基于网络药理学和孟德尔随机化探究硬尖神香草治疗哮喘的作用机制

doi:10.19586/j.2095-2341.2025.0155

生物技术进展 ›› 2026, Vol. 16 ›› Issue (2): 439-451.DOI: 10.19586/j.2095-2341.2025.0155

• 研究论文 • 上一篇

基于网络药理学和孟德尔随机化探究硬尖神香草治疗哮喘的作用机制

李名驰(), 史增芳, 张国帅, 颜齐, 王嘉乐, 张新可, 黄林芳()

中国医学科学院北京协和医学院药用植物研究所，北京 100193

收稿日期:2025-11-10 接受日期:2025-12-25 出版日期:2026-03-25 发布日期:2026-04-27
通讯作者: 黄林芳
作者简介:李名驰 E-mail: 13050722197@139.com；
基金资助:
内蒙古自治区科技计划(2025YFHH0227);中国医学科学院医学科学创新基金项目(2022-2M-1-017);国家自然科学基金项目(82274045);国家自然科学基金项目(82211540726);国家自然科学基金项目(82073960);国家自然科学基金项目(U1812403-1);北京市自然科学基金项目(7242244);新疆维吾尔自治区重点研发专项(2023B02022-1)

Based on Network Pharmacology and Mendelian Randomization to Investigate the Mechanism of Hyssopus cuspidatus Boriss. in the Treatment of Asthma

Mingchi LI(), Zengfang SHI, Guoshuai ZHANG, Qi YAN, Jiale WANG, Xinke ZHANG, Linfang HUANG()

Institute of Medicinal Plant Development，Chinese Academy of Medical Sciences & Peking Union Medical College，Beijing 100193，China

Received:2025-11-10 Accepted:2025-12-25 Online:2026-03-25 Published:2026-04-27
Contact: Linfang HUANG

摘要/Abstract

摘要：

系统探讨了硬尖神香草治疗哮喘的活性成分、作用靶点及其分子机制，为该中药的临床应用提供科学依据。通过UPLC-MS/MS和GC-MS双平台进行硬尖神香草全谱代谢组学分析，鉴定其活性成分；结合TCMSP、PubChem、SwissTargetPrediction等数据库筛选成分靶点；从GeneCards、OMIM、TTD数据库获取哮喘相关靶点；构建蛋白质-蛋白质互作（protein-protein interaction，PPI）网络，并进行基因本体论（gene ontology, GO）和京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes, KEGG）富集分析；利用分子对接验证活性成分与核心靶点的结合能力；最后采用两样本孟德尔随机化（Mendelian randomization，MR）分析验证核心靶点与哮喘的因果关系。结果发现，在硬尖神香草中共鉴定出79个活性成分和410个潜在靶点，与哮喘靶点交集分析后获得76个共同靶点。PPI网络分析显示AKT1、STAT3、EGFR、PTGS2和SRC为核心靶点。GO和KEGG富集分析表明这些靶点显著富集于PI3K/AKT信号通路、炎症反应和细胞凋亡等过程。分子对接结果显示木犀草素、异鼠李素等黄酮类成分与核心靶点具有较强结合能力。孟德尔随机化分析进一步证实AKT1与哮喘存在显著因果关系。硬尖神香草可能通过多种黄酮类活性成分作用于AKT1、STAT3、EGFR、PTGS2、SRC 等核心靶点，主要调控PI3K/AKT信号通路，抑制气道炎症、缓解气道高反应性，从而发挥治疗哮喘的作用。综上，AKT1可能是其发挥治疗作用的关键靶点，具有潜在的临床转化价值。

关键词: 硬尖神香草, 哮喘, 孟德尔随机化, 网络药理学

Abstract:

This study aims to systematically investigate the active components， target genes， and molecular mechanisms of Hyssopus cuspidatus Boriss. in the treatment of asthma， thereby providing a scientific basis for its clinical application. A comprehensive metabolomic analysis of Hyssopus cuspidatus Boriss. was conducted using dual-platform UPLC-MS/MS and GC-MS to identify its active components. Potential therapeutic targets were screened using databases such as TCMSP， PubChem， and SwissTargetPrediction. Asthma-related targets were retrieved from GeneCards， OMIM， and TTD databases. A protein-protein interaction （PPI） network was constructed， followed by Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analyses. Molecular docking was performed to validate the binding affinity between active components and core targets. Finally， a two-sample Mendelian randomization （MR） analysis was employed to verify the causal relationship between core targets and asthma. The results showed that a total of 79 active components and 410 potential targets were identified in Hyssopus cuspidatus Boriss. Intersection with asthma-related targets yielded 76 common targets. PPI network analysis revealed AKT1， STAT3， EGFR， PTGS2， and SRC as core targets. GO and KEGG enrichment analyses indicated significant enrichment in processes such as the PI3K/AKT signaling pathway， inflammatory response， and apoptosis. Molecular docking results demonstrated strong binding affinities between flavonoid components （e.g.， luteolin and isorhamnetin） and core targets. Mendelian randomization analysis further confirmed a significant causal relationship between AKT1 and asthma. Hyssopus cuspidatus Boriss. might exert therapeutic effects on asthma through multiple flavonoid active components targeting core genes such as AKT1， regulating signaling pathways like PI3K/AKT， thereby suppressing airway inflammation and alleviating airway hyperresponsiveness. AKT1 is identified as a key target with potential clinical translational value.

