ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1586937
This article is part of the Research TopicTargets in Cardio-Oncology: Drug Effects and Mechanisms of ActionView all 14 articles
Ophiopogonin D mitigates doxorubicin-induced cardiomyocyte ferroptosis through the β-catenin/GPX4 pathway
Provisionally accepted
- 1University of South China, Hengyang, Hunan Province, China
- 2The First Affiliated Hospital, University of South China, Hengyang, Hunan Province, China
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Background: The chemotherapeutic agent doxorubicin has the side effect of inducing injury to cardiomyocytes. Ferroptosis is essential in the onset and progression of cardiac injury. Ophiopogonin D is considered the active component in the Chinese herbal medicine Mai Dong, commonly used for the treatment of cardiovascular diseases. This study investigates the impact of ophiopogonin D on doxorubicin-induced cardiomyocyte ferroptosis through focusing on the β-catenin/GPX4 signaling pathway. Methods: Mice were injected intraperitoneally with doxorubicin (10 mg/kg) to create a model of cardiotoxicity. Cardiomyocytes exposed to doxorubicin (1 μM) were treated with ophiopogonin D (5 μM). Western blot was utilized to detect β-catenin, FTH1, and GPX4. MDA, GSH, and Fe 2+ were detected by biochemical assays. In addition, GPX4 was detected by immunohistochemistry and immunofluorescence staining. Mitochondrial injury was examined by transmission electron microscopy. Chromatin immunoprecipitation (ChIP) combining dual luciferase reporter gene assay was used to analyze the interaction between βcatenin protein with the promoter of GPX4 gene. Results: Doxorubicin inhibited β-catenin activity and GPX4 expression, promoting cardiomyocytes ferroptosis in vitro and in vivo. Ophiopogonin D increased the expression of β-catenin and promoted GPX4 expression, which then inhibited doxorubicin-induced ferroptosis in cardiomyocytes. Moreover, β-catenin overexpression enhanced GPX4 expression and alleviated homocysteine-induced ferroptosis in cardiomyocytes. Further, results from the ChIP assay and dual-luciferase reporter assay indicated that GPX4 acted as a target gene of β-catenin. Conclusion: Ophiopogonin D inhibits cardiomyocyte ferroptosis induced by doxorubicin through restoring the β-catenin/GPX4 signaling.
Keywords: Chuanshan road, NO 69, Hengyang City, Hunan Province, P.R. China Ophiopogonin D, Doxorubicin, β-catenin, GPx4, ferroptosis
Received: 03 Mar 2025; Accepted: 24 Apr 2025.
Copyright: © 2025 Lei, Xu, Liu and Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yue Zhao, The First Affiliated Hospital, University of South China, Hengyang, 421001, Hunan Province, China
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