Hyperforin and its analogues inhibit CYP3A4 enzyme activity |
| |
Authors: | Lee Ju-young Duke Rujee K Tran Van H Hook James M Duke Colin C |
| |
Institution: | Pharmaceutical Chemistry, Faculty of Pharmacy, University of Sydney, Building A15, Science Road, Sydney, NSW 2006, Australia. |
| |
Abstract: | Literature indicates that herb-drug interaction of St. John's wort is largely due to increased metabolism of the co-administered drugs that are the substrates of cytochrome P450 (CYP) 3A4 enzyme, alteration of the activity and/or expression of the enzyme. The major St. John's wort constituents, acylphloroglucinols, were evaluated for their effects on CYP3A4 enzyme activity to investigate their roles in herb-drug interaction. Hyperforin and four oxidized analogues were isolated from the plant and fully characterized by mass spectral and NMR analysis. These acylphloroglucinols inhibited activity of CYP3A4 enzyme potently in the fluorometric assay using the recombinant enzyme. Furoadhyperforin (IC(50) 0.072 microM) was found to be the most potent inhibitor of CYP3A4 enzyme activity, followed by furohyperforin isomer 1 (IC(50) 0.079 microM), furohyperforin isomer 2 (IC(50) 0.23 microM), hyperforin (IC(50) 0.63 microM) and furohyperforin (IC(50) 1.3 microM). As the acylphloroglucinols are potent inhibitors of the CYP3A4 enzyme, their modulation of the enzyme activity is unlikely to be involved in increased drug metabolism by St. John's wort. |
| |
Keywords: | St John’s wort Acylphloroglucinols Hyperforin Furohyperforin Furoadhyperforin NMR MS and CYP3A4 enzyme |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|