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中华临床医师杂志(电子版) ›› 2021, Vol. 15 ›› Issue (11) : 882 -889. doi: 10.3877/cma.j.issn.1674-0785.2021.11.015

临床研究

基于网络药理学探讨脉通饮治疗冠心病的作用机制研究
陈弦1, 孔俊虹2,(), 沙晨曦1, 龚楚桥1   
  1. 1. 213003 江苏常州,南京中医药大学附属常州市中医医院心血管科
    2. 213003 江苏常州,南京中医药大学附属常州市中医医院治未病中心
  • 收稿日期:2021-06-18 出版日期:2021-11-15
  • 通信作者: 孔俊虹
  • 基金资助:
    江苏省中医药局重点项目(ZD201709); 常州市卫健委青年人才科技项目(QN201937)

Exploration of therapeutic mechanism of Maitong Yin for coronary heart disease based on network pharmacology

Xian Chen1, Junhong Kong2,(), Chenxi Sha1, Chuqiao Gong1   

  1. 1. Department of Cardiovascular Medicine, Changzhou Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Changzhou 213003, China
    2. Cure Disease Center, Changzhou Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Changzhou 213003, China
  • Received:2021-06-18 Published:2021-11-15
  • Corresponding author: Junhong Kong
引用本文:

陈弦, 孔俊虹, 沙晨曦, 龚楚桥. 基于网络药理学探讨脉通饮治疗冠心病的作用机制研究[J]. 中华临床医师杂志(电子版), 2021, 15(11): 882-889.

Xian Chen, Junhong Kong, Chenxi Sha, Chuqiao Gong. Exploration of therapeutic mechanism of Maitong Yin for coronary heart disease based on network pharmacology[J]. Chinese Journal of Clinicians(Electronic Edition), 2021, 15(11): 882-889.

目的

通过网络药理学方法,揭示脉通饮治疗冠心病(CHD)的作用机制。

方法

借助中药系统药理学数据库与分析平台(TCMSP),将口服生物利用度(OB)与类药性(DL)当做限定条件,完成对脉通饮所含药物化学组分与其蛋白靶点的筛选,同时参考数据库UniProt,对蛋白靶点对应的基因名称加以明确。经由在线人类孟德尔遗传数据库(OMIM)、治疗靶标数据库(TTD),完成对CHD相关基因的检索。双方取交集后,再借助蛋白质相互作用数据库(STRING)建立蛋白互作网络,接着由Cytoscape辅助,对网络核心靶点展开分析,构建“疾病/中药/化合物/靶点”网络,根据string平台导出的数据通过R语言分析其治疗CHD的关键靶点,借助数据库bioconductor开展基因本体(GO)富集分析及KEGG通路富集分析。

结果

由网络药理学法辅助,自脉通饮筛选出活性成分共计116个,借助Venn分析疾病相关靶点,从而明确出143个药物潜在作用基因。分析网络中的拓扑参数,筛选出排名前20位的关键靶点,包括蛋白激酶B1(Akt1)、白介素6(IL-6)、丝裂原活化蛋白激酶8(MAPK8)、肿瘤坏死因子(TNF)、基质金属蛋白酶2(MMP-2)等核心靶点。经ClueGO富集分析关键靶点主要被富集在TNF信号通路、MAPK信号通路、PI3K-Akt信号通路等。

结论

脉通饮可能是通过影响Akt1、IL-6、MAPK8、TNF、MMP-2等靶点,调控TNF、MAPK、PI3K-Akt等通路对CHD发挥作用。

Objective

To reveal the therapeutic mechanism of Maitong Yin for coronary heart disease (CHD).

Methods

By means of traditional Chinese medicine system pharmacology database and analysis platform (TCMSP), the medicinal chemical components and protein targets contained in Maitong Yin were screened by taking oral bioavailability (OB) and drug-like properties (DL) as the limiting conditions, and the names of genes corresponding to the protein targets were clarified by referring to the database UniProt. A search of CHD-related genes was completed through Online Mendelian Inheritance in Man (OMIM) and Therapeutic Target Database (TTD). After taking the intersections, the protein interaction network was established by using STRING (protein interaction database), and then the core targets of the network were analyzed with the help of Cytoscape, so that a "disease/Chinese medicine/compound/target" network was constructed. In the data derived from the string platform, the key targets for treating CHD were explored in R, the gene ontology (GO) enrichment analysis was conducted via database bioconductor, and pathway enrichment analysis was carried out through Kyoto Encyclopedia of Genes and Genomes (KEGG).

Results

Using the network pharmacology method, a total of 116 active ingredients were screened from Maitong Yin, and the disease-related targets were analyzed through Venn. In this way, 143 potential action genes were identified, and the top 20 key targets were selected by analyzing topological parameters in the network, including protein kinase B1 (Akt1), interleukin (IL)-6, mitogen-activated protein kinase (MAPK) 8, tumor necrosis factor (TNF), and matrix metalloproteinase (MMP)-2. The ClueGO enrichment analysis showed that the key targets were mainly enriched in the TNF signaling pathway, MAPK signaling pathway, and PI3K-Akt signaling pathway.

