Exploring the Potential of Phytoconstituents for Immunomodulation as Natural Inhibitors of P-glycoprotein - A Computational Study

Background: P-glycoprotein is an efflux transporter found on the walls of internal organs that interact with the environment, to reduce bioavailability of xenobiotics and chemotherapeutic drugs. Co-administration of herbal medicinal components as modulators or inhibitors may configure the transporter in favour of the drug, thus restricting its expulsion. Aim: The present study aims to explore such herbal medicinal components as potential p-glycoprotein inhibitors thus analyzing the possibility for retaining co-administered immunomodulatory medicines within target cells. Methods: Druggability and pharmacokinetic attributes of the natural compounds were analyzed. Molecular docking using CDOCKER program of Discovery studio (version 2019-21) was utilized to analyze the binding affinity between the natural compounds and 6C0V receptor. Molecular dynamics simulation was employed to evaluate the stability of potential binding compounds. Results: Molecular docking analyses of 462 components from 30 herbs revealed that the inhibitors viz., chelidonine, dihydroberberine, stylopine, fumariline from Chelidonium majus; akuammigine, echitamine from Alstonia scholaris; arjunone from Terminalia arjuna and pareirubrine A from Cissampelos pareira displayed strong binding affinity towards p-glycoprotein. Conclusion: These lead compounds viz., chelidonine, akuammigine and echitamine bearing the maximum binding potency, are known components of immune enhancing herbs. We propose that these molecules may be used in conjunction with immunomodulatory drugs to enhance their bioavailability.