clinical trials of T2DM treated with either a GLP-1Ra or another antidiabetic drug for a duration of ≥24 weeks was conducted by two authors (GM, AM) independently. Although 28 eligible studies were identified, only seven trials reported the occurrence of at least a bone fracture in one arm of the trial. The total number of fractures was 19 (13 and six with GLP-1Ra and comparator, respectively). The pooled Mantel-Haenszel odds ratio for GLP-1Ra was 0.75 (95% confidence interval 0.28-2.02, P = 0.569) in trials versus other antidiabetic agents. Although preliminary, our study highlighted that the use of GLP-1Ra does not modify the risk of bone fracture in T2DM compared with the use of other antidiabetic medications. © 2013 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Wiley Publishing Asia Pty Ltd.

Antidiabetic effect of Scoparia dulcis: effect on lipid peroxidation in streptozotocin diabetes.

PubMed

Pari, L; Latha, M

2005-03-01

Oxidative damage has been suggested to be a contributory factor in the development and complications of diabetes. The antioxidant effect of an aqueous extract of Scoparia dulcis, an indigenous plant used in Ayurvedic medicine in India was studied in rats with streptozotocin-induced diabetes. Oral administration of Scoparia dulcis plant extract (SPEt) (200 mg/kg body weight) for 3 weeks resulted in a significant reduction in blood glucose and an increase in plasma insulin. The aqueous extract also resulted in decreased free radical formation in tissues (liver and kidney) studied. The decrease in thiobarbituric acid reactive substances (TBARS) and hydroperoxides (HPX) and increase in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH) and glutathione-S-transferase (GST) clearly show the antioxidant properties of SPEt in addition to its antidiabetic effect. The effect of SPEt at 200 mg/kg body weight was better than glibenclamide, a reference drug.

Antidiabetic Effect of Brain-Derived Neurotrophic Factor and Its Association with Inflammation in Type 2 Diabetes Mellitus

PubMed Central

Kaplon-Cieslicka, Agnieszka; Malek, Lukasz; Postula, Marek

2017-01-01

Brain-derived neurotrophic factor (BDNF) is a neurotrophin, which plays an important role in the central nervous system, and systemic or peripheral inflammatory conditions, such as acute coronary syndrome and type 2 diabetes mellitus (T2DM). BDNF is also expressed in several nonneuronal tissues, and platelets are the major source of peripheral BDNF. Here, we reviewed the potential role of BDNF in platelet reactivity in T2DM and its association with selected inflammatory and platelet activation mediators. Besides that, we focused on adipocytokines such as leptin, resistin, and adiponectin which are considered to take part in inflammation and both lipid and glucose metabolism in diabetic patients as previous studies showed the relation between adipocytokines and BDNF. We also reviewed the evidences of the antidiabetic effect of BDNF and the association with circulating inflammatory cytokines in T2DM. PMID:29062839

Anti-diabetic effect of cinnamon extract on blood glucose in db/db mice.

PubMed

Kim, Sung Hee; Hyun, Sun Hee; Choung, Se Young

2006-03-08

The anti-diabetic effect of Cinnamomi cassiae extract (Cinnamon bark: Lauraceae) in a type II diabetic animal model (C57BIKsj db/db) was studied. Cinnamon extract was administered at different dosages (50, 100, 150 and 200 mg/kg) for 6 weeks. It was found that blood glucose concentration is significantly decreased in a dose-dependent manner (P<0.001) with the most in the 200 mg/kg group compared with the control. In addition, serum insulin levels and HDL-cholesterol levels were significantly higher (P<0.01) and the concentration of triglyceride, total cholesterol and intestinal alpha-glycosidase activity were significantly lower after 6 weeks of the administration. These results suggest that cinnamon extract has a regulatory role in blood glucose level and lipids and it may also exert a blood glucose-suppressing effect by improving insulin sensitivity or slowing absorption of carbohydrates in the small intestine.

Glycaemic control and antidiabetic therapy in patients with diabetes mellitus and chronic kidney disease - cross-sectional data from the German Chronic Kidney Disease (GCKD) cohort.

PubMed

Busch, Martin; Nadal, Jennifer; Schmid, Matthias; Paul, Katharina; Titze, Stephanie; Hübner, Silvia; Köttgen, Anna; Schultheiss, Ulla T; Baid-Agrawal, Seema; Lorenzen, Johan; Schlieper, Georg; Sommerer, Claudia; Krane, Vera; Hilge, Robert; Kielstein, Jan T; Kronenberg, Florian; Wanner, Christoph; Eckardt, Kai-Uwe; Wolf, Gunter

2016-06-11

Diabetes mellitus (DM) is the leading cause of end-stage renal disease. Little is known about practice patterns of anti-diabetic therapy in the presence of chronic kidney disease (CKD) and correlates with glycaemic control. We therefore aimed to analyze current antidiabetic treatment and correlates of metabolic control in a large contemporary prospective cohort of patients with diabetes and CKD. The German Chronic Kidney Disease (GCKD) study enrolled 5217 patients aged 18-74 years with an estimated glomerular filtration rate (eGFR) between 30-60 mL/min/1.73 m(2) or proteinuria >0.5 g/d. The use of diet prescription, oral anti-diabetic medication, and insulin was assessed at baseline. HbA1c, measured centrally, was the main outcome measure. At baseline, DM was present in 1842 patients (35 %) and the median HbA1C was 7.0 % (25(th)-75(th) percentile: 6.8-7.9 %), equalling 53 mmol/mol (51, 63); 24.2 % of patients received dietary treatment only, 25.5 % oral antidiabetic drugs but not insulin, 8.4 % oral antidiabetic drugs with insulin, and 41.8 % insulin alone. Metformin was used by 18.8 %. Factors associated with an HbA1C level >7.0 % (53 mmol/mol) were higher BMI (OR = 1.04 per increase of 1 kg/m(2), 95 % CI 1.02-1.06), hemoglobin (OR = 1.11 per increase of 1 g/dL, 95 % CI 1.04-1.18), treatment with insulin alone (OR = 5.63, 95 % CI 4.26-7.45) or in combination with oral antidiabetic agents (OR = 4.23, 95 % CI 2.77-6.46) but not monotherapy with metformin, DPP-4 inhibitors, or glinides. Within the GCKD cohort of patients with CKD stage 3 or overt proteinuria, antidiabetic treatment patterns were highly variable with a remarkably high proportion of more than 50 % receiving insulin-based therapies. Metabolic control was overall satisfactory, but insulin use was associated with higher HbA1C levels.

Lack of pharmacokinetic interaction for ISIS 113715, a 2'-0-methoxyethyl modified antisense oligonucleotide targeting protein tyrosine phosphatase 1B messenger RNA, with oral antidiabetic compounds metformin, glipizide or rosiglitazone.

PubMed

Geary, Richard S; Bradley, JoAnn D; Watanabe, Tanya; Kwon, Younggil; Wedel, Mark; van Lier, Jan J; VanVliet, André A

2006-01-01

ISIS 113715 is a 20-mer phosphorothioate antisense oligonucleotide (ASO) that is complementary to the protein tyrosine phosphatase 1B (PTP-1B) messenger RNA and subsequently reduces translation of the PTP-1B protein, a negative regulator of insulin receptor. ISIS 113715 is currently being studied in early phase II clinical studies to determine its ability to improve or restore insulin receptor sensitivity in patients with type 2 diabetes mellitus. Future work will investigate the combination of ISIS 113715 with antidiabetic compounds. In vitro ultrafiltration human plasma protein binding displacement studies and a phase I clinical study were used to characterise the potential for pharmacokinetic interaction of ISIS 113715 and three marketed oral antidiabetic agents. ISIS 113715 was co-incubated with glipizide and rosiglitazone in whole human plasma and tested for increased free drug concentrations. In a phase I clinical study, 23 healthy volunteers received a single oral dose of an antidiabetic compound (either metformin, glipizide or rosiglitazone) both alone and together with subcutaneous ISIS 113715 200 mg in a sequential crossover design. A comparative pharmacokinetic analysis was performed to determine if there were any effects that resulted from coadministration of ISIS 113715 with these antidiabetic compounds. In vitro human plasma protein binding displacement studies showed only minor effects on rosiglitazone and no effect on glipizide when co-incubated with ISIS 113715. The results of the phase I clinical study further indicate that there were no measurable changes in glipizide (5 mg), metformin (500 mg) or rosiglitazone (2 mg) exposure parameters, maximum plasma concentration and the area under the concentration-time curve, or pharmacokinetic parameter, elimination half-life when coadministered with ISIS 113715. Furthermore, there was no effect of ISIS 113715, administered in combination with metformin, on the urinary excretion of metformin. Conversely, there were no observed alterations in ISIS 113715 pharmacokinetics when administered in combination with any of the oral antidiabetic compounds. These data provide evidence that ISIS 113715 exhibits no clinically relevant pharmacokinetic interactions on the disposition and clearance of the oral antidiabetic drugs. The results of these studies support further study of ISIS 113715 in combination with antidiabetic compounds.

Analyzing the Chinese landscape in anti-diabetic drug research: leading knowledge production institutions and thematic communities.

PubMed

Deng, Junling; Sitou, Kaweng; Zhang, Yongping; Yan, Ru; Hu, Yuanjia

2016-01-01

The discovery of anti-diabetic drugs is an active Chinese medicine research area. This study aims to map out anti-diabetic drug research in China using a network-based systemic approach based on co-authorship of academic publications. We focused on identifying leading knowledge production institutions, analyzing interactions among them, detecting communities with high internal associations, and exploring future research directions. Target articles published in 2009-2013 under the topic "diabetes" and subject category "pharmacology & pharmacy," with "China," "Taiwan," "Hong Kong," or "Macao" (or "Macau") in the authors' address field were retrieved from the science citation index expanded database and their bibliographic information (e.g., article title, authors, keywords, and authors' affiliation addresses) analyzed. A social network approach was used to construct an institutional collaboration network based on co-publications. Gephi software was used to visualize the network and relationships among institutes were analyzed using centrality measurements. Thematic analysis based on article keywords and R sc value was applied to reveal the research hotspots and directions of network communities. The top 50 institutions were identified; these included Shanghai Jiao Tong University, National Taiwan University, Peking University, and China Pharmaceutical University. Institutes from Taiwan tended to cooperate with institutes outside Taiwan, but those from mainland China showed low interest in external collaboration. Fourteen thematic communities were detected with the Louvain algorithm and further labeled by their high-frequency and characteristic keywords, such as Chinese medicines, diabetic complications, oxidative stress, pharmacokinetics, and insulin resistance. The keyword Chinese medicines comprised a range of Chinese medicine-related topics, including berberine, flavonoids, Astragalus polysaccharide, emodin, and ginsenoside. These keywords suggest potential fields for further anti-diabetic drug research. The correlation of -0.641 (P = 0.013) between degree centrality and the R sc value of non-core keywords indicates that communities concentrating on rare research fields are usually isolated by others and have a lower chance of collaboration. With a better understanding of the Chinese landscape in anti-diabetic drug research, researchers and scholars looking for experts and institutions in a specific research area can rapidly spot their target community, then select the most appropriate potential collaborator and suggest preferential research directions for future studies.

Adenosine monophosphate-activated protein kinase-based classification of diabetes pharmacotherapy

PubMed Central

Dutta, D; Kalra, S; Sharma, M

2017-01-01

The current classification of both diabetes and antidiabetes medication is complex, preventing a treating physician from choosing the most appropriate treatment for an individual patient, sometimes resulting in patient-drug mismatch. We propose a novel, simple systematic classification of drugs, based on their effect on adenosine monophosphate-activated protein kinase (AMPK). AMPK is the master regular of energy metabolism, an energy sensor, activated when cellular energy levels are low, resulting in activation of catabolic process, and inactivation of anabolic process, having a beneficial effect on glycemia in diabetes. This listing of drugs makes it easier for students and practitioners to analyze drug profiles and match them with patient requirements. It also facilitates choice of rational combinations, with complementary modes of action. Drugs are classified as stimulators, inhibitors, mixed action, possible action, and no action on AMPK activity. Metformin and glitazones are pure stimulators of AMPK. Incretin-based therapies have a mixed action on AMPK. Sulfonylureas either inhibit AMPK or have no effect on AMPK. Glycemic efficacy of alpha-glucosidase inhibitors, sodium glucose co-transporter-2 inhibitor, colesevelam, and bromocriptine may also involve AMPK activation, which warrants further evaluation. Berberine, salicylates, and resveratrol are newer promising agents in the management of diabetes, having well-documented evidence of AMPK stimulation medicated glycemic efficacy. Hence, AMPK-based classification of antidiabetes medications provides a holistic unifying understanding of pharmacotherapy in diabetes. This classification is flexible with a scope for inclusion of promising agents of future. PMID:27652986

Infrared-Assisted Extraction and HPLC-Analysis of Prunus armeniaca L. Pomace and Detoxified-Kernel and their Antidiabetic Effects.

