Yang Na, Yu Guanye, Liu Tianhao, Dang Yifang, Deng Pengxi, Lei Zhijun, Zeng Yanxi, Xiong Jing, Yu Qing, Liu Jun, Chen Yingqun, Zhang Xianling, Jian Weixia, Gong Shiyu, Liu Haipeng, Peng Wenhui
Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University, School of Medicine, Shanghai 200072, China.
Central Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine Shanghai 200000, China.
Phytomedicine. 2025 Mar;138:156403. doi: 10.1016/j.phymed.2025.156403. Epub 2025 Jan 17.
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.
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.
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.
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.
