基于网络药理学探讨石丹颗粒治疗慢性萎缩性胃炎的作用机制

Exploring the Mechanism of Shidan Granules in Treating Chronic Atrophic Gastritis Based on Network Pharmacology

目的结合网络药理学和实验验证研究石丹颗粒治疗慢性萎缩性胃炎的作用机制。方法通过TCMSP数据库筛选石丹颗粒的活性成分,并预测其作用靶点;通过GeneCards、OMIM数据库筛选整合慢性萎缩性胃炎相关靶点;将活性成分靶点与慢性萎缩性胃炎靶点取交集后,通过String11.0数据库构建蛋白互作网络,并运用Cytoscape 3.9.0软件筛选核心靶点;通过DAVID数据库对核心靶点进行GO和KEGG富集分析以预测作用机制;通过AutoDock平台进行分子对接验证。构建慢性萎缩性胃炎细胞模型,通过ELISA、qPCR以及Western blot检测验证网络药理学分析结果。结果共筛选得到石丹颗粒活性成分靶点268个,CAG相关靶点484个,取交集后共得到石丹颗粒治疗慢性萎缩性胃炎靶点82个,其中核心靶点是IL-6、Akt1和TNF等。GO和KEGG富集分析提示石丹颗粒主要通过IL-17信号通路、TNF信号通路和PI3K-Akt等信号通路发挥作用。分子对接显示,大部分核心靶点与活性成分有较高的结合活性。细胞实验表明,石丹颗粒能通过调节IL-6、Akt1和TNF-α改善慢性萎缩性胃炎。结论石丹颗粒中的多种有效成分可通过多靶点、多信号通路抑制慢性萎缩性胃炎向胃癌进展而逆转胃萎缩,为后续研究提供参考依据。

OBJECTIVE To explore the mechanism of action of Shidan Granules in the treatment of chronic atrophic gastritis by combining network pharmacology and experimental validation.METHODS The active ingredients of Shidan Granules were screened through the TCMSP database and their target sites were predicted.Screening and integrating targets related to chronic atrophic gastritis through GeneCards and OMIM databases.Screening and integrating related targets of chronic atrophic gastritis through GeneCards and OMIM databases.After the intersection of active ingredient targets and chronic atrophic gastritis targets,PPI network was constructed through String 11.0 database and the core targets were screened by Cytoscape 3.9.0 software.GO and KEGG enrichment analysis of core targets were carried out through DAVID database to predict the mechanism.Molecular docking verification was carried out through the AutoDock platform.The cell model of chronic atrophic gastritis was established and the results of network pharmacological analysis were verified by ELISA qPCR and Western blot.RESULTS A total of 268 active ingredient targets and 484 CAG-related targets were screened and 82 targets were obtained after intersection among which IL-6 Akt1 and TNF were the core targets.The enrichment analysis of GO and KEGG suggested that Shidan Granules mainly acted through IL-17 signal pathway TNF signal pathway and PI3K-Akt signal pathway.Molecular docking results show that most core targets have high binding activity with active components.The results of cell experiments show that Shidan Granules can improve chronic atrophic gastritis by regulating IL-6 Akt1 and TNF-α.CONCLUSION The various effective components in Shidan Granules can inhibit the progression of chronic atrophic gastritis to gastric cancer through multiple targets and signaling pathways,thereby reversing gastric atrophy,which provides a reference basis for subsequent research.