四磨汤治疗功能性胃肠病机制的网络药理学分析

NETWORK PHARMACOLOGY ANALYSIS ON THE MECHANISM OF SIMO DECOTION IN TREATING FUNCTIONAL GASTROINTESTINAL DISORDER

目的构建四磨汤活性成分−作用靶点网络和蛋白相互作用网络,富集靶点信号通路,探讨其治疗功能性胃肠病的作用机制。方法以四磨汤中槟榔次碱、槟榔碱、去甲槟榔次碱、去甲槟榔碱、木香烃内酯、去氢木香内酯等22个活性成分为研究对象,运用TCMSP及BATMAN-TCM数据库以及Pharm Mapper反向分子对接服务器预测四磨汤活性成分对应的靶点,将其与GeneCards、DisGeNET、OpenTargets、CTD数据库中功能性胃肠病靶点进行比对找重,采用Cytoscape 3.5.1软件构建活性成分-靶点网络,STRING平台构建靶蛋白互作网络,借助DAVID平台对靶点KEGG通路进行分析。结果22个四磨汤活性成分作用的190个靶点,主要富集在神经-递质相关的5-羟色胺能突触、多巴胺能突触;平滑肌运动相关的钙信号通路、cAMP信号通路;以及炎症相关的TNF信号通路、NF-κB信号通路等17条信号通路。结论四磨汤治疗功能性胃肠病的主要机制在于其多成分、多靶点调控胃肠神经传导、平滑肌运动以及炎症。

Objective:To construct the target network of the active component of Simo decoction and protein-protein interaction network,enrich the target signal pathway,and explore the mechanism of the treatment of functional gastrointestinal disorder.Methods:22 active components including arecaldine,arecoline,guvacine,norarecoline hydrochloride,costunolide,dehydrocostus lactone and so on in Simo decoction as study objects,their targets were predicted by using TCMSP,BATMAN-TCM database and Pharm Mapper reverse molecular docking server,and the targets were compared with those of GeneCards,DisGeNET,OpenTargets and CTD databases,the target protein interaction network was constructed by Cytoscape 3.5.1 and the target protein interaction network was constructed by STRING platform,and the target KEGG pathway was analyzed by DAVID Platform.Results:22 active components of Simo decoction have 190 targets,which are mainly rich in neurotransmitter-related serotonergic synapse and dopaminergic synapses,17 signal pathways including smooth muscle movement-related calcium signaling pathways and cAMP signaling pathways,inflammation-related TNF signal pathway,NF-κB signal pathway and so on.Conclusion:The main mechanism of Simo decoction in treating functional gastrointestinal disorder lies in its multi-component and multi-target regulating gastrointestinal nerve conduction,smooth muscle movement and inflammation.