Open Access

Echinacoside ameliorates doxorubicin‑induced cardiac injury by regulating GPX4 inhibition‑induced ferroptosis

  • Authors:
    • Yan Ma
    • Xiaoli Yang
    • Nianxin Jiang
    • Cheng Lu
    • Jiehan Zhang
    • Shaowei Zhuang
  • View Affiliations

  • Published online on: November 23, 2023     https://doi.org/10.3892/etm.2023.12317
  • Article Number: 29
  • Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Echinacoside (ECH) is a compound derived from the natural herbs Cistanche and Echinacea, which has considerable protective effects on heart failure (HF). HF is characterized by myocardial damage and abnormal ferroptosis. Glutathione peroxidase 4 (GPX4) is an important regulator of ferroptosis, which plays a role in ferroptosis‑related diseases. Despite this, the therapeutic mechanisms of ECH against HF remain unknown. Therefore, the aim of the present study was to investigate the cardioprotective effect and underlying mechanisms of ECH in the treatment of doxorubicin (DOX)‑induced chronic HF (CHF). Cell proliferation was assessed using a CCK‑8 assay. Furthermore, cardiac cell injury and oxidative stress were determined by measuring the lactate dehydrogenase (LDH), malondialdehyde (MDA), and glutathione (GSH) levels. The levels of Fe2+ and lipid reactive oxygen species (ROS), and expression of the biomarkers of ferroptosis, including GPX4 and prostaglandin‑endoperoxide synthase 2 (PTGS2), were measured to examine cardiomyocyte ferroptosis. Additionally, RNA interference was used to silence Gpx4. In vitro and in vivo, ECH considerably reduced the MDA and LDH levels and increased the GSH level, thereby attenuating DOX‑induced cardiac injury and oxidative stress. Meanwhile, ECH treatment decreased the lipid ROS levels and PTGS2 expression while increasing GPX4 expression, thereby alleviating DOX‑induced cardiomyocyte ferroptosis. Moreover, knockdown of Gpx4 inhibited the protective effects of ECH on DOX‑induced accumulation of lipid ROS in cardiomyocytes. These findings indicate that ECH can reduce DOX‑induced cardiac injury by inhibiting ferroptosis via GPX4, highlighting its value as a potentially valuable therapeutic target in the management of CHF.
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January-2024
Volume 27 Issue 1

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Copy and paste a formatted citation
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Spandidos Publications style
Ma Y, Yang X, Jiang N, Lu C, Zhang J and Zhuang S: Echinacoside ameliorates doxorubicin‑induced cardiac injury by regulating GPX4 inhibition‑induced ferroptosis. Exp Ther Med 27: 29, 2024.
APA
Ma, Y., Yang, X., Jiang, N., Lu, C., Zhang, J., & Zhuang, S. (2024). Echinacoside ameliorates doxorubicin‑induced cardiac injury by regulating GPX4 inhibition‑induced ferroptosis. Experimental and Therapeutic Medicine, 27, 29. https://doi.org/10.3892/etm.2023.12317
MLA
Ma, Y., Yang, X., Jiang, N., Lu, C., Zhang, J., Zhuang, S."Echinacoside ameliorates doxorubicin‑induced cardiac injury by regulating GPX4 inhibition‑induced ferroptosis". Experimental and Therapeutic Medicine 27.1 (2024): 29.
Chicago
Ma, Y., Yang, X., Jiang, N., Lu, C., Zhang, J., Zhuang, S."Echinacoside ameliorates doxorubicin‑induced cardiac injury by regulating GPX4 inhibition‑induced ferroptosis". Experimental and Therapeutic Medicine 27, no. 1 (2024): 29. https://doi.org/10.3892/etm.2023.12317