| 闫思超,杨春静,宝丽.基于网络药理学和分子对接分析桑菊饮治疗COVID-19的潜在机制[J].浙江中医药大学学报,2022,46(4):360-370. |
| 基于网络药理学和分子对接分析桑菊饮治疗COVID-19的潜在机制 |
| Analysis of the Working Mechanism of Sangjuyin in the Treatment of COVID-19 Based on Network Pharmacology |
| DOI：10.16466/j.issn1005-5509.2022.04.003 |
| 中文关键词: 新型冠状病毒肺炎 桑菊饮 网络药理学 分子对接 柚皮素 荷包牡丹碱 丝裂原活化蛋白激酶3 90kDa热休克蛋白αA1 |
| 英文关键词: Corona Virus Disease 2019 Sangjuyin network pharmacology molecular docking naringenin bicuculline mitogen-activated protein kinase 3 heat shock protein 90kDa alpha A1 |
| 基金项目:首都医科大学附属北京世纪坛医院基金项目(2021-C07、2021-C03)；首都医科大学校培育项目(PYZ21160)；国家自然科学基金面上项目(82073741) |
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| 中文摘要: |
| [目的] 基于网络药理学分析桑菊饮的活性成分、靶点和信号通路，并探索桑菊饮治疗新型冠状病毒肺炎(Corona Virus Disease 2019，COVID-19)的潜在分子机制。[方法] 通过中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform，TCMSP)，获得桑菊饮中的化合物及其靶点，利用Cytoscape 3.8.2软件绘制“药物-活性成分-靶点”网络图。通过基因组注释数据平台(genome annotation database platform，GeneCard)获得COVID-19相关致病基因，与药物靶点取交集，获得桑菊饮的潜在靶点。采用DAVID 6.8数据库对潜在靶点进行基因本体(gene ontology，GO)和京都基因和基因组百科全书(Kyoto Encyclopedia of Genes and Genomes，KEGG)富集分析，采用STRING 11.5数据库构建蛋白相互作用(protein-protein interaction，PPI)网络图。基于中医药整合药理学研究平台(Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine，TCMIP)V2.0对作用于网络中核心靶点的成分进行吸收、分配、代谢、排泄和毒性(absorption，distribution，metabolism excretion and toxicity，ADMET)水平分析。利用Python脚本以及AutoDock Vina软件进行分子对接。[结果] 本研究共收集到桑菊饮中8味中药的169个化学成分和308个靶点信息，并获得了2 572个疾病靶点，取交集后获得99个潜在靶点，其中白细胞介素-6(interleukin-6，IL-6)、肿瘤坏死因子(tumor necrosis factor，TNF)、二肽基肽酶Ⅳ(dipeptidyl peptidase Ⅳ，DPP4)等基因与COVID-19相关性较强。GO和KEGG分析结果显示，这些靶点主要富集于对脂多糖的反应和白细胞介素-17(interleukin-17，IL-17)信号通路等生物过程。PPI网络分析结果显示关键靶点主要包括信号转导与转录激活因子3(signal transducer and activator of transcription 3，STAT3)、白细胞介素-10(interleukin-10，IL-10)、丝裂原活化蛋白激酶3(mitogen-activated protein kinase 3，MAPK3)等。桑菊饮中作用于关键靶点的活性成分的ADMET分析结果显示，柚皮素、荷包牡丹碱等成分吸收水平较好。分子对接中柚皮素、荷包牡丹碱与MAPK3、fos原癌基因蛋白(fos proto-oncogene，FOS)、90kDa热休克蛋白αA1(heat shock protein 90kDa alpha A1，HSP90AA1)的结合能均小于≤-5.0 kJ·mol-1，提示亲和力较好。 [结论] 桑菊饮可能通过调节脂多糖反应和IL-17信号通路等治疗COVID-19，其主要活性成分柚皮素和荷包牡丹碱等与关键靶点MAPK3、HSP90AA1等的结合可能是其治疗COVID-19的作用机制。 |
| 英文摘要: |
| [Objective] To analyze active components， targets and signaling pathways of Sangjuyin based on network pharmacology， and explore the molecular mechanism of Sangjuyin in the treatment of Corona Virus Disease 2019(COVID-19). [Methods] The major chemical compounds of the formula and its target proteins were obtained by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The Cytoscape 3.8.2 software was used to explore the key compounds and targets of Sangjuyin. The pathogenic genes responsible for COVID-19 were obtained by genome annotation database platform(GeneCard). Protein targets of drugs and pathogenic genes of diseases were overlapped to obtain predicted targets of Sangjuyin for COVID-19. Then gene ontology(GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) signaling pathway enrichment analysis were adopted to screen out the key targets of Sangjuyin. Protein-protein interaction(PPI) network was built through the STRING 11.5 Database. The levels of absorption， distribution， metabolism， excretion and toxicity(ADMET) of the components in Sangjuyin were gathered through Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine(TCMIP) V2.0. Molecular docking was accomplished through Python scripts and AutoDock Vina software. [Results] There were 169 compounds and 308 protein targets in Sangjuyin. There were 2 572 protein targets related to COVID-19. Then it obtained 99 cross targets based on the two databases. Among them， interleukin-6(IL-6)， tumor necrosis factor(TNF) and dipeptidyl peptidase Ⅳ(DPP4) were strongly correlated with COVID-19. GO enrichment and KEGG pathway enrichment analysis showed that the targets were mainly enriched in biological processes such as response to lipopolysaccharide， interleukin-17(IL-17) signaling pathway， and so on. PPI network analysis showed that the key targets mainly included signal transducer and activator of transcription 3(STAT3)， interleukin-10(IL-10)， mitogen-activated protein kinase 3(MAPK3)， etc. The results of ADMET analysis showed that the absorption levels of naringenin and paonidine were better. The combination of naringenin， bicuculline with MAPK3， fos proto-oncogene (FOS)， heat shock protein 90kDa alpha A1(HSP90AA1) were ≤-5.0 kJ·mol-1 which meant good affinity. [Conclusion] Sangjuyin may treat COVID-19 by regulating response to lipopolysaccharide， IL-17 signaling pathway and so on. The combination of its main active ingredients such as naringenin and bicuculline with the key targets MAPK3 and HSP90AA1 may be the mechanism of its treatment of COVID-19. |
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