Effects of salvianolic acids on oxidative stress and hepatic fibrosis in rats

Toxicol Appl Pharmacol. 2010 Jan 15;242(2):155-64. doi: 10.1016/j.taap.2009.10.002. Epub 2009 Oct 12.


Enhanced oxidative stress is associated with hepatic fibrosis. Salvianolic acids A (Sal A) and B (Sal B) have been reported to be strong polyphenolic antioxidants and free radical scavengers. The present study is to investigate if Sal A and B could attenuate oxidative stress and liver fibrosis in rats. A cell line of rat hepatic stellate cells (HSCs) was stimulated with platelet-derived growth factor (PDGF, 10 ng/ml). The inhibitory effects of Sal A and B on intracellular hydrogen peroxide levels were measured with dichlorofluorescein diacetate (DCF-DA) dye assay. alpha-Smooth muscle actin (alpha-SMA), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits were measured by Western blotting. Liver fibrosis was induced by intraperitoneal injections of thioacetamide (TAA, 200 mg/kg) twice per week for 6 weeks. Sal A (10 mg/kg), Sal B (50 mg/kg) or S-adenosylmethionine (SAMe, 10 mg/kg), was given by gavage twice per day consecutively for 4 weeks starting 2 weeks after TAA injection. In vitro, PDGF increased the accumulation of hydrogen peroxide in HSCs, which was attenuated by Sal A (10 muM) and Sal B (200 muM). Sal A and B attenuated the PDGF-stimulated expressions of alpha-SMA and NADPH oxidase subunits gp91(phox) and p47(phox) in membrane fractions. In vivo studies showed that the hepatic levels of collagen, malondialdehyde, TNF-alpha, IL-6, and IL-1beta, fibrosis scores and protein expressions of alpha-SMA, heme-oxygenase-1, iNOS, and gp91(phox), and serum levels of ALT, AST, IL-6, and IL-1beta were increased in TAA-intoxicated rats, all of which were attenuated by 4-week treatment of Sal A or Sal B. Our results showed that Sal A and B attenuated PDGF-induced ROS formation in HSCs, possibly through inhibition of NADPH oxidase. Sal A and B treatments were also effective against hepatic fibrosis in TAA-intoxicated rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Benzofurans / pharmacology*
  • Blotting, Western
  • Caffeic Acids / pharmacology*
  • Hydrogen Peroxide / metabolism
  • Lactates / pharmacology*
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / prevention & control*
  • Male
  • Oxidative Stress / drug effects*
  • Platelet-Derived Growth Factor / pharmacology
  • Rats
  • Rats, Sprague-Dawley


  • Actins
  • Benzofurans
  • Caffeic Acids
  • Lactates
  • Platelet-Derived Growth Factor
  • salvianolic acid A
  • Hydrogen Peroxide
  • salvianolic acid B