Hydroxytyrosol attenuates obesity-induced myocardial fibrosis by inhibiting NLRP3/CYLD/NOX4 mediated oxidative stress

  • NPJ Sci Food. 2026 May 30. doi: 10.1038/s41538-026-00910-8.
Tao Li  1 ,  Bing Shao  2 ,  Xiao Li  2 ,  Ziyi Wu  2 ,  Dongxin Yi  2 ,  Yuji Xiao  2  3 ,  Xue Zhang  2  4 ,  Yixue Deng  2 ,  Tao Yang  2 ,  Jiaxin Zhu  2 ,  Tiecheng Huang  2 ,  Ningning Wang  5  6 ,  Rongfeng Zhang  7
Affiliations
  • 1. Department of Cardiology, the First Affiliated Hospital of Dalian Medical University, Dalian, PR China.
  • 2. School of Public Health, Dalian Medical University, Dalian, PR China.
  • 3. Bishan Hospital of Chongqing Medical University, Chongqing, PR China.
  • 4. The Second People's Hospital of Dalian, Dalian, PR China.
  • 5. Experimental Teaching Center of Public Health, School of Public Health, Dalian, PR China. [email protected].
  • 6. Global Health Research Center, Dalian Medical University, Dalian, PR China. [email protected].
  • 7. Department of Cardiology, the First Affiliated Hospital of Dalian Medical University, Dalian, PR China. [email protected].
PMID: 42225718 DOI: 10.1038/s41538-026-00910-8
Abstract

Hydroxytyrosol (HT), the most bioactive polyphenol in virgin olive oil, has been shown to have cardiometabolic benefits in obese rats, but the underlying mechanism has not been fully elucidated. The aim of this study was to explore the potential driving mechanism in the initiation node of obesity-induced myocardial fibrosis through in vivo and in vitro experiments, and the role of HT in obesity-induced myocardial fibrosis was investigated based on the above mechanisms. The results demonstrated that HT reduced cardiomyocyte oxidative stress and ultimately ameliorated myocardial injury and fibrosis in obese mice by inhibiting NLRP3 inflammasome-dependent Pyroptosis, which in turn downregulated the deubiquitinating enzyme cylindromatosis (CYLD), thereby reducing NADPH Oxidase (NOX)4 deubiquitination and promoting its degradation.

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