Key words: Hyssopus cuspidatus Boriss., asthma, Mendelian randomization, network pharmacology

中图分类号:

Q946.91

李名驰, 史增芳, 张国帅, 颜齐, 王嘉乐, 张新可, 黄林芳. 基于网络药理学和孟德尔随机化探究硬尖神香草治疗哮喘的作用机制[J]. 生物技术进展, 2026, 16(2): 439-451.

Mingchi LI, Zengfang SHI, Guoshuai ZHANG, Qi YAN, Jiale WANG, Xinke ZHANG, Linfang HUANG. Based on Network Pharmacology and Mendelian Randomization to Investigate the Mechanism of Hyssopus cuspidatus Boriss. in the Treatment of Asthma[J]. Current Biotechnology, 2026, 16(2): 439-451.

图/表 11

参考文献 38

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指数	HC-1	HC-2	HC-3
Zmmp000635	7 469 051.23	4 035 131.87	5 939 557.79
Zbqn001288	49 571.91	482 690.60	424 954.42
Lcsp001861	659 985.09	717 498.71	876 080.42
MWS0933	363 905.57	367 458.19	387 707.09
pme3827	825 843.70	2 234 150.84	989 242.46
pme2914	2 554 762.19	3 656 173.29	4 581 013.42
MWS04559g	1 748 377.85	2 359 113.95	1 812 424.40
pme0181	1 285 062.03	1 291 185.05	1 377 214.11
mws3109	177 738.26	229 557.10	190 673.94
MWSprf117	318 576.06	365 157.04	384 235.64

指数	HC-1	HC-2	HC-3
Zmmp000635	7 469 051.23	4 035 131.87	5 939 557.79
Zbqn001288	49 571.91	482 690.60	424 954.42
Lcsp001861	659 985.09	717 498.71	876 080.42
MWS0933	363 905.57	367 458.19	387 707.09
pme3827	825 843.70	2 234 150.84	989 242.46
pme2914	2 554 762.19	3 656 173.29	4 581 013.42
MWS04559g	1 748 377.85	2 359 113.95	1 812 424.40
pme0181	1 285 062.03	1 291 185.05	1 377 214.11
mws3109	177 738.26	229 557.10	190 673.94
MWSprf117	318 576.06	365 157.04	384 235.64

靶点	木犀草素	异鼠李素	槲皮万寿菊素	高良姜素	金圣草黄素	香叶木素
AKT1	-6.4	-6.3	-6.3	-6.2	-6.2	-6.3
STAT3	-8	-8.2	-8.2	-7.4	-8	-8.0
EGFR	-9.7	-9.6	-10	-9.5	-9.5	-9.8
PTGS2	-9.5	-9.1	-9.7	-8.9	-9.1	-9.2
SRC	-12.5	-11.7	-12.2	-12.2	-11.9	-11.5

靶点	木犀草素	异鼠李素	槲皮万寿菊素	高良姜素	金圣草黄素	香叶木素
AKT1	-6.4	-6.3	-6.3	-6.2	-6.2	-6.3
STAT3	-8	-8.2	-8.2	-7.4	-8	-8.0
EGFR	-9.7	-9.6	-10	-9.5	-9.5	-9.8
PTGS2	-9.5	-9.1	-9.7	-8.9	-9.1	-9.2
SRC	-12.5	-11.7	-12.2	-12.2	-11.9	-11.5

暴露	nSNP	方法	OR(95% CI)	P值
AKT1	7	MR-Egger回归	1.10(0.96~1.27)	0.235
		加权中位数法	1.09(1.00~1.18)	0.038
		逆方差加权法	1.10(1.02~1.18)	0.013
		简单模式法	1.06(0.89~1.26)	0.559
		加权模式法	1.08(0.99~1.18)	0.133
STAT3	3	MR-Egger回归	0.97(0.66~1.45)	0.921
		加权中位数法	1.01(0.87~1.17)	0.897
		逆方差加权法	0.99(0.86~1.13)	0.880
		简单模式法	1.01(0.82~1.24)	0.948
		加权模式法	1.01(0.87~1.18)	0.907
EGFR	16	MR-Egger回归	0.85(0.16~4.46)	0.848
		加权中位数法	1.22(0.61~2.46)	0.573
		逆方差加权法	1.11(0.68~1.82)	0.667
		简单模式法	1.14(0.36~3.63)	0.828
		加权模式法	1.45(0.61~3.46)	0.420
PTGS2	12	MR-Egger回归	1.04(0.94~1.15)	0.436
		加权中位数法	0.97(0.88~1.06)	0.469
		逆方差加权法	0.98(0.92~1.05)	0.551
		简单模式法	0.93(0.79~1.09)	0.372
		加权模式法	1.02(0.92~1.12)	0.752
SRC	5	MR-Egger回归	0.87(0.64~1.18)	0.428
		加权中位数法	0.97(0.83~1.12)	0.655
		逆方差加权法	1.00(0.89~1.14)	0.943
		简单模式法	0.95(0.75~1.20)	0.701
		加权模式法	0.95(0.82~1.11)	0.559

基于网络药理学和孟德尔随机化探究硬尖神香草治疗哮喘的作用机制

Based on Network Pharmacology and Mendelian Randomization to Investigate the Mechanism of Hyssopus cuspidatus Boriss. in the Treatment of Asthma

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