Effects and mechanisms of crude astragalosides fraction on liver fibrosis in rats.
Astragalosides is the major active constituent of Radix Astragali. The present study was carried out to investigate the effect of crude astragalosides fraction (CAF) on rats liver fibrosis and its possible mechanisms. Hepatic fibrosis was induced by subcutaneous injection with 50% CCl(4) in Sprague-Dawley rats. The amount of CCl(4) administered was 1 mg kg(-1). The alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels in plasma and hydroxyproline (Hyp), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) contents in liver tissue were assayed by spectrophotometry. The hyaluronic acid (HA) and procollagen III (PC III) were assessed by radioimmunoassay. Tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) levels in culture supernatants of Kupffer cells (KCs) were determined with ELISA. Liver samples collected after 8 weeks of CCl(4) treatment were stained with hematoxylin-eosin (HE) and massion, and scored. Intragastric administration of CAF (10, 20 and 40 mg kg(-1)) significantly decreased indices of liver and spleen, the serum transaminase activities, HA and PC III levels, and Hyp and MDA contents in liver tissue in rats of hepatic fibrosis. Decreased SOD and GSH-px levels were reversed after administration of CAF. Histopathological scores showed CAF had inhibitory effect on the progression of hepatic fibrosis. In the in vitro experiments, CAF significantly reduced TNF-alpha and TGF-beta1 levels in culture supernatants of KCs. The results showed CAF significantly inhibited the progression of hepatic fibrosis induced by CCl(4), and the inhibitory effect of CAF on hepatic fibrosis might be associated with its ability to scavenge free radical and inhibit the production of TNF-alpha and TGF-beta1 from activated KCs.
Gui
Shuang-Ying
SY
Institute of Clinical Pharmacology, Anhui Medical University, Anhui Province, Hefei 230032, PR China.
Wei
Wei
W
Wang
Hua
H
Wu
Li
L
Sun
Wu-Yi
WY
Chen
Wen-Bi
WB
Wu
Cheng-Yi
CY
D000818:Animals; D027885:Astragalus propinquus; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D010936:Plant Extracts / Q000627:therapeutic use*; D018517:Plant Roots; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; C027492:Huang Qi