2. Academic Validation
  3. Direct inhibition of macrophage sting signaling by curcumol protects against myocardial infarction via attenuating the inflammatory response

Direct inhibition of macrophage sting signaling by curcumol protects against myocardial infarction via attenuating the inflammatory response

  • Phytomedicine. 2025 Mar:138:156403. doi: 10.1016/j.phymed.2025.156403.
Na Yang 1,  Guanye Yu 1,  Tianhao Liu 2,  Yifang Dang 2,  Pengxi Deng 3,  Zhijun Lei 1,  Yanxi Zeng 1,  Jing Xiong 1,  Qing Yu 4,  Jun Liu 5,  Yingqun Chen 5,  Xianling Zhang 1,  Weixia Jian 6,  Shiyu Gong 7,  Haipeng Liu 8,  Wenhui Peng 9
Affiliations

Affiliations

  • 1 Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, China.
  • 2 Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine Shanghai 200000, China.
  • 3 Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health); Institute of Metabonomics & Medical NMR, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
  • 4 Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, China; Pan-Vascular Research Institute of Tongji University, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Middle Yanchang Road, Shanghai 200072, China.
  • 5 Department of Traditional Chinese Medicine, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, China.
  • 6 Department of Endocrinology, Xinhua Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai 200092, China.
  • 7 Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, China. Electronic address: gongshiyu92@163.com.
  • 8 Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine Shanghai 200000, China. Electronic address: haipengliu@tongji.edu.cn.
  • 9 Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, China; Pan-Vascular Research Institute of Tongji University, Shanghai Tenth People's Hospital, Tongji University School of Medicine, 301 Middle Yanchang Road, Shanghai 200072, China. Electronic address: pwenhui@tongji.edu.cn.
PMID: 39889491 DOI: 10.1016/j.phymed.2025.156403
Abstract

Background: Macrophages play a crucial role in the pathological process after myocardial infarction (MI). However, pharmacological therapy targeting this pathway remains undefined. Curcumol, a natural compound extracted from the Curcumae Rhizoma, has demonstrated anti-tumor and anti-inflammatory activities. Therefore, this study aimed to explore the potential of curcumol as a therapeutic agent for MI.

Methods: Wild-type (WT) mice were administered with curcumol orally following left coronary artery ligation. The effects of curcumol on post-MI inflammatory responses were evaluated through phenotypic analysis, histology, and flow cytometry. RNA Sequencing, surface plasmon resonance (SPR), and molecular docking were utilized to identify the molecular target of curcumol. Functional studies were further conducted using stimulator of interferon genes (STING) knockout (STING-/-) mice.

Results: Curcumol treatment improved the survival rate in mice following MI while enhancing cardiac function and mitigating adverse post-infarction ventricular remodeling. Transcriptomic analysis and SPR indicated curcumol directly bound to STING. Functional assays demonstrated that the cardio-protective effects of curcumol were mediated via STING, as these effects were diminished in STING-/- mice. Mechanistically, curcumol disrupted STING-TBK1 interaction, suppressing downstream signaling activation and type I interferon responses. Notably, curcumol exhibited stronger inhibition of activated STING signaling in macrophages and superior cardioprotective effects compared to the STING inhibitor H-151.

Conclusion: Curcumol targets STING to suppress type I interferon responses, improving cardiac function post-MI. These findings highlight curcumol as a promising therapeutic candidate for MI treatment.

Keywords

Curcumol; Inflammation; Macrophage; Myocardial infarction; Stimulator of interferon genes; Type I interferon response.

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