Therapeutic potential of dietary phytochemicals from Drynaria quercifolia to modulate gut microbiome: an in silico approach

Abstract

Drynaria quercifolia is one of the pioneer medicinal plants which exert many beneficial effects on humans. Fatty acids are hydrophobic ligands that act as membrane substrates, metabolic signalling molecules, and metabolic energy sources. It could enhance the mucus production in the intestine which maintain mucosal homeostasis. The inflammatory responses were also regulated by 5-HT receptors. Serotonin 2 A receptors are G-protein coupled receptors targeted by various types of ligands viz. antidepressants, antipsychotics and anti-migraine drugs. The interaction of mucin protein and fatty acid could increase the antimicrobial activity and anti-inflammatory activity of gut microbiome. In this study, dietary phytochemicals were extracted from D. quercifolia and characterized using GC-MS analysis. The result shows presence of 38 various compounds viz. decanoic acid, indole, and dodecanoic acid and etc., Among the all, dodecanoic acid showed good drug likeness and pharmaceutical properties. Target proteins viz. 3IFB (Intestinal fatty acid binding protein) and 7WC4 (5-hydroxytryptamine receptor 2 A) were docked with dodecanoic acid using Auto dock software. The fatty acids produced in the gut could interact with 3IFB and 7WC4 proteins to maintain intestinal integrity and improved gut-brain function respectively. Dodecanoic acid exhibits the highest binding energy with mutated 3IFB (-6.01) than native whereas 7WC4 native protein showed (-7.3 kal/mol) the highest affinity than mutated protein. Structural changes were predicted by using SOPMA and ProSA. Evaluation results indicate that 3IFB was having more stability, good quality, and enhanced affinity than 7WC4. Further, MD simulations were done for 3IFB to check the stability of protein-ligand complex using WebGro platform. The model was investigated by root mean square deviation and fluctuations. Therefore, dodecanoic acids have been considered as a potential agonists and offer opportunities for developing innovative medications for gastrointestinal diseases. Communicated by Ramaswamy H. Sarma