PubMed

Raafat, Karim; El-Darra, Nada; Saleh, Fatima A; Rajha, Hiba N; Maroun, Richard G; Louka, Nicolas

2018-03-01

Prunus armeniaca L. (P. armeniaca) is one of the medicinal plants with a high safety-profile. The aim of this work was to make an infrared-assisted extraction (IR-AE) of P. armeniaca fruit (pomace) and kernel, and analyse them using reverse phase high-performance liquid chromatography (RP-HPLC) aided method. IR-AE is a novel-technique aimed at increasing the extraction-efficiency. The antidiabetic-potentials of the P. armeniaca pomace (AP) and the detoxified P. armeniaca kernel extract (DKAP) were monitored exploring their possible hypoglycemic-mechanisms. Acute (6 h), subchronic (8 days) and long-term (8 weeks) assessment of Diabetes mellitus (DM) using glucometers and glycated hemoglobin (HbA1c) methods were applied. Serum-insulin levels, the inhibitory effects on alpha-glucosidase, serum-catalase (CAT) and lipid peroxidation (LPO) levels were also monitored. AP was shown to be rich in polyphenolics like trans-lutein (14.1%), trans-zeaxanthin (10.5%), trans-ß-cryptoxanthin (11.6%), 13, cis-ß-carotene (6.5%), trans 9, cis-ß-carotene (18.4%), and ß-carotene (21.5%). Prunus armeniaca kernel extract before detoxification (KAP) was found to be rich in amygdaline (16.1%), which caused a high mortality rate (50.1%), while after detoxification (amygdaline, 1.4%) a lower mortality rate (9.1%) was found. AP showed significant (p ≤ 0.05, n = 7/group) antidiabetic-activity more prominent than DKAP acutely, subchronically and on longer-terms. IR-AEs displayed more efficient acute and subchronic blood glucose level (BGL) reduction than a conventional extraction method, which might be attributed to IR-AE superiority in extraction of active ingredients. AP showed more-significant and dose-dependent increase in serum-insulin, CAT-levels and body-weights more prominent than those of DKAP. Alpha-glucosidase and LPO levels were inhibited with AP-groups more-significantly. In comparison to conventional-methods, IR-AE appeared to be an efficient and time-conserving novel extraction method. The antidiabetic-potentials of pomace and detoxified-kernels of P. armeniaca were probably mediated via the attenuation of glucose-provoked oxidative-stress, the inhibition of alpha-glucosidase and the marked insulin-secretagogue effect. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Diabetic Complications and Insight into Antidiabetic Potentialities of Ethno-medicinal Plants: A review.

PubMed

Bilal, Muhammad; Iqbal, Muhammad Sarfaraz; Shah, Syed Bilal; Rasheed, Tahir; Iqbal, Hafiz M N

2018-02-21

The naturally inspired treatment options for several disease conditions and human-health related disorders such as diabetes mellitus have gained considerable research interest. In this context, naturally occurring plants and herbs with medicinal functionalities have gained special place than ever before in the current medicinal world. The objective of this review is to extend the current knowledge in the clinical field related to the diabetic complications. A special focus has also been given to the anti-diabetic potentialities of ethnomedicinal plants. Herein, we reviewed and compiled salient information from the authentic bibliographic databases including PubMed, Scopus, Elsevier, Springer, Bentham Science and other scientific databases. The patents were searched and reviewed from http://www.freepatentsonline.com. Diabetes mellitus is a group of metabolic disorders associated with the endocrine system that resulted in hyperglycemic conditions. Metabolic disorders can cause many complications such as neuropathy, retinopathy, nephropathy, ischemic heart disease, stroke, and microangiopathy. Traditional botanical therapies have been used around the world to treat diabetes. Among several medications and different medicines, various herbs are known to cure and control diabetes; also have no side effects. History has shown that medicinal plants have long been used for traditional healing around the world to treat diabetes. More than 800 plants around the world are shown by ethnobotanical information as traditional remedies for the treatment of diabetes. Several parts of these plants have been evaluated and appreciated for hypoglycemic activity. Medicinal plants have been found to be more effective than conventional drug compounds with no/fewer side effects and relatively inexpensive. In this review paper, we have reviewed plants with anti-diabetic and related beneficial medicinal effects. This review may be helpful for researchers, diabetic patient and decision makers in the field of ethnobotanical sciences. These efforts may also provide treatment to everyone and focus on the role of traditional novel medicine plants that have anti-diabetic abilities. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Randomized study of repaglinide alone and in combination with metformin in Chinese subjects with type 2 diabetes naive to oral antidiabetes therapy.

PubMed

Wang, Weiqing; Bu, Ruifang; Su, Qing; Liu, Jianying; Ning, Guang

2011-12-01

The aim of this research is to determine efficacy and safety of repaglinide alone and in combination with metformin in Chinese subjects with type 2 diabetes naive to oral antidiabetes therapy. A 16-week, open-label, randomized, active-controlled, parallel-group trial was carried out. Subjects were randomized (1:1) to repaglinide 1 mg t.i.d. (maximum dose, 4 mg t.i.d.) or repaglinide plus metformin 1 mg/500 mg t.i.d. (maximum dose, 4 mg/500 mg t.i.d.). Eligible subjects (18 - 75 years old) had type 2 diabetes, A1C > 8.5%, BMI ≤ 35 kg/m(2), and were naive to oral antidiabetes agents. The primary outcome was A1C reduction. Secondary end points included fasting plasma glucose (FPG), 2-h postprandial glucose (PPG), and 7-point plasma glucose. Baseline characteristics (repaglinide/metformin, n = 218; repaglinide-only, n = 214) were similar between groups. Mean A1C reduction (± SD) was 4.51 ± 1.64% (combination) and 4.05 ± 1.59% (monotherapy). Estimated mean treatment difference for repaglinide/metformin versus repaglinide-only was -0.30% (95% CI -0.49 to -0.11; p < 0.01). Combination treatment demonstrated significant improvements versus monotherapy in FPG, 7-point plasma glucose, and lunchtime and dinnertime 2-h PPG (all p < 0.05). Hypoglycemia rates were 2.04 (combination) versus 1.35 (monotherapy) events/subject-year (p = 0.058). Adverse events were comparable between groups. Repaglinide plus metformin and repaglinide alone provided significant improvements in glycemic control and were well tolerated in Chinese patients naive to treatment with oral antidiabetes agents. Combination therapy with repaglinide plus metformin showed superiority to repaglinide monotherapy in this population. Limitations of this study are that subjects were newly diagnosed and had high mean baseline A1C, which may affect generalizability of results.

Antidiabetic Agents.

ERIC Educational Resources Information Center

Plummer, Nancy; Michael, Nancy, Ed.

This module on antidiabetic agents is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

Impact of pioglitazone regulatory withdrawal on antidiabetic drug use and health in diabetic patients.

PubMed

Pariente, Antoine; Mansiaux, Yohann; Jarné, Ana; Salvo, Francesco; Pageot, Cécile; Bezin, Julien; Smith, Andy; Bégaud, Bernard

2017-12-01

In 2011, pioglitazone was withdrawn from the French market owing to a potential risk of bladder cancer. This study aimed at assessing the impact of this pioglitazone withdrawal (PW) considering (i) trends in antidiabetic uses and (ii) changes in hospitalization/death rates in diabetic patients following PW. We first considered the general population of the Echantillon Généraliste des Bénéficiaires (EGB), a 1/97th representative sample of the French healthcare insurance system beneficiaries, for the 2010-2014 period. In this, for each non-insulinic antidiabetic drug class, changes within the numbers of monthly supplied drug units for 1000 subjects were studied through times series and Unobserved Component Models. Second, we identified from the EGB a cohort of patients who were delivered a non-insulinic antidiabetic between 01 April 2011 and 01 August 2011 (date of PW). In this, post-withdrawal incidences of all-cause hospitalization and death were compared amongst pioglitazone users and non-users using proportional subdistribution hazards models. PW was accompanied by an increase in metformin (+ 11.7; 95% CI 1.1-22.3) and glinide (+ 11.0; 95% CI 1.2-20.8) numbers of monthly supplied units for 1000 subjects. No significant change was found for GLP-1 agonists, DPP-4 inhibitors, sulphonylureas or alpha-glucosidase inhibitors. In the cohort of non-insulinic antidiabetic users at the time of PW (1093 pioglitazone users, 17,900 non-users), being a pioglitazone user at PW was not associated with a subsequently higher rate of hospitalization. If PW was accompanied with significant changes in the use of some antidiabetics, no adverse impact of PW on hospitalization or death rates of diabetic type 2 patients was found.

Metformin use and risk of prostate cancer: results from the REDUCE study.

PubMed

Feng, Tom; Sun, Xizi; Howard, Lauren E; Vidal, Adriana C; Gaines, Alexis R; Moreira, Daniel M; Castro-Santamaria, Ramiro; Andriole, Gerald L; Freedland, Stephen J

2015-11-01

The role of metformin in prostate cancer chemoprevention remains unclear. REDUCE, which followed biopsy-negative men with protocol-dictated PSA-independent biopsies at 2- and 4-years, provides an opportunity to evaluate the link between metformin use and prostate cancer diagnosis with minimal confounding from screening biases. In diabetic men from REDUCE, we tested the association between metformin use, use of other antidiabetic medications, versus no antidiabetic medication use, and prostate cancer diagnosis as well as prostate cancer grade (low-grade Gleason 4-6 and high-grade Gleason 7-10) using logistic regression. Of the 540 diabetic men with complete data, 205 (38%) did not report use of any antidiabetic medications, 141 (26%) reported use of at least one antidiabetic medication other than metformin, and 194 (36%) reported use of metformin. During the 4-year study, 122 men (23%) were diagnosed with prostate cancer. After adjusting for various clinical and demographic characteristics, we found that metformin use was not significantly associated with total (OR, 1.19; P = 0.50), low- (OR, 1.01; P = 0.96), or high-grade (OR, 1.83; P = 0.19) prostate cancer diagnosis. Likewise, there was no significant association between the use of non-metformin antidiabetic medications and prostate cancer risk in both crude (OR, 1.02; P = 0.95) and multivariable analysis (OR, 0.85; P = 0.56). Furthermore, the interactions between antidiabetic medication use and BMI, geographic location, coronary artery disease, smoking, and treatment group were not significant (all P > 0.05). Among diabetic men with a negative prestudy biopsy who all underwent biopsies largely independent of PSA, metformin use was not associated with reduced risk of prostate cancer diagnosis. ©2015 American Association for Cancer Research.

The Active Role of Leguminous Plant Components in Type 2 Diabetes

PubMed Central

Gętek, Monika; Muc-Wierzgoń, Małgorzata; Grochowska-Niedworok, Elżbieta; Kokot, Teresa; Nowakowska-Zajdel, Ewa

2014-01-01

Diabetes appears to be one of the most frequent noncommunicable diseases in the world. A permanent growth in the incidence of diabetes can be observed and according to the International Diabetes Federation (IDF) the year 2030 will mark the increase in the number of diabetics to 439 mln worldwide. Type 2 diabetes accounts for about 90% of all diabetes incidence. Nutrition model modification not only features the basic element in type 2 diabetes treatment but also constitutes the fundamental factor influencing a morbidity rate decrease. Leguminous plants are a key factor in the diabetic diet; plants such as pulses or soybeans are nutritious products valued highly in nutrition. These legumes are high in the content of wholesome protein and contain large amounts of soluble alimentary fiber fractions, polyunsaturated fatty acids, vitamins and minerals, and bioactive substances with antioxidant, anti-inflammatory, and anticancer activity. They are distinguished by the high amount of bioactive compounds that may interfere with the metabolism of glucose. The most significant bioactive compounds displaying antidiabetic activity in leguminous plants are as follows: genistein and daidzein, alpha-amylase inhibitors, and alpha-glucosidase inhibitors. In vitro research using leguminous plant extracts has confirmed their antidiabetic properties. Leguminous plants should be employed in the promotion of healthy lifestyles in terms of functional food. PMID:24738003

Antidiabetic Potentiality of the Aqueous-Methanolic Extract of Seed of Swietenia mahagoni (L.) Jacq. in Streptozotocin-Induced Diabetic Male Albino Rat: A Correlative and Evidence-Based Approach with Antioxidative and Antihyperlipidemic Activities.

