网络药理学方法探讨速效心痛滴丸治疗心肌梗死的分子靶标及作用机制。

Exploration of the molecular targets and mechanisms of suxiao xintong dropping pills for myocardial infarction by network pharmacology method.

机构信息

Department of Cardiology, Affiliated Nanping First Hospital, Fujian Medical University, Nanping 353000, Fujian Province, China.

出版信息

Biosci Rep. 2021 Aug 27;41(8). doi: 10.1042/BSR20204211.

BACKGROUND

Suxiao Xintong dropping pills (SXXTDP), a traditional Chinese medicine, is widely applied for treating myocardial infarction (MI). However, its therapy mechanisms are still unclear. Therefore, this research is designed to explore the molecular mechanisms of SXXTDP in treating MI.

METHODS

The active ingredients of SXXTDP and their corresponding genes of the active ingredients were retrieved from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. MI-related genes were identified via analyzing the expression profiling data (accession number: GSE97320). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to study the shared genes of drug and disease. Through protein-protein interaction (PPI) network and the Cytoscape plugin cytoHubba, the hub genes were screened out. The compounds and hub targets binding were simulated through molecular docking method.

RESULTS

We obtained 21 active compounds and 253 corresponding target genes from TCMSP database. 1833 MI-related genes were identified according to P<0.05 and |log2FC| ≥ 0.5. 27 overlapping genes between drug and disease were acquired. GO analysis indicated that overlapping genes were mainly enriched in MAP kinase activity and antioxidant activity. KEGG analysis indicated that overlapping genes were mainly enriched in IL-17 signaling pathway and TNF signaling pathway. We obtained 10 hub genes via cytoHubba plugin. Six of the 10 hub genes, including PTGS2, MAPK14, MMP9, MAPK1, NFKBIA, and CASP8, were acted on molecular docking verification with their corresponding compounds of SXXTDP.

CONCLUSION

SXXTDP may exert cardioprotection effect through regulating multiple targets and multiple pathways in MI.

背景

速效心痛滴丸（SXXTDP）是一种中药，广泛用于治疗心肌梗死（MI）。然而，其治疗机制尚不清楚。因此，本研究旨在探讨 SXXTDP 治疗 MI 的分子机制。

方法

从中药系统药理学（TCMSP）数据库中检索 SXXTDP 的活性成分及其相应的活性成分基因。通过分析表达谱数据（登录号：GSE97320）鉴定与 MI 相关的基因。通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析研究药物和疾病的共同基因。通过蛋白质-蛋白质相互作用（PPI）网络和 Cytoscape 插件 cytoHubba 筛选出枢纽基因。通过分子对接方法模拟化合物和枢纽靶标结合。

结果

我们从 TCMSP 数据库中获得了 21 种活性化合物和 253 个相应的靶基因。根据 P<0.05 和 |log2FC|≥0.5，鉴定出 1833 个与 MI 相关的基因。获得了 27 个药物与疾病之间的重叠基因。GO 分析表明，重叠基因主要富集在 MAP 激酶活性和抗氧化活性中。KEGG 分析表明，重叠基因主要富集在 IL-17 信号通路和 TNF 信号通路中。通过 cytoHubba 插件获得了 10 个枢纽基因。10 个枢纽基因中的 6 个，包括 PTGS2、MAPK14、MMP9、MAPK1、NFKBIA 和 CASP8，与 SXXTDP 相应的化合物进行了分子对接验证。