Table5_Through network pharmacology and molecular docking to explore the underlying mechanism of Artemisia annua L. treating in abdominal aortic aneurysm.xlsx

Background: Abdominal aortic aneurysm (AAA) is a degenerative disease that causes health problems in humans. However, there are no effective drugs for the treatment of AAA. Artemisia annua L. (A. annua) is a traditional herbal that has been widely used in cardiovascular disease. Based on network pharmacology and molecular docking technology, this study predicted the practical components and potential mechanisms of A. annua inhibiting the occurrence and development of AAA.
Methods: The main active ingredients and targets of A. annua were screened through the TCMSP database; the GeneCards, OMIM, PharmGkb, and TTD databases were used to search for the targeted genes of AAA and map them to the targets of the active ingredients to obtain the active ingredient therapy of A. annua. The targets of AAA were to construct a protein interaction network through the STRING platform. R software was used to carry out the enrichment analysis of GO and KEGG for relevant targets, and Cytoscape was used to construct the active ingredient-target network prediction model of A. annua. Finally, AutoDock Vina was used to verify the results of the active ingredients and critical targets.
Results: The main active ingredients obtained from A. annua for the treatment of AAA include quercetin, luteolin, kaempferol, isorhamnetin, and artemetin, as well as 117 effective targets, including RELA, MAPK14, CCND1, MAPK1, AKT1, MYC, MAPK8, TP53, ESR1, FOS, and JUN. The 11 targeted genes might play a key role in disease treatment. Enriched in 2115 GO biological processes, 159 molecular functions, 56 cellular components, and 156 KEGG pathways, inferred that its mechanism of action might be related to PI3K-Akt signaling pathway, fluid shear stress, atherosclerosis, and AGE-RAGE signaling pathway. Molecular docking results showed that the top five active components of A. annua had a good affinity for core disease targets and played a central role in treating AAA. The low binding energy molecular docking results provided valuable information for the development of drugs to treat AAA.
Conclusion: Therefore, A. annua may have multiple components, multiple targets, and multiple signaling pathways to play a role in treating AAA. A. annua may have the potential to treat AAA.

研究背景：腹主动脉瘤（Abdominal aortic aneurysm, AAA）是一种可引发人类健康问题的退行性疾病，目前尚无针对该疾病的有效治疗药物。黄花蒿（Artemisia annua L., A. annua）是一种被广泛应用于心血管疾病治疗的传统草药。本研究基于网络药理学（network pharmacology）与分子对接（molecular docking）技术，预测了黄花蒿抑制腹主动脉瘤发生与发展的潜在活性成分及作用机制。

研究方法：本研究通过中药系统药理学数据库与分析平台（TCMSP）筛选黄花蒿的主要活性成分及作用靶点；借助基因卡（GeneCards）、在线人类孟德尔遗传数据库（OMIM）、药物基因组学知识库（PharmGkb）与治疗靶点数据库（TTD）检索腹主动脉瘤的靶基因，并将其与黄花蒿活性成分的靶点进行映射，以获取黄花蒿治疗该疾病的活性成分-靶点对。针对腹主动脉瘤的靶点，通过STRING数据库（STRING）构建蛋白质相互作用网络；采用R软件对相关靶点进行基因本体（Gene Ontology, GO）与京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）富集分析；使用Cytoscape软件构建黄花蒿活性成分-靶点网络预测模型。最后，利用AutoDock Vina工具对活性成分与核心靶点的结合情况进行验证。

研究结果：从黄花蒿中筛选得到的用于治疗腹主动脉瘤的主要活性成分包括槲皮素（quercetin）、木犀草素（luteolin）、山奈酚（kaempferol）、异鼠李素（isorhamnetin）与蒿黄素（artemetin），共涉及117个有效靶点，包括RELA、MAPK14、CCND1、MAPK1、AKT1、MYC、MAPK8、TP53、ESR1、FOS与JUN等，其中11个靶点可能在疾病治疗中发挥关键作用。富集分析共得到2115个GO生物过程条目、159个GO分子功能条目、56个GO细胞组分条目以及156条KEGG通路，推测其作用机制可能与PI3K-Akt信号通路、流体切应力、动脉粥样硬化及AGE-RAGE信号通路相关。分子对接结果显示，黄花蒿排名前五的活性成分与核心疾病靶点均具有良好的结合亲和力，在腹主动脉瘤的治疗中发挥核心作用；低结合能的分子对接结果为抗腹主动脉瘤药物的开发提供了有价值的参考信息。

研究结论：综上，黄花蒿可通过多成分、多靶点、多信号通路的方式发挥抗腹主动脉瘤的治疗作用，具备开发为腹主动脉瘤治疗药物的潜力。