• Jinfeng Li, Bing Wang, Guangjie Zhou, Xiujuan Yan, and Yuan Zhang.
• Department of Pharmacy, Weihai Municipal Hospital, 264200, Weihai, Shandong Province, China.
• Am. J. Med. Sci. 2018 Jun 1; 355 (6): 588-596.

BackgroundTetrahydroxy stilbene glucoside (TSG) is an active ingredient of Heshouwu and is an antioxidant. The underlying mechanisms of the renoprotective effect of TSG in diabetic nephropathy have not been previously reported. In this study, we investigated the mechanisms of TSG in preventing podocytes injury in high glucose (HG) condition.MethodsCultured mouse podocytes (MPC5) were incubated in HG (30mmol/L) plus various concentration of TSG (0.1, 1 and 10μM) for 48 hours. Reactive oxygen species (ROS) production, malondialdehyde (MDA) levels, terminal deoxynucleotidyl-transferase (TdT)-mediated dUTP-biotin nick end-labeling (TUNEL) fluorescence intensity, caspase-3 activity and the mRNA expression of nephrin in cultured podocytes were determined. The protein expression of Nod-like receptor protein 3 (NLRP3) inflammsome, interleukin-1β (IL-1β) and nephrin was detected by Western blot.ResultsWhen the podocytes were incubated with various concentrations of TSG under HG conditions for 48 hours, TSG decreased ROS production, MDA levels, TUNEL fluorescence intensity and caspase-3 activity, but increased cell viability and the expression of nephrin in HG-induced podocytes in a dose-dependent manner. Subsequently, the podocytes treated with TSG at 10 μΜ decreased the expression of NLRP3 inflammasome and IL-1β compared with that of control. Furthermore, the podocytes transfected with NLRP3- small interfering RNA (siRNA) exhibited a significant decrease in the expression of caspase-1 and IL-1β, but exhibited a significant increase in the expression of nephrin. Eventually, TSG significantly increased the expression of nephrin in IL-1β-treated podocytes.ConclusionsTSG attenuates high glucose-induced cell apoptosis in vitro partly through the suppression of NLRP3 inflammasome signaling.Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

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