基于网络药理学比较调经汤与促排卵西药的作用机制——以卵巢早衰为例

Comparison of Mechanism Between Tiaojing Decoction and Ovulation Promoting Western Medicine Based on Network Pharmacology——Take Premature Ovarian Failure As An Example

[目的]利用网络药理学分析调经汤与克罗米芬治疗卵巢早衰(premature ovarian failure,POF)的机制差异,探讨调经汤治疗POF的可能机制。[方法]利用京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)DRUG数据库、中药系统药理学数据库与分析平台(Traditional Chinese Medicine Database and Analysis Platform,TCMSP)挖掘克罗米芬的分子结构及调经汤潜在活性成分与药物靶点,通过人类基因数据库(Human Gene Database,GeneCards)、在线人类孟德尔遗传数据库(Online Mendelian Inheritance in Man,OMIM)、药物基因组学知识库(Pharmacogenomics Knowledgebase,PharmGKB),筛选POF的相关疾病靶点。将得到的药物靶点与疾病靶点进行匹配,得到药物-疾病交集靶点数据库,利用Cytoscape 3.8.0软件构建中药成分-靶点-疾病网络。使用STRING网站对得到的交集靶点进行蛋白互作分析,利用R语言进行基因本体(gene oncology,GO)分析和KEGG富集分析。[结果]克罗米芬的靶蛋白为雌激素受体,KEGG通路为雌激素信号通路。调经汤中共筛选出181个活性成分和2873个潜在靶点,POF靶点4597个。通过比对调经汤和POF的共同靶点,筛选出192个关键基因。这些共同靶点涉及的生物学过程主要是氧化物及氧化应激的反应、细胞对化学物应激刺激的反应和物质代谢反应等,发挥转录、结合等分子功能;生物学通路包括白细胞介素-17(interleukin-17,IL-17)、肿瘤坏死因子(tumor necrosis factor,TNF)、磷脂酰肌醇3激酶-蛋白激酶B(phosphatidylinositol 3 kinaseprotein kinase B,PI3K-AKT)、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)、叉头框转录因子O亚族(forkhead box transcription factor O,FoxO)、雌激素、Wnt信号通路等。[结论]调经汤与克罗米芬的共有通路为雌激素信号通路,但与克罗米芬相比,调经汤可通过多个靶点、多条通路起到治疗POF的作用。

[Objective]To analyze the mechanism difference between Tiaojing Decoction and Clomiphene in the treatment of premature ovarian failure(POF)by network pharmacology,and to explore the possible mechanism of Tiaojing Decoction in the treatment of POF.[Methods]Kyoto Encyclopedia of Genes and Genomes(KEGG)DRUG database,Traditional Chinese Medicine Database and Analysis Platform(TCMSP)were used to mine the molecular structure of clomiphene and the potential active components and drug targets of Tiaojing Decoction.POF related targets were screened through the Human Gene Database(GeneCards),Online Mendelian Inheritance in Man(OMIM)and Pharmacogenomics Knowledgebase(PharmGKB)databases.The intersection target obtained by matching the drug target with the disease target was used to establish the traditional Chinese medicine component target disease action network by using Cytoscape 3.8.0 software.The protein interaction of the obtained intersection targets was analyzed by STRING website,and the enrichment analysis of gene ontology(GO)and KEGG was carried out by R software.[Results]The target protein of Clomiphene was estrogen receptor,and KEGG pathway was estrogen signaling pathway.A total of 181 active components,2873 potential targets and 4597 POF targets were screened from Tiaojing Decoction.One hundred and ninety-two key genes were screened by comparing the common targets of Tiaojing Decoction and POF.The biological processes involved in these common targets are mainly the reaction of oxides and oxidative stress,the response of cells to chemical stress and material metabolism,which plays molecular functions such as transcription and binding.The biological pathways include interleukin-17(IL-17)signaling pathway,tumor necrosis factor(TNF)signaling pathway and phosphatidylinositol 3 kinase-protein kinase B(PI3K-AKT)signaling pathway,mitogen-activated protein kinase(MAPK)signaling pathway,forkhead box transcription factor O(FoxO)signaling pathway,estrogen signaling pathway,Wnt signaling pathway,etc.[Conclusion]Estrogen signaling pathway are Tiaojing Decoction and Clomiphene common pathway,but compared with Clomiphere,Tiaojing Decoction can treat POF through multiple targets and pathways.