A Chinese herbal medicine, Gexia-Zhuyu Tang (GZT), prevents dimethylnitrosamine-induced liver fibrosis through inhibition of hepatic stellate cells proliferation.
BACKGROUND
Gexia-Zhuyu Tang (GZT), also called Gexiazhuyu decoction (GXZYD), is a traditional Chinese herbal medicine for chronic liver diseases such as cirrhosis and liver fibrosis.


OBJECTIVE
In this study, we have investigated the affects of GZT on a rat model of dimethylnitrosamine (DMN)-induced liver fibrosis.


METHODS
In this study, the protective effects of GZT on DMN-induced liver fibrosis were measured using a rat model. Following 5 weeks of DMN-treatment (8 mg/kg, i.p., given 3 consecutive days each week), oral administration of GZT at 1.8 g/kg daily via oral gavage for 2weeks beginning at week 13.


RESULTS
Both body and liver weights were significantly decreased. The reductions in body and liver weights corresponded with increasing liver damage severity. Furthermore, GZT-treatment remarkably decreased the levels of serum GOT (glutamate oxaloacetate transaminase) and GPT (glutamic pyruvic transaminase), and the mRNA expression levels of collagen alpha-1(I) and alpha-smooth muscle actin (alpha-SMA) in DMN-induced hepatic fibrosis. In addition, hepatic stellate cells (HSCs) play a major role in various types of liver fibrosis through initial myofibroblast transformation. The proliferation of HSCs was inhibited by GZT. Treatment with GZT also induced HSC apoptosis in a dose- and time-dependent manner. GZT treatment induced HSC apoptosis by facilitating Ca(2+) release from the mitochondria within 6h. Subsequently, caspases 3 and 12 were elevated by 72 h after treatment.


CONCLUSIONS
Our studies indicate that GZT exhibited both hepatoprotective and antifibrogenic effects in DMN-induced hepatic injury. These findings suggest that GZT may be useful in preventing the development of hepatic fibrosis.
Department of Life Sciences, and Agricultural Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan.
Jiun-Yu
JY
Chen
Hsiao-Ling
HL
Chen
Ju-Chien
JC
Cheng
Hung-Jen
HJ
Lin
Yu-Tang
YT
Tung
Chia-Fan
CF
Lin
Chuan-Mu
CM
Chen
D000199:Actins / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D053454:Caspase 12 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I / Q000235:genetics; D000090602:Collagen Type I, alpha 1 Chain; D004128:Dimethylnitrosamine; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000517:prevention & control*; D008297:Male; D008517:Phytotherapy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014463:Ultrasonography
D000199:Actins; D002118:Calcium; D053454:Caspase 12; D053148:Caspase 3; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D004128:Dimethylnitrosamine; D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; C498862:Acta2 protein, rat