2. Academic Validation
  3. Eleutheroside E Attenuates Doxorubicin-Induced Cardiotoxicity by Suppressing Ferroptosis Through Activation of the Nrf2/SLC7A11/GPX4 Signaling Pathway

Eleutheroside E Attenuates Doxorubicin-Induced Cardiotoxicity by Suppressing Ferroptosis Through Activation of the Nrf2/SLC7A11/GPX4 Signaling Pathway

  • J Cardiovasc Pharmacol Ther. 2026 Jan-Dec:31:10742484261428559. doi: 10.1177/10742484261428559.
Peng Sun 1 2 3,  Liheng Chen 1 2,  Xiangzhou Chen 1 2,  Xuwei Zhang 1 2,  Junjie Guan 1 2,  Hongwei Mo 1 2,  Yu Liang 1 2,  Jingchao Li 1 2,  Jing Yan 1 2,  Deshu Chen 1 2,  Chongbin Zhong 1 2,  Pingzhen Yang 1 2
Affiliations

Affiliations

  • 1 Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, People's Republic of China.
  • 2 Guangdong Engineering Technology Research Center of Biomedicine for Cardiovascular Disease, Guangzhou, Guangdong, People's Republic of China.
  • 3 Department of Cardiovascular Medicine, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, Shandong, People's Republic of China.
PMID: 41771771 DOI: 10.1177/10742484261428559
Abstract

Doxorubicin (DOX)-induced cardiotoxicity significantly impairs Cancer patient survival rates. Eleutheroside E (EE), a polyphenolic compound with established cardioprotective properties against high-altitude myocardial injury and ischemia/reperfusion damage, has not previously been investigated in the context of DOX-induced cardiac toxicity. This study aimed to elucidate the therapeutic potential of EE against DOX-associated cardiotoxicity and its underlying mechanisms. Cardiomyocyte viability was quantified using the CCK-8 assay and Hoechst 33342/PI dual staining. Cardiac function was evaluated by echocardiography. Morphological alterations in cardiomyocytes were analyzed through phalloidin, hematoxylin-eosin (H&E), and wheat germ agglutinin staining. Ferroptosis-related biomarkers including malondialdehyde (MDA), Ptgs2 mRNA levels, Fe2+ concentration, and lipid peroxidation were assessed respectively. EE administration attenuated DOX-induced cardiomyocyte atrophy in-vitro and improved cardiac function in-vivo. Mechanistically, EE counteracted DOX-mediated suppression of Nrf2 expression and inhibited Ferroptosis via activation of the Nrf2/SLC7A11/GPX4 signaling axis. siRNA-mediated Nrf2 knockdown partly abolished EE's cardioprotective effects. These findings conclusively demonstrate that EE mitigates DOX-induced cardiotoxicity through Nrf2-dependent Ferroptosis regulation, highlighting its therapeutic potential for preventing chemotherapy-associated cardiac complications.

Keywords

Eleutheroside E; Nrf2/SLC7A11/GPX4; doxorubicin-induced cardiotoxicity; ferroptosis.

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