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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. [ABSTRACT FROM AUTHOR]

A critical approach for target identification to detect the significant molecular mechanism of lead molecules via computational methods combined with in vitro procedures defines the modern strategy to combat untreatable diseases. Hence, the present investigation dealt to determine the effect of Erythrina variegata L. bark extract/fraction(s) over acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity followed by target identification and docking analysis of prime phytoconstituents. The in vitro AChE and BChE enzyme inhibitory assay were performed. Phytoconstituents from E. variegata were screened for carcinogenicity and mutagenicity and predicted for their possible targets leading to the identification of two known targets, i.e. AChE and BChE. The alkaloids with non-carcinogenic and non-mutagenic properties were studied for their main moiety responsible for the inhibitory activity. The protein models were checked in ERRAT for their quality and the homology model was created using Modeller9.10v to fill missing amino acid residues. The docking study predicted the binding affinity of bioactive molecules with identified targets using AutoDock 4.2. Molecular dynamics (MD) simulations for top hits were performed by Schrodinger Desmond 6.1v software. Chloroform fraction showed potent inhibition of AChE and BChE with IC50 value of 38.03 ± 1.987 µg/mL and 20.67 ± 2.794 µg/mL, respectively. Among all the six major bioactive compounds, Erysotine and Erythraline scored the highest binding affinity with AChE and Erysodine with BChE. MD simulation for 20 ns production run demonstrated Erysotine and Erysodine stable interaction with Arg49 of AChE and Lys427 of BChE, respectively. The current data provide enough shreds of evidence supporting the utilization of indolo [7a,1-a] isoquinoline derivatives for the identification of a new drug molecule in the management of Alzheimer's disease. [ABSTRACT FROM AUTHOR]