基于网络药理学的黄连解毒汤调节巨噬细胞炎症反应和代谢的作用机制研究

Network pharmacology-based study on mechanisms of Huanglian Jiedu Decoction impact on macrophage inflammation response

运用网络药理学方法探究黄连解毒汤调节巨噬细胞炎症反应、糖酵解、鞘脂代谢和谷氨酰胺代谢等方面的多成分、多靶点、多通路的相互作用规律和调控网络,为创新药物研究奠定基础。通过TCMSP数据库筛选黄连解毒汤活性成分, PharmMapper数据库预测靶点蛋白, DAVID数据库进行通路注释和分析, Cytoscape 3.2.1软件构建"活性成分-靶点-通路"网络图, GENEMANIA数据库进行蛋白相互作用分析, Systems Dock Web Site数据库进行分子对接验证。预测结果表明,黄连解毒汤中共筛选出84个活性成分,作用靶点111个,其中与巨噬细胞炎症相关的靶点蛋白13个,涉及代谢通路14条;与糖酵解、鞘脂代谢、谷氨酰胺代谢相关的靶点蛋白34个,涉及代谢通路8条。炎症相关蛋白和代谢相关蛋白通过物理相关性、蛋白共表达等方式互相作用,小檗碱、黄芩苷和栀子苷与5个重要靶点均能较好结合。黄连解毒汤可能通过作用于糖酵解、鞘脂代谢和谷氨酰胺代谢的相关靶点,影响其代谢过程中的代谢产物和酶,从而调节巨噬细胞炎症反应。

This study was designed to explore the impact of Huanglian Jiedu Decoction（HLJDT） on macrophage inflammation reaction using the network pharmacology method. Glycolysis, sphingolipid metabolism and glutamine metabolism were also investigated for ＂multi-component, multi-target and multi-pathway＂, which supports a foundation for drug innovative research. The TCMSP database was used to screen the active components of HLJDT, the target protein predicted by Pharm Mapper database and the DAVID database for pathways annotation and analysis. The Cytoscape 3.2.1 software was used to construct the active component-target-pathway network map and GENEMANIA database for protein interaction analysis. System Dock Database Site is used in verification of molecular docking. The results showed that 84 active ingredients were screened in HLJDT with a total of 111 target targets. Fourteen pathways are affected according to 13 macrophage-related inflammatory proteins, and 8 pathways including 34 target proteins from glycolysis, sphingolipid metabolism and glutamine metabolism. Inflammation-related proteins and metabolism-related proteins can interact with each other through physical correlation, protein co-expression, etc. Berberine, baicalin and geniposide combined well with 5 important targets. Huanglian Jiedu Decoction may act on the glycolysis and sphingolipid pathways to regulate macrophage inflammatory responses.