Effects of salviainolic acid A (SA-A) on liver injury: SA-A action on hepatic peroxidation.
OBJECTIVE
This study aimed to investigate the actions of salviainolic acid A (SA-A), an antiperoxidative component of Salvia miltiorrhiza (Sm), on rat liver injury and fibrosis.


METHODS
Acute and chronic rat liver injury models were established using carbon tetrachloride (CCl4). After 48 h (acute) or during 6 weeks of CCl4 injection, rats were further divided and treated with biphenyl dimethyl-dicarboxylate (BDD) or colchicine, as a control antifibrotic treatment, with Sm, a herbal compound, or SA-A, a water-soluble extract of Sm. Liver function was investigated by assessing alanine transaminase (ALT) and aspartate transaminase (AST) activities, histological analysis, hydroxyproline (Hyp) and malondiadehyde (MDA) content. In vitro, isolated cultured hepatocytes were injured with CCl4 gas for 24 h, followed by treatment with either vitamin E or various concentrations of SA-A. The extent of hepatocyte injury was monitored by analyzing various lipid peroxidative parameters such as superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), lactase dehydrogenase (LDH), and glutathione peroxidase (GSH-PX) levels in hepatocyte supernatants.


RESULTS
SA-A significantly decreased abnormal serum ALT activity both in acutely and chronically injured rat livers, decreased abnormal serum AST activity, Hyp and MDA content and attenuated hepatic collagen deposition. After CCl4 incubation and injury, the activities of AST, ALT CAT, GSH-PX and LDH and MDA content in hepatocyte supernatants increased significantly, but GSH levels decreased significantly. SA-A markedly improved these pathological changes in a dose-dependent manner. 10(-4) mol/l SA-A had stronger inhibitory action than vitamin E.


CONCLUSIONS
Our studies suggest that SA-A has antiperoxidative effects on injured hepatocytes in liver injury and fibrosis induced by CCl4.
Liu
P
P
Institute of Liver Diseases, Shanghai University of Traditional Chinese Medicine, and Shanghai Institute of Meteria Medica, Chinese Academy of Science, Shanghai, P. R. China. liuliver@online.sh.cn
Hu
Y
Y
Liu
C
C
Liu
C
C
Zhu
D
D
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002109:Caffeic Acids / Q000627:therapeutic use*; D002478:Cells, Cultured / Q000187:drug effects / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D006909:Hydroxyproline / Q000378:metabolism; D007773:Lactates / Q000627:therapeutic use*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D010936:Plant Extracts / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013047:Specific Pathogen-Free Organisms
D002109:Caffeic Acids; D004365:Drugs, Chinese Herbal; D016166:Free Radical Scavengers; D007773:Lactates; D010936:Plant Extracts; C066201:salvianolic acid A; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D006909:Hydroxyproline