Theoretical interaction of epoxybergamoti, hyperforin and hypericin with Cyp3A4 and P-glycoprotein using a theoretical model

Some chemical components involved in grapefruit juice and St. John's wort can produce changes in pharmacological activity of different drugs; however, their interaction with both P-glycoprotein and CyP450 enzyme is not clear. The aim of this study was to evaluate the possible interaction of epoxybergamoti, hyperforin and hypericin with both P-glycoprotein and CyP450 enzyme using 1w0f, 3g5u proteins, midazolam, simvastatin and fexofenadine as theoretical tools in DockingServer program. The results showed differences in the aminoacid residues involved in the interaction of epoxybergamoti, hyperforin and hypericin with 1w0f, 3g5u proteins surface compared with midazolam, simvastatin and fexofenadine. Besides, inhibition (Ki) constant for hyperforin was lower compared with epoxybergamottin and hypericin. Other data, displayed that Ki for epoxybergamottin, hyperforin and hypericin was lower compared with fexofenadine. In conclusion, the results suggest that; 1) hyperforin could act as CyP3A4 inhibitor; 2) epoxybergamottin, hyperforin and hypericin could act as P-glyprotein blocker. This phenomenon suggests that the concomitant use of the chemical components of grapefruit juice and St. John's wort with midazolam, fexofenadine and simvastatin could produce changes in the pharmacological activity of midazolam, simvastatin and fexofenadine.