lignans and Liver-Failure

This study examined the effects of gomisin A, a lignan compound from Schisandra fructus, on D-galactosamine (GalN) and lipopolysaccharide (LPS)-induced hepatic apoptosis and liver failure. Mice were given an intraperitoneal injection of GalN (700 mg/kg) / LPS (10 microg/kg). Gomisin A (25, 50, 100, and 200 mg/kg) was administered intraperitoneally 1 h before the GalN/LPS injection. The liver injury was assessed biochemically and histologically. GalN/LPS increased the serum aminotransferase levels and lipid peroxidation but decreased the reduced glutathione level. The pretreatment with gomisin A attenuated these changes in a dose-dependent manner. The survival rate of the gomisin A group was significantly higher than that of the control. The mitochondria isolated after the mice had been injected with GalN/LPS were swollen, which was attenuated by the gomisin A pretreatment. The elevation of serum tumor necrosis factor-alpha and activation of caspase-3 were observed in the GalN/LPS group, which was attenuated by gomisin A. The gomisin A-pretreated groups showed significantly fewer apoptotic (TUNEL-positive) cells and DNA fragmentation as compared with the GalN/LPS mice. The liver protection afforded by gomisin A is the result of the reduced oxidative stress and its anti-apoptotic activity.

Topics: Alanine Transaminase; Animals; Apoptosis; Caspase 3; Cyclooctanes; Dioxoles; DNA Fragmentation; Galactosamine; Glutathione; Lignans; Lipid Peroxidation; Lipopolysaccharides; Liver Failure; Male; Mice; Mice, Inbred ICR; Mitochondria, Liver; Mitochondrial Swelling; Oxidative Stress; Protective Agents; Tumor Necrosis Factor-alpha

Hepatitis C virus (HCV) infection frequently causes chronic hepatitis, which is linked to the development of liver cirrhosis and hepatocellular carcinoma. Most physicians who practice Kampo medicine in Japan have observed that Kampo medicine can be as effective as interferon therapy in the treatment of chronic hepatitis C. In the present study, to evaluate the effect of Kampo medicine on chronic hepatitis C, clinical treatment was assessed in short-term and long-term study, and it was shown that ninjin-yoei-to (Formula ginseng compositae: TJ-108) was very effective. Therefore, to find the most active herbal component of TJ-108 in the treatment of HCV, Citrus Unshiu Peel, Schisandra Fruit, and Polygala Root, which are specific to TJ-108, were screened using an in vitro HCV infection model. Among the three herbs, Schisandra Fruit was found to be most active. In the next step, Gomisin A, an active component of Schisandra Fruit, was studied using an in vitro model with MOLT-4 cells and an animal model of immunologically induced acute hepatic failures. It is concluded that the therapeutic effect of TJ-108 on chronic hepatitis C is from the inhibitory effect on HCV infection, and also from the protective effect on immunological hepatopathy of Schisandra Fruit and its lignan component, Gomisin A.

Topics: Adult; Aged; Aged, 80 and over; Animals; Cell Line; Cyclooctanes; Dioxoles; Drugs, Chinese Herbal; Hepatitis C, Chronic; Humans; Lignans; Liver Diseases; Liver Failure; Medicine, Kampo; Mice; Middle Aged; Plant Extracts; RNA, Viral; Time Factors