10,11-Dehydrocurvularin attenuates inflammation by suppressing NLRP3 inflammasome activation.
10.1016/S1875-5364(23)60418-2
- Author:
Qun ZHAO
1
,
2
,
3
;
Mengyuan FENG
4
;
Shu JIN
5
;
Xiaobo LIU
5
;
Shengbao LI
5
;
Jian GUO
4
;
Xinran CHENG
4
;
Guangbiao ZHOU
6
;
Xianjun YU
7
,
8
Author Information
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.
4. 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.
5. Department of Gastroenterology, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China.
6. 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. Electronic address: gbzhou@cicams.ac.cn.
7. Department of Gastroenterology, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China
8. 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. Electronic address: xjyu@hbmu.edu.cn.
- Publication Type:Journal Article
- Keywords:
10,11-Dehydrocurvularin;
Inflammation;
NEK7-NLRP3 interaction;
NLRP3 inflammasome
- MeSH:
Animals;
Mice;
Inflammasomes;
NLR Family, Pyrin Domain-Containing 3 Protein/genetics*;
Inflammation/drug therapy*;
Anti-Inflammatory Agents/pharmacology*;
Interleukin-1beta/genetics*;
Mice, Inbred C57BL
- From:
Chinese Journal of Natural Medicines (English Ed.)
2023;21(3):163-171
- CountryChina
- Language:English
-
Abstract:
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-1β secretion 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.