PubMed

De, Debasis; Chatterjee, Kausik; Ali, Kazi Monjur; Bera, Tushar Kanti; Ghosh, Debidas

2011-01-01

Antidiabetic, antioxidative, and antihyperlipidemic activities of aqueous-methanolic (2 : 3) extract of Swietenia mahagoni (L.) Jacq. (family Meliaceae) seed studied in streptozotocin-induced diabetic rats. Feeding with seed extract (25 mg 0.25 mL distilled water(-1)100 gm b.w.(-1)rat(-1) day(-1)) for 21 days to diabetic rat lowered the blood glucose level as well as the glycogen level in liver. Moreover, activities of antioxidant enzymes like catalase, peroxidase, and levels of the products of free radicals like conjugated diene and thiobarbituric acid reactive substances in liver, kidney, and skeletal muscles were corrected towards the control after this extract treatment in this model. Furthermore, the seed extract corrected the levels of serum urea, uric acid, creatinine, cholesterol, triglyceride, and lipoproteins towards the control level in this experimental diabetic model. The results indicated the potentiality of the extract of S. mahagoni seed for the correction of diabetes and its related complications like oxidative stress and hyperlipidemia. The extract may be a good candidate for developing a safety, tolerable, and promising neutraceutical treatment for the management of diabetes.

Microencapsulation Approach for Orally Extended Delivery of Glipizide: In vitro and in vivo Evaluation

PubMed Central

Abdelbary, A.; El-gendy, N. A.; Hosny, A.

2012-01-01

Glipizide is an effective antidiabetic agent, however, it suffers from relatively short biological half-life. To solve this encumbrance, it is a prospective candidate for fabricating glipizide extended release microcapsules. Microencapsulation of glipizde with a coat of alginate alone or in combination with chitosan or carbomer 934P was prepared employing ionotropic gelation process. The prepared microcapsules were evaluated in vitro by microscopical examination, determination of the particle size, yield and microencapsulation efficiency. The filled capsules were assessed for content uniformity and drug release characteristics. Stability study of the optimised formulas was carried out at three different temperatures over 12 weeks. In vivo bioavailability study and hypoglycemic activity of C9 microcapsules were done on albino rabbits. All formulas achieved high yield, microencapsulation efficiency and extended t1/2. C9 and C19 microcapsules attained the most optimised results in all tests and complied with the dissolution requirements for extended release dosage forms. These two formulas were selected for stability studies. C9 exhibited longer shelf-life and hence was chosen for in vivo studies. C9 microcapsules showed an improvement in the drug bioavailability and significant hypoglycemic activity compared to immediate release tablets (Minidiab® 5 mg). The optimised microcapsule formulation developed was found to produce extended antidiabetic activity. PMID:23626387

Antidiabetic Potential of Kefir Combination from Goat Milk and Soy Milk in Rats Induced with Streptozotocin-Nicotinamide.

PubMed

Nurliyani; Harmayani, Eni; Sunarti

2015-01-01

The study aimed to evaluate the effect of kefir combination from goat milk and soy milk on lipid profile, plasma glucose, glutathione peroxidase (GPx) activity and the improvement of pancreatic β-cell in diabetic rats. Male rats were divided into five treatments: normal control, diabetic control, goat milk kefir, combination of goat milk-soy milk kefir and soy milk kefir. All rats were induced by streptooztocin-nicotinamide (STZ-NA), except for normal control. After 35 d experiment, the rats were sampled for blood, sacrificed and sampled for pancreatic tissues. Results showed that diabetic rats fed kefir combination had higher (p<0.05) triglyceride than the rats fed goat milk or soy milk kefir. Decreasing of plasma glucose in diabetic rats fed kefir combination was higher (p<0.05) than rats fed goat millk kefir. The activity of GPx in diabetic rats fed three kinds of kefir were higher (p<0.01) than untreated diabetic rats. The average number of Langerhans and β-cells in diabetic rats fed kefir combination was the same as the normal control, but it was higher than diabetic control. It was concluded that kefir combination can be used as antidiabetic through maintaining in serum triglyceride, decreasing in plasma glucose, increasing in GPx activity and improving in pancreatic β-cells.

Exploratory Characterization of Phenolic Compounds with Demonstrated Anti-Diabetic Activity in Guava Leaves at Different Oxidation States

PubMed Central

Díaz-de-Cerio, Elixabet; Verardo, Vito; Gómez-Caravaca, Ana María; Fernández-Gutiérrez, Alberto; Segura-Carretero, Antonio

2016-01-01

Psidium guajava L. is widely used like food and in folk medicine all around the world. Many studies have demonstrated that guava leaves have anti-hyperglycemic and anti-hyperlipidemic activities, among others, and that these activities belong mainly to phenolic compounds, although it is known that phenolic composition in guava tree varies throughout seasonal changes. Andalusia is one of the regions in Europe where guava is grown, thus, the aim of this work was to study the phenolic compounds present in Andalusian guava leaves at different oxidation states (low, medium, and high). The phenolic compounds in guava leaves were determined by HPLC-DAD-ESI-QTOF-MS. The results obtained by chromatographic analysis reported that guava leaves with low degree of oxidation had a higher content of flavonols, gallic, and ellagic derivatives compared to the other two guava leaf samples. Contrary, high oxidation state guava leaves reported the highest content of cyanidin-glucoside that was 2.6 and 15 times higher than guava leaves with medium and low oxidation state, respectively. The QTOF platform permitted the determination of several phenolic compounds with anti-diabetic properties and provided new information about guava leaf phenolic composition that could be useful for nutraceutical production. PMID:27187352

Exploratory Characterization of Phenolic Compounds with Demonstrated Anti-Diabetic Activity in Guava Leaves at Different Oxidation States.

PubMed

Díaz-de-Cerio, Elixabet; Verardo, Vito; Gómez-Caravaca, Ana María; Fernández-Gutiérrez, Alberto; Segura-Carretero, Antonio

2016-05-11

Psidium guajava L. is widely used like food and in folk medicine all around the world. Many studies have demonstrated that guava leaves have anti-hyperglycemic and anti-hyperlipidemic activities, among others, and that these activities belong mainly to phenolic compounds, although it is known that phenolic composition in guava tree varies throughout seasonal changes. Andalusia is one of the regions in Europe where guava is grown, thus, the aim of this work was to study the phenolic compounds present in Andalusian guava leaves at different oxidation states (low, medium, and high). The phenolic compounds in guava leaves were determined by HPLC-DAD-ESI-QTOF-MS. The results obtained by chromatographic analysis reported that guava leaves with low degree of oxidation had a higher content of flavonols, gallic, and ellagic derivatives compared to the other two guava leaf samples. Contrary, high oxidation state guava leaves reported the highest content of cyanidin-glucoside that was 2.6 and 15 times higher than guava leaves with medium and low oxidation state, respectively. The QTOF platform permitted the determination of several phenolic compounds with anti-diabetic properties and provided new information about guava leaf phenolic composition that could be useful for nutraceutical production.

Molecular understanding of Epigallocatechin gallate (EGCG) in cardiovascular and metabolic diseases.

PubMed

Eng, Qian Yi; Thanikachalam, Punniyakoti Veeraveedu; Ramamurthy, Srinivasan

2018-01-10

The compound epigallocatechin-3-gallate (EGCG), the major polyphenolic compound present in green tea [Camellia sinensis (Theaceae], has shown numerous cardiovascular health promoting activity through modulating various pathways. However, molecular understanding of the cardiovascular protective role of EGCG has not been reported. This review aims to compile the preclinical and clinical studies that had been done on EGCG to investigate its protective effect on cardiovascular and metabolic diseases in order to provide a systematic guidance for future research. Research papers related to EGCG were obtained from the major scientific databases, for example, Science direct, PubMed, NCBI, Springer and Google scholar, from 1995 to 2017. EGCG was found to exhibit a wide range of therapeutic properties including anti-atherosclerosis, anti-cardiac hypertrophy, anti-myocardial infarction, anti-diabetes, anti-inflammatory and antioxidant. These therapeutic effects are mainly associated with the inhibition of LDL cholesterol (anti-atherosclerosis), inhibition of NF-κB (anti-cardiac hypertrophy), inhibition of MPO activity (anti-myocardial infarction), reduction in plasma glucose and glycated haemoglobin level (anti-diabetes), reduction of inflammatory markers (anti-inflammatory) and the inhibition of ROS generation (antioxidant). EGCG shows different biological activities and in this review, a compilation of how this bioactive molecule plays its role in treating cardiovascular and metabolic diseases was discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Traditional Uses, Pharmacological Efficacy, and Phytochemistry of Moringa peregrina (Forssk.) Fiori. —A Review

PubMed Central

Senthilkumar, Annadurai; Karuvantevida, Noushad; Rastrelli, Luca; Kurup, Shyam S.; Cheruth, Abdul J.

2018-01-01

Moringa is a sole genus of Moringaceae family with 13 species distributed in the tropical and sub-tropical regions. Among them, Moringa peregrina is one of the species which has wide range of traditional, nutritional, industrial, and medicinal values. The plant parts are used in folk medicine for many human health care purposes including diabetes, wound healing, disinfectant, fever, constipation, muscle pains, slimness, burns, labor pain, hypertension, malaria, stomach disorder, asthma, skin problems, and to expel a retained placenta. In addition to medicinal value, M. peregrina has cultural, spiritual, and religious connections with the native people of Arabian Peninsula. M. peregrina plant parts were tested for many pharmacological activities viz, antioxidant, anti-microbial, anti-diabetic, anti-spasmodic, hypertension, hepatotoxicity, lipid lowering activity, anti-inflammatory, anti-cancer, and memory disorders. Few active molecules belong to the class isothiocyanate, flavonoid, triterpenoid, phytosterol, polyphenol, and glycoside were also isolated, identified and reported for anti-microbial, anti-oxidant, anthelmintic, anti-mutagenic, neuroprotective, anti-cancer, anti-hypertensive, anti-diabetic, anti-infective, anti-allergic, anti-inflammatory, herbicidal, lipid lowering potential, anti-trypanosomal, and cytotoxic activities. So, the aim of the present review is to provide comprehensive information from recognized sources on the traditional uses, pharmacological efficacy and phytochemistry of the desert medicinal plant, M. peregrina. The information provided in this review will be very useful for further studies to develop novel therapeutic drugs. PMID:29867473

Traditional Uses, Pharmacological Efficacy, and Phytochemistry of Moringa peregrina (Forssk.) Fiori. -A Review.

PubMed

Senthilkumar, Annadurai; Karuvantevida, Noushad; Rastrelli, Luca; Kurup, Shyam S; Cheruth, Abdul J

2018-01-01

Moringa is a sole genus of Moringaceae family with 13 species distributed in the tropical and sub-tropical regions. Among them, Moringa peregrina is one of the species which has wide range of traditional, nutritional, industrial, and medicinal values. The plant parts are used in folk medicine for many human health care purposes including diabetes, wound healing, disinfectant, fever, constipation, muscle pains, slimness, burns, labor pain, hypertension, malaria, stomach disorder, asthma, skin problems, and to expel a retained placenta. In addition to medicinal value, M. peregrina has cultural, spiritual, and religious connections with the native people of Arabian Peninsula. M. peregrina plant parts were tested for many pharmacological activities viz , antioxidant, anti-microbial, anti-diabetic, anti-spasmodic, hypertension, hepatotoxicity, lipid lowering activity, anti-inflammatory, anti-cancer, and memory disorders. Few active molecules belong to the class isothiocyanate, flavonoid, triterpenoid, phytosterol, polyphenol, and glycoside were also isolated, identified and reported for anti-microbial, anti-oxidant, anthelmintic, anti-mutagenic, neuroprotective, anti-cancer, anti-hypertensive, anti-diabetic, anti-infective, anti-allergic, anti-inflammatory, herbicidal, lipid lowering potential, anti-trypanosomal, and cytotoxic activities. So, the aim of the present review is to provide comprehensive information from recognized sources on the traditional uses, pharmacological efficacy and phytochemistry of the desert medicinal plant, M. peregrina . The information provided in this review will be very useful for further studies to develop novel therapeutic drugs.

Characteristics, Treatment Patterns, and Economic Outcomes of Patients Initiating Injectable Medications for Management of Type 2 Diabetes Mellitus in Japan: Results from a Retrospective Claims Database Analysis.

