Hebei Key Laboratory of Study and Exploitation of Chinese Medicine, Chengde Medical College, Anyuan Road, Shuangqiao District, Chengde, 067000, Hebei, China.
Cardiovasc Toxicol. 2024 Feb;24(2):171-183. doi: 10.1007/s12012-024-09825-w. Epub 2024 Feb 20.
Hawthorn leaf has shown therapeutic effects in the patients with myocardial ischemia. Our study combines network pharmacology, molecular docking techniques, and in vitro experiment with the aim of revealing the mechanism of hawthorn leaves in the treatment of myocardial ischemia. The active ingredients and corresponding targets of hawthorn leaf through Traditional Chinese Medicine System Pharmacology and Swiss Target Prediction databases. Targets related to myocardial ischemia were retrieved by Gene Card, Online Mendelian Inheritance in Man, Disgenet, and Therapeutic Targets Database databases. Cytoscape software was used to construct an ingredient-target-organ network and enrichment analysis of common targets was analyzed. Molecular docking verification of the core compound and target interactions was performed using MOE software. In vitro cell experiment was performed to verify the findings from bioinformatics analysis. Six active components and 107 potential therapeutic targets were screened. The protein-protein interaction network analysis indicated that 10 targets, including AKT1 and EGFR, were hub genes. Quercetin, kaempferol and isorhamnetin were taken as core active components. Through pathway enrichment analysis, nearly 455 Gene Ontology entries and 77 Kyoto Encyclopedia of Genes and Genomes pathways were obtained, mainly including PI3K/Akt, estrogen and other signaling pathways. Molecular docking prediction showed that three main active ingredients were firmly combined with the core targets. Cellular experiments showed that quercetin alleviated oxidative damage in cells and regulated the expression of PI3K, P-AKT/AKT and Bax/Bcl-2 proteins. This study identified the potential targets of Hawthorn leaf against myocardial ischemia using network pharmacology and in vitro verification, which provided a new understanding of the pharmacological mechanisms of Hawthorn leaf in treatment of myocardial ischemia.
山楂叶在心肌缺血患者中显示出治疗效果。我们的研究结合网络药理学、分子对接技术和体外实验，旨在揭示山楂叶治疗心肌缺血的作用机制。通过中药系统药理学和瑞士靶点预测数据库筛选山楂叶的活性成分和相应靶点。通过基因卡片、在线孟德尔遗传人类、Disgenet 和治疗靶点数据库数据库检索与心肌缺血相关的靶点。使用 Cytoscape 软件构建成分-靶器官网络，并对共同靶点进行富集分析。使用 MOE 软件对核心化合物和靶标相互作用进行分子对接验证。进行体外细胞实验以验证生物信息学分析的结果。筛选出 6 种活性成分和 107 个潜在治疗靶点。蛋白质-蛋白质相互作用网络分析表明，包括 AKT1 和 EGFR 在内的 10 个靶标是枢纽基因。槲皮素、山奈酚和异鼠李素被选为核心活性成分。通过通路富集分析，获得了近 455 个基因本体条目和 77 个京都基因与基因组百科全书通路，主要包括 PI3K/Akt、雌激素等信号通路。分子对接预测表明，三种主要活性成分与核心靶点紧密结合。细胞实验表明，槲皮素减轻了细胞的氧化损伤，并调节了 PI3K、P-AKT/AKT 和 Bax/Bcl-2 蛋白的表达。本研究通过网络药理学和体外验证鉴定了山楂叶治疗心肌缺血的潜在靶点，为山楂叶治疗心肌缺血的药理机制提供了新的认识。
