Morin activates the Nrf2-ARE pathway and reduces oxidative stress-induced DNA damage in pancreatic beta cells.

Oxidative stress is an important factor contributing to the pathogenesis of diabetes and its complications. In our earlier study, we demonstrated the antidiabetic efficacy of morin by regulating key enzymes of carbohydrate metabolism in diabetic rats. The present study was designed to assess the antigenotoxic potential of morin in pancreatic ß-cells, using the COMET assay. To explore its potential mechanisms of action, three genotoxic agents, H2O2 which induces DNA damage by the generation of reactive oxygen species, streptozotocin (STZ) by RNS and Methyl methanesulfonate (MMS) by DNA alkylation was used. We found that STZ and H2O2- induced genotoxicity was dose dependently reduced by morin as assessed by DNA tail length, tail moment, DNA content and olive moment. Since the protective property was found to be specific against oxidative DNA damage, we explored the molecular mechanism underlying morin-induced Nuclear factor erythroid 2-related factor 2 (Nrf2) activation in pancreatic ß-cells as assessed by ARE-driven downstream target genes with Luciferase reporter assay. In addition, morin inhibited intracellular free radical generation as assessed by using DCFDA and increased the intra cellular antioxidants viz, superoxide dismutase and catalase in INS-1E cells. In addition, morin attenuated glucose-stimulated insulin secretion following exposure to oxidative stress by STZ (P<0.05). Collectively, our data provide evidence that morin protects pancreatic ß-cells against oxidative stress-induced DNA damage by activating the Nrf2 signaling pathway.

In vitro evaluation of free radical scavenging activity of Codariocalyx motorius root extract

OBJECTIVE@#To determine the phenolic content in Codariocalyx motorius root extract and to evaluate its antioxidant properties using various in vitro assay systems.@*METHODS@#The antioxidant activity was evaluated based on scavenging of 1,1-diphenyl-2-picrylhydrazyl, hydroxyl radicals, superoxide anions, nitric oxide, hydrogen peroxide, peroxynitrite, reducing power and by inhibition of lipid peroxidation which was estimated in terms of thiobarbituric acid reactive substances.@*RESULTS@#The root extract of the Codariocalyx motorius (C. motorius) exhibited potent total antioxidant activity that increased with increasing amount of extract concentration, which was compared with standard drug such as quercetin, butylated hydroxytoluene, tocopherol at different concentrations. The different concentrations of the extracts showed inhibition on lipid peroxidation. In addition, the extracts had effective reducing power, free radical scavenging, super oxide anion scavenging, nitric oxide scavenging, lipid peroxidation, and total phenolic content depending on concentration. High correlation between total phenolic contents and scavenging potential of different reactive oxygen species (r(2)=0.831-0.978) indicated the polyphenols as the main antioxidants.@*CONCLUSIONS@#Codariocalyx motorius (C. motorius) root possess the highly active antioxidant substance which can be used for the treatment of oxidative stress-related diseases.

Antidiabetic activity of alcoholic stem extract of Gymnema montanum in streptozotocin-induced diabetic rats.

In the present study, the effect of alcoholic stem extract of Gymnema montanum (GMSt) on blood glucose, plasma insulin, and carbohydrate metabolic enzymes were studied in experimental diabetes. Diabetes mellitus was induced by a single intraperitoneal injection of STZ (60 mg/kg bw). Five days after STZ induction, diabetic rats received GMSt orally at the doses of 25, 50, 100 and 200mg/kg daily for 3 weeks. Graded doses of stem extract showed a significant reduction in blood glucose levels and improvement in plasma insulin levels. The effect was more pronounced in 100 and 200mg/kg than 50mg/kg. GMSt showed significant increase in hexokinase, Glucose-6-phosphate dehydrogenase and glycogen content in liver of diabetic rats while there was significant reduction in the levels of glucose-6-phosphatase and fructose-1,6-bisphosphatase. The present study clearly indicated significant antidiabetic effect with the stem extract of G. montanum and lends support for its traditional usage.