Schisandrin A alleviates renal fibrosis by inhibiting PKCβ and oxidative stress

Hui-Ling Liu1, Zhou Huang2, Qing-Zhen Li2

  • 1State Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China.

Abstract

Insights

Schisandrin A (Sch A) alleviates kidney fibrosis by inhibiting PKC-beta and reducing oxidative stress. This study investigated Sch A

Area of Science:

  • Nephrology
  • Pharmacology
  • Biochemistry

Background:

  • Renal fibrosis is a critical factor in the progression of kidney diseases to end-stage kidney disease (ESKD).
  • Inhibiting renal fibrosis is crucial for managing chronic kidney diseases (CKD).
  • Schisandrin A (Sch A) shows promise for kidney protection, but its role in fibrosis is unknown.

Purpose of the Study:

  • To investigate the antifibrotic effects of Schisandrin A (Sch A) in kidney injury.
  • To elucidate the underlying mechanisms of Sch A's renoprotective action, focusing on PKCβ and oxidative stress.

Main Methods:

  • Utilized a Unilateral Ureteral Obstruction (UUO) mouse model and TGF-β-induced cell lines (HK-2, NIH-3T3).
  • Assessed renal fibrosis progression via serum biochemistry, histology, and protein expression analysis.
  • Employed untargeted metabolomics and PKCβ knockdown/overexpression to explore mechanisms.

Main Results:

  • PKCβ was upregulated in the UUO model; its knockdown ameliorated fibrosis and oxidative stress.
  • Sch A treatment downregulated PKCβ expression and attenuated fibrotic markers (FN, COL-I, Vimentin, α-SMA) in vivo.
  • Sch A improved oxidative stress markers (MDA, SOD, GSH-Px) and its efficacy was counteracted by PKCβ overexpression in vitro.

Conclusions:

  • Schisandrin A (Sch A) demonstrates significant renoprotective effects against renal fibrosis.
  • Sch A alleviates renal fibrosis by inhibiting PKCβ expression and reducing oxidative stress.
  • These findings highlight Sch A as a potential therapeutic agent for kidney fibrosis.