PMID- 32312957
OWN - NLM
STAT- MEDLINE
DCOM- 20210329
LR  - 20210420
IS  - 2041-4889 (Electronic)
VI  - 11
IP  - 4
DP  - 2020 Apr 20
TI  - Carnosol inhibits inflammasome activation by directly targeting HSP90 to treat 
      inflammasome-mediated diseases.
PG  - 252
LID - 10.1038/s41419-020-2460-x [doi]
LID - 252
AB  - Aberrant activation of inflammasomes, a group of protein complexes, is pathogenic 
      in a variety of metabolic and inflammation-related diseases. Here, we report that 
      carnosol inhibits NLRP3 inflammasome activation by directly targeting heat-shock 
      protein 90 (HSP90), which is essential for NLRP3 inflammasome activity, thereby 
      treating inflammasome-mediated diseases. Our data demonstrate that carnosol 
      inhibits NLRP3 inflammasome activation in primary mouse bone marrow-derived 
      macrophages (BMDMs), THP-1 cells and human peripheral blood mononuclear cells 
      (hPBMCs). Mechanistically, carnosol inhibits inflammasome activation by binding 
      to HSP90 and then inhibiting its ATPase activity. In vivo, our results show that 
      carnosol has remarkable therapeutic effects in mouse models of NLRP3 
      inflammasome-mediated diseases, including endotoxemia and nonalcoholic 
      steatohepatitis (NASH). Our data also suggest that intraperitoneal administration 
      of carnosol (120 mg/kg) once daily for two weeks is well tolerated in mice. Thus, 
      our study reveals the inhibitory effect of carnosol on inflammasome activation 
      and demonstrates that carnosol is a safe and effective candidate for the 
      treatment of inflammasome-mediated diseases.
FAU - Shi, Wei
AU  - Shi W
AD  - China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese 
      PLA General Hospital, Beijing, 100039, China.
AD  - School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, 
      330004, China.
FAU - Xu, Guang
AU  - Xu G
AD  - China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese 
      PLA General Hospital, Beijing, 100039, China.
FAU - Zhan, Xiaoyan
AU  - Zhan X
AD  - Integrative Medical Centre, The Fifth Medical Centre, Chinese PLA General 
      Hospital, Beijing, 100039, China.
FAU - Gao, Yuan
AU  - Gao Y
AD  - China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese 
      PLA General Hospital, Beijing, 100039, China.
AD  - School of Traditional Chinese Medicine, Capital Medical University, Beijing, 
      100069, China.
FAU - Wang, Zhilei
AU  - Wang Z
AD  - China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese 
      PLA General Hospital, Beijing, 100039, China.
AD  - School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 
      611137, China.
FAU - Fu, Shubin
AU  - Fu S
AD  - China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese 
      PLA General Hospital, Beijing, 100039, China.
FAU - Qin, Nan
AU  - Qin N
AD  - China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese 
      PLA General Hospital, Beijing, 100039, China.
FAU - Hou, Xiaorong
AU  - Hou X
AD  - China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese 
      PLA General Hospital, Beijing, 100039, China.
FAU - Ai, Yongqiang
AU  - Ai Y
AD  - China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese 
      PLA General Hospital, Beijing, 100039, China.
AD  - School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, 
      330004, China.
FAU - Wang, Chunyu
AU  - Wang C
AD  - China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese 
      PLA General Hospital, Beijing, 100039, China.
FAU - He, Tingting
AU  - He T
AD  - Integrative Medical Centre, The Fifth Medical Centre, Chinese PLA General 
      Hospital, Beijing, 100039, China.
FAU - Liu, Hongbin
AU  - Liu H
AD  - China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese 
      PLA General Hospital, Beijing, 100039, China.
FAU - Chen, Yuanyuan
AU  - Chen Y
AD  - China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese 
      PLA General Hospital, Beijing, 100039, China.
FAU - Liu, Yan
AU  - Liu Y
AD  - China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese 
      PLA General Hospital, Beijing, 100039, China.
FAU - Wang, Jiabo
AU  - Wang J
AD  - China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese 
      PLA General Hospital, Beijing, 100039, China.
FAU - Niu, Ming
AU  - Niu M
AD  - China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese 
      PLA General Hospital, Beijing, 100039, China.
FAU - Guo, Yuming
AU  - Guo Y
AD  - Integrative Medical Centre, The Fifth Medical Centre, Chinese PLA General 
      Hospital, Beijing, 100039, China.
FAU - Xiao, Xiaohe
AU  - Xiao X
AD  - Integrative Medical Centre, The Fifth Medical Centre, Chinese PLA General 
      Hospital, Beijing, 100039, China. pharmacy_302@126.com.
FAU - Bai, Zhaofang
AU  - Bai Z
AD  - China Military Institute of Chinese Materia, The Fifth Medical Centre, Chinese 
      PLA General Hospital, Beijing, 100039, China. baizf2008@hotmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200420
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Abietanes)
RN  - 0 (HSP90 Heat-Shock Proteins)
RN  - 0 (Inflammasomes)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 483O455CKD (carnosol)
SB  - IM
MH  - Abietanes/*pharmacology
MH  - Animals
MH  - HSP90 Heat-Shock Proteins/*drug effects/metabolism
MH  - Humans
MH  - Inflammasomes/*drug effects/metabolism
MH  - Inflammation/drug therapy/pathology
MH  - Leukocytes, Mononuclear/*drug effects/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages/drug effects/metabolism
MH  - Mice, Inbred C57BL
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/drug effects/metabolism
PMC - PMC7170921
COIS- The authors declare that they have no conflict of interest.
EDAT- 2020/04/22 06:00
MHDA- 2021/03/30 06:00
PMCR- 2020/04/20
CRDT- 2020/04/22 06:00
PHST- 2019/11/25 00:00 [received]
PHST- 2020/04/08 00:00 [accepted]
PHST- 2020/04/04 00:00 [revised]
PHST- 2020/04/22 06:00 [entrez]
PHST- 2020/04/22 06:00 [pubmed]
PHST- 2021/03/30 06:00 [medline]
PHST- 2020/04/20 00:00 [pmc-release]
AID - 10.1038/s41419-020-2460-x [pii]
AID - 2460 [pii]
AID - 10.1038/s41419-020-2460-x [doi]
PST - epublish
SO  - Cell Death Dis. 2020 Apr 20;11(4):252. doi: 10.1038/s41419-020-2460-x.