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人参皂苷Rg3对心力衰竭保护作用的药理机制

The Pharmacological Mechanisms Underlying the Protective Effect of Ginsenoside Rg3 against Heart Failure.

作者信息

Jia Yanan, Gong Miao, Ke Zunping

机构信息

Department of Geriatrics Shanghai Fifth People's Hospital Fudan University, Shanghai, China.

出版信息

Cardiol Res Pract. 2024 Jul 30;2024:3373410. doi: 10.1155/2024/3373410. eCollection 2024.

DOI:10.1155/2024/3373410
PMID:39108942
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11303059/
Abstract

BACKGROUND

Heart failure represents the terminal stage of various cardiovascular diseases. This study aims to explore the pharmacological mechanisms underlying the protective effect of Ginsenoside Rg3 against heart failure.

METHODS

Potential targets of Ginsenoside Rg3 were identified using SwissTargetPrediction and the Comparative Toxicogenomics Database, while heart failure-related genes were retrieved from the Comparative Toxicogenomics Database, Therapeutic Target Database, DisGeNET, and PharmGKB. Overlapping of Ginsenoside Rg3 targets with heart failure-related genes identified drug-disease interaction genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on the drug-disease interaction genes to elucidate their biological functions. A protein-protein interaction network was constructed using the drug-disease interaction genes, and the hub genes were identified by topological analysis. Additionally, we validate the expression of IL-6 and TNF by real-time PCR.

RESULTS

The intersection of Ginsenoside Rg3 targets and heart failure-related genes yielded 15 drug-disease interaction genes. Enrichment analysis highlighted the involvement of inflammation-related GO terms and KEGG pathways, such as positive regulation of interleukin-8 and -6 production, regulation of immune effector process, cytokine receptor binding, cytokine activity, adipocytokine signaling pathway, and IL-17 signaling pathway, which are implicated in the cardioprotective effect. Topological analysis revealed four hub genes: , , , and . The application of Ginsenoside Rg3 significantly reversed the elevated levels of IL-6 and TNF in the isoproterenol-treated H9c2 cell line.

CONCLUSIONS

Our findings suggest that the cardioprotective effect of Ginsenoside Rg3 may be mediated through its anti-inflammation properties. Further research is required to elucidate and validate the detailed cardioprotective mechanisms of Ginsenoside Rg3.

摘要

背景

心力衰竭是各种心血管疾病的终末期阶段。本研究旨在探讨人参皂苷Rg3对心力衰竭保护作用的药理学机制。

方法

利用瑞士靶点预测数据库（SwissTargetPrediction）和比较毒理基因组学数据库（Comparative Toxicogenomics Database）确定人参皂苷Rg3的潜在靶点，同时从比较毒理基因组学数据库、治疗靶点数据库（Therapeutic Target Database）、DisGeNET和药物基因组学知识库（PharmGKB）中检索心力衰竭相关基因。将人参皂苷Rg3靶点与心力衰竭相关基因进行比对，确定药物 - 疾病相互作用基因。对药物 - 疾病相互作用基因进行基因本体论（Gene Ontology，GO）和京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）富集分析，以阐明其生物学功能。使用药物 - 疾病相互作用基因构建蛋白质 - 蛋白质相互作用网络，并通过拓扑分析确定枢纽基因。此外，我们通过实时聚合酶链反应验证白细胞介素 - 6（IL - 6）和肿瘤坏死因子（TNF）的表达。

结果

人参皂苷Rg3靶点与心力衰竭相关基因的交集产生了15个药物 - 疾病相互作用基因。富集分析突出了炎症相关的GO术语和KEGG通路的参与，如白细胞介素 - 8和 - 6产生的正调控、免疫效应过程的调节、细胞因子受体结合、细胞因子活性、脂肪细胞因子信号通路和IL - 17信号通路，这些都与心脏保护作用有关。拓扑分析揭示了四个枢纽基因： ， ， ，和 。人参皂苷Rg3的应用显著逆转了异丙肾上腺素处理的H9c2细胞系中升高的IL - 6和TNF水平。

结论

我们的研究结果表明，人参皂苷Rg3的心脏保护作用可能是通过其抗炎特性介导的。需要进一步研究来阐明和验证人参皂苷Rg3详细的心脏保护机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5dc/11303059/0999b3627680/CRP2024-3373410.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5dc/11303059/fb4533da3608/CRP2024-3373410.001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5dc/11303059/0999b3627680/CRP2024-3373410.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5dc/11303059/fb4533da3608/CRP2024-3373410.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5dc/11303059/f685cd1d9250/CRP2024-3373410.002.jpg
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