期刊
ACTA PHARMACEUTICA SINICA B
卷 11, 期 5, 页码 1200-1212出版社
INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
DOI: 10.1016/j.apsb.2020.12.008
关键词
Metabolic syndrome; Celastrol; CAP1; Resistin; Inflammation
资金
- National Natural Science Foundation of China [81673436, 91853109, 81872877, 81872838]
- Natural Science Foundation of Jiangsu Province, China [BK20180079]
- Mountain-Climbing Talents Project of Nanjing University (China)
Celastrol improves metabolic syndrome induced by high fat diet by targeting CAP1 and suppressing resistin-induced inflammation, suggesting its potential as a promising drug candidate for treating inflammatory metabolic diseases.
Metabolic syndrome is a clustering of metabolic disorder with unclear molecular mechanism. Increasing studies have found that the pathogenesis and progression of metabolic syndrome are closely related to inflammation. Here, we report celastrol, a traditional Chinese medicine, can improve high fat diet-induced metabolic syndrome through suppressing resistin-induced inflammation. Mechanistically, celastrol binds to adenylyl cyclase associated protein 1 (CAP1) and inhibits the interaction between CAP1 and resistin, which restrains the cyclic adenylate monophosphate (cAMP)-protein kinase A (PKA)-nuclear factor kappa-B (NF-kB) signaling pathway and ameliorates high fat diet-induced murine metabolic syndrome. Knockdown of CAP1 in macrophages abrogated the resistin-mediated inflammatory activity. In contrast, overexpression of CAP1 in macrophages aggravated inflammation. Taken together, our study identifies celastrol, which directly targets CAP1 in macrophages, might be a promising drug candidate for the treatment of inflammatory metabolic diseases, such as metabolic syndrome. (C) 2021 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
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