Taoren Honghua Jian improves ferroptosis-mediated myocardial damage following myocardial infarction via Nrf2-dependent enhancement of GPX4/FSP1.

IF 3.2 4区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of Pharmacy and Pharmacology Pub Date : 2025-10-17 DOI:10.1093/jpp/rgaf075

Guo-Yong Zhang, Feng Zhang, Ling-Peng Xie, Xin Han, Zhi-Xin Wang, Wen-Long Wang, Yan Peng, Hong-Lin Xu, Tong Xu, Ming-Jie Pang, Bin Liu, Dong Wang, Ying-Chun Zhou, Yu-Ting Wu

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引用次数: 0

Abstract

Objectives: Myocardial infarction (MI) remains a leading cause of global mortality, and the inhibition of ferroptosis has cardioprotective potential. Taoren Honghua Jian (TRHHJ) has been used clinically to improve cardiovascular disorders. However, whether TRHHJ inhibits cardiomyocyte ferroptosis and ameliorates myocardial damage after MI requires further investigation. This study aimed to assess the ferroptosis-inhibiting effects of TRHHJ on post-MI myocardial injury and its underlying mechanisms.

Methods: In vivo MI models were established via left anterior descending coronary artery ligation, and the cardioprotective effects of TRHHJ were assessed by echocardiography and histopathology combined with ferroptosis biomarker detection and Nrf2 signaling protein analysis. In vitro, erastin induced ferroptosis in H9C2 cells, and the anti-ferroptotic effects of TRHHJ was evaluated using the MTT assay, ferroptosis markers, and Nrf2 signaling analysis. Mechanistically, Nrf2 inhibitor and knockout mice were used for validation.

Results: TRHHJ suppressed cardiomyocyte ferroptosis, reduced myocardial damage, and improved cardiac function in post-MI mice by activating the Nrf2 signaling pathway in vivo. TRHHJ enhanced cell viability and inhibited erastin-induced ferroptosis in H9C2 cells by increasing Nrf2 level and activating downstream signaling in vitro. Inhibition or knockout of Nrf2 partially abolished these protective effects.

Conclusions: TRHHJ inhibits cardiomyocyte ferroptosis and improves myocardial damage after MI through activation of Nrf2 signaling.

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桃仁红花健通过nrf2依赖性增强GPX4/FSP1改善心肌梗死后铁中毒介导的心肌损伤。

目的：心肌梗死（MI）仍然是全球死亡的主要原因，抑制铁下垂具有心脏保护潜力。桃仁红花健（TRHHJ）在临床上用于改善心血管疾病。然而，TRHHJ是否能抑制心肌细胞铁下垂并改善心肌梗死后的心肌损伤还有待进一步研究。本研究旨在探讨TRHHJ对心肌梗死后心肌损伤的抑铁作用及其机制。方法：采用左冠状动脉前降支结扎法建立心肌梗死模型，采用超声心动图和组织病理学结合铁下垂生物标志物检测和Nrf2信号蛋白分析评估TRHHJ的心脏保护作用。在体外，erastin诱导H9C2细胞铁凋亡，并通过MTT法、铁凋亡标志物和Nrf2信号分析评估TRHHJ的抗铁凋亡作用。机制上，使用Nrf2抑制剂和敲除小鼠进行验证。结果：TRHHJ在体内通过激活Nrf2信号通路抑制心肌细胞凋亡，减轻心肌损伤，改善心肌功能。TRHHJ通过提高Nrf2水平和激活下游信号通路，提高细胞活力，抑制erastin诱导的H9C2细胞铁凋亡。抑制或敲除Nrf2部分消除了这些保护作用。结论：TRHHJ通过激活Nrf2信号，抑制心肌细胞铁下垂，改善心肌梗死后心肌损伤。

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

Journal of Pharmacy and Pharmacology 医学-药学

CiteScore

6.60

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： JPP keeps pace with new research on how drug action may be optimized by new technologies, and attention is given to understanding and improving drug interactions in the body. At the same time, the journal maintains its established and well-respected core strengths in areas such as pharmaceutics and drug delivery, experimental and clinical pharmacology, biopharmaceutics and drug disposition, and drugs from natural sources. JPP publishes at least one special issue on a topical theme each year.