ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Cell Death and Survival
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1623846
This article is part of the Research TopicMechanisms and Therapeutic Strategies in Cellular Injury and RepairView all 4 articles
Gypensapogenin I alleviates PANoptosis, ferroptosis and oxidative stress in myocardial ischemic-reperfusion injury by targeting NOX2/AMPK pathway
Provisionally accepted
Yuqiong Chen1*
Bo Guan1
Jian Lu1Xiaopei Yan1Chao Huang1Yuli Qiu1
Xinyan Li2
Xiangyu Sun3Lin Chen1Wei Li1Wenjun Mao1Zhongqi Sun1Bin Xu1Su Li4*Chao Chen1*- 1Suzhou Municipal Hospital, Suzhou, China
- 2Chinese Academy of Medical Sciences and Peking Union Medical College, beijing, China
- 3Liaoning Cancer Hospital and Institute, liaoning, China
- 4Zhongshan Hospital, Fudan University, shanghai, China
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Aim: To investigate the benefits of Gypensapogenin I (GI) on myocardial ischemiareperfusion injury (MIRI) and the underlying mechanisms. Methods: MIRI model was established by ligating the anterior descending coronary artery (LAD) following blood flow restoration in mice. Cardiac dysfunction and myocardial infarction size were evaluated by echocardiography and TTC staining. PANoptosis, ferroptosis and mitochondrial redox state were examined by immunofluorescence, western blots and ELISA kit. In addition, molecular and biochemical methods were applied to illustrate the exact mechanisms of GI on MIRI. Results: GI pretreatment alleviated cellular oxidative stress, inhibited PANoptosis and ferroptosis, reduced myocardial infarction area and improved cardiac function during MIRI. Further results revealed that mitochondrial biogenesis and the anti-oxidative system were impaired in mice suffering from MIRI, the effects were significantly alleviated by GI treatment via downregulating NOX2 level. Moreover, NOX2 promoted mitochondrial dysfunction by suppressing the AMPK-PGC-1α-Sirt3 signaling pathway. In addition, NOX2 activator exacerbated oxidative damage and offset all the beneficial effects of GI on mitochondrial function, PANoptosis and ferroptosis. Whereas, reinforced AMPK phosphorylation by GI or AMPK activator (AICAR) maintained mitochondrial redox state and biogenesis, and suppressed PANoptosis and ferroptosis.PANoptosis and ferroptosis by maintaining mitochondrial redox state and biogenesis through modulating the NOX2/AMPK signaling pathway. Our findings indicated that 5 GI pretreatment could be a promising therapeutic agent for MIRI treatment.
Keywords: Gypensapogenin I, Myocardial ischemia-reperfusion injury, PANoptosis, ferroptosis, Oxidative Stress, NOX2 GSDMD, gasdermin D IDH2, isocitrate dehydrogenase 2 LVFS
Received: 06 May 2025; Accepted: 30 Jun 2025.
Copyright: © 2025 Chen, Guan, Lu, Yan, Huang, Qiu, Li, Sun, Chen, Li, Mao, Sun, Xu, Li and Chen. 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:
Yuqiong Chen, Suzhou Municipal Hospital, Suzhou, China
Su Li, Zhongshan Hospital, Fudan University, shanghai, China
Chao Chen, Suzhou Municipal Hospital, Suzhou, China
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