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Journal of Chinese Integrative Medicine ›› 2008, Vol. 6 ›› Issue (9): 928-933.doi: 10.3736/jcim20080910

• Original Experimental Research • Previous Articles     Next Articles

Effects of Qushi Huayu Decoction on cathepsin B and tumor necrosis factor-α expression in rats with non-alcoholic steatohepatitis

Hui Zhang, Qin Feng, Hong-shan Li, Shao-dong Chen, Xiao-ning Wang, Jing-hua Peng, Ning Zhang, Yi-yang Hu()   

  1. Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
  • Received:2008-01-06 Online:2008-09-20 Published:2008-09-15

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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 (CCl4) 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-α (TNF-α) 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-IκB), TNF-α 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-IκB and TNF-α proteins in liver tissues and serum TNF-α 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-α in serum and content of FFA in liver tissue and activity of ALT in serum.
Conclusion: The inhibiting effects of QHD on fat deposition and inflammation in liver are related with its inhibition on the "FFA-Ctsb-TNF-α" pathway of lipo-toxicity.

Key words: non-alcoholic fatty liver disease, Qushi Huayu Decoction, free fatty acid, tumor necrosis factor-a, cathepsin B, rats

CLC Number: 

  • R289.5

Table 1

ALT activity and TNF-α content in serum and TG and FFA levels in liver tissue of rats in different groups (x±s)"

Group n ALT (U/L) TNF-α (ng/L) TG (mg/g) FFA (μmol/g)
Normal control 5 50±11 14.4±1.4 13.6±1.3 757±244
Untreated 10 115±46** 19.9±3.6* 71.8±12.1** 1 475±133**
Ganle 9 72±24△ — 62.0±6.8 1 453±233
QHD 9 71±11△ 15.6±3.4△ 56.8±7.7△ 881±78△△▲▲

Figure 1

Relativity analysis on lipid concentration in liver tissue and parameters of liver injury "

Figure 2

Effect of QHD on protein expression of TNF-α in liver tissue A: Normal control group; B: Untreated group; C: QHD-treated group. *P<0.05, vs normal control group; △P<0.05, vs untreated group."

Figure 3

Effect of QHD on P-IκB level in liver tissue A: Normal control group; B: Untreated group; C: QHD-treated group. **P<0.01, vs normal control group; △P<0.05, vs untreated group."

Figure 4

Effect of QHD on protein expression of Ctsb in liver tissue A: Normal control group; B: Untreated group; C: QHD group. *P<0.05, vs normal control group; △P<0.05, vs untreated group."

Figure 5

Expression and distribution of Ctsb in liver tissues of rats in different groups (Immunohistochemical staining, ×400) A: Normal group; B: Negative control (normal group); C: Untreated group; D: QHD group."

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