Unveiling the therapeutic potential of Quercetin and its metabolite (Q3OG) for targeting inflammatory pathways in Crohn's disease: A network pharmacology and molecular dynamics approach

Abstract

Crohn's disease is a chronic, inflammatory-mediated condition that calls for an innovative therapeutic approach. Quercetin, a bioactive molecule, has a significant therapeutic impact on chronic illnesses mediated by inflammatory processes. Using the network Pharmacology (NP) based approach, top-ranked targets such as AKT1, MMP9, EGFR, MMP2, TNF, PTGS2, SRC, KDR, PARP1, and MCL1 have been identified. Molecular docking were performed for the AKT1 target towards PDB: 7NH5, which shows that Q3OG [Quercetin 3-Glucuronide] (−10.4 kcal/mol) has stronger binding affinity when compared with Quercetin [Q](−8.4 kcal/mol). The Biological process, Cellular component and molecular function was estimated from the network analysis of the Hub-genes. The KEGG enrichment analysis was performed to ensure the enriched targets. To provide a more effective mechanism for demonstrating protein-ligand interaction of Q and Q3OG with Akt1 protein kinase complex were subjected to a molecular dynamic at 300 K for 100 ns. The complex's structural stability, compactness, residual flexibility and hydrogen bond interaction were evaluated. This result inspires hope for future research and prospective therapeutic approaches to identifying lead molecules from quercetin.