摘要
目的:基于网络药理学方法探讨加味二陈汤治疗多囊卵巢综合征(polycystic ovary syndrome,PCOS)的有效成分及其作用机制。方法:采用中药系统药理学数据库和分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)获取半夏、陈皮、茯苓、白术、天南星、枳实、泽兰、菟丝子的主要活性成分及其蛋白质靶点,并用蛋白质数据库(universal protein,UniProt)将其蛋白质靶点规范为基因靶点,再通过Cytoscape 3.7.1软件构建中药-活性成分-基因靶点网络;采用基因名片数据库(GeneCards)、诊疗靶点数据库(therapeutic target database,TTD)、在线人类孟德尔遗传数据库(online mendelian inheritance in man,OMIM)、药物数据库(Drugbank)、疾病相关基因与突变位点数据库(Disgenet)获取PCOS的主要作用基因靶点,并与加味二陈汤基因靶点绘制韦恩图,通过Excel明确共同靶点后,利用网络可视化软件STRING平台对共同靶点进行蛋白互作网络(protein protein interaction,PPI)分析,并用Cytoscape 3.7.1软件进行拓扑参数分析,寻找关键核心靶点;通过DAVID平台进行基因本体(gene ontology,GO)生物功能富集分析和京都基因与基因组百科全书(kyoto encyclopodia of genes and genomes,KEGG)通路富集分析,预测其生物过程及作用通路。结果:加味二陈汤共筛选出72个活性成分,对应基因靶点数目为257个,PCOS疾病靶点为2 354个,二者共有靶点143个;GO及KEGG富集结果显示,其主要涉及转录正调控、负调控、药物反应、凋亡过程及其调控、细胞增殖负调控、雌二醇反应等生物过程以及PI3K/Akt、MAPK、TNF等多条信号通路,其中PI3K/Akt信号通路为主要的作用通路。结论:加味二陈汤主要通过PI3K/Akt信号转导通路发挥治疗PCOS的作用,同时还能通过降低睾丸激素、雌二醇、促黄体生成素的激素水平、抑制胰岛素抵抗及调控自噬水平等,促进卵巢功能恢复。
Objective:To explore the effective components and mechanism of Flavored Two Matured Substances Decoction in the treatment of polycystic ovary syndrome(PCOS).Methods:The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) was used to obtain the main active components and protein targets of Banxia(Rhizoma Pinelliae),Chenpi(Pericarpium Citri Reticulatae),Fuling(Poria),Baizhu(Rhizoma Atractylodis Macrocephalae),Tiannanxing(Rhizoma Arisaematis),Zhishi(Fructus Aurantii Immaturus),Zelan(Herba Lycopi),and Tusizi(Semen Cuscutae).The protein target was standardized as gene target by Universal Protein(UniProt) database,and then the Chinese medicinal-active ingredient-gene target network was constructed by Cytoscape 3.7.1 software.Gene cards database(Genecards),therapeutic target database(TTD),Online Mendelian Inheritance in Man(OMIM),drug database(Drugbank),disease-related gene and mutation site database(Disgenet) were used to obtain the main gene targets of PCOS,which merged with the gene target of Flavored Two Matured Substances Decoction to make a Wayne Map.After the common target was identified by Excel,the protein-protein interaction(PPI) of the common target was analyzed by using the network visualization software STRING platform,and Cytoscape 3 7.1 software was used to carry out topology parameter analysis to find key core targets.Gene ontology(GO) function enrichment analysis was carried out through DAVID platform,and based on the Kyoto Encyclopedia of genes and genomes(KEGG) pathway in order to predict its biological process and action pathway.Results:A total of 72 active components were screened from Flavored Two Matured Substances Decoction,with 257 corresponding gene targets and 2 354 targets for PCOS,with a total of 143 targets together.The enrichment results of GO and KEGG showed that they were mainly involved in biological processes such as positive transcription,negative regulation,drug response,apoptosis process and regulation,negative regulation of cell proliferation,estradiol reaction and many signal pathways such as PI3 K/Akt,MAPK and TNF,of which PI3 K/Akt signal pathway was the main functional pathway.Conclusion:Flavored Two Matured Substances Decoction mainly plays the role of treating PCOS through PI3 K/Akt signal transduction pathway.At the same time,it can restore ovarian function by reducing the hormone levels of testosterone,estradiol and luteinizing hormone,inhibiting insulin resistance and regulating autophagy.
作者
龚文婧
邵超
黄胜男
GONG Wen-jing;SHAO Chao;HUANG Sheng-nan(Guang′anmen Hospital of China Academy of Chinese Medical Sciences,Beijing,China,100000)
出处
《河南中医》
2022年第4期553-562,共10页
Henan Traditional Chinese Medicine
基金
北京药学会研究项目(S2021-01)。
关键词
多囊卵巢综合征
加味二陈汤
作用机制
网络药理学
polycystic ovary syndrome(PCOS)
Flavored Two Matured Substances Decoction
mechanism of action
pharmacology network
