Tetrahydroxystilbene glucoside ameliorates diabetic nephropathy in rats: involvement of SIRT1 and TGF-beta1 pathway.

摘要

Oxidative stress caused by hyperglycaemia is believed to be a major molecular mechanism underlying diabetic nephropathy. 2,3,5,4'-tetrahydroxystilbene-2-O-beta-d-glucoside (TSG), an active component extract from Polygonum multiflorum Thunb, exhibits antioxidative and anti-inflammatory effects. Possible protective mechanisms of TSG on diabetic nephropathy were investigated in rats and cultured rat mesangial cells. Total cholesterol and triglyceride levels of diabetic rats were clearly increased and these increases were diminished by treatment with TSG. Treatment of diabetic rats with TSG also significantly reduced blood urea nitrogen, creatinine, 24 h urinary protein levels, and kidney weight/body weight. The activities of superoxide dismutase and glutathione peroxidase in renal homogenate were increased markedly, whereas malonaldehyde levels were decreased significantly in TSG-treated diabetic rats. TSG dramatically inhibited diabetes-induced overexpression of TGF-beta1 and COX-2, and restored the decrease of SIRT1 expression in diabetic rats. High glucose-induced overexpression of TGF-beta1 in cultured mesangial cells was significantly inhibited, whereas the decease of SIRT1 expression was restored by pretreatment of TSG. Nicotinamide, the inhibitor of SIRT1, partially relieved the inhibitory effect of TSG on TGF-beta1 expression under high glucose condition. These findings indicate that the protective mechanisms of TSG on diabetic nephropathy are involved in the alleviation of oxidative stress injury and overexpression of COX-2 and TGF-beta1, partially via activation of SIRT1.