Effects of CH-100, a Chinese herbal medicine, on acute concanavalin A-mediated hepatitis in control and alcohol-fed rats

Background: Administration of concanavalin A (Con A) leads to acute hepatitis that involves T-cell activation and inflammatory mediator production in mice and rats. We examined the role of CH-100, a Chinese herbal medicine previously trialed in human hepatitis C, in the prevention of Con A-related, T-cell-mediated, acute liver injury in rats. Methods: Female Wistar rats were fed 40% ethanol, 2% sucrose, or isocaloric sucrose for 8 weeks. At the same time, these animals were fed either the Chinese herbal medicine CH-100 (4 tablets/kg body weight/ day) or placebo in chow daily. Blood from the tail vein was collected for endotoxin (lipopolysaccharide) assay at 0, 4, and 8 weeks of ethanol consumption. Twenty-four hours after injection of Con A (20 mg/kg body weight) or phosphate-buffered saline, blood from the tail vein was collected for alanine aminotransferase and tumor necrasis factor (TNF)-alpha assays. Liver-associated C4(+) T cells were isolated from liver perfusates and then cultured with Con A (5 mu g/ml) at 37 degrees C for 24 hr. Supernatants were harvested for TNF-alpha assay. The proportion of CD4(+) T cells in blood and liver perfusates was measured. Liver samples were collected for histopathological analysis. Results: Lipopolpaccharide levels were significantly reduced in CH-100-treated ethanol fed rats compared with placebo-treated rats. After Con A injection, alanine aminotransferase levels were lower at 12 and 24 hr in herb-treated rats compared with placebo-treated rats. Furthermore, serum TNF-a levels were lower in ethanol-fed rats on herbal treatment. A significant decrease in TNF-alpha production by liver-associated CD4(+) T cells in culture was observed in CH-100-treated ethanol-fed rats. CH-100 treatment was associated with a decreased percentage of CD4(+) cells in both blood and liver perfusate in all groups. Herb-treated rats displayed markedly less hepatic necrosis and a reduced CD4(+) T-cell infiltrate in portal areas than did placebo-fed rats. Conclusions: The results demonstrate that CH-100 modified the T-cell response to Con A injection. The effect was more marked in ethanol-fed rats, which suggests a possible role for CH-100 in treating alcoholic liver disease.