Ginsenoside Rh2 regulates cardiomyocyte autophagy-dependent apoptosis through the PI3K-Akt-mTOR signaling pathway to attenuate doxorubicin-induced cardiotoxicity

IF 2.3 3区农林科学 Q3 FOOD SCIENCE & TECHNOLOGY

Applied Biological Chemistry Pub Date : 2025-04-07 DOI:10.1186/s13765-025-00986-y

Youping Wu, Sheng Zhang, Liqiang Gu, Cong Xu, Xiaobo Lin, Hu Wang

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引用次数: 0

Abstract

Doxorubicin (DOX)-induced cardiotoxicity has become a major concern and is considered a limitation for the use of DOX in oncology treatment. Ginsenoside Rh2 (Rh2) is a ginseng extract with anti-inflammatory, antioxidant and cell cycle regulating activities. The aim of this study was to investigate the mechanism of cardioprotective effects of Rh2 in DOX-induced cardiotoxicity. This study utilized network pharmacology to search for potential targets and pathways of Rh2 against doxorubicin-induced heart failure. The mechanism of Rh2 protection of myocardial tissue was further examined using a doxorubicin-formed rat model of heart failure. Network pharmacology predicted 128 potential targets for Rh2 treating to heart failure. Autophagy and apoptosis pathways play critical roles in Rh2 treatment of heart failure accessed by GO and KEGG enrichment analysis. Animal experiment results showed that Rh2 attenuated DOX-induced cardiotoxicity, normalized the morphology of cardiac tissue and reduced cardiomyocyte autophagy as well as apoptosis by up-regulation of the PI3K-AKT-mTOR signaling pathway to antagonize the effect of DOX on cardiomyocyte damage. These results suggest that Rh2 was able to inhibit DOX-activated autophagy signaling and apoptotic pathways in myocardial tissues and reduced cardiomyocyte apoptosis. It has potential effects to protect myocardial tissue as well as antagonize DOX-induced cardiotoxicity.

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人参皂苷Rh2通过PI3K-Akt-mTOR信号通路调节心肌细胞自噬依赖性凋亡，减轻多柔比星诱导的心脏毒性

多柔比星（DOX）诱发的心脏毒性已成为人们关注的一个主要问题，并被认为是在肿瘤治疗中使用 DOX 的一个限制因素。人参皂苷 Rh2（Rh2）是一种人参提取物，具有抗炎、抗氧化和细胞周期调节活性。本研究旨在探讨 Rh2 在 DOX 诱导的心脏毒性中发挥心脏保护作用的机制。本研究利用网络药理学寻找 Rh2 抗多柔比星诱导的心衰的潜在靶点和途径。利用多柔比星诱导的大鼠心力衰竭模型进一步研究了 Rh2 保护心肌组织的机制。网络药理学预测了 Rh2 治疗心力衰竭的 128 个潜在靶点。通过 GO 和 KEGG 富集分析发现，自噬和细胞凋亡通路在 Rh2 治疗心力衰竭中发挥着关键作用。动物实验结果表明，Rh2通过上调PI3K-AKT-mTOR信号通路来拮抗DOX对心肌细胞的损伤，从而减轻DOX诱导的心脏毒性，使心脏组织形态正常化，减少心肌细胞自噬和凋亡。这些结果表明，Rh2 能够抑制 DOX 激活的心肌组织自噬信号传导和凋亡通路，减少心肌细胞凋亡。它具有保护心肌组织和拮抗 DOX 引起的心脏毒性的潜在作用。

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来源期刊

Applied Biological Chemistry Chemistry-Organic Chemistry

CiteScore

5.40

自引率

6.20%

发文量

审稿时长

20 weeks

期刊介绍： Applied Biological Chemistry aims to promote the interchange and dissemination of scientific data among researchers in the field of agricultural and biological chemistry. The journal covers biochemistry and molecular biology, medical and biomaterial science, food science, and environmental science as applied to multidisciplinary agriculture.