PubMed

Suzuki, Shuichi; Desai, Urvi; Strizek, Alena; Ivanova, Jasmina; Garcia-Horton, Viviana; Cai, Zhihong; Schmerold, Luke; Liu, Xinyue; Perez-Nieves, Magaly

2018-06-01

This study's objective was to describe characteristics, treatment patterns, and economic outcomes of type 2 diabetes mellitus (T2DM) patients initiating injectable antidiabetic medications in Japan. Adults (≥ 18 years) with T2DM, ≥ 2 claims for injectable antidiabetics between 1 August 2011 and 31 July 2015 (first claim = index date), no evidence of type 1 diabetes mellitus, ≤ 1 claim for insulin, no claims for GLP-1RA before index, and continuous enrollment for 6 months before (baseline) and 12 months after index (follow-up) were selected from the Japan Medical Center Database. Patient characteristics and outcomes during the baseline and follow-up periods were described overall and by provider, using the proxy setting of index medication [hospital (including outpatient departments) for specialists; clinic for general practitioner (GP)]. Of the 2683 patients included (mean age: 50 years, 67% male), 1879 (70%) initiated injectable antidiabetics with specialists and 804 (30%) with GPs. The specialist cohort had a significantly greater comorbidity burden, but lower HbA1c levels during baseline, and was more likely to receive intensified treatment at index than the GP cohort. Almost 40% of patients (almost 30% of GP cohort) did not use antidiabetics during baseline; the remaining patients received oral medications, primarily from GPs. During follow-up, patients used the index medication for approximately 7 months. Independent of specialist vs. GP setting, patients received antidiabetics and medications for T2DM-related comorbidities and complications during the baseline and follow-up periods from the same provider, primarily GPs. The overall average healthcare costs were ¥350,404 during baseline and ¥1,856,727 during follow-up. In Japan, most T2DM patients initiated injectable antidiabetics with specialists vs. GPs. There were considerable differences in characteristics of patients treated by specialists vs. GPs. After initiation, injectable antidiabetics were largely prescribed by GPs. Future research should evaluate the factors associated with different provider practices and communication channels between specialists and GPs to improve patient management. Eli Lilly and Co.

[Use of new antidiabetics in the elderly population].

PubMed

Besse, Sarah; Besse, Arun; Jornayvaz, François R

2016-06-01

Over the last few years, we have noticed the arrival on the market of new antidiabetic treatments. These represent an potential advantage because of the increase in the prevalence of type 2 diabetes, particularly in the elderly population. Nevertheless, elderly patients have a number of frailties that should be considered in the treatment of this condition. There is a lack of literature in this population as elderly are frequently excluded from randomized controlled trials. Therefore, guidelines were developed based on the consensus of experts in geriatrics and diabetology for this specific population. We have to consider the potential benefits and adverse effects of the new antidiabetics in older patients.

Black bean anthocyanin-rich extracts as food colorants: Physicochemical stability and antidiabetes potential

USDA-ARS?s Scientific Manuscript database

Black beans contain anthocyanins that could be used as colorants in foods with associated health benefits. The objective was to optimize anthocyanins extraction from black bean coats and evaluate their physicochemical stability and antidiabetes potential. Optimal extraction conditions were 24% ethan...

Impact of long-term antihypertensive and antidiabetic medications on the prognosis of post-surgical colorectal cancer: the Fujian prospective investigation of cancer (FIESTA) study.

PubMed

Peng, Feng; Hu, Dan; Lin, Xiandong; Liang, Binying; Chen, Ying; Zhang, Hejun; Xia, Yan; Lin, Jinxiu; Zheng, Xiongwei; Niu, Wenquan

2018-05-24

Hypertension and diabetes mellitus are common comorbidities of colorectal cancer. We designed a prospective cohort study aiming to investigate the impact of long-term antihypertensive and antidiabetic medications on colorectal cancer-specific survival and recurrence among 713 post-surgical patients. All participants received radical resection for colorectal cancer during 2000-08, and they were followed up until July 2017. Colorectal cancer patients without hypertension had better survival than those with hypertension (median survival time [MST]: 190.3 months versus 99.0 months, p <0.001). The impact of antidiabetic medications on prolonging colorectal cancer survival was statistically significant, that is, patients receiving antidiabetic medications had longer survival time than untreated diabetic patients (MST: 135.8 months versus 80.2 months, p : 0.007), whereas the prognosis was greatly improved in colorectal cancer patients without diabetes mellitus ( p <0.001). Medical treatment for hypertension and diabetes mellitus was associated with 28% (hazard ratio [HR]: 0.72; 95% confidence interval [CI]: 0.47-1.10; p : 0.131) and 57% (HR: 0.43; 95% CI: 0.22-0.82; p : 0.010) reduced risk of dying from colorectal cancer relative to those without medications, respectively. Our data indicate that long-term antidiabetic medications can significantly prolong the survival and improve the prognosis of post-surgical colorectal cancer.

Impact of long-term antihypertensive and antidiabetic medications on the prognosis of post-surgical colorectal cancer: the Fujian prospective investigation of cancer (FIESTA) study

PubMed Central

Peng, Feng; Hu, Dan; Lin, Xiandong; Liang, Binying; Chen, Ying; Zhang, Hejun; Xia, Yan

2018-01-01

Hypertension and diabetes mellitus are common comorbidities of colorectal cancer. We designed a prospective cohort study aiming to investigate the impact of long-term antihypertensive and antidiabetic medications on colorectal cancer-specific survival and recurrence among 713 post-surgical patients. All participants received radical resection for colorectal cancer during 2000-08, and they were followed up until July 2017. Colorectal cancer patients without hypertension had better survival than those with hypertension (median survival time [MST]: 190.3 months versus 99.0 months, p <0.001). The impact of antidiabetic medications on prolonging colorectal cancer survival was statistically significant, that is, patients receiving antidiabetic medications had longer survival time than untreated diabetic patients (MST: 135.8 months versus 80.2 months, p: 0.007), whereas the prognosis was greatly improved in colorectal cancer patients without diabetes mellitus (p <0.001). Medical treatment for hypertension and diabetes mellitus was associated with 28% (hazard ratio [HR]: 0.72; 95% confidence interval [CI]: 0.47-1.10; p: 0.131) and 57% (HR: 0.43; 95% CI: 0.22-0.82; p: 0.010) reduced risk of dying from colorectal cancer relative to those without medications, respectively. Our data indicate that long-term antidiabetic medications can significantly prolong the survival and improve the prognosis of post-surgical colorectal cancer. PMID:29846174

Antidiabetic, antioxidant and anti inflammatory properties of water and n-butanol soluble extracts from Saharian Anvillea radiata in high-fat-diet fed mice.

PubMed

Kandouli, Chouaib; Cassien, Mathieu; Mercier, Anne; Delehedde, Caroline; Ricquebourg, Emilie; Stocker, Pierre; Mekaouche, Mourad; Leulmi, Zineb; Mechakra, Aicha; Thétiot-Laurent, Sophie; Culcasi, Marcel; Pietri, Sylvia

2017-07-31

According to Saharian traditional medicine, Anvillea radiata Coss. & Dur. (Asteraceae) has been valued for treating a variety of ailments such as gastro-intestinal, liver and pulmonary diseases, and has gained awareness for its beneficial effect on postprandial hyperglycemia. However, to best of our knowledge, no detailed study of the antidiabetic curative effects of this plant has been conducted yet. To determine the hypoglycemic and antidiabetic effect of dietary supplementation with Anvillea radiata extracts on high-fat-diet (HFD)-induced obesity and insulin resistance in C57BL/6J mice in relation with antioxidant, anti-inflammatory, pancreatic beta-cells and skeletal muscle protection, and digestive enzyme inhibiting properties. Six extracts (water soluble and organic) from aerial parts of the plant were analyzed phytochemically (total phenolic and flavonoid content) and screened for in vitro superoxide (by chemiluminescence) and hydroxyl radical (by electron paramagnetic resonance spin-trapping) scavenging, antioxidant (DPPH, TRAP and ORAC assays), xanthine oxidase, metal chelating, α-amylase and α-glucosidase inhibitory property, and protective effects on copper-induced lipoprotein oxidation. Then selected hydroalcoholic and aqueous extracts were assessed for toxicity in normal human lung fibroblasts and A549 cancer cells using FMCA and MTT assays. Two water-soluble extracts having the best overall properties were assessed for their (i) protective effect at 1-15µg/mL on metabolic activity of rat insulinoma-derived INS-1 cells exposed to hyperglycemic medium, and (ii) acute hypoglycemic effect on 16-weeks HFD-induced diabetic mice. Then diabetic mice were administered HFD supplemented by extracts (up to 150mg/kg/day) for 12 additional weeks using standard diet as control and the antidiabetic drug, metformin (150mg/kg), as positive control. Then the antidiabetic, anti-inflammatory and antioxidant activity of extracts were determined. Of the highly efficient polyphenolics-enriched hydroalcoholic and ethyl acetate extracts, the lyophilized aqueous (AQL) and butanol extracts were not toxic in cells (≤ 400µg/mL) or when given orally in normal mice (≤ 2000mg/kg), exerted a dose-dependent hypoglycemic action in diabetic mice, which was maximal at the dose of 150mg/kg. Upon administering this dose for 12 weeks, both extracts significantly ameliorated body weight control capacity, recovery of plasma glucose and insulin level, reduced oxidative stress in blood, myocardial and skeletal muscles, and improved hyperlipidemic and inflammatory status. Moreover, diabetes-related complications were optimally ameliorated by oral therapy based on halved doses (75mg/kg) of a mixture of AQL and metformin. Current investigation supports the traditional medicinal usage of Anvillea radiata and suggests that both readily accessible and low-cost bio-extracts have the potency to develop an antihyperglycemic, antihyperlipidemic and protective agent against beta-cells and muscle dysfunction at doses compatible with the common practices of indigenous people for the management of metabolic disorders. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Selective Inhibition of PTP1B by Vitalboside A from Syzygium cumini Enhances Insulin Sensitivity and Attenuates Lipid Accumulation Via Partial Agonism to PPARγ: In Vitro and In Silico Investigation.

PubMed

Thiyagarajan, Gopal; Muthukumaran, Padmanaban; Sarath Kumar, Baskaran; Muthusamy, Velusamy Shanmuganathan; Lakshmi, Baddireddi Subhadra

2016-08-01

Although antidiabetic drugs show good insulin-sensitizing property for T2DM, they also exhibit undesirable side-effects. Partial peroxisome proliferator-activated receptor γ agonism with protein tyrosine phosphatase 1B inhibition is considered as an alternative therapeutic approach toward the development of a safe insulin sensitizer. Bioactivity-based fractionation and purification of Syzygium cumini seeds led to the isolation and identification of bifunctional Vitalboside A, which showed antidiabetic and anti-adipogenic activities, as measured by glucose uptake in L6 and 3T3-L1 adipocytes and Nile red assay. A non-competitive allosteric inhibition of protein tyrosine phosphatase 1B by Vitalboside A was observed, which was confirmed by docking studies. Inhibitor studies with wortmannin and genistein showed an IRTK- and PI3K-dependent glucose uptake. A PI3K/AKT-dependent activation of GLUT4 translocation and an inactivation of GSK3β were observed, confirming its insulin-sensitizing potential. Vitalboside A exhibited partial transactivation of peroxisome proliferator-activated receptor γ with an increase in adiponectin secretion, which was confirmed using docking analysis. Vitalboside A is a bifunctional molecule derived from edible plant showing inhibition of PTP1B and partial agonism to peroxisome proliferator-activated receptor γ which could be a promising therapeutic agent in the management of obesity and diabetes. © 2016 John Wiley & Sons A/S.

CoMFA and CoMSIA studies on C-aryl glucoside SGLT2 inhibitors as potential anti-diabetic agents.

PubMed

Vyas, V K; Bhatt, H G; Patel, P K; Jalu, J; Chintha, C; Gupta, N; Ghate, M

2013-01-01

SGLT2 has become a target of therapeutic interest in diabetes research. CoMFA and CoMSIA studies were performed on C-aryl glucoside SGLT2 inhibitors (180 analogues) as potential anti-diabetic agents. Three different alignment strategies were used for the compounds. The best CoMFA and CoMSIA models were obtained by means of Distill rigid body alignment of training and test sets, and found statistically significant with cross-validated coefficients (q²) of 0.602 and 0.618, respectively, and conventional coefficients (r²) of 0.905 and 0.902, respectively. Both models were validated by a test set of 36 compounds giving satisfactory predicted correlation coefficients (r² pred) of 0.622 and 0.584 for CoMFA and CoMSIA models, respectively. A comparison was made with earlier 3D QSAR study on SGLT2 inhibitors, which shows that our 3D QSAR models are better than earlier models to predict good inhibitory activity. CoMFA and CoMSIA models generated in this work can provide useful information to design new compounds and helped in prediction of activity prior to synthesis.

Antidiabetic potential of Caesalpinia sumatrana, a medicinal herbs traditionally used by local tribe in East Kalimantan

NASA Astrophysics Data System (ADS)

Wicaksono, D. A.; Rosamah, E.; Kusuma, I. W.

