Protective effect of Fufang-Liu-Yue-Qing, a traditional Chinese herbal formula, on CCl4 induced liver fibrosis in rats.
BACKGROUND
Chinese prescription Fufang-Liu-Yue-Qing (FLYQ) has long been employed clinically to treat chronic hepatitis B, and we have reported its beneficial effects on liver fibrosis in vitro. The present study was investigated to verify protective effects of FLYQ on liver fibrosis in a rat model and to investigate the underlying mechanisms which have not been explored yet.


METHODS
Liver fibrosis was established by intragastric administration of 2 ml/kg CCl(4) twice a week for 12 weeks. During the experiment, the model group received CCl(4) only, and the normal control group received an equal volume of saline. Treatment groups received not only CCl(4) for 12 weeks, but also the corresponding drugs, colchicine (1.00 mg/kg/day) or FLYQ (300, 150, 75 mg/kg/day) from 5 to 12 weeks.


RESULTS
Analysis experiments showed that FLYQ could significantly alleviate liver injury, as indicated by decreasing levels of ALT, AST, ALP, GGT, IL-6 and TNF-α. Moreover, FLYQ could effectively inhibit collagen deposition and reduce the pathological tissue damage. Research on mechanism showed that FLYQ was able to markedly reduce lipid peroxidation, recruit the anti-oxidative defense system, promote ECM degradation by modulating the levels of TIMP-1 and MMP-2, and induce HSC apoptosis by down-regulating bcl-2 mRNA, as well as inhibit the expressions of α-SMA and TGF-β(1) proteins.


CONCLUSIONS
Our results show that FLYQ is effective in attenuating hepatic injury and fibrosis in the CCl(4)-induced rat model, which should be developed as a new drug for treatment of liver fibrosis and even cirrhosis.
Guangxi Medical University, Nanning 530021, China.
Xing
X
Lin
Shijun
S
Zhang
Quanfang
Q
Huang
Ling
L
Wei
Li
L
Zheng
Zhaoni
Z
Chen
Yang
Y
Jiao
Jianchun
J
Huang
Shujie
S
Fu
Renbin
R
Huang
D000199:Actins / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003078:Colchicine; D003094:Collagen / Q000378:metabolism; D015536:Down-Regulation; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000378:metabolism; 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; D019684:Magnoliopsida; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008517:Phytotherapy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D000637:Transaminases / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000199:Actins; D000975:Antioxidants; D002251:Carbon Tetrachloride; D003078:Colchicine; D003094:Collagen; D004365:Drugs, Chinese Herbal; D015850:Interleukin-6; D020778:Matrix Metalloproteinase 2; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D000637:Transaminases; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C498862:Acta2 protein, rat