Development of an in vitro Pipeline to Detect and Quantify Herb-Drug Interactions

Herb-drug interactions occur when a drug and herb are simultaneously ingested. When both the herb and the drug share a phase I or phase II metabolic enzyme target, enzyme induction or inhibition could be affected. This effect could alter the metabolic pathway of these and other xenobiotics, resulting in potentially toxic outcomes. As natural products become more widely used, it is important to understand how herb-drug interactions impact the metabolism of prescription medications. This work presents a method to study herb-drug interactions in the liver by evaluating a panel of metabolic enzymes. HepaRG cells were dosed with St. John’s wort and buspirone, an herb-drug combination that has been found to exhibit in vivo interactions. Metabolic enzyme activity was measured by an 8-in-1 assay in which cells are dosed with FDA-recommended substrates of 8 phase I and phase II metabolic enzymes. SJW and buspirone were shown to display antagonism on CYP2D6 and dose-dependent effects on CYP3A4 and UGT. Our results show that this method could be used to evaluate herb-drug interactions that have physiological relevance to metabolism.Bachelor of Scienc