Verbascoside attenuates myocardial ischemia/reperfusion-induced ferroptosis following heterotopic heart transplantation via modulating GDF15/GPX4/SLC7A11 pathway
Abstract Myocardial cold ischemia/reperfusion (I/R) injury is an inevitable consequence of heart transplantation, significantly affecting survival rates and therapeutic outcomes. Growth Differentiation Factor 15 (GDF15) has been shown to regulate GPX4-mediated ferroptosis, playing a critical role in...
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Nature Portfolio
2025-05-01
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| Online Access: | https://doi.org/10.1038/s41598-025-00112-4 |
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| author | Yuxi Zhang Junbiao Zhan Zhen Qiu Hao Tian Shaoqing Lei Qin Huang Rui Xue Qian Sun Zhongyuan Xia |
| author_facet | Yuxi Zhang Junbiao Zhan Zhen Qiu Hao Tian Shaoqing Lei Qin Huang Rui Xue Qian Sun Zhongyuan Xia |
| author_sort | Yuxi Zhang |
| collection | DOAJ |
| description | Abstract Myocardial cold ischemia/reperfusion (I/R) injury is an inevitable consequence of heart transplantation, significantly affecting survival rates and therapeutic outcomes. Growth Differentiation Factor 15 (GDF15) has been shown to regulate GPX4-mediated ferroptosis, playing a critical role in mitigating I/R injury. Meanwhile, verbascoside (VB), an active compound extracted from the herbaceous plant, has demonstrated myocardial protective effects. In this study, heart transplantation was performed using a modified non-suture cuff technique, with VB administered at a dose of 20 mg/kg/day via intraperitoneal injection for 3 days in vivo. In vitro, cardiomyocytes were pretreated with 50 µg/ml VB for 24 h. VB treatment significantly reduced histopathological injury, decreased myocardial injury markers, and inhibited ferroptosis and oxidative stress during myocardial cold I/R injury in vivo. In vitro experiments further demonstrated that GDF15 alleviates ferroptosis induced by hypoxic reoxygenation by upregulating GPX4. Therefore, it is concluded that VB preconditioning can effectively reduce ferroptosis induced by myocardial cold I/R after heterotopic heart transplantation, possibly through up-regulation of GDF15/GPX4/SLC7A11 pathway. |
| format | Article |
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| institution | DOAJ |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-05-01 |
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| spelling | doaj-art-4967e28cd0bc43d69b1edf187db9a81e2025-08-20T03:09:20ZengNature PortfolioScientific Reports2045-23222025-05-0115111410.1038/s41598-025-00112-4Verbascoside attenuates myocardial ischemia/reperfusion-induced ferroptosis following heterotopic heart transplantation via modulating GDF15/GPX4/SLC7A11 pathwayYuxi Zhang0Junbiao Zhan1Zhen Qiu2Hao Tian3Shaoqing Lei4Qin Huang5Rui Xue6Qian Sun7Zhongyuan Xia8Department of Anesthesiology, Wuhan University, Renmin HospitalDepartment of Anesthesiology, Wuhan University, Renmin HospitalDepartment of Anesthesiology, Wuhan University, Renmin HospitalDepartment of Anesthesiology, Wuhan University, Renmin HospitalDepartment of Anesthesiology, Wuhan University, Renmin HospitalDepartment of Anesthesiology, Wuhan University, Renmin HospitalDepartment of Anesthesiology, Hubei University of Medicine, Renmin HospitalDepartment of Anesthesiology, Wuhan University, Renmin HospitalDepartment of Anesthesiology, Wuhan University, Renmin HospitalAbstract Myocardial cold ischemia/reperfusion (I/R) injury is an inevitable consequence of heart transplantation, significantly affecting survival rates and therapeutic outcomes. Growth Differentiation Factor 15 (GDF15) has been shown to regulate GPX4-mediated ferroptosis, playing a critical role in mitigating I/R injury. Meanwhile, verbascoside (VB), an active compound extracted from the herbaceous plant, has demonstrated myocardial protective effects. In this study, heart transplantation was performed using a modified non-suture cuff technique, with VB administered at a dose of 20 mg/kg/day via intraperitoneal injection for 3 days in vivo. In vitro, cardiomyocytes were pretreated with 50 µg/ml VB for 24 h. VB treatment significantly reduced histopathological injury, decreased myocardial injury markers, and inhibited ferroptosis and oxidative stress during myocardial cold I/R injury in vivo. In vitro experiments further demonstrated that GDF15 alleviates ferroptosis induced by hypoxic reoxygenation by upregulating GPX4. Therefore, it is concluded that VB preconditioning can effectively reduce ferroptosis induced by myocardial cold I/R after heterotopic heart transplantation, possibly through up-regulation of GDF15/GPX4/SLC7A11 pathway.https://doi.org/10.1038/s41598-025-00112-4VerbascosideHeart transplantationMyocardial cold ischemia /reperfusion injuryFerroptosisGDF15 |
| spellingShingle | Yuxi Zhang Junbiao Zhan Zhen Qiu Hao Tian Shaoqing Lei Qin Huang Rui Xue Qian Sun Zhongyuan Xia Verbascoside attenuates myocardial ischemia/reperfusion-induced ferroptosis following heterotopic heart transplantation via modulating GDF15/GPX4/SLC7A11 pathway Scientific Reports Verbascoside Heart transplantation Myocardial cold ischemia /reperfusion injury Ferroptosis GDF15 |
| title | Verbascoside attenuates myocardial ischemia/reperfusion-induced ferroptosis following heterotopic heart transplantation via modulating GDF15/GPX4/SLC7A11 pathway |
| title_full | Verbascoside attenuates myocardial ischemia/reperfusion-induced ferroptosis following heterotopic heart transplantation via modulating GDF15/GPX4/SLC7A11 pathway |
| title_fullStr | Verbascoside attenuates myocardial ischemia/reperfusion-induced ferroptosis following heterotopic heart transplantation via modulating GDF15/GPX4/SLC7A11 pathway |
| title_full_unstemmed | Verbascoside attenuates myocardial ischemia/reperfusion-induced ferroptosis following heterotopic heart transplantation via modulating GDF15/GPX4/SLC7A11 pathway |
| title_short | Verbascoside attenuates myocardial ischemia/reperfusion-induced ferroptosis following heterotopic heart transplantation via modulating GDF15/GPX4/SLC7A11 pathway |
| title_sort | verbascoside attenuates myocardial ischemia reperfusion induced ferroptosis following heterotopic heart transplantation via modulating gdf15 gpx4 slc7a11 pathway |
| topic | Verbascoside Heart transplantation Myocardial cold ischemia /reperfusion injury Ferroptosis GDF15 |
| url | https://doi.org/10.1038/s41598-025-00112-4 |
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