Effects of salvianolic acids on oxidative stress and hepatic fibrosis in rats.
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.
Tsai
Ming-Kuei
MK
Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan.
Lin
Yun-Lian
YL
Huang
Yi-Tsau
YT
D000199:Actins / Q000378:metabolism; D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D015153:Blotting, Western; D002109:Caffeic Acids / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007773:Lactates / Q000494:pharmacology*; D008103:Liver Cirrhosis / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D053630:Depsides
D000199:Actins; D001572:Benzofurans; D002109:Caffeic Acids; D006861:Hydrogen Peroxide; D007773:Lactates; D010982:Platelet-Derived Growth Factor; C066201:salvianolic acid A; C076944:salvianolic acid B; D053630:Depsides