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Article Open Access

Curcumin attenuates myocardial ischemia‑reperfusion‑induced autophagy‑dependent ferroptosis via Sirt1/AKT/FoxO3a signaling

  • Authors:
    • Shi-Tao Zhao
    • Zhi-Cong Qiu
    • Zhi-Qiang Xu
    • En-De Tao
    • Rong-Bin Qiu
    • Han-Zhi Peng
    • Lian-Fen Zhou
    • Rui-Yuan Zeng
    • Song-Qing Lai
    • Li Wan
  • View Affiliations / Copyright

    Affiliations: Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanchang University, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
    Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 51
    |
    Published online on: January 23, 2025
       https://doi.org/10.3892/ijmm.2025.5492
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Abstract

Curcumin (Cur) effectively attenuates myocardial ischemia/reperfusion injury (MIRI). MIRI has a complex mechanism and is associated with autophagy‑dependent ferroptosis. Therefore, the present study aimed to determine whether autophagy‑dependent ferroptosis occurs in MIRI and assess the mechanism of Cur in attenuating MIRI. The study was conducted on a Sprague‑Dawley rat MIRI model and H9c2 cell anoxia/reoxygenation (A/R) injury model. The effect of Cur pretreatment on A/R or MIRI induced autophagy‑dependent ferroptosis and its molecular mechanism were investigated. Protein expression, lysosomal, reactive oxygen species, Fe2+, oxidative systems, mitochondrial function, subcellular localization of molecules, and cardiac function assays will be employed. Cur decreased MIRI; improved myocardial histopathology; increased cardiomyocyte viability; inhibited ferroptosis, apoptosis and autophagy; reduced infarct size and maintained cardiac function. MIRI decreased silent information regulator 1 (Sirt1), decreased AKT and forkhead box O3A (FoxO3a) phosphorylation, leading to FoxO3a entry into the nucleus to activate translation of autophagy‑related genes and inducing ferroptosis, apoptosis and autophagy. However, Cur pretreatment activated AKT and FoxO3a phosphorylation via Sirt1, thereby transporting FoxO3a out of the nucleus, reducing autophagy‑related gene translation and attenuating MIRI‑induced ferroptosis, apoptosis and autophagy. Of note, the silencing of Sirt1 and administration of triciribine (an AKT inhibitor) both eliminated the protective effect of Cur. Thus, Cur maintained cardiomyocyte function by inhibiting autophagy‑dependent ferroptosis via Sirt1/AKT/FoxO3a signaling.
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Spandidos Publications style
Zhao S, Qiu Z, Xu Z, Tao E, Qiu R, Peng H, Zhou L, Zeng R, Lai S, Wan L, Wan L, et al: Curcumin attenuates myocardial ischemia‑reperfusion‑induced autophagy‑dependent ferroptosis via Sirt1/AKT/FoxO3a signaling. Int J Mol Med 55: 51, 2025.
APA
Zhao, S., Qiu, Z., Xu, Z., Tao, E., Qiu, R., Peng, H. ... Wan, L. (2025). Curcumin attenuates myocardial ischemia‑reperfusion‑induced autophagy‑dependent ferroptosis via Sirt1/AKT/FoxO3a signaling. International Journal of Molecular Medicine, 55, 51. https://doi.org/10.3892/ijmm.2025.5492
MLA
Zhao, S., Qiu, Z., Xu, Z., Tao, E., Qiu, R., Peng, H., Zhou, L., Zeng, R., Lai, S., Wan, L."Curcumin attenuates myocardial ischemia‑reperfusion‑induced autophagy‑dependent ferroptosis via Sirt1/AKT/FoxO3a signaling". International Journal of Molecular Medicine 55.3 (2025): 51.
Chicago
Zhao, S., Qiu, Z., Xu, Z., Tao, E., Qiu, R., Peng, H., Zhou, L., Zeng, R., Lai, S., Wan, L."Curcumin attenuates myocardial ischemia‑reperfusion‑induced autophagy‑dependent ferroptosis via Sirt1/AKT/FoxO3a signaling". International Journal of Molecular Medicine 55, no. 3 (2025): 51. https://doi.org/10.3892/ijmm.2025.5492
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao S, Qiu Z, Xu Z, Tao E, Qiu R, Peng H, Zhou L, Zeng R, Lai S, Wan L, Wan L, et al: Curcumin attenuates myocardial ischemia‑reperfusion‑induced autophagy‑dependent ferroptosis via Sirt1/AKT/FoxO3a signaling. Int J Mol Med 55: 51, 2025.
APA
Zhao, S., Qiu, Z., Xu, Z., Tao, E., Qiu, R., Peng, H. ... Wan, L. (2025). Curcumin attenuates myocardial ischemia‑reperfusion‑induced autophagy‑dependent ferroptosis via Sirt1/AKT/FoxO3a signaling. International Journal of Molecular Medicine, 55, 51. https://doi.org/10.3892/ijmm.2025.5492
MLA
Zhao, S., Qiu, Z., Xu, Z., Tao, E., Qiu, R., Peng, H., Zhou, L., Zeng, R., Lai, S., Wan, L."Curcumin attenuates myocardial ischemia‑reperfusion‑induced autophagy‑dependent ferroptosis via Sirt1/AKT/FoxO3a signaling". International Journal of Molecular Medicine 55.3 (2025): 51.
Chicago
Zhao, S., Qiu, Z., Xu, Z., Tao, E., Qiu, R., Peng, H., Zhou, L., Zeng, R., Lai, S., Wan, L."Curcumin attenuates myocardial ischemia‑reperfusion‑induced autophagy‑dependent ferroptosis via Sirt1/AKT/FoxO3a signaling". International Journal of Molecular Medicine 55, no. 3 (2025): 51. https://doi.org/10.3892/ijmm.2025.5492
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