基于网络药理学探讨丹参在治疗急性胰腺炎中的作用机制

Exploring the Therapeutic Mechanism of Salvia Miltiorrhiza in Acute Pancreatitis Treatment Using Network Pharmacology

摘要: 目的：通过网络药理学探寻丹参治疗急性胰腺炎的药效物质基础和分子作用机制。方法：本研究基于网络药理学方法，系统探讨丹参促进创面愈合的活性成分、作用靶点及通路机制。首先通过TCMSP、Swiss Target Prediction数据库筛选丹参活性成分及靶点；从GeneCards、OMIM数据库获取创面疾病靶点；利用Venny 2.1获取药物–病毒交集靶点；采用Cytoscape 3.9.2构建“成分–靶点”网络；基于STRING平台构建蛋白互作网络筛选核心靶点；应用R语言对交集靶点进行GO功能与KEGG通路富集分析，最后对两者进行分子对接。结果：共筛选出丹参活性成分54个，对应靶点61个，与AP疾病靶点取交集获得59个共同靶点。PPI网络分析确定RELA、IL6、CASP3、BCL2、GSK3B等13个核心靶点。GO富集分析显示靶点显著富集于炎症反应调控、细胞凋亡过程等生物过程；KEGG通路分析揭示其通过PI3K-AKT信号通路、p53信号通路及神经活性配体–受体相互作用通路发挥协同作用；核心化合物与关键核心靶点的结合能均小于−5 kcal/mol。结论：丹参可能通过多组分协同调控炎症风暴、凋亡失衡及神经源性炎症，体现“多靶点–多通路”整合调节特点，为丹参治疗AP的中西医结合应用提供分子依据。

Abstract: Objective: To explore the pharmacodynamic material basis and molecular mechanism of Salvia miltiorrhiza (Danshen) in improving acute pancreatitis (AP) using network pharmacology. Methods: Based on network pharmacology, this study systematically investigated the active components, potential targets, and pathway mechanisms of Salvia miltiorrhiza for treating AP. Firstly, the active components of Salvia miltiorrhiza and their corresponding targets were screened using the TCMSP and Swiss Target Prediction databases. AP disease targets were retrieved from the GeneCards and OMIM databases. Venny 2.1 was used to identify the intersection targets between the drug and the disease. Cytoscape 3.9.2 was employed to construct a “Component-Target” network. A protein-protein interaction (PPI) network was built using the STRING platform to screen core targets. R language was applied for Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the intersection targets. Results: A total of 54 active components of Salvia miltiorrhiza were screened, corresponding to 61 targets. Intersection with AP disease targets yielded 59 common targets. PPI network analysis identified 13 core targets, including RELA, IL6, CASP3, BCL2, and GSK3B. GO enrichment analysis indicated that the targets were significantly enriched in biological processes such as regulation of the inflammatory response and apoptotic processes. KEGG pathway analysis revealed that the therapeutic effects involve synergistic actions through the PI3K-AKT signaling pathway, p53 signaling pathway, and neuroactive ligand-receptor interaction pathway. Molecular docking studies revealed that all binding energies between the hub targets and the ingredients were less than −5 kcal/mol. Conclusion: Salvia miltiorrhiza may exert its therapeutic effect on AP by multi-component synergy regulating cytokine storm, apoptotic imbalance, and neurogenic inflammation, reflecting the characteristics of “multi-target and multi-pathway” integrated regulation. This study provides a molecular basis for the integrated traditional Chinese and Western medicine application of Salvia miltiorrhiza in treating AP.