2, 3, 5, 4′-Tetrahydroxystilbene-2-O-Beta-D-Glucoside Improves Gastrointestinal Motility Disorders in STZ-Induced Diabetic Mice

Oxidative stress has recently been considered as a pivotal player in the pathogenesis of diabetic gastrointestinal dysfunction. We therefore investigated the role of 2, 3, 5, 4'-tetrahydroxystilbene-2-O-beta-D-glucoside (THSG) that has a strong anti-oxidant property, in diabetic gastrointestinal dysmotility as well as the underlying protective mechanisms. THSG restored the delayed gastric emptying and the increased intestinal transit in streptozotocin (STZ)-induced diabetic mice. Loss of neuronal nitric oxide synthase (nNOS) expression and impaired nonadrenergic, noncholinergic (NANC) relaxations in diabetic mice were relieved by long-term preventive treatment with THSG. Meanwhile, THSG (10(-7),10(-4) mol/L) enhanced concentration-dependently NANC relaxations of isolated colons in diabetic mice. Diabetic mice displayed a significant increase in Malondialdehyde (MDA) level and decrease in the activity of glutathione peroxidase (GSH-Px), which were ameliorated by THSG. Inhibition of caspase-3 and activation of ERK phosphorylation related MAPK pathway were involved in prevention of enhanced apoptosis in diabetes afforded by THSG. Moreover, THSG prevented the significant decrease in PPAR-gamma and SIRT1 expression in diabetic ileum. Our study indicates that THSG improves diabetic gastrointestinal disorders through activation of MAPK pathway and upregulation of PPAR-gamma and SIRT1. Citation: Chang M-J, Xiao J-H, Wang Y, Yan Y-L, Yang J, et al. (2012) 2, 3, 5, 4'-Tetrahydroxystilbene-2-O-Beta-D-Glucoside Improves Gastrointestinal Motility Disorders in STZ-Induced Diabetic Mice. PLoS ONE 7(12): e50291. doi:10.1371/journal.pone.0050291