Effects of Sho-saiko-to, a Japanese herbal medicine, on hepatic fibrosis in rats

It has been shown that lipid peroxidation is associated with hepatic fibros is and stellate cell activation. Shosaiko-to (TJ-9) is an herbal medicine, which is commonly used to treat chronic hepatitis in Japan, although the me chanism by which TJ-9 protects against hepatic fibrosis is not known. As a result, we assayed the preventive and therapeutic effects of TJ-9 on experi mental hepatic fibrosis, induced in rats by dimethylnitrosamine (DMN) or pi g serum (PS), and on rat stellate cells and hepatocytes in primary culture, and assessed the antioxidative activities and the active components of TJ- 9, Male Wistar rats were given a single intraperitoneal injection of 40 mg/ kg DMN or 0.5 mt PS twice weekly for 10 weeks. In each model, rats were fed a basal diet throughout, or the same diet, which also contained 1.5% TJ-9, for 2 weeks before treatment or for the last 2 weeks of treatment. TJ-9 su ppressed the induction of hepatic fibrosis, increased hepatic retinoids, an d reduced the hepatic levels of collagen and malondialdehyde (MDA), a produ ction of lipid peroxidation. Immunohistochemical examination showed that TJ -9 reduced the deposition of type I collagen and the number of at-smooth mu scle actin (alpha-SMA) positive-stellate cells in the liver and inhibited, not only lipid peroxidation in cultured rat hepatocytes that were undergoin g oxidative stress, but also the production of type I collagen, ar-SMA. exp ression, cell proliferation, and oxidative burst in cultured rat stellate c ells. In addition, TJ-9 inhibited Fe2+/adenosine 5'-diphosphate-induced lip id peroxidation in rat Liver mitochondria in a dose-dependent manner and sh owed radical scavenging activity. Among the active components of TJ-9, baic alin and baicalein were found to be mainly responsible for the antioxidativ e activity. These findings suggest that Sho-saiko-to (TJ-9) functions as a potent antifibrosuppressant by inhibition of lipid peroxidation in hepatocy tes and stellate cells in vivo.