What is the clinical evidence from this study?

Study design: Other. Population: Male C57BL/6 mice, 8 weeks old, with doxorubicin-induced cardiotoxicity model (n=20). Intervention: Engeletin vs. Doxorubicin alone and control groups. Primary outcome: Left ventricular ejection fraction (LVEF) and cardiac function assessed by echocardiography, myocardial fibrosis area, serum BNP levels (LVEF improved from 26.1% in DOX group to 51.3% in DOX + ENG group, p=<0.05).

What question did this study set out to answer?

The study aims to explore the protective effects of engeletin against doxorubicin-induced cardiotoxicity and understand the mechanisms involved.

March 1, 2026Open Access

Engeletin alleviates doxorubicin-induced cardiotoxicity via the AMPK pathway in mice

Q: What are the key findings of this study?

Engeletin treatment (20 mg/kg/day) significantly improved LVEF from 26.1% to 51.3% and reduced myocardial fibrosis and serum BNP levels compared to doxorubicin alone in mice with doxorubicin-induced cardiotoxicity.

Q: What question did this study set out to answer?

The study aims to explore the protective effects of engeletin against doxorubicin-induced cardiotoxicity and understand the mechanisms involved.

Key Result

Engeletin treatment (20 mg/kg/day) significantly improved LVEF from 26.1% to 51.3% and reduced myocardial fibrosis and serum BNP levels compared to doxorubicin alone in mice with doxorubicin-induced cardiotoxicity.

Key Points

The study aims to explore the protective effects of engeletin against doxorubicin-induced cardiotoxicity and understand the mechanisms involved.
Established in vitro and in vivo models using H9C2 cardiomyocytes and C57BL/6 mice.
Assessed cardiac function and structure through ultrasound and other staining techniques.
Analyzed apoptosis, oxidative stress, and inflammatory responses using various biochemical assays.
Used an AMPK inhibitor to validate the involvement of the AMPK pathway.
Doxorubicin induced cardiac dysfunction, fibrosis, and significant apoptosis in mice.
Engeletin treatment significantly improved cardiac function and reduced cell apoptosis and oxidative stress.
The protective effect of engeletin was linked to the activation of the AMPK pathway.
Inhibition of AMPK reversed the protective effects of engeletin.

Structured PICO

Does engeletin prevent doxorubicin-induced cardiotoxicity and improve cardiac function in preclinical models?

Population

8-week-old male C57BL/6 mice (n=20) and H9C2 cardiomyocytes used to establish in vivo and in vitro models of doxorubicin-induced cardiotoxicity (DIC).

Intervention

Engeletin (ENG) 20 mg/kg/day via intraperitoneal injection for 2 weeks (in vivo) and 80 µM for 24 hours (in vitro).

Comparator

Doxorubicin alone (5 mg/kg/week for 5 weeks in vivo; 1 µM for 24 hours in vitro) and saline/solvent control.

Outcome

Cardiac function (LVEF, LVFS, LVEDd, LVESd) assessed by echocardiography at week 6, and structural/cellular changes including apoptosis, autophagy, oxidative stress, and mitochondrial damage.surrogate

Engeletin demonstrates significant cardioprotective effects against doxorubicin-induced cardiotoxicity in preclinical models by activating the AMPK pathway, suggesting its potential as a future preventive agent.

Main Result

Effect estimate: LVEF improved from 26.1% in DOX group to 51.3% in DOX + ENG group

Absolute Event Rate: 51.3% vs 26.1%

p-value: p=<0.05

Limitations

Study conducted in a mouse model, limiting direct clinical extrapolation to humans.
ENG effect on anti-tumor efficacy of doxorubicin was not assessed.
In vitro experiments used H9C2 cell line instead of primary cardiomyocytes.
Role of AMPK confirmed with inhibitor only; no genetic knockout validation.

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.

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