基于网络药理学探讨麻杏石甘汤治疗流感的作用机制

A Network Pharmacology Study on the Effects of Ma Xing Shi Gan Decoction on Influenza

目的采用网络药理学方法筛选麻杏石甘汤对流感的作用靶点及信号通路,从而预测麻杏石甘汤抗流感的潜在机制。方法通过检索中药系统药理数据库(TCMSP)及相关文献、设定一定条件筛选主要化合物和主要化合物所对应的靶点。从STRING数据库预测成分靶标蛋白质的互相作用。利用WebGestalt平台和reatome数据库分别对麻杏石甘汤作用于流感的PPI网络中涉及的核心靶点进行GO功能富集分析和KEGG途径分析。用iGEMDOCK对受体和配体进行对接后获得相应的对接分数,对接结果通过Autodock及PyMOL可视化处理。结果筛选获得126种主要化合物及其所对应的靶点。从STRING数据库预测到355个流感的靶标蛋白和1221条流感的蛋白质相互作用关系。麻杏石甘汤的药效靶点高度富集到与流感相关的信号通路和生物学过程,细胞成分和分子功能,如免疫系统中的细胞因子信号传导、白介素的信号传递、对刺激的响应等。分子对接结果显示麻杏石甘汤中RELALicochalcone A对接优于其他靶蛋白和有效成分,提示该对接位点可能是麻杏石甘汤抗流感的主要位点。结论麻杏石甘汤在干预病毒吸附、抑制病毒增殖、调节抗体免疫系统、保护宿主细胞等方面都发挥着抗流感的作用,并以抗过度炎症反应损伤组织为主。

Objective Pharmacological methods were used to screen targets and signaling pathways of Ma Xing Shi Gan Decoction(MXSGD)during influenza treatments,and mechanisms underlying antiinfluenza effects were elucidated.Methods The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and relevant literature were searched under predefined conditions to identify the main compounds and their targets.Interactions between the target proteins were predicted using the STRING database.Gene Ontology(GO)functional enrichment analyses and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were performed on the core targets involved in the influenza protein-protein interaction(PPI)network,using WebGestalt and the reactome database.iGEMDOCK was used for molecular docking of receptors and ligands to produce docking scores,and the results were visualized using Autodock and PyMOL.Results In total,126 major compounds and their respective targets were screened.355 influenza target proteins and 1221 influenza protein interactions were predicted using the STRING database.Influenza-related signaling pathways were strongly enriched in pharmacodynamic targets of MXSGD such as cytokine signaling in immune system and signaling by interleukin.The main biological process was response to the stimulates.Molecular docking results showed that RELALicochalcone A docking elicited by MXSGD,was superior to that of other target proteins and active compounds,suggesting that the docking site is also the main effector site of MXSGD during influenza treatments.Conclusions The results showed that MXSGD exerts antiinfluenza effects by interfering with virus adsorption,inhibiting virus proliferation,influencing immune functions and protecting host cells,which may prevent inflammation-induced tissue damage.