Liang Deng, Yixuan Duan, Chang Liu, Jingjing Sun, Sihai Zhao, Jie Deng
School of Medicine, Shanxi Datong University, Datong, 037009, Shanxi, China.
Department of Cardiology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, China.
Mol Divers. 2024 Oct;28(5):3225-3242. doi: 10.1007/s11030-023-10750-3. Epub 2023 Oct 29.
This study was to evaluate the potential mechanism of action of Artemisia annua L. (A. annua) in the treatment of acute myocardial infarction (AMI) using network pharmacology, molecular docking and in vivo experiments. 22 active chemical compounds and 193 drug targets of A. annua were screened using the Traditional Chinese Medicine System Pharmacological (TCMSP) database. 3876 disease targets were also collected. Then 158 intersection targets between AMI and A. annua were obtained using R 4.2.0 software. String database was used to construct the protein-protein interaction (PPI) network and 6 core targets (MAPK1, TP53, HSP90AA1, RELA, AKT1, and MYC) were screened. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed using the R package. GO enrichment results were mainly related to cell responses to chemical stress and cell membrane microregions. KEGG pathways were mainly involved in lipids, atherosclerosis and fluid shear stress. In addition, molecular docking between A. annua active compounds and core targets showed high binding activity. As for in vivo validation, A. annua extract showed significant effects on improving post-infarction ventricular function, delaying ventricular remodeling, and reducing myocardial fibrosis and apoptosis. This study has revealed the potential components and molecular mechanisms of A. annua in the treatment of AMI. Our work also showed that A. annua has great effect on reducing myocardial fibrosis and scar area after infarction.
本研究旨在运用网络药理学、分子对接和体内实验评估青蒿在治疗急性心肌梗死(AMI)中的潜在作用机制。利用中药系统药理学数据库(TCMSP)筛选出了22种青蒿的活性化学成分和193个药物靶点。还收集了3876个疾病靶点。然后使用R 4.2.0软件获得了AMI与青蒿之间的158个交集靶点。利用String数据库构建蛋白质-蛋白质相互作用(PPI)网络,并筛选出6个核心靶点(MAPK1、TP53、HSP90AA1、RELA、AKT1和MYC)。使用R包进行基因本体(GO)富集分析和京都基因与基因组百科全书(KEGG)通路分析。GO富集结果主要与细胞对化学应激的反应和细胞膜微区有关。KEGG通路主要涉及脂质、动脉粥样硬化和流体剪切应力。此外,青蒿活性化合物与核心靶点之间的分子对接显示出高结合活性。至于体内验证,青蒿提取物对改善梗死后心室功能、延缓心室重构以及减少心肌纤维化和细胞凋亡具有显著作用。本研究揭示了青蒿治疗AMI的潜在成分和分子机制。我们的工作还表明,青蒿对减少梗死后心肌纤维化和瘢痕面积有很大作用。