Antibiotic potential of phytochemicals in Punica granatum pericarp and their proposed mechanism of action by in silico studies

Abstract

Aim: Punica granatum is a very important plant with commercial interest and is known for its antioxidant potential. The pericarp is a leftover unwanted part of the fruit that has been reported to have several medicinal uses in traditional medicine. This study focuses on analyzing the antibacterial potential of the pericarp extracts and predicts its mechanism of action by in silico studies. Materials and Methods: Antibacterial activity of P. granatum extracts was analyzed using agar-well-diffusion assay. The phytochemicals reported from pericarp of P. granatum were analyzed for ADMET properties using SwissADME tool. The molecules were subjected to protein-ligand docking study using AutoDock-4. Results: Polar extracts of the pericarp demonstrated significant antibacterial activity against Gram-positive bacteria Staphylococcus aureus and methicillin-resistant S. aureus (MRSA), i.e., acetone extract showed highest activity with 18 mm zone of inhibition against MRSA and ethanol extract showed 16 mm zone of inhibition against S. aureus. The non-polar extract had no significant antibacterial activity. All ten molecules were predicted to be suitable drug-like molecules, with biocompatible physiochemical parameters. Among the analyzed ten phytochemical molecules, flavogallol and ursolic acid demonstrated significant enzyme inhibition potential against dihydrofolate reductase and topoisomerase-IV with a free binding energy of −11.0 kcal/mol and −10.7 kcal/mol, respectively. Conclusion: This suggests that the phytochemicals in the polar extracts of P. granatum pericarp exhibit a synergistic antagonism against Gram-positive bacteria. Further purification of individual molecules and investigation of their antagonistic activity are currently IN progress.