2018-04-01

The aims of the research was to analyze the content of phytochemicals, to examine the antioxidant and antidiabeticpotentials of n-hexane, chloroform, ethyl acetate, and ethanol extracts of Caesalpinia sumatrana. Method to measure antioxidant capacity of sample involves the use of the free radical, 1,1-diphenyl-2-picrylhydrazyl (DPPH) which is widely used to test the ability of compounds to act as free radical. Analysis the potential of antidiabeticactivity of the extracts was determined by α-glucosidase and α-amylase inhibitory assay. Of all extracts obtained by successive maceration, ethanol maceration gave the highest extract by 2.63% of extract on the dry weigh basis. The result of phytochemicals showed that all extracts contain alkaloid and flavonoid. The highest antioxidant activity was 82.32% with IC50 value of 5.00 µg/ml obtained by ethanol extract. The results of enzyme inhibitory assay of α-glucosidase showed that ethanol extract of C. sumatrana had IC50 value 17.16 µg/mL to inhibit ɑ-glucosidase activity and IC50 value 16.78 µg/mL for ɑ-amylase. The present result displayed potential of the plant to be developed as natural antidiabetic and antioxidant agents.

Houttuynia cordata Facilitates Metformin on Ameliorating Insulin Resistance Associated with Gut Microbiota Alteration in OLETF Rats.

PubMed

Wang, Jing-Hua; Bose, Shambhunath; Lim, Soo-Kyoung; Ansari, AbuZar; Chin, Young-Won; Choi, Han Seok; Kim, Hojun

2017-09-22

Metformin and Houttuynia cordata are representative anti-diabetic therapeutics in western and oriental medicine, respectively. The current study examined the synergistic anti-diabetic effect of Houttuynia cordata extraction (HCE) and metformin combination in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Fecal microbiota were analyzed by denaturing gradient gel electrophoresis (DGGE) and real-time PCR. Combining HCE + metformin resulted in significantly ameliorated glucose tolerance (oral glucose tolerance test (OGTT))-the same as metformin alone. Particularly, results of the insulin tolerance test (ITT) showed that combining HCE + metformin dramatically improved insulin sensitivity as compared to metformin treatment alone. Both fecal and serum endotoxin, as well as cytokines (tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6)) were significantly ameliorated by HCE + metformin compared to metformin alone. Meanwhile, the activation of AMPK (adenosine monophosphate-activated protein kinase) by metformin was distinctly enhanced by HCE. Both of HCE and metformin evidently changed the gut microbiota composition, causing the alteration of bacterial metabolite, like short-chain fatty acids. H. cordata , together with metformin, exerts intensive sensibilization to insulin; the corresponding mechanisms are associated with alleviation of endotoxemia via regulation of gut microbiota, particularly Roseburia , Akkermansia , and Gram-negative bacterium.

Houttuynia cordata Facilitates Metformin on Ameliorating Insulin Resistance Associated with Gut Microbiota Alteration in OLETF Rats

PubMed Central

Bose, Shambhunath; Lim, Soo-Kyoung; Ansari, AbuZar; Chin, Young-Won; Choi, Han Seok; Kim, Hojun

2017-01-01

Metformin and Houttuynia cordata are representative anti-diabetic therapeutics in western and oriental medicine, respectively. The current study examined the synergistic anti-diabetic effect of Houttuynia cordata extraction (HCE) and metformin combination in Otsuka Long–Evans Tokushima Fatty (OLETF) rats. Fecal microbiota were analyzed by denaturing gradient gel electrophoresis (DGGE) and real-time PCR. Combining HCE + metformin resulted in significantly ameliorated glucose tolerance (oral glucose tolerance test (OGTT))—the same as metformin alone. Particularly, results of the insulin tolerance test (ITT) showed that combining HCE + metformin dramatically improved insulin sensitivity as compared to metformin treatment alone. Both fecal and serum endotoxin, as well as cytokines (tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6)) were significantly ameliorated by HCE + metformin compared to metformin alone. Meanwhile, the activation of AMPK (adenosine monophosphate-activated protein kinase) by metformin was distinctly enhanced by HCE. Both of HCE and metformin evidently changed the gut microbiota composition, causing the alteration of bacterial metabolite, like short-chain fatty acids. H. cordata, together with metformin, exerts intensive sensibilization to insulin; the corresponding mechanisms are associated with alleviation of endotoxemia via regulation of gut microbiota, particularly Roseburia, Akkermansia, and Gram-negative bacterium. PMID:28937612

Phytol in a pharma-medico-stance.

PubMed

Islam, Md Torequl; de Alencar, Marcus Vinícius Oliveira Barros; da Conceição Machado, Katia; da Conceição Machado, Keylla; de Carvalho Melo-Cavalcante, Ana Amélia; de Sousa, Damiao Pergentino; de Freitas, Rivelilson Mendes

2015-10-05

This study aims to review phytol (PYT), through published articles, periodicals, magazines and patents, which were retrieved from the PM, SD, WS, SP; DII, WIPO, CIPO, USPTO and INPI databases. Among the 149 articles and 62 patents, 27.52% articles and 87.09% patients were found on the searched topic, PYT and its sources and synthesis and metabolism; then followed by 15.44% and 14.77% articles on PYT in cytotoxicity/cancer/mutagenicity/teratogenicity and PYT in neurological diseases, respectively. In the pharma-medico viewpoint, PYT and its derivatives have been evident to have antimicrobial, cytotoxic, antitumorous, antimutagenic, anti-teratogenic, antibiotic-chemotherapeutic, antidiabetic, lipid lowering, antispasmodic, anticonvulsant, antinociceptive, antioxidant, anti-inflammatory, anxiolytic, antidepressant, immunoadjuvancy, hair growth facilitator, hair fall defense and antidandruff activities. Otherwise, the important biometebolite of PYT is phytanic acid (PA). Evidence shows PA to have cytotoxic, anticancer, antidiabetic, lipid lowering and aniteratogenic activities. In addition, it may be considered as an important biomarker for some diseases such as Refsum's Disease (RD), Sjögren Larsson syndrome (SLS), rhizomelic chondrodysplasia punctata (RZCP), chronic polyneuropathy (CP), Zellweger's disease hyperpipecolic academia (ZDHA) and related diseases. Thus, phytol may be considered as a new drug candidate. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Modified Metformin as a More Potent Anticancer Drug: Mitochondrial Inhibition, Redox Signaling, Antiproliferative Effects and Future EPR Studies.

PubMed

Kalyanaraman, Balaraman; Cheng, Gang; Hardy, Micael; Ouari, Olivier; Sikora, Adam; Zielonka, Jacek; Dwinell, Michael B

2017-12-01

Metformin, one of the most widely prescribed antidiabetic drugs in the world, is being repurposed as a potential drug in cancer treatment. Epidemiological studies suggest that metformin exerts anticancer effects in diabetic patients with pancreatic cancer. However, at typical antidiabetic doses the bioavailability of metformin is presumably too low to exert antitumor effects. Thus, more potent analogs of metformin are needed in order to increase its anticancer efficacy. To this end, a new class of mitochondria-targeted metformin analogs (or mito-metformins) containing a positively-charged lipophilic triphenylphosphonium group was synthesized and tested for their antitumor efficacy in pancreatic cancer cells. Results indicate that the lead compound, mito-metformin 10 , was nearly 1000-fold more potent than metformin in inhibiting mitochondrial complex I activity, inducing reactive oxygen species (superoxide and hydrogen peroxide) that stimulate redox signaling mechanisms, including the activation of adenosinemonophosphate kinase and inhibition of proliferation of pancreatic cancer cells. The potential use of the low-temperature electron paramagnetic resonance technique in assessing the role of mitochondrial complexes including complex I in tumor regression in response to metformin and mito-metformins in the in vivo setting is discussed.

Antioxidant, antihyperglycemic, and antidiabetic activity of Apis mellifera bee tea.

PubMed

Melo da Cunha, Janielle da Silva; Alfredo, Tamaeh Monteiro; Dos Santos, Jéssica Maurino; Alves Junior, Valter Vieira; Rabelo, Luiza Antas; Lima, Emerson Silva; Boleti, Ana Paula de Araújo; Carollo, Carlos Alexandre; Dos Santos, Edson Lucas; de Picoli Souza, Kely

2018-01-01

Diabetes has emerged as one of the largest global epidemics; it is estimated that by 2035, there will be 592 million diabetic people in the world. Brazilian biodiversity and the knowledge of traditional peoples have contributed to the treatment of several diseases, including diabetes. Apis mellifera bee tea is used by indigenous Brazilians to treat diabetes, and this traditional knowledge needs to be recorded and studied.The objective of this study was to record the use and to evaluate the antioxidant, antihyperglycemic, and antidiabetic activity of Apis mellifera bee tea, which is used by the Guarani and Kaiowá indigenous people for the treatment of diabetes. Semi-structured interviews were performed with Guarani and Kaiowá ethnic indigenous people from the State of Mato Grosso do Sul, Brazil, seeking to identify the animal species used for medicinal purposes. For the experimental procedures, tea prepared with macerated Apis mellifera bees was used. In vitro assays were performed to evaluate antioxidant activity; direct free radical scavenging, protection against oxidative hemolysis, lipid peroxidation were evaluated in human erythrocytes and potential in inhibiting the formation of advanced glycation end products (AGEs). In vivo, normoglycemic Swiss male mice treated with Apis mellifera tea (AmT) were subjected to the oral glucose tolerance test and compared with control and metformin-treated groups. Diet-induced diabetic mice were treated for 21 days with AmT and evaluated for glycemia and malondialdehyde levels in the blood, liver, nervous system, and eyes. During interviews, the indigenous people described the use of Apis mellifera bee tea for the treatment of diabetes. In in vitro assays, AmT showed direct antioxidant activity and reduced oxidative hemolysis and malondialdehyde generation in human erythrocytes. The AmT inhibited the formation of AGEs by albumin-fructose pathways and methylglyoxal products. In vivo, after oral glucose overload, normoglycemic mice treated with AmT had reduced hyperglycemia at all times evaluated up to 180 min. AmT also reduced hyperglycemia and malondialdehyde levels in the blood, liver, nervous system, and eyes of diabetic mice to similar levels as those in metformin-treated mice and normoglycemic controls. In summary, Apis mellifera bee tea showed antioxidant, antihyperglycemic, and antidiabetic activity, which provides support for the therapeutic application of Guarani and Kaiowá indigenous knowledge.

Potential use of bitter melon (Momordica charantia) derived compounds as antidiabetics: In silico and in vivo studies.

PubMed

Elekofehinti, Olusola Olalekan; Ariyo, Esther Opeyemi; Akinjiyan, Moses Orimoloye; Olayeriju, Olanrewaju Sam; Lawal, Akeem Olalekan; Adanlawo, Isaac Gbadura; Rocha, Joao Batista Teixeira

2018-05-12

Momordica charantia (bitter lemon) belongs to the cucurbitaceae family which has been extensively used in traditional medicines for the cure of various ailments such as cancer and diabetes. The underlying mechanism of M. charantia to maintain glycemic control was investigated. GLP-1 and DPP-4 gene modulation by M. charantia (5-20% inclusion in rats diet) was investigated in vivo by RT-PCR and possible compounds responsible for diabetic action predicted through in silico approach. Phytochemicalss previously characterized from M. charantia were docked into glucacon like peptide-1 receptor (GLP-1r), dipeptidyl peptidase (DPP4) and Takeda-G-protein-receptor-5 (TGR5) predicted using Autodock Vina. The results of the in silico suggests momordicosides D (ligand for TGR5), cucurbitacin (ligand for GLP-1r) and charantin (ligand for DPP-4) as the major antidiabetic compounds in bitter lemon leaf. M. charantia increased the expression of GLP-1 by about 295.7% with concomitant decreased in expression of DPP-4 by 87.2% with 20% inclusion in rat's diet. This study suggests that the mechanism underlying the action of these compounds is through activation of TGR5 and GLP-1 receptor with concurrent inhibition of DPP4. This study confirmed the use of this plant in diabetes management and the possible bioactive compounds responsible for its antidiabetic property are charantin, cucurbitacin and momordicoside D and all belong to the class of saponins. Copyright © 2018 Elsevier B.V. All rights reserved.

C-Aryl glucoside SGLT2 inhibitors containing a biphenyl motif as potential anti-diabetic agents.

