Genistein has been reported to exert beneficial effects on type 2 diabetes mellitus (T2DM); however, the underlying molecular mechanisms involved therein have not been clearly elucidated. To address this question, the effect of genistein on the expression of phosphoenolpyruvate carboxykinase (PEPCK), and glucose production in HepG2 cells and in alloxan-induced diabetic mice was investigated. HepG2 cells were exposed to different concentration of genistein in presence or absence of modulators, and the expression of cytosolic PEPCK (PEPCK-C) and the signaling pathways was studied. Further, the biological relevance of the in vitro study was tested in alloxan-induced diabetic mice. Genistein lowered PEPCK-C expression and glucose production in HepG2 cells accompanied with increased in phosphorylation states of AMPK, MEK½, ERK½, and CRTC2. Treatment with the AMPK inhibitor (compound C) enhanced genistein-induced MEK½ and ERK½ activity indicating a potential cross-talk between the two signaling pathways. In vivo, genistein also reduced fasting glucose levels accompanied with reduced PEPCK-C expression and increased in AMPK and ERK½ phosphorylation states in the liver of genistein-treated alloxan-induced diabetic mice. Genistein fulfills the criteria of a suitable anti-diabetic agent by reducing glucose production and inhibiting PEPCK-C expression in HepG2 cells and also in alloxan-induced diabetic mice. These results indicate that genistein is an effective candidate for preventing T2DM through the modulation of AMPK-CRTC2 and MEK/ERK signaling pathways, which may allow a novel approach to modulate dysfunction in hepatic gluconeogenesis in T2DM.
Available synthetic antioxidants such as butylated hydroxyl anisole, butylated hydroxyl toluene, propyl gallate, and ascorbic acid exhibit several side effects. To curb these side effects, more effective, less toxic, and cost-effective drugs are required. Therefore, this study aims to screen and evaluate the antioxidant as well as the anti-inflammatory and antidiabetic potential of Houttuynia cordata collected from Mairang village, West Khasi Hills, Meghalaya, India using several standard methods. The aqueous and methanolic extracts of H. cordata were evaluated by screening their ability to scavenge 1,1-diphenyl-2-dipicrylhydrozyl, 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid), hydrogen peroxide, and nitric oxide. Total phenol and flavonoid content was measured by Folin-Ciocalteau and by AlCl3 colorimetric method respectively. The anti-inflammatory activity of the plant was determined using the protein denaturation method. Methanolic and aqueous extracts of Houttuynia cordata exhibit varying free radical scavenging and anti-inflammatory activity. Among the extracts used in the study, the methanolic extract of Houttuynia cordata elicited a higher activity than the aqueous extract. Houttuynia cordata also elicited a marked reduction in blood glucose level of normal and alloxan-induced diabetic mice. Flavonoids, which have been reported to possess anti-inflammatory, enzyme inhibition, antimicrobial, anticancer, antiallergy, and antioxidant properties may contribute towards the free radical scavenging and anti-inflammatory effect of Houttuynia cordata.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.