Exploring the Therapeutic Potentials and Molecular Mechanisms of <i>Coscinium fenestratum</i> Alkaloids in Ulcerative Colitis: An Integrative Network Pharmacology and Molecular Docking Approach

<i>Coscinium fenestratum</i>, a medicinal plant traditionally used in Southeast Asia, exerts protective effects against various inflammatory diseases, primarily due to its rich alkaloid content. Despite substantial evidence supporting its anti-inflammatory properties, the biological activities of <i>C. fenestratum</i> are unclear. This study aimed to elucidate anticolitis mechanisms of <i>C. fenestratum</i> alkaloids (CFAs) using an integrative approach of network pharmacology and molecular docking analyses. Key active alkaloids and core target genes were identified through pharmacological and protein-protein interaction networks. The core targets were enriched in the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways to determine the functional properties of active CFA. Finally, the binding affinity of the key compounds with the core targets was determined using molecular docking. The results showed that 11 active CFAs interactively interfered with 10 hub genes related to ulcerative colitis, including prostaglandin-endoperoxide synthase 2 (<i>PTGS2</i>), selectin E (<i>SELE</i>), kinase insert domain receptor (<i>KDR</i>), fms-related receptor tyrosine kinase 1 (<i>FLT1</i>), intracellular adhesion molecule 1 (<i>ICAM1</i>), C-X-C motif chemokine receptor 4 (<i>CXCR4</i>), hypoxia-inducible factor-1 (<i>HIF1A</i>), matrix metalloproteinase (<i>MMP</i>)-<i>2</i>, <i>MMP3</i>, and <i>MMP9</i>, which were functionally involved in the immunological response, tumor necrosis factor signaling pathway, and interleukin-17 signaling pathway. The molecular docking results indicated that CFA compounds had a strong binding affinity for the hub genes. The findings reveal, for the first time, a therapeutic role of CFA in alleviating ulcerative colitis through its predicted interactions with relevant biological targets.