[Effects of Qushi Huayu Decoction on cathepsin B and tumor necrosis factor-alpha expression in rats with non-alcoholic steatohepatitis].
OBJECTIVE
To study the mechanism of Qushi Huayu Decoction (QHD), a compound of traditional Chinese herbal medicine, in prevention and treatment of non-alcoholic steatohepatitis (NASH).


METHODS
Thirty-five Wistar male rats were randomly divided into normal group, untreated group, QHD group and Ganle (diisopropylamine dichloroacetate) group. The rats except those in normal group were subcutaneously injected with carbon tetrachloride (CCl(4)) for 4 weeks (twice per week) and simultaneously fed with high-fat and low-protein diet for 2 weeks to induce NASH. Then, the rats were administrated with QHD, Ganle, or distilled water for 2 weeks, respectively. After harvest, alanine aminotransferase (ALT) activity and tumor necrosis factor-alpha (TNF-alpha) content in serum as well as triglyceride (TG) and free fatty acid (FFA) in liver tissue were evaluated, and relativity analysis among these parameters was performed. Cathepsin B (Ctsb), phospho-inhibitor kappa B (P-IkappaB), TNF-alpha protein expressions in liver tissue were assayed with western-blot. The expression and distribution of ctsb in liver tissue were observed with immunohistochemical method.


RESULTS
The contents of TG, FFA and activity of ALT were significantly decreased in QHD group. While in the Ganle group, only the activity of ALT in serum was decreased significantly. Expressions of Ctsb, P-IkappaB and TNF-alpha proteins in liver tissues and serum TNF-alpha level were all enhanced in untreated group which, however, were significantly inhibited in the QHD group. And as expected, there were significant relativities among contents of TG in liver tissues and the content of FFA in liver tissue and activity of ALT in serum, content of TNF-alpha in serum and content of FFA in liver tissue and activity of ALT in serum.


CONCLUSIONS
The inhibiting effects of QHD on fat deposition and inflammation in liver are related with its inhibition on the "FFA-Ctsb-TNF-alpha" pathway of lipo-toxicity.
Zhang
Hui
H
Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Feng
Qin
Q
Li
Hong-Shan
HS
Chen
Shao-Dong
SD
Wang
Xiao-Ning
XN
Peng
Jing-Hua
JH
Zhang
Ning
N
Hu
Yi-Yang
YY
D000818:Animals; D002251:Carbon Tetrachloride; D002252:Carbon Tetrachloride Poisoning; D002401:Cathepsin B / Q000235:genetics / Q000378:metabolism*; D004041:Dietary Fats / Q000008:administration & dosage; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D005234:Fatty Liver / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008517:Phytotherapy; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D004041:Dietary Fats; D004365:Drugs, Chinese Herbal; D014409:Tumor Necrosis Factor-alpha; C533465:qushi huayu; D002251:Carbon Tetrachloride; D002401:Cathepsin B