探索四妙汤（Simiao Decoction, SMD）干预动脉粥样硬化（atherosclerosis, AS）的分子机制。四妙汤的主要成分和潜在机制尚不明确。本研究旨在基于网络药理学和分子对接技术初步阐明四妙汤治疗动脉粥样硬化的潜在机制。在中药系统药理数据库和分析平台上搜索四妙汤的主要成分和相应蛋白靶标，并利用Cytoscape3.9.1构建复合物-靶标网络。在DrugBank、OMIM和TTD数据库上搜索动脉粥样硬化的靶标。根据复合物靶标和疾病靶标的交集获取相应的一致性靶标，并将其导入STRING数据库构建蛋白质相互作用网络。进一步对靶标进行基因本体论（Gene Ontology）和Kyoto基因组百科全书（Kyoto Encyclopedia of Genes and Genomes）通路富集分析。采用分子对接方法验证四妙汤的核心成分与靶标之间的相互作用。基于中药系统药理数据库和分析平台、DrugBank、OMIM和TTD等网络数据库构建了活性化合物-靶标网络以及活性化合物-动脉粥样硬化-靶标网络。我们发现，四妙汤治疗动脉粥样硬化涉及到3个关键物质-槲皮素、山奈酚和芦丁-以及5个关键靶标-白蛋白、蛋白激酶B、肿瘤坏死因子、白细胞介素6和肿瘤蛋白53。基因本体论和Kyoto基因组百科全书富集分析揭示出共享靶标涉及多条信号通路，包括糖基化终产物受体与年龄相关疾病信号通路、乙肝、脂质和动脉粥样硬化、化学致癌物激活受体信号通路以及癌症通路等。分子对接表明槲皮素、山奈酚和芦丁与5个重要靶标的结合能均较好。本研究揭示了四妙汤治疗动脉粥样硬化的活性成分和潜在分子机制，并为后续的基础研究提供参考。版权所有 © 2023 作者，由Wolters Kluwer Health, Inc.出版。

To explore the molecular mechanism of Simiao Decoction (SMD) intervening atherosclerosis (AS). The main components and potential mechanisms of SMD remain unknown. This study aims to initially clarify the potential mechanism of SMD in the treatment of AS based on network pharmacology and molecular docking techniques. The principal components and corresponding protein targets of SMD were searched on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and the compound-target network was constructed by Cytoscape3.9.1. AS targets were searched on DrugBank, OMIM, and TTD databases. The intersection of compound target and disease target was obtained and the coincidence target was imported into STRING database to construct a protein-protein interaction network. We further performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis on the targets. The molecular docking method was used to verify the interaction between core components of SMD and targets. We created the active compounds-targets network and the active compounds-AS-targets network based on the network database containing Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, DrugBank, OMIM, and TTD. We discovered that the therapy of AS with SMD involves 3 key substances-quercetin, kaempferol, and luteolin-as well as 5 crucial targets-ALB, AKT1, TNF, IL6, and TP53. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that the shared targets involved a number of signaling pathways, including the advanced glycosylation end product-receptor of AGE signaling pathway in diabetic complications, Hepatitis B, Lipid and atherosclerosis, Chemical Carcinogenesis-Receptor Activation, and Pathways in Cancer. The molecular docking demonstrated that the binding energies of quercetin, kaempferol, and luteolin with 5 important targets were favorable. This study reveals the active ingredients and potential molecular mechanism of SMD in the treatment of AS, and provides a reference for subsequent basic research.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.