Integrated network pharmacology and molecular modeling approach for the discovery of novel potential MAPK3 inhibitors from whole green jackfruit flour targeting obesity-linked diabetes mellitus

Abstract

The current study investigates the effectiveness of phytocompounds from the whole green jackfruit flour methanol extract (JME) against obesity-linked diabetes mellitus using integrated network pharmacology and molecular modeling approach. Through network pharmacology, druglikeness and pharmacokinetics, molecular docking simulations, GO analysis, molecular dynamics simulations, and binding free energy analyses, it aims to look into the mechanism of the JME phytocompounds in the amelioration of obesity-linked diabetes mellitus. There are 15 predicted genes corresponding to the 11 oral bioactive compounds of JME. The most important of these 15 genes was MAPK3. According to the network analysis, the insulin signaling pathway has been predicted to have the strongest affinity to MAPK3 protein, which was chosen as the target. With regard to the molecular docking simulation, the greatest notable binding affinity for MAPK3 was discovered to be caffeic acid (-8.0 kJ/mol), deoxysappanone B 7,3’-dimethyl ether acetate (DBDEA) (-8.2 kJ/mol), and syringic acid (-8.5 kJ/mol). All the compounds were found to be stable inside the inhibitor binding pocket of the enzyme during molecular dynamics simulation. During binding free energy calculation, all the compounds chiefly used Van der Waal’s free energy to bind with the target protein (caffeic acid: 102.296 kJ/mol, DBDEA: -104.268 kJ/mol, syringic acid: -100.171 kJ/mol). Based on these findings, it may be inferred that the reported JME phytocompounds could be used for in vitro and in vivo research, with the goal of targeting MAPK3 inhibition for the treatment of obesity-linked diabetes mellitus.

Elucidating the anti-cancer potential of Cinnamomum tamala essential oil against non-small cell lung cancer: A multifaceted approach involving GC-MS profiling, network pharmacology, and molecular dynamics simulations

“…The free binding energy of interaction was −5.3 kcal/mol. It is reported that vicenin-2, purvalonol and rutin also interacted with VAL56, LEU173, ALA69, CYS183, ILE48 residues of MAPK3 by forming hydrophobic interactions [ 60 ]. Numerous hydrophobic residues surrounding the ligands within the binding pocket suggest that hydrophobic interactions play a role in stabilizing the complex.…”

Waste to Wealth: Dynamics and metabolic profiles of the conversion of jackfruit flake into value-added products by different fermentation methods

“… Rao et al (2021) demonstrated that consumption of jackfruit flour can be selected as a medical nutritional therapy in place of equivalent amounts of rice or wheat flour of daily meal in patients with T2DM. Besides, jackfruit extracts has also been proved possess the ability for the management of diabetes mellitus ( Ajiboye et al, 2018 , Maradesha et al, 2023 ).Regulation of carbohydrate and fat digestion and/or absorption in the gastrointestinal tract may be another promising strategy for the prevention of T2DM. Recent studies have shown that the consumption of fermentation food is linked to reducing the risks of obesity, and the inhibition of digestive enzyme activities has been regarded as one of the most crucial action mechanisms underlying the beneficial effects ( Yoon et al, 2022 ).…”

Exploring the therapeutic mechanism of potential phytocompounds from Kalanchoe pinnata in the treatment of diabetes mellitus by integrating network pharmacology, molecular docking and simulation approach

“…Further network pharmacology was employed to thoroughly investigate the mechanism of action of pharmaceuticals, facilitating the advancement of novel drugs through a multi-target, multi-component strategy. ( Maradesha et al, 2023 ).…”