Interpreting the Multi-Target Molecular Mechanisms of Holoptelea integrifolia (Roxb.) Planch., against Ulcerative Colitis by Network Pharmacology

Abstract:Ulcerative colitis (UC) is a chronic, relapsing inflammatory disorder of the coloncharacterized by persistent mucosal inflammation, immune dysregulation, oxidative stress,and disruption of intestinal homeostasis.Holoptelea integrifolia (Ulmaceae) comprisesofvaried bioactive phytoconstituents that potentially interact with multiple molecular targetsand signalling pathways. The current research is primarily focused at interpreting therestorativeefficacy and underlying molecular mechanisms of five phytoconstituents fromH.integrifolia: 1-octacosanol, 1,4-naphthoquinone, 1-hexacosanol, β-amyrin, and β-sitosterolagainst UC using network pharmacology approach. Plant constituent-associated targets wereintersected with UC-related targets to identify common targets, followed by protein–proteininteraction (PPI) network construction and Gene Ontology (GO), Kyoto Encyclopaedia ofGenes and Genomes (KEGG), and OMIM enrichment analyses. A total of 69 common targetswere identified. GO analysis indicated significant enrichment in inflammatory response,response to lipopolysaccharide, cellular regulation, and receptor-mediated signallingprocesses, while KEGG pathway analysis highlighted Toll-like receptor, PI3K-AKT, JAKSTAT, HIF-1, and cytokine-related signalling pathways. PPI network analysis identified IL6,TNF, AKT1, STAT3, EGFR, TLR4, SRC, PTGS2, and MMP9 as key hub targets.Collectively, these findings suggest that the selected H. integrifoliaconstituents may exertpotential anti- ulcerative colitic effects through coordinated modulation of inflammatory,immune, oxidative stress, cell survival, and tissue remodelling pathways. These resultsprovide a mechanistic foundation for further experimental validation of H. integrifolia and itscompounds in UC.