基于网络药理学与分子对接研究厚朴-麻黄治疗支气管哮喘的作用机制

侯学文; 孟泳; 侯从岭; 朱丹娜; 胡延申; 侯超峰

doi:10.16766/j.cnki.issn.1674-4152.002964

基于网络药理学与分子对接研究厚朴-麻黄治疗支气管哮喘的作用机制

doi: 10.16766/j.cnki.issn.1674-4152.002964

1.
河南中医药大学第二临床医学院，河南郑州 450000
2.
河南省中医院肺病科，河南郑州 450000

基金项目:

河南省中医药科学研究专项课题 2019JDZX049

详细信息

通讯作者:
孟泳，E-mail: mywd1966@sina.com

中图分类号: R562.25 R285
计量
- 文章访问数: 213
- HTML全文浏览量: 230
- PDF下载量: 16
- 被引次数: 0
出版历程
- 收稿日期: 2022-02-18
- 网络出版日期: 2023-05-31

Mechanism of Houpo-Mahuang Pair in treating bronchial asthma based on network pharmacology and molecular docking

1.
The Second Clinical Medical College, Henan University of Traditional Chinese Medicine, Zhengzhou, Henan 450000, China

摘要

摘要: 目的通过网络药理学与分子对接研究厚朴-麻黄药对治疗支气管哮喘的作用机制, 为临床应用提供依据。方法利用中药系统药理学数据库(TCMSP)、人类基因数据库(Gene Cards)等数据库筛选出药物与疾病靶点，规范化处理后找出两者共有靶点。分别运用Cytoscape 3.7.2软件及String数据库找出主要活性成分及靶点。运用Metascape平台对数据进行基因本体论(gene ontology，GO)及京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes，KEGG)富集分析，预测中药有效成分作用于疾病的分子机制。最后将主要有效活性成分与疾病核心靶点通过分子对接进行初步验证。结果厚朴-麻黄主要有效成分为槲皮素(quercetin)、山奈酚(kaempferol)、木犀草素(luteolin)、β-谷甾醇(beta-sitosterol)等；核心靶点蛋白为蛋白激酶B1(AKT1)、白介素6(IL6)、肿瘤坏死因子(TNF)、肿瘤蛋白p53(TP53)。GO功能富集得到生物过程2 044个、细胞组成70个、分子功能165个，KEGG富集分析得到329条信号通路，主要有PI3K-Akt信号通路、胆碱能突触、咖啡因代谢、腺苷酸活化蛋白激酶(AMPK)信号通路等，分子对接显示主要活性成分与核心靶点有较好的结合力。结论厚朴-麻黄药治疗支气管哮喘涉及多个信号通路及生物学过程，其中主要可能通过PI3K-Akt信号通路、胆碱能突触、咖啡因代谢、AMPK信号通路等途径，达到改善气道重塑、抑制气道炎症、调节免疫、减轻氧化应激的作用，从而治疗支气管哮喘，这对下一步临床研究及新药研发有一定的指导意义。
- 厚朴 /
- 麻黄 /
- 支气管哮喘 /
- 网络药理学 /
- 分子对接
Abstract: Objective To determine the mechanism of Houpo-Mahuang in treating bronchial asthma through network pharmacology and molecular docking and provide evidence for clinical application. Methods Traditional Chinese medicine systems pharmacology database (TCMSP) and Gene Cards databases were used to screen drug and disease targets. Common targets were found after standardised treatment. Cytoscape 3.7.2 software and String database were used to identify main active components and key target information. Gene ontology (GO) and Kyoto encyclopaedia of genes and genomes (KEGG) enrichment analysis were performed using Metascape platform to predict the molecular mechanism of effective components of traditional Chinese medicine acting on diseases. The main effective active components were preliminarily verified by molecular docking with the core targets of diseases. Results The main active ingredients of Houpo-Mahuang were quercetin, kaempferol, luteolin, β-sitosterol. The core target proteins were AKT1, IL-6, TNF and TP53. The GO function enrichment obtained 2 044 biological processes, 70 cell components and 165 molecular functions. The KEGG enrichment analysis obtained 329 signalling pathways, mainly including PI3K-Akt signalling pathway, cholinergic synapses, caffeine metabolism and AMPK signalling pathway. The molecular docking showed that the main active ingredients had good binding ability to the core target. Conclusion The Houpo-Mahuang treatment of bronchial asthma involves multiple signalling pathways and biological processes, among which the effects of improving airway remodelling, inhibiting airway inflammation, regulating immunity and reducing oxidative stress are mainly achieved through PI3K-Akt signalling pathway, cholinergic synapse, caffeine metabolism and AMPK signalling pathway. Results have certain guiding significance for further clinical research and new drug development.
- Houpo /
- Mahuang /
- Bronchial asthma /
- Network pharmacology /
- Molecular docking

HTML全文

图 1 PPI核心网络图

Figure 1. PPI core network diagram

下载: 全尺寸图片幻灯片

图 2 GO分析功能气泡图

注：A代表生物过程，B代表分子功能，纵轴为功能富集，横轴为富集倍数，气泡大小为基因数：越大则基因数越多，颜色深浅为P值大小：由红到绿，代表P值由小到大。

Figure 2. GO analysis function bubble diagram

下载: 全尺寸图片幻灯片

图 3 KEGG通路富集分析

注：纵轴代表各个信号通路，横轴代表通路上所存在的靶点蛋白数，颜色代表P值：红色P值最小，蓝色P值最大。

Figure 3. KEGG pathway enrichment analysis

下载: 全尺寸图片幻灯片

图 4 分子对接结果

注：A为β-谷甾醇与AKT1;B为β-谷甾醇与TP53。

Figure 4. Molecular docking results

下载: 全尺寸图片幻灯片

表 1 厚朴-麻黄成分

Table 1. The ingredients of Houpo-Mahuang

编码	化学成分	OB(%)	DL值	来源
MOL005970	Eucalyptol	60.62	0.32	厚朴
MOL005980	Neohesperidin	57.44	0.27	厚朴
MOL010788	leucopelargonidin	57.97	0.24	麻黄
MOL002823	Herbacetin	36.07	0.27	麻黄
MOL010489	Resivit	30.84	0.27	麻黄
MOL000422	kaempferol	41.88	0.24	麻黄
MOL004798	delphinidin	40.63	0.28	麻黄
MOL000098	quercetin	46.43	0.28	麻黄
MOL000006	luteolin	36.16	0.25	麻黄
MOL000358	beta-sitosterol	36.91	0.75	麻黄
MOL000449	Stigmasterol	43.83	0.76	麻黄
MOL000492	(+)-catechin	54.83	0.24	麻黄
MOL001494	Mandenol	42.00	0.19	麻黄
MOL001755	24-Ethylcholest-4-en-3-one	36.08	0.76	麻黄
MOL002881	Diosmetin	31.14	0.27	麻黄
MOL004328	naringenin	59.29	0.21	麻黄
MOL004576	taxifolin	57.84	0.27	麻黄
MOL005190	eriodictyol	71.79	0.24	麻黄
MOL005573	Genkwanin	37.13	0.24	麻黄
MOL005842	Pectolinarigenin	41.17	0.30	麻黄
MOL007214	(+)-Leucocyanidin	37.61	0.27	麻黄
MOL011319	Truflex OBP	43.74	0.24	麻黄

下载: 导出CSV

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