Rauwolfia serpentina in P-Glycoprotein Inhibition of Cancer & Diabetes - A Computational Study

Abstract

Background: The efficient treatment of cancer and diabetes is often constrained by reduced permeation of chemotherapeutic and antidiabetic medications due to p-glycoprotein-mediated efflux, impeding their therapeutic potential and necessitating higher doses or prolonged treatments, which can lead to increased toxicity and financial burden. Ayurveda, an ancient holistic healthcare system, advocates the use of herbal remedies for various ailments. Objective: This study aims to explore the potential of Rauwolfia serpentina and other selected antidiabetic and anticancer medicinal herbs as inhibitor of p-glycoprotein. Materials and Methods: Druggability and pharmacokinetic profile of 185 herbal constituents were evaluated and their binding affinity were interpreted against 6C0V structure of p-glycoprotein utilizing molecular docking with CDOCKER program of Discovery Studio. The stability of the docked complex was validated using molecular dynamics simulation for 40 nanoseconds. ChemMine software was employed for clustering p-glycoprotein herbal inhibitors against standard drug verapamil on the basis of physicochemical properties. Results: Docking analyses revealed that deserpidine and ajmalicine from Rauwolfia serpentina exhibited strong favourable binding interactions with p-glycoprotein, along with other herbal compounds viz., hydrastine from Hydrastis canadensis, palmatine from Tinospora cordifolia and hexadecanoic acid 2-hydroxy-1(hydroxymethyl)ethyl ester from Ipomoea aquatica. Conclusion: This study underscores the potential of combining Rauwolfia serpentina and other medicinal herbs with allopathic drugs to augment their bioavailability and efficacy, providing a novel avenue for advancing therapeutic strategies in oncology and diabetes management. Further experimental validation is necessary to confirm the clinical relevance of these findings.