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.
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).
