基于网络药理学研究半夏治疗功能性消化不良的作用机制

Study on the mechanism of Pinellia ternate in the treatment of functional dyspepsia based on network pharmacology

目的探讨半夏治疗功能性消化不良的作用机制。方法本研究起止2020年1—2月。通过TCMSP数据库检索得到半夏的活性成分和作用靶点,同时借助UniProt、HCBI和PubMed等数据库,得到药物活性成分靶点对应的基因名。利用Gene Cards和OMIM数据库得到功能性消化不良的相关治疗靶点,将其与半夏活性成分靶点取交集后得到药效靶点。将交集靶点通过STRING 11.0数据库进行蛋白质-蛋白质的相互作用网络分析得到潜在的治疗核心蛋白。最后采用KOBAS 3.0平台和DAVID 6.8数据库进行GO功能富集分析和KEGG信号通路富集分析,研究半夏治疗功能性消化不良靶点的作用机制。结果筛选得出半夏的13个活性成分和74个活性成分靶点基因以及35个交集基因。通过蛋白质-蛋白质相互作用网络分析,半夏治疗功能性消化不良可能与B淋巴细胞瘤-2基因(Bcl-2)、RACα丝氨酸/苏氨酸蛋白激酶(AKT1)、半胱氨酸蛋白酶-3(CASP3)、半胱氨酸蛋白酶-9(CASP9)等靶点蛋白相关。GO功能富集分析得到66个GO条目(P<0.05),通过分析我们可以知道半夏治疗功能性消化不良主要与儿茶酚胺结合、内肽酶活性、核受体活性、转录因子活性、凋亡过程中的半胱氨酸型内肽酶活性等功能相关。KEGG信号通路分析得到97条信号通路(P<0.05),通过筛选主要与凋亡-多物种、凋亡-乙型肝炎、大肠癌、肿瘤坏死因子等信号通路相关,我们发现这些通路中均含有B淋巴细胞瘤-2基因(Bcl-2)、半胱氨酸蛋白酶(Caspase)、凋亡基因(Bax)等凋亡因子。结论半夏可以通过多成分、多靶点、多途径共同发挥对功能性消化不良的治疗作用,其中在对凋亡通路上的其因子表达抑制或者增强,最终达到抑制组织细胞的凋亡将可能是半夏治疗功能性消化不良的重要机制之一。

Objective To explore the mechanism of Pinellia ternate in the treatment of functional dyspepsia.Method This study started and ended from January to February 2020,the active components and action targets of Pinellia ternata were retrieved from TCMSP database.At the same time,the gene names corresponding to the drug active component targets were obtained with the help of UniProt,hcbi and PubMed databases.Gene cards and OMIM database were used to obtain the relevant therapeutic targets of functional dyspepsia,and the pharmacodynamic targets were obtained after intersection with the active component targets of Pinellia ternata.The intersection targets were analyzed by protein-protein interaction network through STRING 11.0 database to obtain potential therapeutic core proteins.Finally,KOBAS 3.0 platform and DAVID 6.8 database were used for GO function enrichment analysis and KEGG signal pathway enrichment analysis to study the mechanism of Pinellia ternata in the treatment of functional dyspepsia.Results 13 active components,74 target genes and 35 cross genes of Pinellia ternata were screened.The analysis of protein protein interaction network found that Pinellia ternata treatment of functional dyspepsia might be related to Bcl-2,AKT1,CASP3,CASP9,Jun and other target proteins.66 GO items were obtained by GO functional enrichment analysis(P<0.05).The analysis results found that Pinellia treatment for functional dyspepsia was mainly related to catecholamine binding,endopeptidase activity,nuclear receptor activity,transcription factor activity,cysteine endopeptidase activity in the process of apoptosis and other functions.KEGG signal pathway analysis showed 97 signal pathways(P<0.05),which were mainly related to apoptosis-multiple fields,apoptosis,hepatitis B,colorative cancer,TNF signaling pathway and other signal pathways,and these pathways all contained Bcl-2,caspase,Bax and other apoptosis factors.Conclusion Pinellia ternate can play a role in the treatment of functional dyspepsia through multi-component,multi-target and multi-channel.Among them,the inhibition or enhancement of its factor expression in the apoptotic pathway,and ultimately the inhibition of apoptosis of tissue cells will be one of the important mechanisms of Pinellia ternate in the treatment of functional dyspepsia.