title: Inhibition of human cytochrome P450 enzymes by Bacopa monnieri standardized extract and constituents.
abstract: Bacopa monnieri and the constituents of this plant, especially bacosides, possess various neuropharmacological properties. Like drugs, some herbal extracts and the constituents of their extracts alter cytochrome P450 (CYP) enzymes, causing potential herb-drug interactions. The effects of Bacopa monnieri standardized extract and the bacosides from the extract on five major CYP isoforms in vitro were analyzed using a luminescent CYP recombinant human enzyme assay. B. monnieri extract exhibited non-competitive inhibition of CYP2C19 (IC50/Ki = 23.67/9.5 µg/mL), CYP2C9 (36.49/12.5 µg/mL), CYP1A2 (52.20/25.1 µg/mL); competitive inhibition of CYP3A4 (83.95/14.5 µg/mL) and weak inhibition of CYP2D6 (IC50 = 2061.50 µg/mL). However, the bacosides showed negligible inhibition of the same isoforms. B. monnieri, which is orally administered, has a higher concentration in the gut than the liver; therefore, this herb could exhibit stronger inhibition of intestinal CYPs than hepatic CYPs. At an estimated gut concentration of 600 µg/mL (based on a daily dosage of 300 mg/day), B. monnieri reduced the catalytic activities of CYP3A4, CYP2C9 and CYP2C19 to less than 10% compared to the total activity (without inhibitor = 100%). These findings suggest that B. monnieri extract could contribute to herb-drug interactions when orally co-administered with drugs metabolized by CYP1A2, CYP3A4, CYP2C9 and CYP2C19.
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia. seetah@hotmail.com.
authors.forename: Seetha
authors.initials: S
authors.lastname: Ramasamy
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia. lvkiew@um.edu.my.
authors.forename: Lik Voon
authors.initials: LV
authors.lastname: Kiew
authors.affiliation: Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia. chungly@um.edu.my.
authors.forename: Lip Yong
authors.initials: LY
authors.lastname: Chung
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D034681:Bacopa / Q000737:chemistry; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065692:Cytochrome P-450 CYP3A Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D041743:Herb-Drug Interactions; D006801:Humans; D008658:Inactivation, Metabolic; D008862:Microsomes, Liver / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry; D012503:Saponins / Q000008:administration & dosage; D014315:Triterpenes / Q000008:administration & dosage
chemical_list: D065609:Cytochrome P-450 CYP1A2 Inhibitors; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D065692:Cytochrome P-450 CYP3A Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D010936:Plant Extracts; D012503:Saponins; D014315:Triterpenes; C500175:bacoside A; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D019388:Cytochrome P-450 CYP1A2; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human