ShenKang injection suppresses kidney fibrosis and oxidative stress via transforming growth factor-β/Smad3 signalling pathway in vivo and in vitro

J Pharm Pharmacol. 2015 Aug;67(8):1054-65. doi: 10.1111/jphp.12412. Epub 2015 Apr 13.

Abstract

Objectives: The purpose of this study is to investigate the antifibrosis and antioxidation of ShenKang injection (SKI) in vivo and in vitro and to evaluate potential mechanisms involved in the treatment of chronic kidney disease (CKD).

Methods: In experimental animal studies, CKD was established by 5/6 nephrectomy (5/6Nx). Serum creatinine (Scr) and blood urea nitrogen (BUN) were determined. Histopathological tests were performed by H&E and Masson trichrome stained. The protein expressions of fibronectin (FN), collagen Ι, α-smooth muscle actin (α-SMA) and transforming growth factor-β (TGF-β) and phosphorylation of Smad3 were measured in 5/6Nx rats. In Human kidney proximal tubular cell line (HK-2) cells, the effects of TGF-β/Smad3 signalling pathway on renal fibrosis and oxidative injury were examined.

Key findings: 5/6Nx induced severe renal damages. Treatment of rats with SKI markedly reduced levels of Scr and BUN, alleviated expression of fibrosis-associated signalling molecules and reduced expression of TGF-β and phosphorylated Smad3. Meanwhile, in HK-2 cells, after exposure to TGF-β and H2 O2 , the protein expression of renal fibrosis was significantly increased. The generation of oxidative stress was also elevated. The severity of fibrosis and oxidative damage appears to be reduced after treatment with SKI.

Conclusion: SKI inhibits renal fibrosis and oxidative stress through downregulation of TGF-β/Smad3 signalling pathway.

Keywords: ShenKang injection; chronic renal disease; oxidative stress; renal fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Urea Nitrogen
  • Cell Line
  • Creatinine / blood
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / administration & dosage
  • Drugs, Chinese Herbal / pharmacology*
  • Enalapril / pharmacology
  • Fibrosis / drug therapy*
  • Fibrosis / pathology
  • Glyceraldehyde-3-Phosphate Dehydrogenases / metabolism
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Male
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / pathology
  • Signal Transduction / drug effects
  • Smad3 Protein / drug effects*
  • Smad3 Protein / metabolism
  • Transforming Growth Factor beta / drug effects*
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / pharmacology

Substances

  • Drugs, Chinese Herbal
  • Smad3 Protein
  • Transforming Growth Factor beta
  • shenkang
  • Enalapril
  • Creatinine
  • Hydrogen Peroxide
  • Glyceraldehyde-3-Phosphate Dehydrogenases