Hypericum perforatum protects against hepatic injury induced by carbon tetrachloride

Extracts of Hypericum perforatum (St. John’s wort) have gained much interest for their antidepressant effects. The aim of the present study was to investigate the effect H. perforatum on the development of liver injury induced by treatment with carbon tetrachloride (CCl4) in rats. Liver damage was induced by administration of carbon tetrachloride (2.8 ml/kg in olive oil). H. perforatum (25, 50, and 100 mg/kg) alone or combined with silymarin (25 mg/kg) was given once daily orally simultaneously with CCl4 and for 14 days thereafter. Liver damage was assessed by determining serum enzyme activities and hepatic histopathology. In CCl4-treated rats given H. perforatum at 25 mg/kg per day for 2 weeks, the elevations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in serum were significantly less than in the CCl4 control group. Serum ALT level decreased by 14.4% and AST level by 16.6% of their corresponding control value, respectively. Serum alkaline phosphatase (ALP) level was not significantly reduced by H. perforatum at 25 mg/kg. The addition of silymarin at the dose of 25 mg/kg to H. perforatum resulted in further decrease in liver enzymes compared with H. perforatum treatment alone. Serum ALT decreased by 40.2%, AST by 37.9%, and ALP by 38.1% of the control value, respectively, after combining H. perforatum at 25 mg/kg and silymarin. On the other hand, treatment with H. perforatum at 50 or 100 mg/kg reduced serum ALT levels by 37.9–52.6%, AST levels by 30.2–53.2%, and ALP by 48.5–51.5%, respectively. Silymarin given in combination with the above doses of H. perforatum reduced serum ALT by 58.7–63.3%, AST by 56.6– 60.9%, and ALP levels by 54.7–58.8%, respectively. Meanwhile, silymarin alone decreased serum ALT by 56.8%, AST by 62.6%, and ALP levels by 55.1%, respectively. The administration of CCl4 resulted in marked increase in nitric oxide level in serum (the concentrations of nitrite/nitrate) as compared to the normal group. Treatment with H. perforatum resulted in a dosedependent decrease in serum nitric oxide level compared with the CCl4 control group. Blood levels of reduced glutathione were markedly decreased in CCl4-treated rats. Reduced glutathione levels were increased significantly by 100 mg/kg H. perforatum and restored to near normal values by silymarin treatment. Histopathological examination also indicated that CCl4-induced liver injury was less severe in the H. perforatum-treated groups. Taken together, the present results show that H. perforatum reduces the extent of hepatic injury caused by CCl4 in rats and this effect is increased by co-administration of silymarin. This suggests the beneficial effect of silymarin administration to depressed patients with liver disease treated with H. perforatum.