Protective effects of astragaloside IV on porcine-serum-induced hepatic fibrosis in rats and in vitro effects on hepatic stellate cells.
BACKGROUND
Astragaloside IV is the primary pure saponin isolated from Astragalus membranaceus, one of the valuable traditional medical herbs. Antifibrotic activities of Astragalus membranaceus have been extensively proved.


OBJECTIVE
To investigate the effects of astragaloside IV on hepatic stellate cells (HSCs) and hepatic fibrosis in rats induced by porcine-serum (PS).


METHODS
Liver fibrosis was induced by PS injection (0.5 ml, twice a week) for 12 weeks. Astragaloside IV (2.0, 4.0 mg kg(-1)) was administered intragastrically. Liver samples were subjected to histological and immunohistochemical studies. In vitro effects of astragaloside IV on primary cultured HSCs were detected by incorporation assays.


RESULTS
Astragaloside IV delayed the formation of liver fibrosis and decrease the serum levels of hyaluronic acid (HA), procollagen type III (PCIII) and hydroxyproline (Hyp) content in liver. The levels of transforming growth factor-beta(1) (TGF-beta(1)) in serum and expression in liver were significantly decreased by astragaloside IV. Collagen synthesis and proliferation were significantly inhibited by astragaloside IV (1.5, 3.0, 6.0, 12.0 and 24.0 mg L(-1)) in HSCs.


CONCLUSIONS
The results showed that astragaloside IV displays antifibrotic effects in rats induced by PS, the mechanism by which might be associated with its inhibitory effects on collagen synthesis and proliferation in HSCs.
Anhui Key Laboratory of Anti-inflammatory and Immunopharmacology, Anhui Engineering Technology Research Center of Anti-inflammatory and Immunodrugs, Institute of Clinical Pharmacology, Anhui Medical University, Hefei, Anhui Province, China.
Hao
H
Liu
Wei
W
Wei
Wu-yi
WY
Sun
Xiang
X
Li
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D027883:Astragalus Plant / Q000737:chemistry*; D001835:Body Weight / Q000187:drug effects; D003094:Collagen / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D024061:Collagen Type III / Q000097:blood; D055166:Hepatic Stellate Cells / Q000187:drug effects*; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D006909:Hydroxyproline / Q000378:metabolism; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012503:Saponins / Q000494:pharmacology* / Q000627:therapeutic use; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use
D024061:Collagen Type III; D010936:Plant Extracts; D012503:Saponins; D053773:Transforming Growth Factor beta1; D014315:Triterpenes; C052064:astragaloside A; D006820:Hyaluronic Acid; D003094:Collagen; D000410:Alanine Transaminase; D006909:Hydroxyproline