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Ophiopogon japonicus polysaccharide reduces doxorubicin-induced myocardial ferroptosis injury by activating Nrf2/GPX4 signaling and alleviating iron accumulation

  • Authors:
    • Yongting Chen
    • Linlin Ma
    • Yuzhong Yan
    • Xiaoying Wang
    • Lizhi Cao
    • Yanfei Li
    • Ming Li
  • View Affiliations / Copyright

    Affiliations: Graduate School, Xinxiang Medical University, Xinxiang, Henan 453003, P.R. China, Scientific Research Department, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai 201318, P.R. China, School of Life Sciences and Technology, Tongji University, Shanghai 200092, P.R. China, Scientific Research Department, Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai 201318, P.R. China, Administration Office, East Hospital Affiliated to Tongji University, Shanghai 201318, P.R. China
    Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 36
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    Published online on: November 21, 2024
       https://doi.org/10.3892/mmr.2024.13401
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Abstract

Doxorubicin (DOX) is a principal chemotherapeutic agent in the domain of oncological intervention. However, its clinical application is constrained due to its severe and irreversible side effects, particularly heart damage. Ferroptosis, characterized by iron accumulation and redox system imbalance, serves a key role in DOX‑induced cardiotoxicity. Ophiopogon japonicus polysaccharide (OJP) exhibits diverse pharmacological activities, including cardiovascular protection, and anti‑inflammatory, anti‑oxidative and immune regulatory effects. However, the role and mechanism of OJP in DOX‑mediated ferroptosis‑triggered injury in cardiomyocytes remain elusive. The present study aimed to assess the effect of OJP on DOX‑induced myocardial ferroptosis injury and to reveal its underlying anti‑ferroptosis mechanism. The detection of myocardial injury markers, such as LDH, indicated that OJP can ameliorate myocardial damage. Additionally, western blot analyses reveal that OJP decreases the expression levels of the ferroptosis‑related marker transferrin receptor 1 (TFR1) while simultaneously increasing expression levels of glutathione peroxidase 4 (GPX4) in a concentration‑dependent manner. Furthermore, fluorescence probe assays demonstrate that OJP not only reduces iron accumulation and oxidative stress but also inhibits the production of lipid peroxidation, as evidenced by a decrease in malondialdehyde (MDA) levels measured. In addition, OJP simultaneously decreased ferroptosis by enhancing mitochondrial function. Mechanistically, OJP attenuated ferroptosis by upregulating the endogenous key antioxidant factor nuclear factor erythroid 2‑related factor 2 (Nrf2), which in turn increased the expression of the downstream signaling molecule GPX4 and reduced the accumulation of the labile iron pool. Therefore, OJP may be a novel therapeutic intervention for DOX‑induced ferroptosis‑triggered myocardial injury.
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Copy and paste a formatted citation
Spandidos Publications style
Chen Y, Ma L, Yan Y, Wang X, Cao L, Li Y and Li M: <em>Ophiopogon japonicus</em> polysaccharide reduces doxorubicin-induced myocardial ferroptosis injury by activating Nrf2/GPX4 signaling and alleviating iron accumulation. Mol Med Rep 31: 36, 2025.
APA
Chen, Y., Ma, L., Yan, Y., Wang, X., Cao, L., Li, Y., & Li, M. (2025). <em>Ophiopogon japonicus</em> polysaccharide reduces doxorubicin-induced myocardial ferroptosis injury by activating Nrf2/GPX4 signaling and alleviating iron accumulation. Molecular Medicine Reports, 31, 36. https://doi.org/10.3892/mmr.2024.13401
MLA
Chen, Y., Ma, L., Yan, Y., Wang, X., Cao, L., Li, Y., Li, M."<em>Ophiopogon japonicus</em> polysaccharide reduces doxorubicin-induced myocardial ferroptosis injury by activating Nrf2/GPX4 signaling and alleviating iron accumulation". Molecular Medicine Reports 31.2 (2025): 36.
Chicago
Chen, Y., Ma, L., Yan, Y., Wang, X., Cao, L., Li, Y., Li, M."<em>Ophiopogon japonicus</em> polysaccharide reduces doxorubicin-induced myocardial ferroptosis injury by activating Nrf2/GPX4 signaling and alleviating iron accumulation". Molecular Medicine Reports 31, no. 2 (2025): 36. https://doi.org/10.3892/mmr.2024.13401
Copy and paste a formatted citation
x
Spandidos Publications style
Chen Y, Ma L, Yan Y, Wang X, Cao L, Li Y and Li M: <em>Ophiopogon japonicus</em> polysaccharide reduces doxorubicin-induced myocardial ferroptosis injury by activating Nrf2/GPX4 signaling and alleviating iron accumulation. Mol Med Rep 31: 36, 2025.
APA
Chen, Y., Ma, L., Yan, Y., Wang, X., Cao, L., Li, Y., & Li, M. (2025). <em>Ophiopogon japonicus</em> polysaccharide reduces doxorubicin-induced myocardial ferroptosis injury by activating Nrf2/GPX4 signaling and alleviating iron accumulation. Molecular Medicine Reports, 31, 36. https://doi.org/10.3892/mmr.2024.13401
MLA
Chen, Y., Ma, L., Yan, Y., Wang, X., Cao, L., Li, Y., Li, M."<em>Ophiopogon japonicus</em> polysaccharide reduces doxorubicin-induced myocardial ferroptosis injury by activating Nrf2/GPX4 signaling and alleviating iron accumulation". Molecular Medicine Reports 31.2 (2025): 36.
Chicago
Chen, Y., Ma, L., Yan, Y., Wang, X., Cao, L., Li, Y., Li, M."<em>Ophiopogon japonicus</em> polysaccharide reduces doxorubicin-induced myocardial ferroptosis injury by activating Nrf2/GPX4 signaling and alleviating iron accumulation". Molecular Medicine Reports 31, no. 2 (2025): 36. https://doi.org/10.3892/mmr.2024.13401
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