Effects of sho-saiko-to, a japanese herbal medicine, on hepatic fibrosis in rats

Abstract

It has been shown that lipid peroxidation is associated with hepatic fibrosis and stellate cell activation. Shosaiko-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 ␣-smooth muscle actin (␣-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, ␣-SMA expression, cell proliferation, and oxidative burst in cultured rat stellate cells. In addition, TJ-9 inhibited Fe 2؉ /adenosine 5Ј-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. (HEPATOLOGY 1999;29:149-160)

Blockade of 12-lipoxygenase expression protects cortical neurons from apoptosis induced by β-amyloid peptide

“…Indeed, the 12-LOX inhibitor baicalein is the main component of an herbal medicine (Sho-Saiko-To) commonly administered in Asian countries to outpatients with chronic hepatitis. 62 Our findings suggest that such compounds may also offer new potential strategies in the pharmacological treatment of AD.…”

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

“…A later prospective, randomized (albeit nonblind) study by Oka et al [410] could elucidate the use of TJ-9 in preventing the development of HCC in patients with cirrhosis, particularly in patients without HBsAg. Successive studies continued to confirm that TJ-9 could protect experimental liver injury caused by D-galactosamine and liver fibrosis by inhibition of lipid peroxide formation in liver cells [411,412].…”

Antifibrotic effects of a herbal combination regimen on hepatic fibrotic rats

“…Recently, it has been proposed that plant-derived antioxidants may emerge as potential antifibrotic agents (Gebhardt, 2002;Schuppan et al, 1999). For example, it has been reported that herbal extracts such as Sho-saiko-to (TJ-9) (Shimizu et al, 1999), silymarin (Boigk et al, 1997) and Inchin-ko-to (TJ-135) (Sakaida et al, 2003) can inhibit HSC activation and thereby exert antifibrotic effects in animals.…”