Virtual screening, pharmacokinetics & MD simulation study of active phytoconstituents of Ficus Carica Linn. against PPAR-γ in diabetes mellitus

AbstractF. carica is a small tree and commonly used as a traditional medicine against several disorders. Diabetes is currently treated with insulin and oral hypoglycemic medicines such as sulphonyl urea derivatives, bigunides, thiazolidinediones and alpha-glucosidase inhibitors. Peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists were found to be very much beneficial in the management of diabetes by inhibiting hepatic gluconeogenesis. The aim of this study is to evaluate the bioactive phytoconstituents from Ficus carica Linn. against the target PPAR-γ agonist by in silico docking approach. We investigated 68 phytoconstituents as potential inhibitors of PPAR-γ agonists and the top 24 phytoconstituents were further selected for molecular docking studies. Drug ability, side effects, and ADMET analysis were determined by using MolSoft, toxtree freeware, and ADMET SAR web server, respectively. The phytoconstituents were docked with the target PPAR-γ (PDB ID: 4Y29, 1.98 Å) receptor. Quercetin-3-o-rutinoside possessed the highest G score −14.22 kcal/mol, followed by Angelicin with a G score of −13.56 kcal/mol. All the other phytoconstituents displayed good pharmacokinetic and toxicological parameters with values within the permissible limits. The ligand-protein interaction was calculated by molecular dynamic (MD) simulation study. Subsequently, the binding free energy of the Quercetin-3-o-rutinosideand Pioglitazone complex was calculated using MMPBSA analysis. The results indicated that some of the phytoconstituents from Ficus carica have potency as an anti-diabetic agents. So, these bioactive phytoconstituents like Quercetin-3-o-glucoside, 5-O-caffeoylquinic acids may act as a good agonist for PPAR-γ.Communicated by Ramaswamy H. SarmaKeywords: Ficus caricadiabetes mellitusin-silico analysismolecular dockingPPAR-γ AcknowledgmentThe authors acknowledge the support of NGSM Institute of Pharmaceutical Sciences, Nitte (Deemed to be a university), Mangalore, Karnataka, NGSM-CADD Lab for providing all the necessary infrastructure and resources to devote to this research project. I like to thank all the authors for their valuable suggestions.Disclosure statementThere are no competing financial interests or personal relationships influencing the findings of this paper.Additional informationFundingThe author(s) reported there is no funding associated with the work featured in this article.