Herbal P-glycoprotein Inhibitors Enhance Bioavailability of Cardioprotective Drugs – An In Silico Study

Background: The efficient treatment of cardiovascular diseases may face challenge owing to the presence of an efflux transporter p-glycoprotein in the cardiac tissue, which plays pivotal role in limiting the penetration of allopathic medications into target cell, thereby contributing to drug resistance. Objective: This study is aimed at identifying herbal inhibitors of p-glycoprotein which would enhance the intracellular concentration of co-administered drugs and potentially improve their therapeutic outcomes. Materials and Methods: The study encompassed assessment of druggability and pharmacokinetic attributes of herbal compounds. Additionally, their binding affinity with 6C0V structure of p-glycoprotein was examined through molecular docking utilizing CDOCKER program within Discovery Studio. The stability of the resulting docked complex was verified using molecular dynamics simulation. Results: The herbal inhibitors viz., palmatine from Tinospora cordifolia, arjunone from Terminalia arjuna, pareirubrine A from Cissampelos pareira, have been identified as best interacting molecules against p-glycoprotein, demonstrating strong binding efficacy. Conclusion: These therapeutic herbs if used in conjunction with allopathic drugs, are expected to play crucial role in circumvention of drug efflux and serve as potential candidates for amelioration of cardiovascular diseases. The lead compounds hold promise for exploration through in vivo experiments and subsequent clinical trials, aiming to complement medical treatments effectively.