Antifibrotic effects of matrine on in vitro and in vivo models of liver fibrosis in rats.
OBJECTIVE
To study the antifibrotic effects of matrine in vitro a nd in vivo.


METHODS
Rat hepatic stellate cell HSC-T6 and mouse fibroblast cell NIH3T3 proliferation stimulated with serum and platelet-derived growth factor (PDGF) was measured b y crystal violet staining assay. Collagen synthesis stimulated with serum and transforming growth factor beta1 (TGF-beta1) was determined by [3H]proline incorporation. Liver fibrosis was induced by carbon tetrachloride (CCl4) in rats an d evaluated with plasma hyaluranic acid level and hepatic hydroxyproline content.


RESULTS
Matrine (1-2 mmol/L) markedly reduced serum-driven proliferation and collagen synthesis of HSC-T6 cells as well as NIH3T3 cells. PDGF-driven proliferative activity and TGF-beta1-driven collagen synthesis in HSC-T6 cel ls were attenuated by matrine (0.25-2 mmol/L) in a concentration-dependent manner. In vivo matrine (50 mg/kg and 100 mg/kg) significantly decreased serum hyaluranic acid levels and hepatic hydroxyproline contents in rats treated with CCl4.


CONCLUSIONS
Inhibition of PDGF and TGF-beta1 actions on hepatic stellate cell by matrine might provide a possible mechanism of its antifibrotic activities.
Zhang
J P
JP
Department of Biochemical Pharmacy, School of Pharma cy, Second Military Medical University, Shanghai 200433, China. zjp@smmu.edu.cn
Zhang
M
M
Zhou
J P
JP
Liu
F T
FT
Zhou
B
B
Xie
W F
WF
Guo
C
C
D016475:3T3 Cells; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002252:Carbon Tetrachloride Poisoning; D002455:Cell Division; D002460:Cell Line; D003094:Collagen / Q000096:biosynthesis; D022781:Hepatocytes / Q000166:cytology; D006820:Hyaluronic Acid / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism*; D008297:Male; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D011807:Quinolizines; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D053773:Transforming Growth Factor beta1; D000093842:Matrines
D000470:Alkaloids; D010982:Platelet-Derived Growth Factor; D011807:Quinolizines; C508961:Tgfb1 protein, mouse; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D006820:Hyaluronic Acid; D003094:Collagen; D006909:Hydroxyproline; D000093842:Matrines