ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Cardiovascular and Smooth Muscle Pharmacology
Engeletin alleviates doxorubicin-induced cardiotoxicity via the AMPK pathway in mice
Xin Chen
Xing Zhong
Dan Luo
Qingning Huang
Pusong Tang
Lu Ye
Yuhua Lei
Rui Huang
The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China
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Abstract
Background: The extensively employed antineoplastic drug doxorubicin (DOX) is constrained in clinical utilization on account of its severe cardiotoxicity, and there persists a dearth of protective agents against doxorubicin-induced cardiotoxicity (DIC). Engeletin (ENG) is a natural product endowed with multiple biological activities and has manifested significant protective effects in various diseases. This study purports to explore the protective effects of ENG in DIC and elucidate the underlying mechanisms. Methods: H9C2 cardiomyocytes and C57BL/6 mice were used to establish in vitro and in vivo models of DIC, and ENG was used for treatment. Cardiac function and structural changes in the mice were assessed by ultrasound, pathological section staining and transmission electron microscopy. Western blotting, Real-Time Quantitative PCR, immunofluorescence staining, enzyme-linked immunosorbent assay (ELISA), serum biochemical detection, TUNEL staining, dihydroethidium (DHE) assay, and flow cytometry were employed to evaluate apoptosis, autophagy, oxidative stress, inflammation, mitochondrial damage, ANP and BNP both in vitro and in vivo. An AMPK inhibitor Compound C was utilized to validate the effect of ENG on the AMPK pathway. Results: DOX diminished cardiac function and induced fibrosis in mice, resulting in significant cell apoptosis, oxidative stress, inflammation, autophagy dysregulation, and mitochondrial damage both in vitro and in vivo. Following ENG treatment, these conditions can be markedly ameliorated, especially in mitigating myocardial cell apoptosis, autophagy, and oxidative stress responses. It has been found that this effect is realized through the activation of the AMPK pathway. Moreover, utilization of an AMPK inhibitor CC impeded the protective effect of ENG on DIC. Conclusion: ENG has mitigated DIC through the activation of the AMPK pathway, thereby rendering it a potential drug for the prevention and treatment of DIC.
Summary
Keywords
AMPK pathway, Apoptosis, cardiotoxicity, Doxorubicin, Engeletin
Received
07 November 2025
Accepted
18 February 2026
Copyright
© 2026 Chen, Zhong, Luo, Huang, Tang, Ye, Lei and Huang. 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: Yuhua Lei; Rui Huang
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