基于网络药理学探讨辣椒改善心律失常作用机制

To Explore the Mechanism of Capsicum in Improving Arrhythmia Based on Network Pharmacology

摘要: 目的：通过网络药理学和分子对接技术探讨辣椒改善心律失常作用机制。方法：检索文献查找辣椒的主要活性成分，利用pubchem和Swiss Target Prediction预测辣椒活性化合物的靶点基因；借助Gene Cards、OMIM数据库筛选心律失常靶点信息；利用Cytoscape 3.9.1软件构建药物–成分–靶点的可视化网络；通过STRING数据库对关键靶点构建蛋白相互作用(PPI)网络图；使用David数据库对共同靶点进行GO、KEGG通路富集分析；最后将活性成分与核心靶点进行分子对接，初步验证网络药理学结果。结果：检索文献选出常见的5种辣椒碱(辣椒碱、二氢辣椒碱、降二氢辣椒碱、高二氢辣椒碱和高辣椒碱)，15个辣椒素类物质治疗心律失常核心靶点(AKT1, HSP90AA1, ESR1, STAT3, ERBB2, PRKCA, HIF1A, MMP9, GRIN2B, RAC1, SLC6A4, CNR1, CHRNA7, TRPV1, NR3C2)。KEGG通路富集结果显示，辣椒素改善心律失常通路涉及神经活性配体–受体相互作用、钙信号通路、PI3K-Akt信号通路等。分子对接结果显示，辣椒碱、二氢辣椒碱、降二氢辣椒碱、高二氢辣椒碱和高辣椒碱均与核心靶点的结合性较好，推测这些成分可能为治疗心律失常的主要活性成分。辣椒碱可能通过作用于AKT1、HSP90AA1、ESR1、STAT3、ERBB2、PRKCA、HIF1A、MMP9、GRIN2B、RAC1、SLC6A4、CNR1、CHRNA7、TRPV1、NR3C2等关键靶点，调节神经活性配体–受体相互作用、钙信号通路、PI3K-Akt信号通路等3条信号通路来改善心律失常，初步揭示辣椒改善心律失常的潜在作用机制。

Abstract: Objective: To explore the mechanism of capsicum in improving arrhythmia through network phar-macology and molecular docking technology. Methods: By searching the literature to find the main active ingredients of capsicum, the target genes of active compounds in capsicum were predicted by pubchem and Swiss Target Prediction. Gene Cards and OMIM database were used to screen ar-rhythmia target information. Cytoscape 3.9.1 software was used to construct the visual network of drug-component-target. The protein interaction (PPI) network of key targets was constructed by STRING database. David database was used to perform GO and KEGG pathway enrichment analysis of the common targets. Finally, molecular docking of active ingredients with core targets was per-formed to preliminarily verify the network pharmacology results. Results: Five common capsai-cinoids (capsaicin, dihydrocapsaicin, nordihydrocapsaicin, homocapsaicin and homodihydrocapsai-cin) were selected by searching the literature. 15 core targets of capsaicin for arrhythmia (AKT1, HSP90AA1, ESR1, STAT3, ERBB2, PRKCA, HIF1A, MMP9, GRIN2B, RAC1, SLC6A4, CNR1, CHRNA7, TRPV1, NR3C2). KEGG pathway enrichment results showed that the improvement of arrhythmia by capsaicin involved neuroactive ligand-receptor interaction, calcium signaling pathway, PI3K-Akt signaling pathway, etc. The results of molecular docking showed that capsaicin, dihydrocapsaicin, reduced dihydrocapsaicin, high dihydrocapsaicin and high capsaicin all had good binding to the core targets, suggesting that these components may be the main active ingredients for the treat-ment of arrhythmia. Capsaicin may act on key targets such as AKT1, HSP90AA1, ESR1, STAT3, ERBB2, PRKCA, HIF1A, MMP9, GRIN2B, RAC1, SLC6A4, CNR1, CHRNA7, TRPV1, NR3C2, etc. To im-prove arrhythmia by regulating neuroactive ligand-receptor interaction, calcium signaling pathway, PI3K-Akt signaling pathway, and preliminarily reveal the potential mechanism of pepper in im-proving arrhythmia.