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

被引:202
作者
Shimizu, I
Ma, YR
Mizobuchi, Y
Liu, F
Miura, T
Nakai, Y
Yasuda, M
Shiba, M
Horie, T
Amagaya, S
Kawada, N
Hori, H
Ito, S
机构
[1] Univ Tokushima, Sch Med, Dept Internal Med 2, Tokushima 7708503, Japan
[2] Luzhou Med Coll, Dept Preclin Med, Luzhou, Peoples R China
[3] Shanghai Med Univ, Dept Biochem, Shanghai 200032, Peoples R China
[4] Tsumura Co, Tsumura Kampo Pharmacol Dept, Ibaraki, Osaka, Japan
[5] Osaka City Univ, Sch Med, Dept Internal Med 3, Osaka 545, Japan
[6] Univ Tokushima, Fac Engn, Dept Biol Sci & Technol, Tokushima 770, Japan
关键词
D O I
10.1002/hep.510290108
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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 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 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 at-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, ar-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.
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页码:149 / 160
页数:12
相关论文
共 73 条
[1]  
Amagaya S., 1988, J MED PHARM SOC WAKA, V5, P129
[2]  
Amagaya S., 1988, J MED PHARM SOC WAKA, V5, P137
[3]   HEPATIC LIPID-PEROXIDATION INVIVO IN RATS WITH CHRONIC IRON OVERLOAD [J].
BACON, BR ;
TAVILL, AS ;
BRITTENHAM, GM ;
PARK, CH ;
RECKNAGEL, RO .
JOURNAL OF CLINICAL INVESTIGATION, 1983, 71 (03) :429-439
[4]  
Baroni GS, 1998, HEPATOLOGY, V27, P720
[5]  
Baroni GS, 1996, HEPATOLOGY, V23, P1189
[6]  
BASS DA, 1983, J IMMUNOL, V130, P1910
[7]   SUPEROXIDE ANION GENERATION IN THE LIVER DURING THE EARLY STAGE OF ENDOTOXEMIA IN RATS [J].
BAUTISTA, AP ;
MESZAROS, K ;
BOJTA, J ;
SPITZER, JJ .
JOURNAL OF LEUKOCYTE BIOLOGY, 1990, 48 (02) :123-128
[8]   STIMULATION OF COLLAGEN ALPHA(1)(I) GENE-EXPRESSION IS ASSOCIATED WITH LIPID-PEROXIDATION IN HEPATOCELLULAR INJURY - A LINK TO TISSUE FIBROSIS [J].
BEDOSSA, P ;
HOUGLUM, K ;
TRAUTWEIN, C ;
HOLSTEGE, A ;
CHOJKIER, M .
HEPATOLOGY, 1994, 19 (05) :1262-1271
[9]  
Bissell D.M., 1990, HEPATOLOGY TXB LIVER, P424
[10]   ANTIOXIDANT DETERMINATIONS BY THE USE OF A STABLE FREE RADICAL [J].
BLOIS, MS .
NATURE, 1958, 181 (4617) :1199-1200