Inhibitory and Inducing Effects of Herbal Medicines on CYP Enzymes

Morehouse School Of Medicine, Atlanta GA

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Abstract

DESCRIPTION (provided by applicant): In recent years there has been an increased consumption of herbal medicines. Most of those that take these medicines also consume other conventional medicines, and do not inform their physicians about the use of herbal medicines and other alternate medical practice. In addition, most of these herbal medicines have not been rigorously studied and have not been subjected to the same standards as conventional medicines. As a result of this, there is a dearth of information on possible interactions between herbal products and drugs. Contrary to the opinion of most consumers that these herbal products are benign, a number of interactions have recently been reported between herbal medicines and conventional drugs. This increased use of herbal medicines exposes a significant percentage of the population to unknown herb drug interactions. Our hypotheses are that the metabolism of drugs mediated by cytochrome P450 (CYP) enzymes, can be modulated by ingestion of herbal medicines such as ginseng, ginkgo biloba and St. John's wart, and that ethnicity is a factor in this modulation. The resulting induction or inhibition will therefore affect the metabolism of the drugs that are substrates of these enzymes. Since many clinically important drugs are CYP substrates, there are implications for herb-drug interactions. In light of the above, the specific aims of this grant proposal are the realization of the following objectives: 1) To determine if the active pharmaceutical ingredients of American ginseng, Korean ginseng, gingko biloba and St. John's wart inhibit CYP2C9, CYP2C19, CYP2D6, and CYP3A4 activities, with tolbutamide, mephenytoin, bufuralol and testosterone as an in vitro probes, using microsomes prepared from human liver. 2) To determine if genotype is a factor on these inhibitory effects. 3) To determine the inducing or inhibiting effects of the important components of St. John's wart, American ginseng, Korean ginseng and gingko biloba on CYP2C9, CYP2C 19, CYP2D6, CYP3A activities in human hepatocytes obtained from Caucasians and African Americans. 4) To determine if there are interethnic differences between African Americans and Caucasians in the possible CYP enzymes modulating effects of herbal medicines in human hepatocytes.