Effect of Danshao Huaxian capsule on expression of matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 in fibrotic liver of rats

AIM： To investigate the effects of Danshao Huaxian （DSHX） capsules, a preparation of traditional Chinese medicine, on the expression of matrix metalloproteinase-1 （MMP-1）, and tissue inhibitor of metalloproteinase-1 （TIMP-1） in the fibrous livers of rats. METHODS： Eighty male Wistar rats were randomly divided into normal control group （group A）, CCl4-induced hepatic fibrosis group （group B）, non-DSHX-treated group （group C）, low dose-treated group （group D）, and high dose-treated group （group E）. Fibrous liver models in rats were induced by subcutaneous injection of CCI4, oral administration of alcohol and high-lipid/low-protein diet for 8 wk. After the models were established, the rats in groups D and E were orally given a low dose （0.5 g/kg） and a high dose （1.0 g/kg） of DSHX daily for 8 wk, respectively. Then, the liver indexes, serum hyaluronic acid （HA） and alanine aminotransferase （ALT） were examined. The degree of hepatic fibrosis was evaluated by optical microscopy. Hydroxyproline （Hyp） in the urine was determined, and the expression of MMP-1 and TIMP-1 was detected by immunohistochemical techniques. RESULTS： In groups D and E, the liver indexes, levels of serum HA and ALT reduced and development of hepatic fibrosis weakened significantly. The urinary Hyp and expression of MMP-1 in the liver tissues elevated, but the expression of TIMP-1 decreased obviously, as compared to groups B and C.CONCLUSION： DSHX enhances the expression of MMP-1 but decreases that of TIMP-1 in liver tissues of CCI4-induced hepatic fibrotic rats, which may result in its elevated activity that contributes to fighting against hepatic fibrosis.

Danshao Huaxian capsule in treatment of decompensated cirrhosis resulting from chronic hepatitis B

BACKGROUND: The prognosis of decompensated cirrhosis resulting from chronic hepatitis B is poor, and the benefits of treatment with interferon are ourweight serious sideeffects and the risk of fatal exacerbation of disease. Danshao Huaxian capsule rapidly reduces hepatitis B virus(HBV)-DNA in serum to undetectable levels. METHODS: A total of 35 patients with chronic hepatitis B and decompensated cirrhosis were treated with Danshao Huaxian 1.2g. po. tid daily. Before the treatment, HBVDNA in serum was positive in all patients. Ten patients had Child-Pugh class B and 25, class C hepatitis B. Seven patients underwent liver transplantation within 6 months of initial treatment. Of the 10 patients of class B, 5 died within 6 months, and the other 5 did not complete the treatment for some reasons; the 25 patients of class C were treated for at least 6 months (mean =19 months). RESULTS: In most of the 25 patients, liver function was improved slowly but markedly after 9 months of treatment, showing a decreased level of serum bilirubin from 67±13 to 30±4μmol/L (P<0.05, baseline vs.6 months), an increased level of serum albumin from 27±1 to 34±1 g/L(P<0.05) and a decreased level of Child-Pugh score from 10.3±0.4 to 7.5+0.5 (P<0.05). Three patients developed resistance to Danshao Huaxian because of a mutation in the YMDD motif, but liver function was not deteriorated. Inhibition of viral replication with Danshao Huaxian resulted in a significant improvement of liver function in patients with decompensated HBV cirrhosis, but the long-term results remain uncertain. CONCLUSION: Danshao Huaxian capsule is effective in inhibiting viral DNA replication in patients with decompensated cirrhosis and making clinical improvement.