Schisandrin A alleviates renal fibrosis by inhibiting PKCβ and oxidative stress

Background: Renal fibrosis is a common pathway that drives the advancement of numerous kidney maladies towards end-stage kidney disease (ESKD). Suppressing renal fibrosis holds paramount clinical importance in forestalling or retarding the transition of chronic kidney diseases (CKD) to renal failure. Schisandrin A (Sch A) possesses renoprotective effect in acute kidney injury (AKI), but its effects on renal fibrosis and underlying mechanism(s) have not been studied. Study Design: Serum biochemical analysis, histological staining, and expression levels of related proteins were used to assess the effect of PKC beta knockdown on renal fibrosis progression. Untargeted metabolomics was used to assess the effect of PKC beta knockdown on serum metabolites. Unilateral Ureteral Obstruction (UUO) model and TGF-beta induced HK-2 cells and NIH-3T3 cells were used to evaluate the effect of Schisandrin A (Sch A) on renal fibrosis. PKC beta overexpressed NIH-3T3 cells were used to verify the possible mechanism of Sch A. Results: PKC beta was upregulated in the UUO model. Knockdown of PKC beta mitigated the progression of renal fibrosis by ameliorating perturbations in serum metabolites and curbing oxidative stress. Sch A alleviated renal fibrosis by downregulating the expression of PKC beta in kidney. Treatment with Sch A significantly attenuated the upregulated proteins levels of FN, COL-I, PKC beta, Vimentin and alpha-SMA in UUO mice. Moreover, Sch A exhibited a beneficial impact on markers associated with oxidative stress, including MDA, SOD, and GSH-Px. Overexpression of PKC beta was found to counteract the renoprotective efficacy of Sch A in vitro. Conclusion: Sch A alleviates renal fibrosis by inhibiting PKC beta and attenuating oxidative stress.