Fan J, Li X, Li P, Siow C, Gong Y

Saikosaponin-d prevents the development of dimethylnitrosamine-induced liver fibrosis in rats.

Faculties of Pharmacy and Medicine, University of Manitoba, 50 Sifton Rd, Winnipeg, Manitoba R3T 2N2, Canada. ygong@cc.umanitoba.ca

PURPOSE: Liver disease is one of the most common diseases in the world and there is no effective treatment for liver fibrosis and cirrhosis, therefore current study is to investigate the effect and mechanism of an extract of Chinese herb—Saikosaponin-d (Ssd) on liver fibrosis. We propose that Saikosaponin-d can reduce injury of hepatocytes and prevent development of liver fibrosis.

METHODS: Saikosaponin-d was extracted and purified from Chinese herb—ChaiHu. Liver fibrosis in rats was induced by dimethylnitrosamine (DMN) in a protocol of i.p. injection of DMN for four days and resting for three days. The procedure was repeated for four weeks. Rats were divided into three groups of normal, DMN, and DMN with 1.8mg/kg Ssd. Serum biochemistry and liver histology were evaluated at the end of experiment. Rat hepatoma cell line—1548 was employed for in vitro study. Cells were incubated with Ssd for different time periods and then treated with different concentrations of carbon tetrachloride (CCl4). Lactate dehydrogenase (LDH) was determined by spectrophotometer.

RESULTS: DMN induced significant elevations of serum ALT (normal=25.33±4.76, DMN=60.33±13.72) and pro-collagen IV (normal=8.73±4.64, DMN=34.47±12.68). However, Ssd was able to reduce DMN induced serum ALT and pro-collangen IV levels (DMN=60.33±13.72, Ssd=33.85±7.92 for ALT and DMN=34.47±12.68, Ssd=10.93±8.88 for pro-collagen IV respectively). Liver HE staining indicated that Ssd treatment prevented liver injury caused by DMN and there was lesser collagen staining in DMN+Ssd treated animals than that of DMN alone treated animals. In addition, the treatment of rat hepatoma cells (1548) with Ssd for 48 hours prevented CCl4 induced release of LDH in 1548 cells.

CONCLUSION: Saikosaponin-d prevents the development of liver fibrosis in rats and the mechanism of Saikosaponin-d in the prevention of liver fibrosis is due to its protection against hepatocyte injury.

 

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