Ginsenoside Rh2 regulates cardiomyocyte autophagy-dependent apoptosis through the PI3K-Akt-mTOR signaling pathway to attenuate doxorubicin-induced cardiotoxicity
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 inve...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2025-04-01
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| Series: | Applied Biological Chemistry |
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| Online Access: | https://doi.org/10.1186/s13765-025-00986-y |
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| author | Youping Wu Sheng Zhang Liqiang Gu Cong Xu Xiaobo Lin Hu Wang |
| author_facet | Youping Wu Sheng Zhang Liqiang Gu Cong Xu Xiaobo Lin Hu Wang |
| author_sort | Youping Wu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-636f40efe9ed485bb5f325484300b51c |
| institution | OA Journals |
| issn | 2468-0842 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Applied Biological Chemistry |
| spelling | doaj-art-636f40efe9ed485bb5f325484300b51c2025-08-20T02:17:13ZengSpringerOpenApplied Biological Chemistry2468-08422025-04-0168111310.1186/s13765-025-00986-yGinsenoside Rh2 regulates cardiomyocyte autophagy-dependent apoptosis through the PI3K-Akt-mTOR signaling pathway to attenuate doxorubicin-induced cardiotoxicityYouping Wu0Sheng Zhang1Liqiang Gu2Cong Xu3Xiaobo Lin4Hu Wang5The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child HealthCenter of Safety Evaluation, Hangzhou Medical CollegeCenter of Safety Evaluation, Hangzhou Medical CollegeCenter of Safety Evaluation, Hangzhou Medical CollegeCenter of Safety Evaluation, Hangzhou Medical CollegeHangzhou Hospital of Traditional Chinese MedicineAbstract 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.https://doi.org/10.1186/s13765-025-00986-yDoxorubicinGinsenoside Rh2Cardioprotective effectAutophagyApoptosisPI3K-Akt-mTOR signaling |
| spellingShingle | Youping Wu Sheng Zhang Liqiang Gu Cong Xu Xiaobo Lin Hu Wang Ginsenoside Rh2 regulates cardiomyocyte autophagy-dependent apoptosis through the PI3K-Akt-mTOR signaling pathway to attenuate doxorubicin-induced cardiotoxicity Applied Biological Chemistry Doxorubicin Ginsenoside Rh2 Cardioprotective effect Autophagy Apoptosis PI3K-Akt-mTOR signaling |
| title | Ginsenoside Rh2 regulates cardiomyocyte autophagy-dependent apoptosis through the PI3K-Akt-mTOR signaling pathway to attenuate doxorubicin-induced cardiotoxicity |
| title_full | Ginsenoside Rh2 regulates cardiomyocyte autophagy-dependent apoptosis through the PI3K-Akt-mTOR signaling pathway to attenuate doxorubicin-induced cardiotoxicity |
| title_fullStr | Ginsenoside Rh2 regulates cardiomyocyte autophagy-dependent apoptosis through the PI3K-Akt-mTOR signaling pathway to attenuate doxorubicin-induced cardiotoxicity |
| title_full_unstemmed | Ginsenoside Rh2 regulates cardiomyocyte autophagy-dependent apoptosis through the PI3K-Akt-mTOR signaling pathway to attenuate doxorubicin-induced cardiotoxicity |
| title_short | Ginsenoside Rh2 regulates cardiomyocyte autophagy-dependent apoptosis through the PI3K-Akt-mTOR signaling pathway to attenuate doxorubicin-induced cardiotoxicity |
| title_sort | ginsenoside rh2 regulates cardiomyocyte autophagy dependent apoptosis through the pi3k akt mtor signaling pathway to attenuate doxorubicin induced cardiotoxicity |
| topic | Doxorubicin Ginsenoside Rh2 Cardioprotective effect Autophagy Apoptosis PI3K-Akt-mTOR signaling |
| url | https://doi.org/10.1186/s13765-025-00986-y |
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