2. Academic Validation
  3. Stachyose ameliorates myocardial ischemia-reperfusion injury by inhibiting cardiomyocyte ferroptosis and macrophage pyroptosis

Stachyose ameliorates myocardial ischemia-reperfusion injury by inhibiting cardiomyocyte ferroptosis and macrophage pyroptosis

  • Int Immunopharmacol. 2024 Dec 25;143(Pt 1):113334. doi: 10.1016/j.intimp.2024.113334.
Ao-Yuan Zhang 1,  Jia-Bao Su 2,  He-Ting Sun 3,  Qiao Liu 4,  Rui Li 1,  Yuan Zhang 2,  Yan Wang 2,  Meng-Yuan Wang 2,  Le-Ming Ji 2,  Sheng-Qi Gao 2,  Qi Ding 2,  Li-Ying Qiu 2,  Yan Jin 5,  Hai-Jian Sun 6,  Zhi-Jun Han 7,  Xue-Xue Zhu 8
Affiliations

Affiliations

  • 1 Department of Clinical Research Center, Jiangnan University Medical Center (Wuxi No.2 People's Hospital), Wuxi School of Medicine, Jiangnan University, Wuxi, China.
  • 2 Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University Medical Center, Jiangnan University, Wuxi 214122, China.
  • 3 School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai 264005, China.
  • 4 Department of Cardiovascular Medicine, Jiangnan University Medical Center, Wuxi 214002, China.
  • 5 Department of Cardiovascular Medicine, Jiangnan University Medical Center, Wuxi 214002, China. Electronic address: wxeyjinyan@163.com.
  • 6 Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University Medical Center, Jiangnan University, Wuxi 214122, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing 210009, China. Electronic address: sunhaijian927@163.com.
  • 7 Department of Clinical Research Center, Jiangnan University Medical Center (Wuxi No.2 People's Hospital), Wuxi School of Medicine, Jiangnan University, Wuxi, China. Electronic address: zjhan1125@163.com.
  • 8 Department of Clinical Research Center, Jiangnan University Medical Center (Wuxi No.2 People's Hospital), Wuxi School of Medicine, Jiangnan University, Wuxi, China; Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University Medical Center, Jiangnan University, Wuxi 214122, China. Electronic address: zhuxuexue117@163.com.
PMID: 39383784 DOI: 10.1016/j.intimp.2024.113334
Abstract

Myocardial ischemia-reperfusion injury (MIRI) is a complex pathological process that results from the restoration of blood flow to ischemic myocardium, leading to a series of detrimental effects including oxidative stress and inflammation. Stachyose, a naturally occurring oligosaccharide found in traditional Chinese medicinal herbs, has been suggested to possess therapeutic properties against various pathological conditions. However, its impact on MIRI and the underlying mechanisms have not been fully elucidated. In this study, we aimed to investigate the therapeutic effects of stachyose on MIRI and to uncover the molecular mechanisms involved. Using both in vivo and in vitro models of MIRI, we evaluated the effects of stachyose on cardiac function and cell death pathways. Our results indicate that stachyose significantly improves cardiac function and reduces infarct size in MIRI mice. Mechanistically, stachyose modulates the ferroptotic pathway in cardiomyocytes by upregulating the expression of Glutathione Peroxidase 4 (GPX4) and reducing lipid peroxides and iron levels. Additionally, stachyose inhibits the pyroptotic pathway in macrophages by downregulating the expression of NLRP3, gasdermin D (GSMD-N), and cleaved-caspase-1, leading to decreased levels of proinflammatory cytokines interleukin (IL)-1β and IL-18. This study demonstrates that stachyose exerts a protective effect against MIRI by targeting both Ferroptosis and Pyroptosis pathways, suggesting its potential as a novel therapeutic agent for the treatment of MIRI. Further research is warranted to explore the detailed mechanisms and therapeutic potential of stachyose in clinical settings.

Keywords

Ferroptosis; MIRI; Pyroptosis; Stachyose.

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