It has been shown that lipid peroxidation is associated with hepatic
fibrosis and stellate cell activation.
Sho-saiko-to (TJ-9) is an herbal medicine, which is commonly used to treat
chronic hepatitis in Japan, although the mechanism 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 experimental hepatic
fibrosis, induced in rats by
dimethylnitrosamine (DMN) or pig 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 mL 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 suppressed the induction of hepatic
fibrosis, increased hepatic
retinoids, and reduced the hepatic levels of
collagen and
malondialdehyde (MDA), a production of lipid peroxidation. Immunohistochemical examination showed that
TJ-9 reduced the deposition of
type I collagen and the number of alpha-smooth muscle actin (alpha-SMA) positive-stellate cells in the liver and inhibited, not only lipid peroxidation in cultured rat hepatocytes that were undergoing oxidative stress, but also the production of
type I collagen, alpha-SMA expression, cell proliferation, and oxidative burst in cultured rat stellate cells. In addition,
TJ-9 inhibited Fe2+/
adenosine 5'-diphosphate-induced lipid peroxidation in rat liver mitochondria in a dose-dependent manner and showed radical scavenging activity. Among the active components of
TJ-9,
baicalin and
baicalein were found to be mainly responsible for the antioxidative activity. These findings suggest that
Sho-saiko-to (TJ-9) functions as a potent antifibrosuppressant by inhibition of lipid peroxidation in hepatocytes and stellate cells in vivo.