Herb medicine Gan-fu-kang attenuates liver injury in a rat fibrotic model.
OBJECTIVE
To verify therapeutic effects of Gan-fu-kang (GFK), a traditional Chinese medicine compound, in a rat model and to investigate the underlying mechanisms.


METHODS
Liver fibrosis was established by 12 weeks of carbon tetrachloride (CCl(4)) treatment (0.5mg/kg, twice per week) followed by 8 weeks of "recovery" in rats. Rats randomly received GFK (31.25, 312.5 and 3125 mg/kg/day, p.o.) or vehicle from weeks 9 to 20, and were sacrificed at the end of week 20 for histological, biochemical, and molecular biological examinations. In a separate set of experiments, rats received 12 weeks of CCl(4) treatment, concomitant with GFK (312.5mg/kg/day, p.o.) during the same period in some subjects, but were then sacrificed immediately. An additional group of rats receiving no CCl(4) treatment served as normal controls.


CONCLUSIONS
(1) CCl(4) treatment resulted in severe liver damage and fibrosis. (2) In the main block of the 20-week study, GFK attenuated liver damage and fibrosis. (3) In the 12-week study, GFK produced prevention effect against hepatic injury. (4) GFK suppressed the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), type I collagen, platelet-derived growth factor-BB (PDGF-BB)/PDGF receptor-beta chains (PDGFRbeta) and mitogen-activated protein kinases (MAPKs)/active protein-1 (AP-1) signal pathways. Taken together, these results indicated that GFK could attenuate liver injuries in both settings. Our findings also suggest that the AP-1 pathway is the likely molecular substrate for the observed GFK effects.
Lou
Jing-Lei
JL
Department of Pathophysiology, Dalian Medical University, South Road West Section 9, Lvshunkou District, Dalian, Liaoning Province 116044, China.
Jiang
Miao-Na
MN
Li
Cong
C
Zhou
Qing
Q
He
Xin
X
Lei
Hong-Yan
HY
Li
Jin
J
Jia
Yu-Jie
YJ
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008103:Liver Cirrhosis / Q000517:prevention & control*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D004365:Drugs, Chinese Herbal; C550090:gan-fu-kang; D020928:Mitogen-Activated Protein Kinases