灵宝护心丹治疗缓慢性心律失常合并冠心病的作用机制:网络药理学分析。

Han Huagang, L I Ziqiang, Ouyang Jingfeng, Wang Tianquan, Dong Lingyan, Cao Junling
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引用次数: 0

摘要

目的:应用网络药理学方法探讨灵宝护心丹治疗缓慢性心律失常伴冠心病(BA-CHD)的作用机制。方法:在中药系统药理学数据库与分析平台和设计用于中药分子机制分析平台的生物信息学工具上筛选灵宝护心丹的有效成分;使用SwissTargetPrediction数据库进行靶标预测,并使用Cytoscape 3.8构建药物成分靶标网络。在基因卡、人类在线孟德尔遗传和DrugBank数据库中搜索疾病靶点。Venn图用于显示BA-CHD和活性成分的共同靶标。STRING平台用于构建蛋白质-蛋白质相互作用网络。利用Metascape数据平台进行基因本体论(GO)富集分析和京都基因与基因组百科全书(KEGG)通路分析,构建灵宝虎心丹有效成分的信号通路网络,39个在BA-CHD中重要的靶标和14个在活性成分和BA-CHD之间相交的靶标。GO富集分析共获得27种核心治疗成分、153种生物学过程、18种细胞成分和20种分子功能。KEGG通路分析产生了19个信号通路。结论:RBA-CHD可通过调节肾上腺素受体β-1、α1-α肾上腺素受体、钙电压门控通道亚单位α1C、α-1β肾上腺素受体、一氧化氮合酶2、β-2肾上腺素受体、电压依赖性钙通道亚基α-2/δ-1、血管紧张素转换酶、Raf-1原癌基因丝氨酸/苏氨酸蛋白激酶、,和其他靶点,可能通过影响肾上腺素受体结合和钙通道开放来调节心肌细胞的活性。
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Mechanism of Lingbao Huxin Dan in the treatment of bradyarrhythmia complicated with coronary heart disease: a network pharmacology analysis.

Objective: To investigate the mechanism of action of the Lingbao Huxin Dan in treating bradycardia arrhythmia with coronary heart disease (BA-CHD) by network pharmacology.

Methods: The active ingredients of the Lingbao Huxin Dan were screened on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Bioinformatics tools designed for the analysis of molecular mechanisms of Chinese medicine platform; target prediction was conducted with the SwissTargetPrediction database, and Cytoscape 3.8 was used to construct a drug ingredient-target network. The Genecards, Online Mendelian Inheritance in Man, and DrugBank databases were searched for disease targets. Venn plots were used to display the common targets of BA-CHD and active ingredients. The STRING platform was used to construct a protein-protein interaction network. The Metascape data platform was used for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to construct a signaling pathway network of the active ingredients of the Lingbao Huxin Dan.

Results: There were 121 active ingredients, 899 related targets, 39 targets important in BA-CHD and 14 targets which intersected between the active ingredients and BA-CHD. There were 27 core therapeutic ingredients, 153 biological processes, 18 cell ingredients and 20 molecular functions obtained by GO enrichment analysis. The KEGG pathway analysis yielded 19 signaling pathways.

Conclusion: RBA-CHD may treat BA-CHD by regulating adrenergic receptor beta-1, alpha 1-α adrenergic receptor, calcium voltage-gated channel subunit alpha1 C, alpha-1β-adrenergic receptor, nitric oxide synthase 2, beta-2 adrenergic receptor, voltage-dependent calcium channel subunit alpha-2/delta-1, an- giotensin-converting enzyme, Raf-1 proto-oncogene serine/threonine-protein kinase, and other targets, potentially by affecting adrenergic receptor binding and calcium channel opening, to regulate the activity of cardiomyocytes.

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