Bergenin ameliorates diabetic nephropathy in rats via suppressing renal inflammation and TGF-β1-Smads pathway

Context: Diabetic nephropathy (DN) is a serious complication of diabetes. Bergenin (BEG) was previously confirmed to be effective in treating type 2 diabetes in rats.Objective: The objective of this study was to investigate the effects of BEG on renal function in diabetic rats, and meanwhile explore the molecular mechanism.Methods: DN was induced in rats by a single intraperitoneal injection of streptozotocin. The renal function was evaluated by serum creatinine (SCr), blood urea nitrogen (BUN), urinary albumin and renal histopathology. The proliferation of mesangial cells (MCs) was assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H tetrazolium bromide. The production of inflammatory cytokines was detected by ELISA kits, and the levels of Smads were measured by western blotting.Results and conclusion: In DN rats, there were significantly increased levels of SCr, BUN, urinary albumin, plasma glucose and renal index. The histological changes in diabetic kidney revealed noteworthy focal mesangial matrix expansion. In vitro experiment, high glucose markedly promoted MCs proliferation. However, treatment with BEG obviously normalized these functional parameters, improved diabetic histological changes in vivo and inhibited MCs' proliferation in vitro. Moreover, the levels of tumor necrosis factor-alpha, interleukin-1 (IL-1) and IL-6 in BEG-treated renal tissue and MCs were both reduced. Finally, it showed that BEG markedly reduced transforming growth factor-1 (TGF-1) production, down-regulated p-Smad2/3 expression and promoted Smad7 expression both in vivo and in vitro. In conclusion, BEG exerts the effective protective role against kidney injuries of diabetic rat, in which the underlying mechanisms are associated with reducing renal inflammation and blocking TGF-1-Smads pathway.