Network pharmacology and LC-MS approachs to explore the active compounds and mechanisms of Yuanjiang decoction for treating bradyarrhythmia
Network pharmacology and LC-MS approachs to explore the active compounds and mechanisms of Yuanjiang decoction for treating bradyarrhythmia
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DOI：
10.1016/j.compbiomed.2022.106435
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发表时间：
2022-12-18
影响因子：
7.7
通讯作者：
Li，Qiuyan
中科院分区：
文献类型：
--
作者：
Wang，Xujie;Zhang，Xuexue;Li，Qiuyan
元降汤(YJD)是一种传统中药方剂，已有研究发现其具有显著的心率加快作用，对症状性缓慢性心律失常有较好的治疗作用。但其具体成分和可能的作用机制尚不清楚。方法本研究采用液-质联用技术(LC-MS)对养精汤的主要成分进行了检测和鉴定。通过网络药理学的方法，对有效成分的核心靶点--缓慢性心律失常靶点进行预测，得到养精汤潜在的抗缓慢性心律失常靶点。我们进一步以蛋白质相互作用(PPI)、基因本体论(GO)浓缩分析和京都基因与基因组百科全书(KEGG)信号通路分析为核心靶点，构建了养精汤关键活性成分-核心靶点网络。最后对关键活性成分和核心靶点进行了分子对接和分子动力学模拟。结果该制剂共含有35种主要化学成分。关键有效成分-核心靶点网络包含36个节点和90条边，包括20个关键有效成分和16个核心靶点。PPI网络的核心靶点是TP53、TNF、HRAS、PPARG、IL1B、KCNH2、SCN5A、IDH1、LMNA、AChE、F2、DRD2、CALM1、KCNQ1、TNNI3、IDH2和TNNT2。KEGG通路分析显示，养精汤治疗缓慢性心律失常主要涉及神经活性配体-受体相互作用、心肌细胞内肾上腺素能信号、cAMP信号通路、钙信号通路、胆碱能突触和5-羟色胺能突触信号通路。这些生物过程主要包括激素水平的调节、心脏收缩的调节、化学突触传递、昼夜节律、心率的正调节、平滑肌的收缩、对金属离子的反应、氧化还原过程、神经递质的转运和跨质膜的输入。分子对接和分子动力学模拟结果表明橙皮苷和延胡索乙素分别与DRD2和KCNQ1具有较高的亲和力。结论本研究揭示了养精汤的药效学物质基础及其潜在的多组分、多靶点、多途径的药理作用，预测其潜在的抗心律失常机制可能与调节心肌自主神经功能及相关离子通道有关。本研究结果表明，养心汤作为辅助药物治疗缓慢性心律失常具有很大的潜力，可为养心汤的开发和临床应用提供理论依据。
BackgroundYuanjiang decoction (YJD), a traditional Chinese medicinal prescription, has been found to have a significant heart rate-increasing effect and is effective in the treatment of symptomatic bradyarrhythmia in previous studies. However, its specific components and potential mechanisms remain unclear.MethodsIn this study, we detected and identified the main compounds of YJD using liquid chromatography-mass spectrometry (LC-MS). Through the approach of network pharmacology, we predicted the core targets of the active components, bradyarrhythmia targets, and obtained potential anti-bradyarrhythmia targets of YJD. We further performed protein to protein interaction (PPI), gene ontology (GO) enrichment analyses and kyoto encyclopedia of genes and genomes (KEGG) signaling pathway analyses for core targets, and constructed network of key active ingredients-core targets of YJD. Finally, molecular docking and molecular dynamics simulation were performed for key active ingredients and core targets.ResultsThe YJD contains a total of 35 main chemical components. The key active ingredients-core targets network contains 36 nodes and 90 edges, including 20 key active ingredients and 16 core targets. The core targets in the PPI network were TP53, TNF, HRAS, PPARG, IL1B, KCNH2, SCN5A, IDH1, LMNA, ACHE, F2, DRD2, CALM1, KCNQ1, TNNI3, IDH2 and TNNT2. KEGG pathway analysis showed that YJD treatment of bradyarrhythmia mainly involves neuroactive ligand-receptor interaction, adrenergic signaling in cardiomyocytes, cAMP signaling pathway, calcium signaling pathway, cholinergic synaptic and serotonergic synapse signaling pathway. The biological processes mainly include regulation of hormone levels, regulation of cardiac contraction, chemical synaptic transmission, circadian rhythm, positive regulation of heart rate, smooth muscle contraction, response to metal ion, oxidation-reduction process, neurotransmitter transport and import across plasma membrane. Molecular docking and molecular dynamics simulation results showed that hesperidin and tetrahydropalmatine had higher affinity with DRD2 and KCNQ1, respectively.ConclusionThis study reveals the pharmacodynamic material basis of YJD and its potential multicomponent–multitarget–multipathway pharmacological effects, predicted its potential anti-bradyarrhythmia mechanism may be related to the regulation of myocardial autonomic nervous function and related ion channels. Our work demonstrates that YJD has great potential for treating bradyarrhythmias as a complementary medicine, and the results can provide a theoretical basis for the development and clinical application of YJD.