摘要
目的:通过网络药理学方法和分子对接技术,寻找“卷柏-猕猴桃根”药对的主要活性成分,探讨其在肺结节治疗中的作用机制。方法:在TCMSP网站中检索草药卷柏和猕猴桃根,获得两药所含化合物。经过ADME筛选与文献检索,确定药对主要活性化合物。利用PubChem、ChEMBL寻找该药对化合物的预测靶点。利用GeneCard、DisGeNET寻找肺结节的相关基因。利用Venny 2.1在线工具进行韦恩分析,寻找药对与肺结节共有的基因靶点。在OmicShare tools中进行基因本体(GO)功能、京都基因与基因组百科全书(KEGG)通路富集分析。在KEGG ORTHOLOGY数据库中进行基因靶点KO映射。利用分子对接技术验证化合物与预测靶点的对接能力,并进行筛选。在Cytoscape 3.7.1软件中,构建对接成功的“药物-关键化合物-关键靶点-关键通路”网络。结果:本研究共获得9种关键化合物、21个关键靶点。卷柏和猕猴桃根的关键化合物为苏铁黄酮、穗花杉双黄酮、秦皮素、儿茶素、芹菜素、表儿茶素、芦荟大黄素、香草酸、原儿茶酸。关键靶点为磷脂酰肌醇-4,5-二磷酸3-激酶催化亚单位δ(PIK3CD)、磷酸二酯酶4D(PDE4D)、热休克蛋白90α家族A类成员1(HSP90AA1)、醛酮还原酶家族1成员B10(AKR1B10)、囊性纤维化跨膜转导调节因子(CFTR)、原癌基因酪氨酸蛋白激酶(ROS1)、髓样细胞白血病蛋白1(MCL1)等,关键作用通路为磷脂酰肌醇-3-激酶-蛋白激酶B(PI3K-Akt)信号通路、叉头框蛋白O(FoxO)信号通路、凋亡(Apoptosis)、环磷酸腺苷(cAMP)信号通路等。结论:“卷柏-猕猴桃根”的多种活性化合物通过作用于多通路的靶点蛋白而发挥治疗肺结节的作用。
Objective:To investigate the main active components of Selaginella tamariscina-Chinese actinidia root drug combination and its mechanism of action in the treatment of pulmonary nodules based on the techniques of network pharmacology and molecular docking.Methods:TCMSP website was used to search for the compounds in Selaginella tamariscina and Chinese actinidia root,and the main active components of this drug combination were determined after ADME screening and literature search.PubChem and ChEMBL were used to obtain the predictive targets of the compounds in this drug combination,and GeneCard and DisGeNET were used to search for the genes associated with pulmonary nodules.Venny 2.1 online tool was used to obtain the common gene targets between the drug combination and pulmonary nodules.OmicShare tools were used to perform gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis.KO mapping was performed for gene targets in KEGG ORTHOLOGY database.The molecular docking technique was used to validate the docking ability between compounds and predictive targets and perform screening.Cytoscape 3.7.1 software was used to construct a“drug-key compound-key target-key pathway”network after successful docking.Results:A total of 9 key compounds and 21 key targets were obtained in this study.The key compounds of the Selaginella tamariscina-Chinese actinidia root drug combination were sotetsuflavone,amentoflavone,fraxetin,catechinic acid,apigenin,epicatechin,aloe-emodin,vanilloid,and protocatechuic acid.The key targets included phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform(PIK3CD),phosphodiesterase 4D(PDE4D),heat shock protein 90 alpha family class A member 1(HSP90AA1),Aldo-keto reductase family 1 member B10(AKR1B10),proto-oncogene ROS1,and myeloid cell leukemia-1(MCL1),and the key pathways included the PI3K-Akt signaling pathway,the FoxO signaling pathway,Apoptosis,and the cAMP signaling pathway.Conclusion:The multiple ac
作者
吴朗杰
鹿竞文
徐力
WU Langjie;LU Jingwen;XU Li(Nanjing University of Chinese Medicine,Nanjing 210023,Jiangsu,China)
出处
《湖南中医杂志》
2022年第11期151-159,199,共10页
Hunan Journal of Traditional Chinese Medicine
基金
江苏省科技厅科技支撑计划社会发展项目(BE2015691)。
关键词
肺结节
卷柏
猕猴桃根
物质基础
作用机制
网络药理学
分子对接
pulmonary nodules
Selaginella tamariscina
Chinese actinidia root
material basis
mechanism of action
network pharmacology
molecular docking
