1. Corilagin alleviates atherosclerosis by inhibiting NLRP3 inflammasome activation via the Olfr2 signaling pathway in vitro and in vivo .
- Author
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Mao J, Chen Y, Zong Q, Liu C, Xie J, Wang Y, Fisher D, Hien NTT, Pronyuk K, Musabaev E, Li Y, Zhao L, and Dang Y
- Subjects
- Animals, Mice, Male, Disease Models, Animal, Mice, Inbred C57BL, Mice, Knockout, ApoE, Hydrolyzable Tannins pharmacology, Hydrolyzable Tannins therapeutic use, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Atherosclerosis drug therapy, Atherosclerosis metabolism, Signal Transduction drug effects, Inflammasomes metabolism, Glucosides pharmacology, Glucosides therapeutic use, Macrophages metabolism, Macrophages immunology, Macrophages drug effects
- Abstract
Introduction: Atherosclerosis, a leading cause of global cardiovascular mortality, is characterized by chronic inflammation. Central to this process is the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome, which significantly influences atherosclerotic progression. Recent research has identified that the olfactory receptor 2 (Olfr2) in vascular macrophages is instrumental in driving atherosclerosis through NLRP3- dependent IL-1 production., Methods: To investigate the effects of Corilagin, noted for its anti-inflammatory attributes, on atherosclerotic development and the Olfr2 signaling pathway, our study employed an atherosclerosis model in ApoE
-/- mice, fed a high-fat, high-cholesterol diet, alongside cellular models in Ana-1 cells and mouse bone marrow-derived macrophages, stimulated with lipopolysaccharides and oxidized low-density lipoprotein., Results: The vivo and vitro experiments indicated that Corilagin could effectively reduce serum lipid levels, alleviate aortic pathological changes, and decrease intimal lipid deposition. Additionally, as results showed, Corilagin was able to cut down expressions of molecules associated with the Olfr2 signaling pathway., Discussion: Our findings indicated that Corilagin effectively inhibited NLRP3 inflammasome activation, consequently diminishing inflammation, macrophage polarization, and pyroptosis in the mouse aorta and cellular models via the Olfr2 pathway. This suggests a novel therapeutic mechanism of Corilagin in the treatment of atherosclerosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Mao, Chen, Zong, Liu, Xie, Wang, Fisher, Hien, Pronyuk, Musabaev, Li, Zhao and Dang.)- Published
- 2024
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