乌梅丸治疗溃疡性结肠炎的活性成分与机制研究：谱效关系、网络药理与分子对接

Abstract

Wumei Wan (WMW), a renowned classic traditional Chinese medicine formula, is traditionally indicated for regulating cold-heat imbalance, exerting intestinal astringent effects, and arresting diarrhea. Clinically, it is widely employed in the treatment of ulcerative colitis (UC), which primarily manifests as chronic diarrhea and mucopurulent bloody stools. However, its material basis and pharmacological mechanisms involved remain obscure. This study employed spectrum-effect relationships, network pharmacology, molecular docking and experimental validation to identify the bioactive components of WMW and clarify its mechanisms in treating UC. The chemical fingerprint of various extract fractions of WMW was established via UPLC-Q-TOF-MS/MS. The ameliorate colitis activity of each polar component of WMW was explored using dextran sulfate sodium-induced colitis mice, among which ethyl acetate and n -butanol extracts were the best. Sixteen potential bioactive components were identified by spectrum-effect relationship analysis, encompassing kaempferol, magnocurarine, magnoflerine, oxyberberine, malic acid, isocitric acid, limonin, and ginsenoside Rd, etc. Subsequent studies combined with network pharmacology analysis indicated that WMW exerts synergistic therapeutic effects against UC by modulating multiple targets (e.g., PIK3R1 , STAT3 , AKT1 , MAPK1 ). The key pathways included Th17 cell differentiation, NF-κB signaling, tyrosine metabolism and PPAR signaling. Molecular docking confirmed the strong binding affinities between these targets and the identified compounds, with limonin exhibiting particularly high affinity. Finally, the pharmacological effects of WMW and limonin were corroborated in the colonic tissues of colitis mice or in lipopolysaccharide-induced cellular inflammation model. These findings establish a theoretical foundation for the clinical use and rational development of WMW as an anti-colitis agent.