Background: Severe acute pancreatitis (SAP) is one of the most prevalent acute abdominal conditions encountered in general surgery, often complicated by multiple organ dysfunction. In SAP, the intestine is one of the first and most severely affected organs. Intestinal barrier injury (IBI) plays a key role in disease progression and poor prognosis. Qingyi Decoction (QYD), a traditional Chinese medicine, is widely used to treat SAP clinically. Although clinical observations suggest that QYD improves IBI in patients with SAP, the underlying mechanisms remain unclear. This study aimed to evaluate QYD’s multi-target mechanisms in treating SAP-associated IBI via network pharmacology and machine learning, with significance in clarifying IBI pathology and providing a technical paradigm for TCM mechanism research. Methods: The components of QYD and the targets of IBI were identified by searching different databases. Furthermore, integrated analyses including network pharmacology, machine learning, and molecular docking were conducted using Auto Dock Vina. Results: A total of 30 potential therapeutic targets of QYD for IBI were identified through network pharmacology and bioinformatics analyses. KEGG pathway enrichment analysis revealed significant involvement of the IL-17 signaling pathway, TNF signaling pathway, and NF-kappa B signaling pathway. Protein–protein interaction and drug-ingredient-target network analyses identified IL-6, HIF1A, and PTGS2 as primary targets. Machine-learning methods further identified IGFBP3 and Sonic Hedgehog ( SHH ) as hub genes. Gene set enrichment analysis (GSEA) indicated that IGFBP3 was primarily associated with the p53 signaling pathway, whereas SHH was associated with cancer-related signaling pathways. Immune infiltration analysis showed that QYD may affect immune cell infiltration in IBI through multiple targets. IGFBP3 was negatively correlated with macrophage (M0) and neutrophil infiltration, whereas SHH was positively correlated with both. Molecular docking identified 5 major active compounds targeting the hub genes: 7,8,4’-trihydroxyisoflavone, 2,6,2’,4’-tetrahydroxy-6’-methoxychalcone, quercetin, scutevulin, and daucosterol. Conclusions: The results of this study indicated that QYD ameliorates IBI through multiple targets and signaling pathways, with the p53 signaling pathway playing a key role in its therapeutic effect.
Xu et al. (Fri,) studied this question.