An insight on the nature of biochemical interactions between glycyrrhizin, myricetin and CYP3A4 isoform

Drug interaction studies are imperative to gain insights into the beneficial or harmful effects of therapeutic and dietary agents. This study investigated the mechanism of modulatory roles of glycyrrhizin (GLH) and myricetin (MYC) on the human CYP3A4 isoform using in silico and in vitro methods. While MYC had concentration‐dependent inhibitory effect on CYP3A4 (IC50: 10.5 ± 0.55 μM) with characteristic Km and Vmax values of 1.13 μM and 1.54 nM/min, respectively, GLH exhibited no inhibitory effect on CYP3A4 activity in vitro. These observations are consistent with the results of in silico evaluations where the effect of MYC compared well with that of ketoconazole (a known CYP3A4 inhibitor) against CYP3A4. Overall, the established interactions between the study compounds and CYP3A4 could potentiate clinically vital drug–drug interactions and has lent credence to the mechanism of modulatory effect of MYC and GLH on CYP3A4 that could guide their safe use as therapeutic agents. Practical implications Myricetin (MYR) and glycyrrhizin (GLH) occur freely in commonly ingested foods and their supplements are recommended for the treatment of several debilitating diseases such as diabetes, cancer, and cardiovascular complications. This study provided an insight on the possible interactions that could be established between these compounds (MYR and GLH) and CYP3A4 when ingested and metabolized by the liver. The results suggested possibilities of potential clinical drug–drug interactions and advocates for their cautious use within the therapeutic dose in food supplements or medications to avoid probable liver damage. The mechanism of modulatory roles of glycyrrhizin (GLH) and myricetin (MYC) on the CYP3A4 was investigated in silico and in vitro. MYC uncompetitively inhibited CYP3A4, while GLH had no inhibitory effect in vitro. In vitro results were consistent with the in silico and the ADME predictions, where MYC compared well with ketoconazole, a known CYP3A4 inhibitor. Considering its pharmacokinetic properties, GLH was suggested as a probable CYP3A4 inducer. MYC and GLH could potentiate clinically vital drug‐drug interactions.