A comprehensive literature search conducted by the Pharmacology Core, combined with compelling preliminary in vitro data, identified intestinal UDP-glucuronosyltransferases (UGTs) as a high priority target for green tea-precipitated natural product-drug interactions. Specifically, methanolic and aqueous extracts prepared from representative green teas (by the Analytical Core) were screened for inhibitory effects on intestinal UGT activity by the Pharmacology Core. All of these extracts showed clear concentration-dependent inhibition. Five abundant green tea catechins [(+)-catechin, (-)-epicatechin, and (-)-epigallocatechin, (-)-epicatechin gallate, and (-)-epigallocatechin gallate] were subsequently tested individually as inhibitors of intestinal UGT activity. The inhibitory potency (IC50) of two of these catechins, (-)-epicatechin gallate and (-)-epigallocatechin 3-gallate, were near or below concentrations measured in one cup (250 mL) of brewed tea prepared from a reference standard obtained from the National Institute of Standards and Technology. These data suggest a potential interaction between green tea and drugs metabolized by intestinal UGT. In response, further mechanistic in vitro studies and clinical evaluation were conducted by the NaPDI Center to assess the clinical relevance of a green tea-drug interaction mediated via intestinal UGT inhibition.
