Screening Ingredients from Herbs against Pregnane X Receptor in the Study of Inductive Herb-Drug Interactions: Combining Pharmacophore and Docking-Based Rank Aggregation

摘要

An issue of integrative medicine about herb-drug interactions has been increasing concerned [1]. Herbal ingredients can activate nuclear receptors to induce drug-metabolizing enzyme and/or transporter expression, which result in altering efficacy and toxicity of co-administrated drugs. This process is called inductive herb-drug interactions [2]. Pregnane X Receptor (PXR) and drug-metabolizing target genes are involved in most of inductive herb-drug interactions. To predict this kind of herb-drug interaction, identifying ligands of nuclear receptors and drug-metabolizing enzyme/transporter could be done respectively. In addition, because drugs and their metabolizing enzymes are well known, the prediction would be simplified to only screen agonists of nuclear receptors. Finally, 421 herbs were collected to build a curated herb-drug interaction database, which records 380 herb-drug interactions including 90 herbs and 230 drags. This database was used to validate our computational results.