Wang Zhigang, Fang Longzhi, Han Meng, Liu Kangzhe, Zheng Yuanmei, Zhan Yibei
Hubei Key Laboratory for Kidney Disease Pathogenesis and Intervention, School of Medicine, Hubei Polytechnic University, Hubei, China.
College of Chemistry and Chemical Engineering, Hubei Polytechnic University, Huangshi, Hubei, China.
Medicine (Baltimore). 2024 Dec 20;103(51):e40932. doi: 10.1097/MD.0000000000040932.
Atherosclerosis (AS) is a disease characterized by the buildup of fat and fibrous elements within the walls of arteries and is a primary factor in the occurrence of heart failure and mortality. The potential targets and mechanisms underlying the anti-atherosclerotic effects of avenanthramide (Avn) were investigated using network pharmacology, molecular docking, and molecular dynamics simulations. Target information for Avn A, B, and C was collected from the PubChem and Swiss Target Prediction databases. Potential therapeutic targets for AS were identified by mining the OMIM, DrugBank, DisGeNET, and GeneCards databases. A protein-protein interaction (PPI) network of shared targets was constructed and visualized using the STRING database and Cytoscape 3.9.1. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted to explore the functions of core targets within the PPI network. Molecular docking was performed using the AutoDockTool to verify the correlation between the 3 types of Avns and the core targets. Furthermore, molecular dynamics simulations were performed using the 3 highest molecular docking binding energies to validate and confirm the binding of potent compounds to the target. The results revealed 109 respective targets for Avn, with 55 common targets identified by intersection with AS-related targets. Five pivotal genes, matrix metalloproteinase-9 (MMP9), epidermal growth factor receptor (EGFR), ICAM1, CASP3, and MMP2, were selected from the PPI network. Molecular docking results showed a strong binding affinity between Avn and MMP9 as well as EGFR. Molecular dynamics simulations showed good binding capacity of Avn A, B, and C with EGFR, validating the reliability of the molecular docking results. Avn potentially exerts its effects through multiple targets and displays anti-inflammatory and anti-oxidative stress properties.
动脉粥样硬化（AS）是一种以动脉壁内脂肪和纤维成分堆积为特征的疾病，是心力衰竭发生和死亡的主要因素。利用网络药理学、分子对接和分子动力学模拟研究了燕麦酰胺（Avn）抗动脉粥样硬化作用的潜在靶点和机制。从PubChem和瑞士靶点预测数据库收集了Avn A、B和C的靶点信息。通过挖掘OMIM、DrugBank、DisGeNET和GeneCards数据库确定AS的潜在治疗靶点。使用STRING数据库和Cytoscape 3.9.1构建并可视化共享靶点的蛋白质-蛋白质相互作用（PPI）网络。进行基因本体论和京都基因与基因组百科全书分析，以探索PPI网络中核心靶点的功能。使用AutoDockTool进行分子对接，以验证3种类型的Avn与核心靶点之间的相关性。此外，使用3个最高的分子对接结合能进行分子动力学模拟，以验证和确认强效化合物与靶点的结合。结果显示Avn分别有109个靶点，与AS相关靶点交叉确定了55个共同靶点。从PPI网络中选择了5个关键基因，基质金属蛋白酶-9（MMP9）、表皮生长因子受体（EGFR）、ICAM1、CASP3和MMP2。分子对接结果显示Avn与MMP9以及EGFR之间具有很强的结合亲和力。分子动力学模拟显示Avn A、B和C与EGFR具有良好的结合能力，验证了分子对接结果的可靠性。Avn可能通过多个靶点发挥作用，并具有抗炎和抗氧化应激特性。
