Sanziguben Polysaccharides Attenuate Renal Epithelial-Mesenchymal Transition in Diabetic Nephropathy through Nrf2-Mediated Regulation of TGF-β1/Smad7 Signaling Pathway

Context . Sanziguben polysaccharides (SZP) have renal protection properties and can reduce renal fibrosis in diabetic nephropathy (DM). However, the mechanism of SZP’s renal protection effect is not yet clear. Objectives . Our study intended to clarify the mechanism of SZP’s renal protection effect in DM. Materials and Methods . In this study, streptozotocin-induced C57BL/6J diabetic nephropathy mice and high glucose combined with TGF- β 1-induced EMT in HK-2?cells were used to investigate the effect of Sanziguben polysaccharides. ShRNA-constructed Nrf2 knockdown HK-2?cells were used to explore the role of Nrf2 in Sanziguben polysaccharides inhibiting epithelial-mesenchymal transition. Results . In vivo, the results showed that Sanziguben polysaccharides improved renal epithelial-mesenchymal transition and oxidative stress, and SZP was shown to activate the renal Nrf2, increase Smad7, and inhibit the expression of TGF- β 1 (1.05- to 0.71-fold, 1.66- to 0.40-fold and 0.96- to 1.31-fold, respectively). In vitro, SZP ameliorated HK-2?cell epithelial-mesenchymal transition induced by HG combined with TGF- β 1, increased the expression of Nrf2 and Smad7, and suppressed the expression of TGF- β 1 (1.50- to 1.12-fold, 1.49- to 1.07-fold, and 0.94- to 1.38-fold, respectively). In addition, the above effects of Sanziguben polysaccharides on Nrf2 knockdown HK-2?cells were weakened. Conclusions . The findings suggest that Sanziguben polysaccharides may improve renal epithelial-mesenchymal transition in diabetic nephropathy through Nrf2-mediated regulation of TGF- β 1/Smad7 signaling pathway.

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