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

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

  • J Pharm Pharmacol. 2025 Oct 17:rgaf075. doi: 10.1093/jpp/rgaf075.
Guo-Yong Zhang 1 2,  Feng Zhang 3,  Ling-Peng Xie 4,  Xin Han 5,  Zhi-Xin Wang 3,  Wen-Long Wang 3,  Yan Peng 1,  Hong-Lin Xu 1 6,  Tong Xu 1 2,  Ming-Jie Pang 1 2,  Bin Liu 7,  Dong Wang 3,  Ying-Chun Zhou 1 2,  Yu-Ting Wu 1 2 3
Affiliations

Affiliations

  • 1 School of Traditional Chinese Medicine, Southern Medical University, No. 1023-1063 Shatai South Road, Baiyun District, Guangzhou, Guangdong Province 510515, China.
  • 2 Department of Traditional Chinese Medicine, Nanfang Hospital (ZengCheng Branch), Southern Medical University, No. 28 Chuangxin Avenue, Ningxi Subdistrict, Zengcheng District, Guangzhou, Guangdong Province 510515, China.
  • 3 Binzhou Medical University Hospital, No. 661 Huanghe 2nd Road, Bincheng District, Binzhou, Shandong Province 256603, China.
  • 4 The Affiliated Traditional Chinese Medicine Hospital, Guangzhou Medical University, No. 95 Tiankun 3rd Road, Tianhe District, Guangzhou, Guangdong Province 510410, China.
  • 5 Department of Chinese Traditional Medicine, Medical College, Yanbian University, No. 977 Park Road, Yanji, Jilin Province 133002, China.
  • 6 The Tenth Affiliated Hospital of Southern Medical University (Dongguan People's Hospital), No. 78 Wandao Road, Wanjiang Subdistrict, Dongguan, Guangdong Province 523058, China.
  • 7 Department of Traditional Chinese Medicine, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, No. 250 Changgang East Road, Haizhu District, Guangzhou, Guangdong Province 510260, China.
PMID: 41105727 DOI: 10.1093/jpp/rgaf075
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.

Keywords

FSP1; GPX4; Nrf2; Taoren Honghua Jian; ferroptosis; myocardial infarction.

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