In Silico Rationalization for Leads from Oldenlandia umbellata L. to Inhibit Multiple Molecular Targets Regulating Osteoporosis

Background Osteoporosis is a chronic metabolic bone disease caused due to the dysregulation in the functioning of osteoblast and osteoclast cells leading to increased bone resorption predominantly in postmenopausal women and the elderly, thereby affecting a significant global population. Purpose The present study aims to computationally screen the phytochemical constituents of Oldenlandia umbellata Linn against the unique molecular therapeutic targets of osteoporosis and validate the results using Molecular Dynamics (MD) Simulation. Methods The molecular docking analysis of the selected phytoconstituents against the molecular targets were performed using AutoDock 4.2.6 – AutoDock Tools 1.5.6. In addition, the drug likeliness, ADME, bioactivity, and toxicity were predicted using Molinspiration ADMELAB2.0, ProTox-II and Orisis DataWarrior online tools. Molecular Dynamic Simulation studies were performed using WebGRO macromolecular simulation server. Results Molecular docking results and data analysis revealed that deacetylasperuloside possesses good drug-likeness, ADME properties, and bioactive scores and did not indicate any toxicity compared to other phytochemicals exhibiting binding energies below –8.00 Kcal/mol against the targets. Together, the study emphasized that deacetylasperuloside could bind with the molecular targets of osteoporosis, and the lead is a potential therapeutic candidate for osteoporosis treatment. Further, molecular dynamic simulation analysis for 100 ns revealed that the ligand–protein complexes, including glycogen synthase kinase 3β (GSK3β)-deacetylasperuloside and cathepsin K (CTSK)-deacetylasperuloside complexes, were stable and highly compact assessed from their trajectories. Hence, it can be emphasized that deacetylasperuloside could be a potential therapeutic molecule that could inhibit the targets, including GSK3β and CTSK. Conclusion Oldenlandia umbellata L. is a potential candidate for identifying therapeutic leads for osteoporosis treatment. Further, in vitro and in vivo studies are needed as an output of this research to evaluate its therapeutic efficacy.