Kaempferol protects against doxorubicin-induced myocardial damage by inhibiting mitochondrial ROS-dependent ferroptosis
Background Doxorubicin (DOX), a widely used chemotherapeutic agent, is limited in clinical application due to its dose-dependent cardiotoxicity. Therefore, it is crucial to explore alternative therapeutic molecules or drugs for mitigating DOX-induced cardiomyopathy (DIC). In this study aimed to expl...
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Taylor & Francis Group
2025-12-01
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| Series: | Redox Report |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/13510002.2025.2503130 |
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| author | Lin Zhang Xiaorui Liu Juan Wang Zimu Li Siqi Wang Wen Yang Yang Hai Dongling Liu |
| author_facet | Lin Zhang Xiaorui Liu Juan Wang Zimu Li Siqi Wang Wen Yang Yang Hai Dongling Liu |
| author_sort | Lin Zhang |
| collection | DOAJ |
| description | Background Doxorubicin (DOX), a widely used chemotherapeutic agent, is limited in clinical application due to its dose-dependent cardiotoxicity. Therefore, it is crucial to explore alternative therapeutic molecules or drugs for mitigating DOX-induced cardiomyopathy (DIC). In this study aimed to explore underlying mechanisms of the cardioprotective effects of Kaempferol (KP) against DIC.Methods H9c2 cell-based DIC model were established to explore the pharmacological mechanism. The levels of mitochondrial membrane potential, mitochondrial ROS, mitochondrial Fe2+ and lipid peroxidation were detected using JC-1, TMRE, Mito-SOX, Mito-Ferro Green and C11-BODIPY 581/591 probes. Furthermore, Western blot analysis measured the expression of key regulatory proteins, and NRF2-targeting siRNA was transfected into H9c2 cells. The nuclear translocation of NRF2 was assessed by immunofluorescence.Results Data revealed that KP mitigated DOX-induced mitochondrial damage and ferroptosis via reducing membrane potential, mitochondrial ROS/Fe²+, and regulating lipid metabolism. Mechanistically, Western blot analysis revealed that KP inhibited DOX-induced ferroptosis by activating NRF2/SLC7A11/GPX4 axis. Moreover, KP promoted the accumulation and nuclear translocation of NRF2 protein.Conclusion These findings demonstrated that KP protected against DOX-induced myocardial damage by inhibiting mitochondrial ROS-dependent ferroptosis. This provides novel insights into KP as a promising drug candidate for cardioprotection. |
| format | Article |
| id | doaj-art-e422cc2a6a6949c6bc620c1d4f785cd3 |
| institution | DOAJ |
| issn | 1351-0002 1743-2928 |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Redox Report |
| spelling | doaj-art-e422cc2a6a6949c6bc620c1d4f785cd32025-08-20T02:58:29ZengTaylor & Francis GroupRedox Report1351-00021743-29282025-12-0130110.1080/13510002.2025.2503130Kaempferol protects against doxorubicin-induced myocardial damage by inhibiting mitochondrial ROS-dependent ferroptosisLin Zhang0Xiaorui Liu1Juan Wang2Zimu Li3Siqi Wang4Wen Yang5Yang Hai6Dongling Liu7School of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of ChinaSchool of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of ChinaSchool of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of ChinaSchool of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of ChinaSchool of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of ChinaSchool of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of ChinaSchool of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of ChinaSchool of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, People’s Republic of ChinaBackground Doxorubicin (DOX), a widely used chemotherapeutic agent, is limited in clinical application due to its dose-dependent cardiotoxicity. Therefore, it is crucial to explore alternative therapeutic molecules or drugs for mitigating DOX-induced cardiomyopathy (DIC). In this study aimed to explore underlying mechanisms of the cardioprotective effects of Kaempferol (KP) against DIC.Methods H9c2 cell-based DIC model were established to explore the pharmacological mechanism. The levels of mitochondrial membrane potential, mitochondrial ROS, mitochondrial Fe2+ and lipid peroxidation were detected using JC-1, TMRE, Mito-SOX, Mito-Ferro Green and C11-BODIPY 581/591 probes. Furthermore, Western blot analysis measured the expression of key regulatory proteins, and NRF2-targeting siRNA was transfected into H9c2 cells. The nuclear translocation of NRF2 was assessed by immunofluorescence.Results Data revealed that KP mitigated DOX-induced mitochondrial damage and ferroptosis via reducing membrane potential, mitochondrial ROS/Fe²+, and regulating lipid metabolism. Mechanistically, Western blot analysis revealed that KP inhibited DOX-induced ferroptosis by activating NRF2/SLC7A11/GPX4 axis. Moreover, KP promoted the accumulation and nuclear translocation of NRF2 protein.Conclusion These findings demonstrated that KP protected against DOX-induced myocardial damage by inhibiting mitochondrial ROS-dependent ferroptosis. This provides novel insights into KP as a promising drug candidate for cardioprotection.https://www.tandfonline.com/doi/10.1080/13510002.2025.2503130KPDOXcardiotoxicitycardiomyocytesmitochondrial ROSferroptosis |
| spellingShingle | Lin Zhang Xiaorui Liu Juan Wang Zimu Li Siqi Wang Wen Yang Yang Hai Dongling Liu Kaempferol protects against doxorubicin-induced myocardial damage by inhibiting mitochondrial ROS-dependent ferroptosis Redox Report KP DOX cardiotoxicity cardiomyocytes mitochondrial ROS ferroptosis |
| title | Kaempferol protects against doxorubicin-induced myocardial damage by inhibiting mitochondrial ROS-dependent ferroptosis |
| title_full | Kaempferol protects against doxorubicin-induced myocardial damage by inhibiting mitochondrial ROS-dependent ferroptosis |
| title_fullStr | Kaempferol protects against doxorubicin-induced myocardial damage by inhibiting mitochondrial ROS-dependent ferroptosis |
| title_full_unstemmed | Kaempferol protects against doxorubicin-induced myocardial damage by inhibiting mitochondrial ROS-dependent ferroptosis |
| title_short | Kaempferol protects against doxorubicin-induced myocardial damage by inhibiting mitochondrial ROS-dependent ferroptosis |
| title_sort | kaempferol protects against doxorubicin induced myocardial damage by inhibiting mitochondrial ros dependent ferroptosis |
| topic | KP DOX cardiotoxicity cardiomyocytes mitochondrial ROS ferroptosis |
| url | https://www.tandfonline.com/doi/10.1080/13510002.2025.2503130 |
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