10,11-Dehydrocurvularin attenuates inflammation by suppressing NLRP3 inflammasome activation  

作　　者：ZHAO Qun FENG Mengyuan JIN Shu LIU Xiaobo LI Shengbao GUO Jian CHENG Xinran ZHOU Guangbiao YU Xianjun 

机构地区：[1]State Key Laboratory of Molecular Oncology,National Cancer Center,National Clinical Research Center for Cancer,Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021,China [2]Department of Gastroenterology,Taihe Hospital,Hubei University of Medicine,Shiyan 442000,China [3]Laboratory of Inflammation and Molecular Pharmacology,School of Basic Medical Sciences&Biomedical Research Institute,School of Pharmacy,Hubei Key Laboratory of Wudang Local Chinese Medicine Research,Hubei University of Medicine,Shiyan 442000,China

出　　处：《Chinese Journal of Natural Medicines》2023年第3期163-171,共9页中国天然药物（英文版）

基　　金：the National Natural Science Foundation of China(No.81902852);China Postdoctoral Science Foundation(No.2020M670220);the Natural Science Foundation of Hubei Province of China(No.2022CFB481);the Natural Science Foundation of Hubei Provincial Department of Education(No.T2022021);Wudang Local Chinese Medicine Research of Hubei University of Medicine(No.WDCM2020004).

摘　　要：10,11-Dehydrocurvularin(DCV)is a natural-product macrolide that has been shown to exert anti-inflammatory activity.However,the underlying mechanism of its anti-inflammatory activity remains poorly understood.Aberrant activation of the NLRP3 inflammasome is involved in diverse inflammation-related diseases,which should be controlled.The results showed that DCV specifically inhibited the activation of the NLRP3 inflammasome in association with reduced IL-1βsecretion and caspase-1 activation,without effect on the NLRC4 and AIM2 inflammasomes.Furthermore,DCV disturbed the interaction between NEK7 and NLRP3,resulting in the inhibition of NLRP3 inflammasome activation.The C=C double bond of DCV was required for the NLRP3 inflammasome inhibition induced by DCV.Importantly,DCV ameliorated inflammation in vivo through inhibiting the NLRP3 inflammasome.Taken together,our study reveals a novel mechanism by which DCV suppresses inflammation,which indicates the potential role of DCV in NLRP3 inflammasome-driven inflammatory disorders.

关 键 词：10 11-Dehydrocurvularin INFLAMMATION NLRP3 inflammasome NEK7-NLRP3 interaction 

分 类 号：R965[医药卫生—药理学]