Conclusion

The therapeutic mechanism of Maitong Yin for CHD may be affecting targets such as Akt1, IL-6, MAPK8, TNF, and MMP-2, and regulating the TNF, MAPK, and PI3K-Akt signaling pathways.

表1 脉通饮候选化合物基本信息
分子ID 化合物 来源药材 分子ID 化合物 来源药材
M7088 Cryptotanshinone 丹参 M7514 Methyl icosa-11,14-dienoate 党参
M7093 Dan-shexinkum D 丹参 M8406 Spinoside A 党参
M7094 Danshenspiroketallactone 丹参 M8411 11-Hydroxyrankinidine 党参
M7098 Deoxyneocryptotanshinone 丹参 M3896 7-Methoxy-2-methyl isoflavone 党参
M7100 Dihydrotanshinlactone 丹参 M1006 Poriferasta-7,22E-dien-3beta-ol 党参
M7101 Dihydrotanshinone Ⅰ 丹参 M4355 Spinasterol 党参
M7105 Epidanshenspiroketallactone 丹参 M2879 Diop 党参
M7107 C09092 丹参 M3036 ZINC03978781 党参
M7108 Isocryptotanshi-none 丹参 M8407 MOL8 党参
M7111 Isotanshinone Ⅱ 丹参 M8397 Daturilin 党参
M7115 Manool 丹参 M8400 Glycitein 党参
M7118 Microstegiol 丹参 M5321 Frutinone A 党参
M7119 Miltionone Ⅰ 丹参 M211 Mairin 黄芪
M7120 Miltionone Ⅱ 丹参 M239 Jaranol 黄芪
M7121 Miltipolone 丹参 M296 Hederagenin 黄芪
M7122 Miltirone 丹参 M033 MOL9 黄芪
M7123 Miltirone Ⅱ 丹参 M354 Isorhamnetin 黄芪
M7124 Neocryptotanshinone Ⅱ 丹参 M371 3,9-Di-O-methylnissolin 黄芪
M7125 Neocryptotanshinone 丹参 M374 5'-Hydroxyiso-muronulatol-2',5'-di-O-glucoside 黄芪
M7127 1-methyl-8,9-dihydro-7H-naphtho[5,6-g]benzofuran-6,10,11-trione 丹参 M378 7-O-methylisomucronulatol 黄芪
M379 9,10-Dimethoxypterocarpan-3-O-β-D-glucoside 黄芪
M7130 prolithospermic acid 丹参 M380 MOL10 黄芪
M7132 MOL4 丹参 M387 Bifendate 黄芪
M7140 MOL5 丹参 M392 Formononetin 黄芪
M7141 Salvianolic acid G 丹参 M398 Isoflavanone 黄芪
M7142 Salvianolic acid J 丹参 M417 Calycosin 黄芪
M7143 Salvilenone Ⅰ 丹参 M422 Kaempferol 黄芪
M7145 Salviolone 丹参 M438 (3R)-3-(2-hydroxy-3,4-dimethoxyphenyl)chroman-7-ol 黄芪
M7149 NSC 122421 丹参
M7150 MOL6 丹参 M439 Isomucronulatol-7,2'-di-O-glucosiole 黄芪
M7151 Tanshindiol B 丹参 M442 1,7-Dihydroxy-3,9-dimethoxy pterocarpene 黄芪
M7152 Przewaquinone E 丹参 M098 Quercetin 黄芪
M7154 TanshinoneⅡa 丹参 M493 Campesterol 姜黄
M7155 MOL7 丹参 M953 CLR 姜黄
M7156 Tanshinone Ⅵ 丹参 M449 Stigmasterol 姜黄、党参
M8391 5alpha-Stigmastan-3,6-dione 党参 M433 FA 黄芪、川芎
M6774 Stigmast-7-enol 党参 M2140 Perlolyrine 党参、川芎
M8393 7-(Beta-xylosyl)cephalomannine_qt 党参 M7059 3-beta-Hydroxymethyllenetanshiquinone 党参、丹参
M6554 Taraxerol 党参 M006 Luteolin 党参、丹参
M4492 Chrysanthemaxanthin 党参
表1 脉通饮候选化合物基本信息
图1 脉通饮治疗冠心病的潜在靶点网络及关键靶点。图a为潜在靶点蛋白互作网络(PPI);图b为排名前20位的关键靶点
图2 脉通饮活性成分治疗冠心病的潜在靶点GO富集分析(前20位)
图3 脉通饮活性成分治疗冠心病的潜在靶点KEGG富集分析(前20位)
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