Bioactive Compounds from Momordica charantia, Nigella sativa, and Anethum graveolens against Metabolic Syndrome: Untangling the Complex Relationship

Background: Momordica charantia (MC), Nigella sativa (NS), and Anethum graveolens (AG) are widely utilized vegetables and as an herbal medicines, despite widespread use, there is no evidence of molecular mechanisms of compound-protein-pathway interaction for the treatment of metabolic syndrome (MetS). Materials and Methods: Reported phytochemicals were collated from the botanical databases and SwissTargetPrediction was utilized to predict likely protein targets. Both the STRING and KEGG databases were used to infer the protein target pathway analysis. Cytoscape v3.6.1 was employed to build the compound-protein-pathway network. AutoDock vina executed through POAP pipeline was employed for therapeutic target and compounds docking study. Molecular dynamics was performed by GROMACS. Results: 34, 19, 34 phytocompounds from three plants MC, NS, and AG were predicted to target 30, 30, 28 protein targets and these targets modulated 20, 18, 22 molecular pathways respectively involved in metabolic syndrome. Neuroactive ligand-receptor interaction, Calcium, cGMP-PKG, cAMP, AMPK, PI3K-Akt, PPAR, Metabolic signaling pathways, etc were modulated by compounds. PPARG was hub gene within the network. Nigellidine from NS, Nigellimine-N-Oxide from NS, Cryptoxanthin from MC scored lowest BE with PPARG (-7.5kcal/mol), FABP1 (-8.8kcal/mol), and HMGCR (-7.1kcal/mol) protein targets respectively. MD simulation for 100ns revealed stable interactions of phytocompounds comparable to standard molecules. Conclusion: The current study identified multi-compounds containing enhanced fraction of MC, NS, and AG could be the effective therapy regimen for diabetes, obesity, and MetS.