PMID- 34047713
OWN - NLM
STAT- MEDLINE
DCOM- 20220117
LR  - 20220117
IS  - 1479-6813 (Electronic)
IS  - 0952-5041 (Linking)
VI  - 67
IP  - 2
DP  - 2021 Jun 21
TI  - NLRP3 inflammasome inhibitor cucurbitacin B suppresses gout arthritis in mice.
PG  - 27-40
LID - 10.1530/JME-20-0305 [doi]
AB  - Gouty arthritis is a common inflammatory disease characterized by monosodium 
      urate (MSU) crystal-induced nucleotide-binding oligomerization domain (NOD)-like 
      receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome activation 
      with upregulated caspase 1 protease and IL-1beta in macrophages. Cucurbitacin B 
      (CuB) is a tetracyclic triterpene that possesses a potential anti-inflammatory 
      activity. However, the immunomodulatory and anti-inflammatory effects of CuB on 
      gout have not been well characterized. Therefore, the purpose of the present 
      study was to determine whether CuB exhibits anti-inflammatory effects on gout and 
      to analyze the underlying molecular mechanism. We examined the effects of CuB on 
      various stimuli-activated bone marrow-derived macrophages (BMDMs) and in a mouse 
      model with MSU-induced acute gouty arthritis. Our results demonstrated that CuB 
      effectively suppressed multiple stimuli-activated IL-1beta secretion by interrupting 
      NLRP3 inflammasome complex formation, inhibiting NLRP3 inflammasome activation 
      and suppressing key enzymes of glycolysis in macrophages. Consistent with this, 
      CuB pretreatment also ameliorated MSU-induced arthritis in vivo models of gout 
      arthritis, manifested by reduced foot swelling and inflammatory cell 
      infiltration. Taken together, our data provide the evidence that CuB is an NLRP3 
      inflammasome inhibitor with therapeutic potential for treating NLRP3 
      inflammasome-mediated diseases, especially gouty arthritis.
FAU - Xue, Ying
AU  - Xue Y
AD  - Department of Endocrinology, Tongji, Hospital, School of Medicine, Tongji 
      University, Shanghai, China.
FAU - Li, Ran
AU  - Li R
AD  - Department of Endocrinology, Tongji, Hospital, School of Medicine, Tongji 
      University, Shanghai, China.
FAU - Fang, Ping
AU  - Fang P
AD  - Department of Endocrinology, Tongji, Hospital, School of Medicine, Tongji 
      University, Shanghai, China.
FAU - Ye, Zheng-Qin
AU  - Ye ZQ
AD  - Department of Endocrinology, Tongji, Hospital, School of Medicine, Tongji 
      University, Shanghai, China.
FAU - Zhao, Yong
AU  - Zhao Y
AD  - Department of Endocrinology, Tongji, Hospital, School of Medicine, Tongji 
      University, Shanghai, China.
FAU - Zhou, Yun
AU  - Zhou Y
AD  - Department of Endocrinology, Tongji, Hospital, School of Medicine, Tongji 
      University, Shanghai, China.
FAU - Zhang, Ke-Qin
AU  - Zhang KQ
AD  - Department of Endocrinology, Tongji, Hospital, School of Medicine, Tongji 
      University, Shanghai, China.
FAU - Li, Ling
AU  - Li L
AD  - Department of Endocrinology, Tongji, Hospital, School of Medicine, Tongji 
      University, Shanghai, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210621
PL  - England
TA  - J Mol Endocrinol
JT  - Journal of molecular endocrinology
JID - 8902617
RN  - 0 (Biomarkers)
RN  - 0 (Inflammasomes)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Triterpenes)
RN  - 0115W5MABF (cucurbitacin B)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Arthritis, Gouty/drug therapy/etiology/*metabolism/pathology
MH  - Biomarkers
MH  - Disease Models, Animal
MH  - Disease Susceptibility
MH  - Glycolysis
MH  - Gout/drug therapy/etiology/metabolism/pathology
MH  - Inflammasomes/*antagonists & inhibitors/*metabolism
MH  - Interleukin-1beta/metabolism
MH  - Lipopolysaccharides/adverse effects
MH  - Macrophage Activation/drug effects/immunology
MH  - Macrophages/drug effects/immunology/metabolism
MH  - Male
MH  - Mice
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/*metabolism
MH  - Toll-Like Receptor 4/metabolism
MH  - Triterpenes/*pharmacology
OTO - NOTNLM
OT  - NLRP3
OT  - cucurbitacin B
OT  - glycolysis
OT  - gouty arthritis
EDAT- 2021/05/29 06:00
MHDA- 2022/01/18 06:00
CRDT- 2021/05/28 12:13
PHST- 2021/04/25 00:00 [received]
PHST- 2021/05/19 00:00 [accepted]
PHST- 2021/05/29 06:00 [pubmed]
PHST- 2022/01/18 06:00 [medline]
PHST- 2021/05/28 12:13 [entrez]
AID - JME-20-0305.R2 [pii]
AID - 10.1530/JME-20-0305 [doi]
PST - epublish
SO  - J Mol Endocrinol. 2021 Jun 21;67(2):27-40. doi: 10.1530/JME-20-0305.