Xin-Ji-Er-Kang modulates NRF2 to inhibit ferroptosis and attenuate doxorubicin-induced myocardial injury.

IF 8.3 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-09-25 DOI:10.1016/j.phymed.2025.157302

Si-Min Yang, Zhang-le Hu, Hui-Yu Jia, Pang-Bo Yang, Zhi-Wei Xu, Cong Ma, Sheng-Yong Luo, Wei Chen, Shan Gao

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引用次数: 0

Abstract

Background: Xin-Ji-Er-Kang (XJEK), a traditional Chinese medicine formulation, has shown protective effects in various murine models of cardiovascular disease. However, its potential mechanisms in mitigating drug-induced cardiotoxicity, particularly its role in regulating ferroptosis, remain unclear.

Aim of the study: This study aimed to evaluate the cardioprotective effects of XJEK against doxorubicin (DOX)-induced myocardial injury and to elucidate its potential mechanisms.

Materials and methods: The protective effects of XJEK were assessed using in vivo and in vitro models of DOX-induced cardiotoxicity (DIC). Cardiac function, related biomarkers, mitochondrial function, and indicators of ferroptosis were evaluated. To clarify the mechanism, NRF2 expression was silenced using small interfering RNA (siRNA).

Results: XJEK significantly alleviated DIC both in vivo and in vitro by restoring mitochondrial function, reducing lipid peroxidation, lowering reactive oxygen species (ROS) production, and decreasing iron accumulation and ferroptosis-related protein expression. Mechanistically, XJEK exerted these protective effects by inhibiting ferroptosis through activation of the NRF2 pathway.

Conclusion: XJEK effectively attenuates DOX-induced cardiotoxicity by suppressing ferroptosis via NRF2 activation. These findings suggest that NRF2-mediated anti-ferroptosis signalling contributes to the cardioprotective effects of XJEK, highlighting its therapeutic potential for managing drug-induced myocardial injury.

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心机二康调节NRF2抑制铁下垂，减轻阿霉素所致心肌损伤。

背景：心继尔康（XJEK）是一种中药制剂，在多种小鼠心血管疾病模型中显示出保护作用。然而，其减轻药物性心脏毒性的潜在机制，特别是其在调节铁下垂中的作用仍不清楚。研究目的：本研究旨在评价XJEK对阿霉素（DOX）诱导心肌损伤的心脏保护作用，并阐明其可能的机制。材料与方法：采用dox诱导的心脏毒性（DIC）体内和体外模型，评价XJEK的保护作用。评估心功能、相关生物标志物、线粒体功能和铁下垂指标。为了阐明其机制，我们使用小干扰RNA （siRNA）沉默NRF2的表达。结果：XJEK通过恢复线粒体功能、减少脂质过氧化、降低活性氧（ROS）产生、降低铁积累和凋亡相关蛋白表达，在体内和体外均显著缓解DIC。从机制上讲，XJEK通过激活NRF2途径抑制铁下垂发挥这些保护作用。结论：XJEK通过NRF2激活抑制铁凋亡，有效减轻dox诱导的心脏毒性。这些发现表明nrf2介导的抗铁凋亡信号有助于XJEK的心脏保护作用，突出了其在治疗药物性心肌损伤方面的治疗潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.