JinSanE decoction, a chinese herbal medicine, inhibits expression of TGF-beta1/Smads in experimental hepatic fibrosis in rats.
The study is to investigate the effects of a Chinese herbal medicine, JinSanE decoction, on the TGF-beta1/Smads signal transduction pathway in a carbon tetrachloride (CCl(4))-induced hepatic fibrosis model in rats. Rats were randomly divided into 4 study groups: namely, a normal control group, a hepatic fibrosis model group, and 2 treatment groups with different doses of JinSanE (6 and 12 g/kg). Ten rats in each group were sacrificed at 4 and 8 weeks after exposure to CCl(4) respectively. The levels of TGF-beta1 and TRII mRNA in liver tissue were analyzed by RT-PCR. The expressions of TGF-beta1, Smad3 and Smad7 in liver tissues were evaluated by immunohistochemistry. The liver histopathology was examined by hematoxylin and eosin (HE) staining and electron microscopy respectively. The liver hydroxyproline (HYP), liver function and hyaluronic acid (HA) were examined by biochemistry and radioimmunoassay (RIA) respectively. Compared with the hepatic fibrosis model group, the levels of TGF-beta1, TRII mRNA and Smad3 expression significantly decreased in the 2 treatment groups. The expression of Smad7 was significantly increased in the liver of the rats treated with JinSanE (p < 0.05 or p < 0.01). The histological changes of fibrotic liver were obviously improved in the treatment rats. The levels of liver HYP, serum liver function and HA were also remarkably improved in the treatment rats. Moreover, the effects of JinSanE occurred in a dose- and time-dependent manner in the process of the protection of liver injury and fibrosis. JinSanE decoction had a protective effect on liver injury and could ameliorate hepatic fibrosis in rats. The mechanisms might be associated with their effects of down-regulating TGF-beta1, TRII mRNA and Smad3, and up-regulating Smad7.
Song
Shi-Ling
SL
State Key Laboratory of Virology, Department of Infectious Diseases, Renmin Hospital, Wuhan University, Wuhan 430060, China.
Gong
Zuo-Jiong
ZJ
Huang
Yan-Qing
YQ
Zhang
Quan-Rong
QR
Huang
Tuan-Xin
TX
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002251:Carbon Tetrachloride / Q000009:adverse effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006820:Hyaluronic Acid / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D051900:Smad3 Protein / Q000378:metabolism*; D051906:Smad7 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D051906:Smad7 Protein; C497808:Smad7 protein, rat; D053773:Transforming Growth Factor beta1; D006820:Hyaluronic Acid; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D006909:Hydroxyproline