PubMed

Ding, Yuyang; Mao, Liufeng; Xu, Dengfeng; Xie, Hui; Yang, Ling; Xu, Hongjiang; Geng, Wenjun; Gao, Yong; Xia, Chunguang; Zhang, Xiquan; Meng, Qingyi; Wu, Donghai; Zhao, Junling; Hu, Wenhui

2015-07-15

A series of highly active C-aryl glucoside SGLT2 inhibitors containing a biphenyl motif were designed and synthesized for biological evaluation. Among the compounds tested, compound 16l demonstrated high inhibitory activity against SGLT2 (IC50=1.9 nM) with an excellent pharmacokinetic profile. Further study indicated that the in vivo efficacy of compound 16l was comparable to that of dapagliflozin, suggesting that further development would be worthwhile. Copyright © 2015 Elsevier Ltd. All rights reserved.

Antidiabetes and Anti-obesity Activity of Lagerstroemia speciosa

PubMed Central

Klein, Guy; Kim, Jaekyung; Himmeldirk, Klaus; Cao, Yanyan

2007-01-01

The leaves of Lagerstroemia speciosa (Lythraceae), a Southeast Asian tree more commonly known as banaba, have been traditionally consumed in various forms by Philippinos for treatment of diabetes and kidney related diseases. In the 1990s, the popularity of this herbal medicine began to attract the attention of scientists worldwide. Since then, researchers have conducted numerous in vitro and in vivo studies that consistently confirmed the antidiabetic activity of banaba. Scientists have identified different components of banaba to be responsible for its activity. Using tumor cells as a cell model, corosolic acid was isolated from the methanol extract of banaba and shown to be an active compound. More recently, a different cell model and the focus on the water soluble fraction of the extract led to the discovery of other compounds. The ellagitannin Lagerstroemin was identified as an effective component of the banaba extract responsible for the activity. In a different approach, using 3T3-L1 adipocytes as a cell model and a glucose uptake assay as the functional screening method, Chen et al. showed that the banaba water extract exhibited an insulin-like glucose transport inducing activity. Coupling HPLC fractionation with a glucose uptake assay, gallotannins were identified in the banaba extract as components responsible for the activity, not corosolic acid. Penta-O-galloyl-glucopyranose (PGG) was identified as the most potent gallotannin. A comparison of published data with results obtained for PGG indicates that PGG has a significantly higher glucose transport stimulatory activity than Lagerstroemin. Chen et al. have also shown that PGG exhibits anti-adipogenic properties in addition to stimulating the glucose uptake in adipocytes. The combination of glucose uptake and anti-adipogenesis activity is not found in the current insulin mimetic drugs and may indicate a great therapeutic potential of PGG. PMID:18227906

Drug repurposing: In-vitro anti-glycation properties of 18 common drugs

PubMed Central

Rasheed, Saima; Sánchez, Sara S.; Yousuf, Sammer; Honoré, Stella M.; Choudhary, M. Iqbal

2018-01-01

Drug repositioning or repurposing, i.e. identifying new indications for existing drugs, has gained increasing attention in the recent years. This approach enables the scientists to discover “new targets” for known drugs in a cost and time efficient manner. Glycation, the non-enzymatic reaction of sugars with proteins or nucleic acids to form early glycation (Amadori or fructosamine) products, is a key molecular basis of diabetic complications. Inhibiting the process of non-enzymatic protein glycation is one of the key strategies to prevent glycation-mediated diabetic complications. The present study focuses on the anti-glycation activity of 18 drugs, commonly used for the treatment of gastrointestinal, central nervous system, inflammatory diseases, bacterial infections, and gout. This study was carried out by using two in-vitro protein anti-glycation assay models. Results revealed that nimesulide (3), a non-steroidal anti-inflammatory drug, possesses a good anti-glycation activity in in-vitro BSA-MG and BSA-glucose glycation models with IC50 values of 330.56 ± 2.90, and 145.46 ± 16.35 μM, respectively. Phloroglucinol dihydrate (11), a drug used for the treatment of gastrointestinal diseases, showed a weak activity in BSA-MG glycation model (IC50 = 654.89 ± 2.50 μM), while it showed a good activity in BSA-glucose assay (IC50 = 148.23 ± 0.15 μM). Trimethylphloroglucinol (9), a drug used for the treatment of pain related to functional disorders of the digestive and biliary tracts, also showed a good antiglycation activity in BSA-MG model (IC50 = 321.15 ± 1.26 μM), while it was found to be inactive in in-vitro BSA-glucose assay (IC50 = 12.95% inhibition). These activities of drugs were compared with the anti-glycation activity of the standard, rutin (IC50 = 294.5 ± 1.50 μM in BSA-MG glycation model, and IC50 = 86.94 ± 0.24 μM in BSA- glucose model). Rest of the drugs exhibited a relatively weak antiglycation activity. This study identifies nimesulide (3), and phloroglucinol dihydrate (11) as new inhibitors of in-vitro protein glycation for further investigations as potential anti-diabetic agents. PMID:29300762

Antidiabetic Drugs in Alzheimer's Disease: Mechanisms of Action and Future Perspectives

PubMed Central

Femminella, Grazia Daniela; Bencivenga, Leonardo; Petraglia, Laura; Visaggi, Lucia; Gioia, Lucia; Grieco, Fabrizio Vincenzo; de Lucia, Claudio; Komici, Klara; Edison, Paul

2017-01-01

Diabetes mellitus (DM) and Alzheimer's disease (AD) are two highly prevalent conditions in the elderly population and major public health burden. In the past decades, a pathophysiological link between DM and AD has emerged and central nervous system insulin resistance might play a significant role as a common mechanism; however, other factors such as inflammation and oxidative stress seem to contribute to the shared pathophysiological link. Both preclinical and clinical studies have evaluated the possible neuroprotective mechanisms of different classes of antidiabetic medications in AD, with some promising results. Here, we review the evidence on the mechanisms of action of antidiabetic drugs and their potential use in AD. PMID:28656154

A stewardship intervention program for safe medication management and use of antidiabetic drugs.

PubMed

Zhao, Rui-yi; He, Xiao-wen; Shan, Yan-min; Zhu, Ling-ling; Zhou, Quan

2015-01-01

Diabetes patients are complex due to considerations of polypharmacy, multimorbidities, medication adherence, dietary habits, health literacy, socioeconomic status, and cultural factors. Meanwhile, insulin and oral hypoglycemic agents are high-alert medications. Therefore it is necessary to require a multidisciplinary team's integrated endeavors to enhance safe medication management and use of antidiabetic drugs. A 5-year stewardship intervention program, including organizational measures and quality improvement activities in storage, prescription, dispensing, administration, and monitoring, was performed in the Second Affiliated Hospital of Zhejiang University, People's Republic of China, a 3,200-bed hospital with 3.5 million outpatient visits annually. The Second Affiliated Hospital of Zhejiang University has obtained a 100% implementation rate of standard storage of antidiabetic drugs in the Pharmacy and wards since August 2012. A zero occurrence of dispensing errors related to highly "look-alike" and "sound-alike" NovoMix 30(®) (biphasic insulin aspart) and NovoRapid(®) (insulin aspart) has been achieved since October 2011. Insulin injection accuracy among ward nurses significantly increased from 82% (first quarter 2011) to 96% (fourth quarter 2011) (P<0.05). The number of medication administration errors related to insulin continuously decreased from 20 (2011) to six (2014). The occurrence rate of hypoglycemia in non-endocrinology ward diabetes inpatients during 2011-2013 was significantly less than that in 2010 (5.03%-5.53% versus 8.27%) (P<0.01). Percentage of correct management of hypoglycemia by nurses increased from 41.5% (April 2014) to 67.2% (August 2014) (P<0.01). The percentage of outpatient diabetes patients receiving standard insulin injection education increased from 80% (April 2012) to 95.2% (October 2012) (P<0.05). Insulin injection techniques among diabetes outpatients who started to receive insulin were better than indicated in data from two questionnaire surveys in the literature, including the percentage checking injection sites prior to injection (85.6%), priming before injection (98.1%), rotation of injecting sites (98.1%), remixing before use (94.5%), keeping the pen needle under the skin for >10 seconds (99.4%), and using the pen needle only once (88.7%). On-site inspection indicated of great improvement in the percentage of drug-related problems in the antidiabetes regimen between the first and second quarter of 2014 (1.08% versus 0.28%) (P<0.05). Quality improvements in safe medication management and use of antidiabetic drugs can be achieved by multidisciplinary collaboration among pharmacists, nurses, physicians, and information engineers.

Rosmarinic acid content in antidiabetic aqueous extract of Ocimum canum Sims grown in Ghana

USDA-ARS?s Scientific Manuscript database

Rosmarinic acid (RA) is an important polyphenol that is found in a variety of herbs including Ocimum canum sims (locally called eme or akokobesa in Ghana). Aqueous extracts from the leaves of O.canum are used as an antidiabetic herbal medicine in Ghana. Interestingly, rosmarinic acid content and p...

Anti-diabetic effects of rice hull smoke extract in alloxan-induced diabetic mice

USDA-ARS?s Scientific Manuscript database

We investigated the protective effect of a liquid rice hull smoke extract (RHSE) against diabetes in alloxan-induced diabetic mice. Anti-diabetic effects of RHSE were evaluated in both the rat insulinoma-1 cell line (INS-1) and diabetic ICR mice induced by inraperitoneal (ip) injection of alloxan. ...

Unique Features of Metformin: A Combined Experimental, Theoretical, and Simulation Study of Its Structure, Dynamics, and Interaction Energetics with DNA Grooves.

PubMed

Mondal, Sayantan; Samajdar, Rudra N; Mukherjee, Saumyak; Bhattacharyya, Aninda J; Bagchi, Biman

2018-03-01

There are certain small molecules that exhibit extraordinarily diverse biological activities. Metformin is one of them. It is widely used as an antidiabetic drug for type-two diabetes. Recent lines of evidence of its role in antitumor activities and increasing the survival rates of cancer patients (namely, colorectal, breast, pancreas, and prostate cancer) are emerging. However, theoretical studies of the structure and dynamics of metformin have not yet been fully explored. In this work, we investigate the characteristic structural and dynamical features of three monoprotonated forms of metformin hydrochloride with the help of experiments, quantum chemical calculations, and atomistic molecular dynamics simulations. We validate our force field by comparing simulation results to those of the experimental findings. Energetics of proton transfer between two planar monoprotonated forms reveals a low energy barrier, which leads us to speculate a possible coexistence of them. Nevertheless, among the protonation states, we find that the nonplanar tautomeric form is the most stable. Our calculated values of the self-diffusion coefficient agree quantitatively with NMR results. Metformin forms strong hydrogen bonds with surrounding water molecules, and its solvation dynamics shows unique features. Because of an extended positive charge distribution, metformin possesses features of being a permanent cationic partner toward several targets. We study its interaction and binding ability with DNA using UV spectroscopy, circular dichroism, fluorimetry, and metadynamics simulation. We find a nonintercalative mode of interaction. Metformin feasibly forms a minor/major groove-bound state within a few tens of nanoseconds, preferably with AT-rich domains. A significant decrease in the free energy of binding is observed when it binds to a minor groove of DNA.

6-Shogaol ameliorates diabetic nephropathy through anti-inflammatory, hyperlipidemic, anti-oxidative activity in db/db mice.

PubMed

Xu, Yun; Bai, Liwei; Chen, Xuehui; Li, Yan; Qin, Yan; Meng, Xiangyu; Zhang, Qinggui

2018-01-01

The prevalence of type 2 diabetes mellitus has been increasing worldwide and more than two thirds of the patients may develop diabetic nephropathy (DN). However, the efficiency of existing approaches on DN progression is limited. 6-Shogaol (6-SG), a major dehydrated derivative of gingerols, possesses various biological properties. The present study was designed to evaluate the possible effects of 6-SG on DN in db/db mice and to investigate the mechanisms. We revealed that 6-SG reduced the levels of fasting blood glucose, serum insulin, C-peptide, glycosylated hemoglobin A1c, and systolic blood pressure. 6-SG decreased the levels of blood urea nitrogen (BUN), serum creatinine, urinary albumin content and albumin/creatinine ratio (ACR), ameliorated the pathological injuries of kidneys, reduced the surface area of Bowman's capsule, Bowman's space, glomerular tuft, and decreased the expression of collagen IV and fibronectin in kidneys of db/db mice. The high levels of systemic and renal triglyceride and cholesterol were decreased by 6-SG. Moreover, 6-SG exhibited anti-inflammatory effects, as reflected by reduction of tumor necrosis factor ɑ (TNFɑ), monocyte chemotactic protein-1 (MCP-1), and IL-6 levels in circulation and kidneys, and decrease of NF-κB expression. Furthermore, 6-SG also inhibited oxidative stress and restored the expression of NF-E2-related factor 2 (Nrf2) in kidneys of db/db mice. In conclusion, we have demonstrated that 6-SG exhibits anti-diabetic and renal protective effects against DN, in which effect the anti-inflammatory, hyperlipidemic, anti-oxidative activities may be involved. Overall, 6-SG could be a promising therapeutic treatment to ameliorate diabetes and the development of DN. Copyright © 2017. Published by Elsevier Masson SAS.

