Establishment and optimization of the LC-MS-based strategy for screening of passively absorbed açaí and maca constituents for CYP3A4 inhibition

Abstract

The escalation of cancer morbidity and mortality has increased the use of botanical dietary supplements among cancer patients undergoing chemotherapy. Euterpe oleracea Mart. (açaí) berry and Lepidium meyenii Walpers (maca) root are some of the most common botanical dietary supplements used concomitantly with anticancer agents. CYP3A4 is an important enzyme in the metabolism and clearance of anticancer agents. While often used for their scientific claims against cancer, the supplements may also cause botanical-drug pharmacokinetic interactions of which one is through CYP3A4 inhibition. Consideration of bioavailable constituents of botanical dietary supplements has been identified as a route to counteract the discrepancy between preclinical and clinical botanical-drug interaction data. Passive absorption is the most common mechanism of absorption for medicines in the market. The goal of this study is to screen passively absorbable açaí berry and maca root constituents and their Phase I and Phase II metabolites for CYP3A4 inhibition. Chapter one is an overview of cancer prevalence, treatment, botanical dietary supplements use and the herbal-drug interactions. The chapter also goes into the chemical characterization of açaí berry and maca root extracts. Chapter two describes in detail, the methods used in açaí and maca plant extracts fingerprinting, establishment of intestinal passive absorption model, metabolism and CYP3A4 inhibition assays. The experimental work used LC-MS and other orthogonal confirmatory assays. Chapter three presents the results, discussion and conclusions. The findings of this study, after identifying the extracts with moderate to strong CYP3A4 inhibition, suggest that açaí and maca botanical dietary supplements have a potential to cause significant botanical-drug interactions in the clinical setting.