Molecular Docking and ADMET Evaluation of Phytoconstituents from Shepolas Hyper Capsules for Anti-hypertensive Activity

The current research work focuses on the therapeutic potential of Shepolas hyper capsules, an Ayurvedic formulation containing eight medicinal herbs, for treating hypertension. Thirty-two phytochemicals from these herbs were screened through molecular docking against human renin (PDB: 2V0Z) using AutoDock Vina. The docking analysis revealed significant binding affinities for several compounds, with Withaferin A and Withanone showing the highest binding energies of -9.7 kcal/mol, followed by Ellagic acid (-9.5 kcal/mol), Physagulin-d (-9.4 kcal/mol), and Withanolide A (-9.4 kcal/mol). Drug-likeness analysis using Lipinski's rule of five and SwissADME indicated favorable pharmacokinetic properties for these compounds. The ADMET profiling through pkCSM demonstrated acceptable absorption, distribution, metabolism, excretion, and toxicity characteristics for the top-performing compounds. Detailed interaction analysis has shown the binding interactions with the renin active site, including hydrogen bonds and aromatic interactions. The computational study indicated that these phytoconstituents, particularly those derived from Withania somnifera, may effectively inhibit renin activity and potentially help manage hypertension. The favorable drug-like properties and safety profiles of these compounds support their development as natural therapeutic agents for hypertension management