I4, a synthetic anti-diabetes agent, attenuates atherosclerosis through its lipid-lowering, anti-inflammatory and anti-apoptosis properties.

PubMed

Ma, Lingman; Qian, Lifen; Ying, Qidi; Zhang, Yan; Zhou, Changlin; Wu, Guanzhong

2017-01-15

Here, we investigated whether I 4 , which was initially developed as a hypoglycemic agent, possesses anti-atherosclerotic activity and attempted to elucidate the probable mechanism of action underlying this activity. ApoE -/- mice were fed a Western diet and simultaneously administered I 4 , glimepiride, or pioglitazone once daily for 12 weeks, and the atherosclerotic vascular lesions, lipid content, and expression levels of LOX-1, ICAM-1, VCAM-1 and Bax/Bcl-2 in mouse aortas were assessed. RAW264.7 macrophage-derived foam cells were obtained via ox-LDL stimulation to investigate the lipid-lowering, anti-atherosclerotic inflammation and anti-apoptotic effect of I 4 . The data indicated that I 4 significantly decreased the lipid accumulation in the circulation and tissue, especially for TG and FFA levels (p < 0.05 vs model group), alleviating the arterial and liver lesions induced by lipotoxicity. Its lipid-reducing effects may due to LOX-1and CD36 expression suppression. I 4 , at doses of 20 mg/kg and 10 mg/kg, significantly decreased serum IL-6, IL-1β, and TNF-α production and suppressed the expression of p-ERK, p-p38, VCAM-1 and ICAM-1 protein. I 4 attenuated atherosclerotic inflammation by blocking NF-κB nuclear translocation, suppressing MAPK/NF-κB signaling pathway and diminishing NF-κB-VCAM-1 promoter region binding. Additionally, I 4 suppressed p-p53 and cleaved-caspase-3 expression to inhibit foam cell apoptosis induced by ox-LDL uptake. Overall, I 4 exerts potent inhibitory effects on atherosclerosis onset and development. Copyright © 2016. Published by Elsevier Ireland Ltd.

Recent development of single preparations and fixed-dose combination tablets for the treatment of non-insulin-dependent diabetes mellitus : A comprehensive summary for antidiabetic drugs.

PubMed

Li, Jianwen; Lian, He

2016-06-01

As a complex endocrine and metabolic disorder, type 2 diabetes mellitus (non-insulin-dependent diabetes mellitus, NIDDM) has become a major threat to human health. Because of the heterogeneous and progressive disorders induced by insulin resistance and pancreatic b-cell dysfunction, the treatment of NIDDM is still challenging. Although antidiabetic drugs with different pharmacological mechanisms of action have been used clinically, different degrees of undesirable glucose control and the incidences of a variety of side effects, including hypoglycemia, cardiovascular complications and weight gain require the better treatment options. This article has overviewed the current literature about commercially available antidiabetic drugs with different pharmacological mechanisms of action in the treatment of NIDDM, and summarized the published data regarding the efficacy, tolerability, and safety of currently available single preparations and fixed-dose combinations, aiming to provide important information for the development and application of antidiabetic drugs in the future. The literature search from 1989 to 2015 was conducted by PubMed, ScienceDirect, Springer, American Diabetes Association, and U.S. FDA Drugs databases.

Antidiabetic Properties of Germinated Brown Rice: A Systematic Review

PubMed Central

Bhanger, Muhammad Iqbal; Ismail, Norsharina; Ismail, Maznah

2012-01-01

Diet is an important variable in the course of type 2 diabetes, which has generated interest in dietary options like germinated brown rice (GBR) for effective management of the disease among rice-consuming populations. In vitro data and animal experiments show that GBR has potentials as a functional diet for managing this disease, and short-term clinical studies indicate encouraging results. Mechanisms for antidiabetic effects of GBR due to bioactive compounds like γ-aminobutyric acid (GABA), γ-oryzanol, dietary fibre, phenolics, vitamins, acylated steryl β-glucoside, and minerals include antihyperglycemia, low insulin index, antioxidative effect, antithrombosis, antihypertensive effect, hypocholesterolemia, and neuroprotective effects. The evidence so far suggests that there may be enormous benefits for diabetics in rice-consuming populations if white rice is replaced with GBR. However, long-term clinical studies are still needed to verify these findings on antidiabetic effects of GBR. Thus, we present a review on the antidiabetic properties of GBR from relevant preclinical and clinical studies, in order to provide detailed information on this subject for researchers to review the potential of GBR in combating this disease. PMID:23304216

Molecular Insights into Human Monoamine Oxidase B Inhibition by the Glitazone Antidiabetes Drugs

PubMed Central

2011-01-01

The widely employed antidiabetic drug pioglitazone (Actos) is shown to be a specific and reversible inhibitor of human monoamine oxidase B (MAO B). The crystal structure of the enzyme–inhibitor complex shows that the R-enantiomer is bound with the thiazolidinedione ring near the flavin. The molecule occupies both substrate and entrance cavities of the active site, establishing noncovalent interactions with the surrounding amino acids. These binding properties differentiate pioglitazone from the clinically used MAO inhibitors, which act through covalent inhibition mechanisms and do not exhibit a high degree of MAO A versus B selectivity. Rosiglitazone (Avandia) and troglitazone, other members of the glitazone class, are less selective in that they are weaker inhibitors of both MAO A and MAO B. These results suggest that pioglitazone may have utility as a “repurposed” neuroprotectant drug in retarding the progression of disease in Parkinson's patients. They also provide new insights for the development of reversible isoenzyme-specific MAO inhibitors. PMID:22282722

Preparation of S-Allylcysteine-Enriched Black Garlic Juice and Its Antidiabetic Effects in Streptozotocin-Induced Insulin-Deficient Mice.

PubMed

Kim, Jun Ho; Yu, Su Hyun; Cho, Yun Jeong; Pan, Jeong Hoon; Cho, Hyung Taek; Kim, Jeong Ho; Bong, Hyejin; Lee, Yeojin; Chang, Moon Han; Jeong, Ye Jin; Choi, Garam; Kim, Young Jun

2017-01-18

S-Allylcysteine (SAC), produced in large amounts during the aging process of garlic via enzymatic hydrolysis, is known as a key compound responsible for the multiple pharmacological activities of aged black garlic. This study investigated the effects of enzyme- and high hydrostatic pressure (HHP)-assisted extraction on the content of the bioactive compounds, including SAC, in black garlic juice (BGJ) and evaluated the antidiabetic effects of SAC-enriched BGJ in streptozotocin (STZ)-treated mice. The aging process increased the contents of SAC, total polyphenols, and total flavonoids in garlic juice. More importantly, pretreatment of pectinase cocktail with HHP resulted in a greater increase in those compounds during aging. Enzyme-treated BGJ reduced hyperglycemia and improved islet architecture and β-cell function in STZ-treated mice. Moreover, these effects were more potent than those of BGJ prepared by the conventional aging process. These findings provide useful information for the production of black garlic with improved bioactivities.

Quinoa seeds leach phytoecdysteroids and other compounds with anti-diabetic properties

PubMed Central

Graf, Brittany L.; Poulev, Alexander; Kuhn, Peter; Grace, Mary H.; Lila, Mary Ann; Raskin, Ilya

2014-01-01

Quinoa (Chenopodium quinoa Willd.) contains high levels of biologically active phytoecdysteroids, which have been implicated in plant defense from insects, and have shown a range of beneficial pharmacological effects in mammals. We demonstrated that the most prevalent phytoecdysteroid, 20-hydroxyecdysone (20HE), was secreted (leached) from intact quinoa seeds into water during the initial stages of seed germination. Leaching efficiency was optimized by ethanol concentration (70% ethanol), temperature (80°C), time (4 h), and solvent ratio (5 ml/g seed). When compared to extraction of macerated seeds, the leaching procedure released essentially all the 20HE available in the seeds (491 μg/g seed). The optimized quinoa leachate (QL), containing 0.86% 20HE, 1.00% total phytoecdysteroids, 2.59% flavonoid glycosides, 11.9% oil, and 20.4% protein, significantly lowered fasting blood glucose in obese, hyperglycemic mice. Leaching effectively releases and concentrates bioactive phytochemicals from quinoa seeds, providing an efficient means to produce a food-grade mixture that may be useful for anti-diabetic applications. PMID:24912714

Brown Adipose Tissue Improves Whole-Body Glucose Homeostasis and Insulin Sensitivity in Humans

PubMed Central

Chondronikola, Maria; Volpi, Elena; Børsheim, Elisabet; Porter, Craig; Annamalai, Palam; Enerbäck, Sven; Lidell, Martin E.; Saraf, Manish K.; Labbe, Sebastien M.; Hurren, Nicholas M.; Yfanti, Christina; Chao, Tony; Andersen, Clark R.; Cesani, Fernando; Hawkins, Hal

2014-01-01

Brown adipose tissue (BAT) has attracted scientific interest as an antidiabetic tissue owing to its ability to dissipate energy as heat. Despite a plethora of data concerning the role of BAT in glucose metabolism in rodents, the role of BAT (if any) in glucose metabolism in humans remains unclear. To investigate whether BAT activation alters whole-body glucose homeostasis and insulin sensitivity in humans, we studied seven BAT-positive (BAT+) men and five BAT-negative (BAT−) men under thermoneutral conditions and after prolonged (5–8 h) cold exposure (CE). The two groups were similar in age, BMI, and adiposity. CE significantly increased resting energy expenditure, whole-body glucose disposal, plasma glucose oxidation, and insulin sensitivity in the BAT+ group only. These results demonstrate a physiologically significant role of BAT in whole-body energy expenditure, glucose homeostasis, and insulin sensitivity in humans, and support the notion that BAT may function as an antidiabetic tissue in humans. PMID:25056438

Antidiabetic Mechanisms of Rosa canina Fruits

PubMed Central

Fattahi, Ali; Niyazi, Fatemeh; Shahbazi, Behzad; Farzaei, Mohammad Hosein; Bahrami, Gholamreza

2016-01-01

Rosa canina fruits have been used traditionally for the treatment of diabetes mellitus and its complications. The aim of current study was to evaluate the in vitro mechanism of action of R canina in managing diabetes mellitus. Cell proliferation and cytotoxicity assay were performed on pancreatic β-cells, βTC6. The protective activity of the extract on streptozotocin-induced death in βTC6 cells was studied. The effect of R canina on the metabolism of glucose in HepG2, a hepatocellular carcinoma cell line, was evaluated. The effect of the extract on glucose diffusion across the dialysis membrane, which is a comfortable model for assessing cellular glucose absorption, was evaluated. The results obtained from current study confirmed that R canina extract can act as a growth factor for pancreatic β-cell line providing a novel mechanism for the observed antidiabetic effect of this natural agent. Further preclinical studies are necessary to evaluate the perfect mechanism of action of R canina in diabetes mellitus. PMID:27352916

Protective role of Scoparia dulcis plant extract on brain antioxidant status and lipidperoxidation in STZ diabetic male Wistar rats

PubMed Central

Pari, Leelavinothan; Latha, Muniappan

2004-01-01

Background The aim of the study was to investigate the effect of aqueous extract of Scoparia dulcis on the occurrence of oxidative stress in the brain of rats during diabetes by measuring the extent of oxidative damage as well as the status of the antioxidant defense system. Methods Aqueous extract of Scoparia dulcis plant was administered orally (200 mg/kg body weight) and the effect of extract on blood glucose, plasma insulin and the levels of thiobarbituric acid reactive substances (TBARS), hydroperoxides, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) were estimated in streptozotocin (STZ) induced diabetic rats. Glibenclamide was used as standard reference drug. Results A significant increase in the activities of plasma insulin, superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and reduced glutathione was observed in brain on treatment with 200 mg/kg body weight of Scoparia dulcis plant extract (SPEt) and glibenclamide for 6 weeks. Both the treated groups showed significant decrease in TBARS and hydroperoxides formation in brain, suggesting its role in protection against lipidperoxidation induced membrane damage. Conclusions Since the study of induction of the antioxidant enzymes is considered to be a reliable marker for evaluating the antiperoxidative efficacy of the medicinal plant, these findings suggest a possible antiperoxidative role for Scoparia dulcis plant extract. Hence, in addition to antidiabetic effect, Scoparia dulcis possess antioxidant potential that may be used for therapeutic purposes. PMID:15522116

Protective role of Scoparia dulcis plant extract on brain antioxidant status and lipidperoxidation in STZ diabetic male Wistar rats.

