基于网络药理学、分子对接和分子动力学探讨乌梅丸治疗溃疡性结肠炎的作用机制OA

To elucidate the pharmacodynamic material basis and molecular mechanism of Wumei pill in the treatment of ulcerative colitis(UC)by integrating network pharmacology,molecular docking,and molecular dynamics(MD)simula-tions.Twenty-one key active components of Wumei pill and 97 UC-related therapeutic targets were identified.PPI net-work analysis highlighted 20 core targets,including IL-6,TNF,IL-1β,and PTGS2.GO and KEGG enrichment analyses revealed that these targets were mainly involved in inflammatory regulation,immune homeostasis,and mucosal barrier pro-tection,and were enriched in UC-related pathways such as TNF,L-17,NF-κB,HIF-1,and PI3K-Akt signaling.Molecular docking demonstrated strong binding affinities between core components(e.g.zingerone,ligustilide,berberine,cinnamal-dehyde)and core targets.MD simulations further confirmed the structural stability of IL-6-zingerone,IL-1β-ligustilide,PTGS2-berberine,and TNF-cinnamaldehyde complexes during 100 ns simulations.Human normal colonic epithelial cell line NCM-460 was used to establish a colonic epithelial inflammation model.The experiment was divided into the control group,model group,mesalazine group,and berberine low-,medium-,and high-concentration treatment groups.The protein expression levels of TNF-α and IL-1β were detected by immunofluorescence assay.Compared with the control group,the expressions of IL-1β and TNF-α in the model group were significantly upregulated(P＜0.001).All treatment groups(berberine low-,medium-,and high-dose groups and mesalazine group)could significantly inhibit the expressions of these two factors(compared with the model group,P＜0.05,P＜0.001).Compared with the positive drug mesalazine group,berberine exhibited a dose-dependent manner:the effect of its high-dose group was comparable to that of mesala-zine,while the expression levels of the two factors in the low-and medium-dose groups were significantly higher(P＜0.05,P＜0.01).These findings suggest that Wumei pill exerts therapeutic effects on UC through multi-component and multi-target synergistic regulation of inflammation,oxidative stress,and mucosal repair pathways.This study provides a theoretical foundation for the modern pharmacological elucidation and clinical application of Wumei pill.