MODULATION OF CYTOCHROME P-450-DEPENDENT MONOOXYGENASES, GLUTATHIONE AND GLUTATHIONE-S-TRANSFERASE IN RAT-LIVER BY GENIPOSIDE FROM GARDENIAJASMINOIDES

Geniposide is an iridoid glycoside extracted from the fruits of Garden ia jasminoides, which are used as a food colorant and as a traditional Chinese medicine for treatment of hepatic and inflammatory diseases. The effects of geniposide and G. jasminoides fruit crude extract on li ver cytochrome P-450 (P-450)-dependent monooxygenases, glutathione and glutathione S-transferase were investigated using rats treated orally with the iridoid glycoside (0.1 g/kg body weight/day) or the fruit cr ude extract (2 g/kg/day) for 4 days. The treatments decreased serum ur ea nitrogen level but increased liver to body weight ratio, total hepa tic glutathione content and hepatic cytosolic glutathione S-transferas e activity. Treatments with geniposide and G. jasminoides decreased P- 450 content, benzo[a]pyrene hydroxylation, 7-ethoxycoumarin O-deethyla tion, and erythromycin N-demethylation activities in liver microsomes without affecting aniline hydroxylation activity. The natural products had no effect on glutathione content and monooxygenase activities in kidney microsomes. Immunoblotting analyses of liver microsomal protein s using mouse monoclonal antibody 2-13-1 to rat P4503A1/2 revealed tha t geniposide and G. jasminoides crude extract decreased the intensity of a P4503A-immunorelated protein. Protein blots probed with mouse mon oclonal antibody 1-12-3 to rat P4501A1 and rabbit polyclonal antibody against human P4502E1 showed that both treatments had little or no eff ect on P4501A and 2E proteins. The present findings demonstrate that g eniposide from G. jasminoides has the ability to inhibit a P4503A mono oxygenase and increase glutathione content in rat liver. (C) 1997 Else vier Science Ltd. All rights reserved.