Hongxia Li1,2,3, Lin Xiao1,2,3,4, Hui He5, Hongmei Zeng1,2,3, Jingjing Liu1,2,3, Chunjie Jiang1,2,3, Guibin Mei1,2,3, Jiasheng Yu6, Hao Chen6, Ping Yao1,2,3, Yuhan Tang1,2,3. 1. Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. 2. Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. 3. Ministry of Education Key Laboratory of Environment, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. 4. Department of Nutrition Science and Food Hygiene, Xiangya School of Public Health, Central South University, Changsha, 410078, China. 5. Department of Preventive Medicine, Changzhi Medical College, Changzhi, 046000, China. 6. Department of Neurologysurgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Abstract
SCOPE: Atherosclerosis is the underlying pathogenesis of cardiovascular events caused by inflammation, and dietary intervention has been recommended as one fundamental prevention strategy. Herein, the anti-arteriosclerotic properties of quercetin are investigated by modulating galectin-3 (Gal-3)-NLR family, pyrin domain-containing 3 (NLRP3) pathway. METHODS AND RESULTS: Plaques from ApoE-/- mice fed by high-fat diet (HFD) with or without quercetin (100 mg (kg·bw)-1 ) for 16 weeks, and carotid plaques from patients with carotid stenosis are collected for histopathological examinations and molecular mechanism assays. Quercetin significantly alleviates atherosclerotic lesions and reduces lipid retention caused by HFD. Proteomic technology identified Gal--3 increased by HFD but lowered by quercetin. Furthermore, immunofluorescence and immunohistochemistry exhibit higher expressions of Gal-3 and NLRP3 in carotid plaques and plaques from HFD-fed mice, which are concurrently down-regulated by quercetin. Similar to TD139, quercetin dramatically suppresses NLRP3 inflammasome activation in oxidized low-density lipoprotein-laden macrophages, and accordingly alleviates cellular steatosis and IL-1β secretion, which is abolished by recombinant Gal-3. Co-immunoprecipitation shows Gal-3 binding to NLRP3 promotes inflammasome activation. CONCLUSION: Gal-3 initiates inflammatory lesions by activating NLRP3 inflammasome which functions as a candidate target of quercetin exerting favorable anti-atherogenic effects. The findings highlight a promising strategy for atherosclerosis prevention and treatment by naturally-occurring quercetin.
SCOPE: Atherosclerosis is the underlying pathogenesis of cardiovascular events caused by inflammation, and dietary intervention has been recommended as one fundamental prevention strategy. Herein, the anti-arteriosclerotic properties of quercetin are investigated by modulating galectin-3 (Gal-3)-NLR family, pyrin domain-containing 3 (NLRP3) pathway. METHODS AND RESULTS: Plaques from ApoE-/- mice fed by high-fat diet (HFD) with or without quercetin (100 mg (kg·bw)-1 ) for 16 weeks, and carotid plaques from patients with carotid stenosis are collected for histopathological examinations and molecular mechanism assays. Quercetin significantly alleviates atherosclerotic lesions and reduces lipid retention caused by HFD. Proteomic technology identified Gal--3 increased by HFD but lowered by quercetin. Furthermore, immunofluorescence and immunohistochemistry exhibit higher expressions of Gal-3 and NLRP3 in carotid plaques and plaques from HFD-fed mice, which are concurrently down-regulated by quercetin. Similar to TD139, quercetin dramatically suppresses NLRP3 inflammasome activation in oxidized low-density lipoprotein-laden macrophages, and accordingly alleviates cellular steatosis and IL-1β secretion, which is abolished by recombinant Gal-3. Co-immunoprecipitation shows Gal-3 binding to NLRP3 promotes inflammasome activation. CONCLUSION: Gal-3 initiates inflammatory lesions by activating NLRP3 inflammasome which functions as a candidate target of quercetin exerting favorable anti-atherogenic effects. The findings highlight a promising strategy for atherosclerosis prevention and treatment by naturally-occurring quercetin.
Authors: Shuang Zhang; Yu Wang; Fang Lu; Shadi A D Mohammed; Hanxing Liu; Song Ding; Shu-Min Liu Journal: Front Pharmacol Date: 2022-04-05 Impact factor: 5.988
Authors: Sandra Maria Barbalho; Rosa Direito; Lucas Fornari Laurindo; Ledyane Taynara Marton; Elen Landgraf Guiguer; Ricardo de Alvares Goulart; Ricardo José Tofano; Antonely C A Carvalho; Uri Adrian Prync Flato; Viviane Alessandra Capelluppi Tofano; Cláudia Rucco Penteado Detregiachi; Patrícia C Santos Bueno; Raul S J Girio; Adriano Cressoni Araújo Journal: Antioxidants (Basel) Date: 2022-03-09