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

PLoS One

Jun-Hua Xiao¹  Jia-Ling Wang¹  Yong-Li Yan¹  Mu-Jun Chang¹  Jun Yang¹  Yong Wang¹ 

[1] Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Rode, Wuhan, China

关键词: Diabetes mellitus;    Apoptosis;    Gastrointestinal tract;    Neurons;    Colon;    Oxidative stress;    Gastrointestinal motility disorders;    MAPK signaling cascades;   

DOI  :  10.1371/journal.pone.0050291

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

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