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.