Subchronic effects of the standardized extract of centella asiatica on rat hepatic cytochrome p450

Abstract

Centella asiatica (L.) Urban (Umbelliferae) has been used traditionally in various diseases. The aim of this study was to examine subchronic effects of the standardized extract of C. asiatica on hepatic xenobiotic drug metabolizing enzymes, particularly cytochrome P450 (CYP) such as CYP1A1, CYP1A2, CYP2B1/2B2, CYP2E1 and CYP3A in rats. Forty male and female rats were randomly divided into 4 groups of 10 rats each. Rats in the treatment groups were given orally with the standardized extract of C. asiatica at 10, 100 and 1000 mg/kg/day whereas rats in the control group were given distilled water for 90 consecutive days. At the end of treatment, rats were sacrificed and liver microsomes were prepared for enzyme activity assay. The results showed that the standardized extract of C. asiatica did not affect total CYP content as well as the activities of CYP1A1, CYP1A2, CYP2B1/2B2, CYP2E1 and CYP3A in both male and female rats. Inhibitory effect of the standardized extract of C. asiatica was examined in vitro, using rat liver microsomes. The standardized extract of C. asiatica caused a concentration-dependent decrease of the activity of CYP2B1/CYP2B2 (BROD: IC50 = 523 µg/ml, PROD: IC50 = 563 µg/ml) and very slightly effect on CYP1A2 (MROD: IC50 > 1000 µg/ml). The standardized extract of C. asiatica had no inhibitory effect on the activities of CYP1A1, CYP2E1 and CYP 3A at concentrations up to 2000 μg/ml. The inhibitory effect of the standardized extract of C. asiatica on CYP2B1/2B2 indicated a possibly beneficial effect of the compound regarding the protection of chemical-induced carcinogenesis but the concern regarding the possibilities of drug-drug interaction with the medicines metabolized by these CYPs. Effects of the standardized extract of C. asiatica on the activities of other CYP isoformes should be further investigated.