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

Abstract

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.

Cheminformatics Identification and Validation of Dipeptidyl Peptidase-IV Modulators from Shikimate Pathway-Derived Phenolic Acids towards Interventive Type-2 Diabetes Therapy

“…Using PTRAJ, the systems were subsequently saved, and each trajectory was analyzed every 1 ps, and the RMSD, Radius of Gyration (RoG), Root Mean Square Fluctuation, Solvent Accessible Surface Area (SASA), and the H-bond flexibility were analysed with AMBER 18 suite of CPPTRAJ module. The Molecular Mechanics/GB Surface Area method (MM/GBSA) was used for the analysis of the negative free binding energy (∆G) over 100,000 snapshots extracted from the 100 ns trajectory [ 25 ].…”

Orientin Enhances Colistin-Mediated Bacterial Lethality through Oxidative Stress Involvement

“…The CYP3A4 is one of the most vital isoenzymes belonging to the P450 family and is responsible for metabolism of several (> 60%) drugs, hence potentiating a crucial biological and medicinal application [ 36 , 37 ]. Studies have revealed a higher risk of adverse effects and negative impact on the efficacy of coadministered drugs under influence of CYP3A4 [ 38 , 39 ]. Thus, assessing the probable interactions between therapeutic agents and CYP3A4 is imperative to their application.…”

Toxicological Evaluation and In Silico Identification of Acetylcholinesterase Inhibitors in a Commercial Polyherbal Formulation (KWAPF01)

“…However, the P-glycoprotein e ux system found in the GI tract, blood-brain barrier, and several regions of the body [20,36] could limit the bioavailability of the molecules that were predicted to be P-gp substrates. Except for arjungenin, friedelin, nicotine, and terminalin-A, the compounds found in KWAPF01 could bring about some form of drug-drug interactions when they are administered with other drugs as they all inhibit some signi cant cytochrome isoforms, which are responsible for most cytochrome biotransformation [37,38].…”