CYP3A4 Interaction with Green Tea Catechins: Insights from MolecularDocking Simulations

Introduction: Green tea contains abundant bioactive polyphenols recognized for their various pharmacological effects, including the regulation of drug-metabolizing enzymes. Cytochrome P450 3A4 (CYP3A4) is essential for the metabolism of a broad range of drugs. This study examines the binding interactions between prominent green tea polyphenols and CYP3A4 to assess their potential impact on drug metabolism and diet-medicine interactions. Methods: Molecular docking simulations using AutoDock Vina were conducted to evaluate the binding affinities of five main components of green tea, myricetin, kaempferol, gallocatechin (GC), epigallocatechin (EGC), and epigallocatechin gallate (EGCG), with the active site of CYP3A4. Emphasis was centered on interactions mediated by hydrogen bonding and π-π stacking, enabled by polyphenolic hydroxyl groups. Results: EGCG had the highest binding affinity (-10.6 kcal/mol), closely followed by EGC and GC, both at -10.4 kcal/mol. Myricetin and kaempferol demonstrated moderate affinities of -8.7 and -8.8 kcal/mol, respectively. The strong interactions observed for EGCG, EGC, and GC were mainly facilitated by hydrogen bonding and aromatic stacking with essential amino acid residues in the enzyme's active site. The findings suggest a possibility of competitive inhibition of CYP3A4 by green tea polyphenols. Discussion: This study highlights the importance of considering dietary components, such as green tea polyphenols, in drug metabolism. The findings suggest that green tea polyphenols, particularly EGCG, EGC, and GC, may competitively inhibit CYP3A4, potentially altering the pharmacokinetics of co-administered drugs. Conclusion: These results underscore the need for further experimental validation and molecular dynamics simulations to assess the long-term stability and clinical relevance of these interactions.