目的：本研究旨在通过中药网络药理学及体外实验方法分析青蒿治疗急性心肌梗死（acute myocardial infarction,AMI）的潜在机制。方法：利用TCMSP、Uniprot数据库获取青蒿有效成分及其靶基因。通过检索Gene-cards、OMIM、TTD、PharmGkb、DrugBank等数据库获得AMI相关的靶基因,并筛选出青蒿有效成分直接作用于AMI的靶基因。利用String数据库构建蛋白–蛋白相互作用（PPI）网络,并使用Cytoscape3.8.0软件构建药物活性成分–疾病靶基因网络,进而筛选出共同核心基因,随后将核心基因进行GO和KEGG富集分析。通过体外实验观察青蒿活性成分青蒿素（artemisinin,ART）对CoCl2诱导的H9C2细胞增殖、凋亡的影响。结果：从青蒿筛选出20种有效成分,主要包括异鼠李素、槲皮素、青蒿素、双氢青蒿素等。这些有效成分相关靶基因总计193个,而AMI相关的基因有3 278个,最终筛选出155个药物–疾病共同靶基因,其中包括TP53、AKT1、MAPK1、RELA、ESR1、MAPK14等。GO功能富集分析显示青蒿治疗AMI生物学过程条目和功能主要集中在异种排斥反应、氧化应激、脂多糖反应等。KEGG通路富集分析表明,青蒿治疗AMI主要与AGE-RAGE信号通路、TNF信号通路、IL-17信号通路、PI3K-Akt信号通路、细胞凋亡等相关。体外实验结果表明,青蒿素能够促进CoCl2诱导的H9C2增殖,并抑制其凋亡。结论：本研究揭示了青蒿及其有效成分青蒿素治疗AMI中的潜在靶点,为传统中药在AMI治疗领域提供了新的思路和研究线索。
Abstract
Objective To investigate the target and potential mechanism of the action of Artemisia annua in the treatment of acute myocardial infarction (AMI) based on traditional Chinese medicine network pharmacology and in vitro experiments. Methods The chemical active ingredients and target genes of Artemisia annua were retrieved from TCMSP and Uniprot databases. We then searched for AMI-related genes using GeneCards, OMIM, TTD, PharmGKB, and DrugBank databases, screened out the common targets of Artemisia annua for the treatment of AMI, constructed a drug-disease-target network using Cytoscape 3.8.0 software, and constructed a protein-protein interaction(PPI) network using the String database. Core genes were screened out and analysed for GO functional enrichment and KEGG pathway enrichment. The effects of artemisinin (ART) on CoCl2-induced proliferation and apoptosis in H9C2 cells were assessed in in vitro studies. Results 20 active ingredients were obtained from Artemisia annua, including isorhamnetin, quercetin, artemisinin, and dihydroartemisinin.193 targets were obtained by removing duplicates.3278 targets were related to AMI, and 155 drug-disease co-targets were screened out, including TP53, AKT1, MAPK1, RELA, ESR1, and MAPK14. And the GO function enrichment analysis showed that the biological processes and function of Artemisia annua in the treatment of AMI were mainly focused on oxidative stress, inflammation, and xenograft rejection et al. KEGG pathway enrichment analysis showed that the treatment of AMI by Artemisia annua were mainly related to AGE-RAGE signaling pathway, TNF pathway, IL-17 pathway, PI3K-Akt pathway and apoptosis. ART promoted H9C2 cell proliferation and inhibited apoptosis and in vitro. Conclusion The study elucidated the potential targets of Artemisia annua L. and its active compound, artemisinin, in the treatment of AMI. It offers novel insights and methods for the application of traditional Chinese medicine in managing AMI.
关键词
青蒿 /
心肌梗死 /
网络药理学 /
实验验证
Key words
artemisia annua /
myocardial infarction /
network pharmacology /
experimental validation
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基金
广东省中医药局科研项目“基于HSF1/HSP70通路探讨小茴香来源纳米囊泡调控巨噬细胞极化对动脉斑块稳定性的机制研究”（20251330）; 广东省基础与应用基础基金研究项目“内皮祖细胞来源外泌体miR-372介导FBX011-P53-miR-1246/miR-1290信号通路调控间质-内皮转化抗心肌纤维化的机制研究”（2021A1515010178）; 深圳市科技计划项目“辣椒来源纳米囊泡抑制AMPK介导的铁死亡促进损伤血管内皮修复的机制研究”（JCYJ20230807150803007）
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