In-Vitro assessment of the inhibitory effects of dietary flavones on the regulated metabolism of CYP 450: Potential for Herb-drug interactions

Abstract

Background and objective: Dietary flavones like chrysin are found in foods and can contribute to human health through prevention of cardiovascular and cancer supplements. Recently, as herbal medicines and traditional allopathic medicines are used together, drug food or herbal drug interactions have become the target of our body and can lead to potential herbal-drug interactions. The present study aims to determine the metabolic stability and CYP inhibition liabilities in human liver microsomes in order to rule out the association between herb drugs and the dietary flavone chrysin. Methods: Standard procedures were used for metabolic stability study in human liver microsomes (Phase I) and metabolic stability study in cryopreserved human hepatocytes (Phase II). Human liver microsomes (HLMs) were added to each selective probe substrates of cytochrome P450 enzymes with or without of chrysin and IC50 was calculated. Results: Metabolic stability data reveals that Chrysin underwent phase II metabolism predominantly as it was highly stable in HLM and comparatively faster metabolism in hepatocytes. Chrysin was found to be a potent inhibitor of CYP1A2 and CYP2C9 with IC50 values of 0.6 μM and 1.6μM, respectively. Chrysin has weak inhibitory effect on other CYP isoforms such as CYP2C9, CY2D6 (~25μM) and no inhibition of CYP3A4 up to 100μM. Conclusion: These results could be useful in clinical practice for safely and effectively use of flavone chrysin. Our report showed that in vivo interactions of drugs and pharmaceuticals with dietary flavones must be examined for CYP1A2 and CYP2C9 substrates.