Inosine, AMP, and Vidarabine: Network Pharmacology and LC-MS Reveal Key Bioactive Compounds in Periplaneta americana for Ulcerative Colitis Management

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with unmet therapeutic needs. This study investigates the therapeutic potential of <i>Periplaneta americana</i> L. extract (PAE) and its molecular mechanisms, integrating network pharmacology and experimental validation. Liquid chromatography-mass spectrometry identified 1355 compounds in PAE. Network pharmacology analysis revealed that inosine, vidarabine, and adenosine 5'-monophosphate (AMP) were core components and the core components synergistically regulated key targets and acted on inflammation-related pathways, thereby establishing a multi-target anti-inflammatory regulatory network. In vivo experiments demonstrated that these compounds significantly alleviated colitis symptoms in dextran sulfate sodium-induced mice, as evidenced by reduced disease activity index scores, preserved colonic mucosal architecture, and decreased inflammatory infiltration. Mechanistically, core compounds down-regulated granulocyte-macrophage colony-stimulating factor (GM-CSF), inducible nitric oxide synthase (iNOS)/NOS2, monocyte chemoattractant protein 1 (MCP-1), and transforming growth factor beta 1 (TGF-β1), while they up-regulated interleukin-10 (IL-10) and epidermal growth factor (EGF). Additionally, they activated epidermal growth factor receptor (EGFR)-mediated pathways. Molecular docking analysis revealed that adenosine analogs preferentially bound to A1/A2a receptors, triggering signaling cascades essential for epithelial repair and inflammation resolution. This study established the multi-component, multi-pathway mechanism of PAE in UC, highlighting its dual role in suppressing inflammation and promoting mucosal healing. By bridging traditional herbal use with modern molecular insights, these findings provided a translational foundation for developing PAE-based therapies for UC.