Exploring the bioactives and the mechanism of Aegle marmelos in the treatment of Inflammatory bowel disease through network pharmacology and molecular docking approach

Abstract

Abstract Inflammatory bowel diseases (IBD) are recurrent inflammatory conditions that occur in the gastrointestinal tract, and current treatment does not have satisfactory results, we still need newer therapies to combat the complex pathogenesis of IBD. Herbal medicines have been used for years to cure IBD. One of the plants from Ayurveda, Aegle marmelos (AM), commonly known as Bael and belonging to the family Rutaceae has ethnomedicinal properties in treating IBD due to its various phytochemicals. However, the mechanisms underlying the effect of AM remain to be elucidated. In the study, 46 effective compounds and 358 targets of AM were identified and further analyzed, 80 hub targets depending on the degree were considered effective against IBD. Through the Cyto Hubba plugin of Cytoscape (3.10.0), we identified AKT1, SRC, MAPK3, MAPK1, EGFR, IL6, TNF, HSP90AA1, and CASP3 as the top 10 hub targets that may contribute to the mechanistic role of AM in treating IBD. Aegeline, auraptene, bergapten, imperatorin, marmesin, and nodakenin were the potent compounds of AM and the molecular docking studies with the hub target depict their higher binding affinity to PI3K, AKT, and EGFR. The Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis suggest that PI3-AKT signaling pathway, EGFR tyrosine kinase inhibitor, and MAP Kinase signaling pathway are the major pathways correlating with AM in combating IBD. The network pharmacological and molecular docking approach unveils the mechanism of AM in alleviating IBD through the EGFR-mediated PI3K/AKT pathway, stating its multi-component, multi-targeted therapeutic efficacy through multiple pathways.