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The Effect of Chinese Herbs In the Treatment of Liver Fibrosis

Bing-Zhong Chen, MD (The University of Melbourne)

Associate Professor, The University of Hong Kong, School of Chinese Medicine

Liver fibrosis resulted from diverse chronic injuries particularly viral hepatitis and alcohol is quite common. For example, there are 2 billion people infected with hepatitis B virus (HBV) worldwide, and 350 million suffering from chronic HBV infection. It is the 10th leading cause of death worldwide.Many patients with liver fibrosis develop hepatocellular carcinoma or portal hypertension.

To explore the effective treatment of liver fibrosis, many drugs including interferon, ribavirin, lamivudine, entecavir, the angiotensin-converting enzyme (ACE) inhibitors, selenium and prolyl 4-hydroxylase inhibitors have been studied. Unexpected outcome of Chinese herbs in the treatment of many diseases has been encouraging further studies. Some researches performed in recent years to explore the effect of Chinese herbs in the treatment of liver fibrosis are introduced in the present paper.

A study using six kinds of Chinese herbs (Salvia miliorrhiza, Sparganium stoloniferum, Angelica sinensis, Amyda sinensis, Curcuma aromatica, Carex phacota) showed benefical effects on liver fibrosis in rats by enhancing immunity and inhibiting nuclear factor-kB (NF-kB) and TGF-β1 expression. The herbs boiled with water and extracted by alcohol were given to rats with liver fibrosis induced by carbon tetrachloride for 6 weeks. The serum level of ALT, AST, laminin and hyaluronic acid (HA) decreased. laminin and HA are used as maker of liver fibrosis. In another study, Salvia miliorrhiza and Angelica sinensis showed the effect to lower the portal hypertension caused by liver fibrosis induced by bile duct ligation of dogs. They also decreased the portal hypertension of patients with liver fibrosis. The action appeared slowly but lasted longer time without side-effects compared with nifedipine. In an animal experiment using four kinds of Chinese herbs (Radix Salviae miltlorrhizae, Flos Carthami, Radix Angelicae sinensis and Semen persicae), the results showed that Radix Salviae miltlorrhizae (RSM) and Flos Carthami inhibited fibrogenesis and the effect of RSM was remarkable. There was no cirrhosis found in the rats given RSM. It was reported that some Chinese herbs with Wen-yang action can mitigate the rats’ hepatic fibrosis and promote a recovery of their experimental illness.

In a prospective, nonblind controlled study, 260 patients with cirrhosis were randomly assigned to two groups given Chinese herbs and conventional drugs respectively. The herbs have antitumor effects in experimental animals. The two groups of patients were monitored for 60 months. The results showed that the herbs prevented the development of hepatocellular carcinoma (HCC) in patients with cirrhosis.

It was reported that herbal medicine TJ-135 significantly reduced liver fibrosis by reducing the expression of type III procollagen mRNA and the number of activated stellate cells in the liver. It also reduced the area of preneoplastic lesions. TJ-135 is prepared as an extract powder from three Chinese herbs: Artemisiae capillaris spica, Gardenia fructus and Rhei rhizome.

In a study using techniques including immunohistochemical studies for a-SMA, type I collagen and in situ hybridization of TIMP-1 mRNA of HSCs,anti-lipid peroxidation in isolated mitochondria and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT)(5-Diphenyltetrazolium Bromide) colorimetric assay for proliferation and terminal deoxynucleotidyl transferase-medicated dUTP-biotin nick end-labeling (TUNEL), flow cytometry and electron microscopy for apoptosis, it was found that Chinese medicine Yi-gan-kang can effectively inhibit or inverse the course of liver fibrogenesis in CCl(4)- and pig serum-induced rat models.

TGF-β/Smad signaling pathway system plays a prominent role in the control of cell growth and extracellular matrix formation in the progression of liver fibrogenesis. Smad proteins can either positively or negatively regulate TGF-βresponses. It was found that Chinese medicine JinSanEprevents the progression of hepatic damage and fibrosis through the inhibition of TGF-β1, TRII and Smad3 signal proteins, and increases expression of Smad7 signal protein in vivo.

The effects of Chinese medicine Rhei rhizome wasstudied in vivo using CDAA diet-induced liver fibrosis model as well as in vitro using isolated HSCs. In vivo Rhei rhizome prevented fibrosis in a dose-dependent manner up to 1.0% (w/w) with a reduced number of activated stellate cells. In vitro the Rhei rhizome prevented stellate cell activation resulting in reduced type I procollagen mRNA, alpha-SMA and TIMP-1, 2 expression. Rhei rhizome significantly reduces liver fibrosis by the direct inhibition of stellate cell activation without reducing hepatocyte cell death.

In conclusion, some Chinese herbs showed the effects to improve the function of the liver and inhibit the development of liver fibrosis, they also decreased the portal hypertension of patients with liver fibrosis. Chinese herbs may play an important role in the treatment of liver fibrosis.

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