Polydatin ameliorates renal fibrosis in a streptozotocin-induced rat model of diabetic nephropathy by inhibiting TLR4/NF-κB signaling

Purpose: To determine the effects of polydatin (PD) on a streptozotocin (STZ)-induced rat model of diabetic nephropathy (DN) and NRK-52E cells treated with high glucose (HG). Methods: Sprague Dawley rats received 65 mM STZ to model DN in vivo. NRK-52E cells were treated with HG, to model DN in vitro. Both models were treated with PD. Fasting blood glucose, kidney/body weight, urinary protein, serum creatinine, and blood urea nitrogen levels, interstitial injury score, as well as protein expression levels of connective tissue growth factor (CTGF), fibronectin, and collagen I were determined in DN rats after PD treatment. Enzyme-linked immunosorbent assay was used to measure inflammatory factors. Protein expression was determined by Western blot analysis while apoptosis was assessed by flow cytometty. Results: STZ successfully induced DN in rats. PD treatment significantly reduced kidney/body weight; decreased fasting blood glucose, urinary protein, serum creatinine, and blood urea nitrogen levels; lowered interstitial injury scores; and downregulated protein expression levels of CTGF, fibronectin, and collagen I. It also inhibited inflammatory reaction and suppressed Toll-like receptor (TLR4)/nuclear factor (NF)-kappa B signaling. Furthermore, PD suppressed apoptosis, reduced inflammatory factor levels, and suppressed TLR4/NF-kappa B signaling induced by HG in NRK-52E cells. Conclusion: PD exerts a protective role in DN by decreasing interstitial injury, reducing renal fibrosis, inhibiting inflammatory responses, and suppressing cell apoptosis, at least, partly via inactivation of TLR4/NF-kappa B pathway.