基于网络药理学模式的柴胡加芒硝汤治疗便秘的系统功效研究与机制预测

Systematic efficacy study and mechanism prediction of Chaihu Plus Mangxiao Decoction in treatment of constipation based on network pharmacology model

目的运用网络药理学方法预测柴胡加芒硝汤治疗功能性便秘的功效作用网络和潜在机制。方法通过TCMSP、TCMID及SwissTargetPrediction在线预测数据库,以口服利用度(OB)和类药性(DL)作为限定条件对柴胡加芒硝汤的成分及其靶点进行收集和筛选;从PubMed、CTD、TTD、Drug Bank等数据库对功能性便秘相关的靶点进行检索;利用STRING和Cytoscape分析软件对所得靶点进行网络可视化处理,并筛选节点度较高的关键成分和核心靶点;借助Cytoscape及其插件对其核心靶点进行富集分析,预测作用机制。结果筛选出柴胡加芒硝汤总成分共206个,其对应靶标有998个;功能性便秘的疾病靶点有295个;经分析获知涉及柴胡加芒硝汤治疗功能性便秘作用的有64个关键成分和30个核心靶点,对核心靶点进行GO富集分析及KEGG途径分析,SCN9A、CFTR、HTR2A、OPRD1、PTGS1、FGFR1等30个核心靶标主要通过阿片受体活性、机体的水平衡、萜类物质的代谢和生物胺配基结合受体的活性等多个生物过程和分子功能,以调节5-羟色胺受体、花生四烯酸代谢、MECP2的转录调控、细胞色素P450、生物胺配基结合受体、PI3K的异常表达、络氨酸蛋白激酶信号通路、外源性异物刺激等作用通路发挥对便秘的治疗作用。结论柴胡加芒硝汤治疗功能性便秘的作用机制呈现多靶点、多通路的特点,其皂苷类、黄酮类、甾醇类物质可能是其发挥核心功效的物质基础,5-羟色胺类受体、阿片类受体、氯离子通道调控受体可能是其关键作用靶点。

Objective To investigate the function network and potential mechanisms of effects of Chaihu Plus Mangxiao Decoction in the treatment of functional constipation by using network pharmacology methods.Methods TCMSP,TCMID,and Swiss Target Prediction online prediction databases were used to screen the components and their potential targets of Chaihu Plus Mangxiao Decoction using oral availability(OB)and drug-like(DL)as the qualification conditions.PubMed,CTD,TTD,and DrugBank were used to search functional constipation-related targets.STRING and Cytoscape were used to make targets network visualization,screen the key components and core targets with high a degree of the node;Finally,relevant software was applied to analyze core targets and predict the mechanism.Results A number of 206 total components of Chaihu Plus Mangxiao Decoction were screened,and there were 998 corresponding targets,which were contained 295 targets associated with functional constipation.According to the analysis,there were 64 key components and 30 core targets involving the Chaihu Plus Mangxiao Decoction-induced treatment of functional constipation.After enrichment analysis and KEGG pathway analysis of 30 core targets,it was found that SCN9 A,CFTR,HTR2 A,OPRD1,PTGS1,and FGFR1 were involved in regulating biological processes including opioid receptor activity,water balance of the organism,terpenoids and biological receptors and subsequent mediating the function of serotonin receptors,arachidonic acid metabolism,transcriptional regulation of MECP2,cytochrome P450,biogenic amine-binding receptors,PI3 K the aberrant expression,tyrosine-protein kinase signaling pathway,and exogenous foreign body stimulation.These biological targets and molecular signaling pathways may play a therapeutic role in the treatment of functional constipation.Conclusion The mechanism of effect of Chaihu Plus Mangxiao Decoction in the treatment of functional constipation is characterized by multiple targets and pathways.Saponins,flavonoids,and sterols may be the material basis for core functions,and serotonin receptors,opioid receptors and chloride channel-regulated receptors may be key targets of Chaihu Plus Mangxiao Decoction.