title: 2, 3, 5, 4'-Tetrahydroxystilbene-2-O-beta-D-glucoside improves gastrointestinal motility disorders in STZ-induced diabetic mice.
abstract: 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-γ and SIRT1 expression in diabetic ileum. Our study indicates that THSG improves diabetic gastrointestinal disorders through activation of MAPK pathway and upregulation of PPAR-γ and SIRT1.
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Rode, Wuhan, China.
authors.forename: Mu-Jun
authors.initials: MJ
authors.lastname: Chang
authors.forename: Jun-Hua
authors.initials: JH
authors.lastname: Xiao
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Yong-Li
authors.initials: YL
authors.lastname: Yan
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Jia-Ling
authors.initials: JL
authors.lastname: Wang
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D005960:Glucosides / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D018384:Oxidative Stress; D010766:Phosphorylation; D013267:Stilbenes / Q000494:pharmacology*; D013311:Streptozocin
chemical_list: D005960:Glucosides; D013267:Stilbenes; C093026:2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside; D008315:Malondialdehyde; D013311:Streptozocin; D005979:Glutathione Peroxidase; D052248:Nitric Oxide Synthase Type I; D053148:Caspase 3