PubMed

Pari, Leelavinothan; Latha, Muniappan

2004-11-02

The aim of the study was to investigate the effect of aqueous extract of Scoparia dulcis on the occurrence of oxidative stress in the brain of rats during diabetes by measuring the extent of oxidative damage as well as the status of the antioxidant defense system. Aqueous extract of Scoparia dulcis plant was administered orally (200 mg/kg body weight) and the effect of extract on blood glucose, plasma insulin and the levels of thiobarbituric acid reactive substances (TBARS), hydroperoxides, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and reduced glutathione (GSH) were estimated in streptozotocin (STZ) induced diabetic rats. Glibenclamide was used as standard reference drug. A significant increase in the activities of plasma insulin, superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and reduced glutathione was observed in brain on treatment with 200 mg/kg body weight of Scoparia dulcis plant extract (SPEt) and glibenclamide for 6 weeks. Both the treated groups showed significant decrease in TBARS and hydroperoxides formation in brain, suggesting its role in protection against lipidperoxidation induced membrane damage. Since the study of induction of the antioxidant enzymes is considered to be a reliable marker for evaluating the antiperoxidative efficacy of the medicinal plant, these findings suggest a possible antiperoxidative role for Scoparia dulcis plant extract. Hence, in addition to antidiabetic effect, Scoparia dulcis possess antioxidant potential that may be used for therapeutic purposes.

Effectiveness of Antihyperglycemic Effect of Momordica charantia: Implication of T-Cell Cytokines

PubMed Central

2017-01-01

Background/Objective We investigate the effect of antidiabetic Momordica charantia fruit juice on T cells' differentiation, through plasmatic cytokine quantification in type 1 diabetic rats (T1D). Methods Male Wistar rats were rendered diabetic by the injection of five low doses of streptozotocin. Then, animals were treated with Momordica charantia fruit juice for 28 consecutive days. Plasmatic levels of Th1 interleukin- (IL-) 02 and interferon- (IFN-) γ, Th2 (IL-4), and regulatory (IL-10) cytokines were determined in rats. Results We observed that fruit juice induced a significant decrease in blood glucose of T1D rats. Besides, the concentrations of IL-2 and IFN-γ significantly increased while those of IL-4 and IL-10 diminished in diabetic rats compared to control animals. Interestingly, after treatment with Momordica charantia fruit juice, IL-4 and IL-10 levels significantly increased in diabetic rats, while IL-2 and IFN-γ concentrations decreased, suggesting a Th2 phenotype in these animals. Phytochemical analysis of the fruit juice revealed the presence of tannins, flavonoids, and coumarins, compounds which possess antioxidant activity. Conclusion This study shows that Momordica charantia fruit juice, by lowering the hyperglycemia, induced a shift of proinflammatory Th1 phenotype in T1D rats towards a favorable anti-inflammatory Th2 status. These effects might be due to the presence of antioxidant compounds in the juice and confirms the use of this plant in the treatment of autoimmune type 1 diabetes. PMID:29317893

Effectiveness of Antihyperglycemic Effect of Momordica charantia: Implication of T-Cell Cytokines.

PubMed

Fachinan, Rufine; Yessoufou, Akadiri; Nekoua, Magloire Pandoua; Moutairou, Kabirou

2017-01-01

We investigate the effect of antidiabetic Momordica charantia fruit juice on T cells' differentiation, through plasmatic cytokine quantification in type 1 diabetic rats (T1D). Male Wistar rats were rendered diabetic by the injection of five low doses of streptozotocin. Then, animals were treated with Momordica charantia fruit juice for 28 consecutive days. Plasmatic levels of Th1 interleukin- (IL-) 02 and interferon- (IFN-) γ , Th2 (IL-4), and regulatory (IL-10) cytokines were determined in rats. We observed that fruit juice induced a significant decrease in blood glucose of T1D rats. Besides, the concentrations of IL-2 and IFN- γ significantly increased while those of IL-4 and IL-10 diminished in diabetic rats compared to control animals. Interestingly, after treatment with Momordica charantia fruit juice, IL-4 and IL-10 levels significantly increased in diabetic rats, while IL-2 and IFN- γ concentrations decreased, suggesting a Th2 phenotype in these animals. Phytochemical analysis of the fruit juice revealed the presence of tannins, flavonoids, and coumarins, compounds which possess antioxidant activity. This study shows that Momordica charantia fruit juice, by lowering the hyperglycemia, induced a shift of proinflammatory Th1 phenotype in T1D rats towards a favorable anti-inflammatory Th2 status. These effects might be due to the presence of antioxidant compounds in the juice and confirms the use of this plant in the treatment of autoimmune type 1 diabetes.

Hypoglycemic and Hypocholesterolemic Effects of Botryosphaeran from Botryosphaeria rhodina MAMB-05 in Diabetes-Induced and Hyperlipidemia Conditions in Rats

PubMed Central

Miranda-Nantes, Carolina C. B. O.; Fonseca, Eveline A. I.; Zaia, Cassia T. B. V.; Dekker, Robert F. H.; Khaper, Neelam; Castro, Inar A.

2011-01-01

Botryosphaeran, a water-soluble exopolysaccharide of the β-(1 → 3;1 → 6)-D-glucan type that has been isolated from the culture medium of Botryosphaeria rhodina MAMB-05 grown in submerged fermentation using glucose as the sole carbon source, was previously demonstrated to be non-genotoxic in peripheral blood and bone marrow, and exhibited strong anticlastogenic activity. In the present study, the effects of botryosphaeran were investigated in streptozotocin-induced diabetic rats as well as in high-fat diet-fed hyperlipidemic Wistar rats. The plasma glucose level was reduced by 52% in the diabetic group of rats after administration of 12 mg botryosphaeran/kg body weight of the rats (b.w.)/day by gavage over 15 days. A reduction in the median ration intake was accompanied by an increase in the median body weight gain, as well as the efficiency of food conversion. These results demonstrate that botryosphaeran has protective effects by reducing the symptoms of cachexia in Diabetes mellitus. Botryosphaeran administered by gavage at a concentration of 12 mg botryosphaeran/kg b.w./day over 15 days also reduced the plasma levels of total cholesterol and low density lipoprotein-cholesterol by 18% and 27%, respectively, in hyperlipidemic rats. Based on these findings, we conclude that botryosphaeran possesses hypoglycemic and hypocholesterolemic properties in conditions of diabetes mellitus and hyperlipidemia, respectively, and may be used as an oral anti-diabetic agent. PMID:22783102

Hypoglycemic and Hypocholesterolemic Effects of Botryosphaeran from Botryosphaeria rhodina MAMB-05 in Diabetes-Induced and Hyperlipidemia Conditions in Rats.

PubMed

Miranda-Nantes, Carolina C B O; Fonseca, Eveline A I; Zaia, Cassia T B V; Dekker, Robert F H; Khaper, Neelam; Castro, Inar A; Barbosa, Aneli M

2011-09-01

Botryosphaeran, a water-soluble exopolysaccharide of the β-(1 → 3;1 → 6)-D-glucan type that has been isolated from the culture medium of Botryosphaeria rhodina MAMB-05 grown in submerged fermentation using glucose as the sole carbon source, was previously demonstrated to be non-genotoxic in peripheral blood and bone marrow, and exhibited strong anticlastogenic activity. In the present study, the effects of botryosphaeran were investigated in streptozotocin-induced diabetic rats as well as in high-fat diet-fed hyperlipidemic Wistar rats. The plasma glucose level was reduced by 52% in the diabetic group of rats after administration of 12 mg botryosphaeran/kg body weight of the rats (b.w.)/day by gavage over 15 days. A reduction in the median ration intake was accompanied by an increase in the median body weight gain, as well as the efficiency of food conversion. These results demonstrate that botryosphaeran has protective effects by reducing the symptoms of cachexia in Diabetes mellitus. Botryosphaeran administered by gavage at a concentration of 12 mg botryosphaeran/kg b.w./day over 15 days also reduced the plasma levels of total cholesterol and low density lipoprotein-cholesterol by 18% and 27%, respectively, in hyperlipidemic rats. Based on these findings, we conclude that botryosphaeran possesses hypoglycemic and hypocholesterolemic properties in conditions of diabetes mellitus and hyperlipidemia, respectively, and may be used as an oral anti-diabetic agent.

Reduced diabetic, hypertensive, and cholesterol medication use with walking.

PubMed

Williams, Paul T

2008-03-01

To assess the relationships of walking distance, frequency, and intensity to the prevalence of antidiabetic, antihypertensive, and LDL cholesterol-lowering medications use. Cross-sectional analyses of 32,683 female and 8112 male participants of the National Walkers' Health Study, of whom 2.8% and 7.4% reported antidiabetic, 14.3% and 29.0% reported antihypertensive, and 7.3% and 21.5% reported LDL cholesterol-lowering medication use, respectively. Weekly walking distance, longest walk, and walking intensity were inversely related to the prevalence of antidiabetic (males: P < 0.001, females: P < 0.0001), antihypertensive (males: P < 0.01, females: P < 0.0001), and LDL cholesterol-lowering medications (males: P < 0.01, females: P < 0.0001). Each medication remained significantly related to both walking intensity and longest weekly walk when adjusted for total weekly distance. Compared with men and women who walked at a speed of < 1.2 m.s, those who walked > 2.1 m.s had 48% and 52% lower odds for antihypertensive, 68% and 59% lower odds for antidiabetic, and 53% and 40% lower odds for LDL cholesterol-lowering medications, respectively, when adjusted for age, smoking, and diet. The longest usual weekly walk was a better discriminator of medication status than the total cumulative distance per week, particularly in men. These results are consistent with the hypothesis that antidiabetic, antihypertensive, and LDL cholesterol-lowering medication use may be reduced substantially by walking more intensely and farther each week, and by including longer walks.

Novel drug delivery system: an immense hope for diabetics.

PubMed

Rai, Vineet Kumar; Mishra, Nidhi; Agrawal, Ashish Kumar; Jain, Sanyog; Yadav, Narayan Prasad

2016-09-01

Existing medication systems for the treatment of diabetes mellitus (DM) are inconvenient and troublesome for effective and safe delivery of drugs to the specific site. Therefore, investigations are desired to deliver antidiabetics using novel delivery approaches followed by their commercialization. The present review aims to provide a compilation on the latest development in the field of novel drug delivery systems (NDDSs) for antidiabetics with special emphasis on particulate, vesicular and miscellaneous systems. Review of literature (restricted to English language only) was done using electronic databases like Pubmed® and Scirus, i.e. published during 2005-2013. The CIMS/MIMS India Medical Drug Information eBook was used regarding available marketed formulation of antidiabetic drugs. Keywords used were "nanoparticle", "microparticle", "liposomes", "niosomes", "transdermal systems", "insulin", "antidiabetic drugs" and "novel drug delivery systems". Single inclusion was made for one article. If in vivo study was not done then article was seldom included in the manuscript. The curiosity to develop NDDSs of antidiabetic drugs with special attention to the nanoparticulate system followed by microparticulate and lipid-based system is found to emerge gradually to overcome the problems associated with the conventional dosage forms and to win the confidence of end users towards the higher acceptability. In the current scientific panorama when the area of novel drug delivery system has been recognized for its palpable benefits, unique potential of providing physical stability, sustained and site-specific drug delivery for a scheduled period of time can open new vistas for precise, safe and quality treatment of DM.

Anti-diabetic medications and risk of primary liver cancer in persons with type II diabetes.

PubMed

Hagberg, K W; McGlynn, K A; Sahasrabuddhe, V V; Jick, S

2014-10-28

Type II diabetes increases liver cancer risk but the risk may be mitigated by anti-diabetic medications. However, choice of medications is correlated with diabetes duration and severity, leading to confounding by indication. To address this association, we conducted a nested case-control study among persons with type II diabetes in the Clinical Practice Research Datalink. Cases had primary liver cancer and controls were matched on age, sex, practice, calendar time, and number of years in the database. Exposure was classified by type and combination of anti-diabetic prescribed and compared to non-use. Odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated using conditional logistic regression. In 305 cases of liver cancer and 1151 controls, there was no association between liver cancer and anti-diabetic medication use compared to non-use (OR=0.74 (95% CI=0.45-1.20) for metformin-only, 1.10 (95% CI=0.66-1.84) for other oral hypoglycaemic (OH)-only, 0.89 (95% CI=0.58-1.37) for metformin+other OH, 1.11 (95% CI=0.60-2.05) for metformin+insulin, 0.81 (95% CI=0.23-2.85) for other OH+insulin, and 0.72 (95% CI=0.18-2.84) for insulin-only). Stratification by duration of diabetes did not alter the results. Use of any anti-diabetic medications in patients with type II diabetes was not associated with liver cancer, though there was a suggestion of a small protective effect for metformin.