PMID- 31539844
OWN - NLM
STAT- MEDLINE
DCOM- 20210520
LR  - 20210520
IS  - 1096-0023 (Electronic)
IS  - 1043-4666 (Linking)
VI  - 125
DP  - 2020 Jan
TI  - 6-Gingerol attenuates macrophages pyroptosis via the inhibition of MAPK signaling 
      pathways and predicts a good prognosis in sepsis.
PG  - 154854
LID - S1043-4666(19)30283-2 [pii]
LID - 10.1016/j.cyto.2019.154854 [doi]
AB  - BACKGROUND: Sepsis is a major cause of death for ICU patients. Sepsis development 
      depends heavily on the presence of mature IL-1beta cytokine. This study evaluates 
      the potential therapeutic properties of a bioactive compound known as 6-gingerol 
      on sepsis. This compound has previously been demonstrated to possess 
      anti-inflammatory properties both in vivo and in vitro. METHODS: C57BL/6 mice was 
      used to establish models of sepsis by means of cecal ligation and puncture (CLP). 
      Upon treatment with 6-gingerol, we assessed the survival rate of mice and 
      measured the levels of key pro-inflammatory cytokines in serum and colon tissues. 
      Sepsis pathogenesis was further explored using the RAW264.7 cell line and bone 
      marrow-derived macrophages (BMDMs) treated with ATP and lipopolysaccharide (LPS). 
      The impact of 6-gingerol on pyroptosis was also examined. In addition, we 
      assessed the role of MAPK signaling in 6-gingerol-induced effects in BMDMs and 
      RAW264.7 cells. RESULTS: In CLP mice, 6-gingerol significantly ameliorated sepsis 
      development, which was associated with the reduction of serum IL-1beta. In BMDMs and 
      RAW264.7 cells, 6-gingerol strongly attenuated pyroptosis as well as the release 
      of caspase-1p20, HMGB1, mature IL-1beta, IL-18 in response to ATP and LPS treatment. 
      6-Gingerol conferred these effects by blocking MAPK activation. Exposure to an 
      ERK agonist (EGF) reversed effects of 6-gingerol, causing pyroptosis, LDH and 
      caspase-1p20 release. CONCLUSIONS: By targeting MAPK signaling, 6-gingerol 
      significantly suppressed secretion of pro-inflammatory cytokines and inhibited 
      macrophage cells pyroptosis resulting in overall inhibition of sepsis 
      development.
CI  - Copyright (c) 2019 Elsevier Ltd. All rights reserved.
FAU - Zhang, Fang-Ling
AU  - Zhang FL
AD  - Department of Anesthesiology, Nanfang Hospital, Southern Medical University, 
      Guangzhou 510515, China.
FAU - Zhou, Bo-Wei
AU  - Zhou BW
AD  - Department of Anesthesiology, Nanfang Hospital, Southern Medical University, 
      Guangzhou 510515, China.
FAU - Yan, Zheng-Zheng
AU  - Yan ZZ
AD  - Department of Anesthesiology, Nanfang Hospital, Southern Medical University, 
      Guangzhou 510515, China.
FAU - Zhao, Jin
AU  - Zhao J
AD  - Department of Anesthesiology, Nanfang Hospital, Southern Medical University, 
      Guangzhou 510515, China.
FAU - Zhao, Bing-Cheng
AU  - Zhao BC
AD  - Department of Anesthesiology, Nanfang Hospital, Southern Medical University, 
      Guangzhou 510515, China.
FAU - Liu, Wei-Feng
AU  - Liu WF
AD  - Department of Anesthesiology, Nanfang Hospital, Southern Medical University, 
      Guangzhou 510515, China.
FAU - Li, Cai
AU  - Li C
AD  - Department of Anesthesiology, Nanfang Hospital, Southern Medical University, 
      Guangzhou 510515, China.
FAU - Liu, Ke-Xuan
AU  - Liu KX
AD  - Department of Anesthesiology, Nanfang Hospital, Southern Medical University, 
      Guangzhou 510515, China. Electronic address: liukexuan705@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190917
PL  - England
TA  - Cytokine
JT  - Cytokine
JID - 9005353
RN  - 0 (Catechols)
RN  - 0 (Cytokines)
RN  - 0 (Fatty Alcohols)
RN  - 0 (HMGB1 Protein)
RN  - 0 (HMGB1 protein, mouse)
RN  - 0 (Interleukin-18)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Lipopolysaccharides)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - 925QK2Z900 (gingerol)
RN  - EC 3.4.22.36 (Casp1 protein, mouse)
RN  - EC 3.4.22.36 (Caspase 1)
SB  - IM
MH  - Adenosine Triphosphate/pharmacology
MH  - Animals
MH  - Caspase 1/metabolism
MH  - Catechols/*pharmacology/therapeutic use
MH  - Cytokines/*blood/metabolism
MH  - Disease Models, Animal
MH  - Epidermal Growth Factor/pharmacology
MH  - Fatty Alcohols/*pharmacology/therapeutic use
MH  - HMGB1 Protein
MH  - Interleukin-18/metabolism
MH  - Interleukin-1beta/blood
MH  - Lipopolysaccharides/pharmacology
MH  - MAP Kinase Signaling System/drug effects/immunology
MH  - Macrophages/*drug effects/immunology/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Prognosis
MH  - Pyroptosis/*drug effects
MH  - RAW 264.7 Cells
MH  - Sepsis/*drug therapy/metabolism/physiopathology
OTO - NOTNLM
OT  - 6-Gingerol
OT  - Cecal ligation and puncture
OT  - IL-1beta
OT  - Pyroptosis
OT  - Sepsis
EDAT- 2019/09/21 06:00
MHDA- 2021/05/21 06:00
CRDT- 2019/09/21 06:00
PHST- 2019/03/02 00:00 [received]
PHST- 2019/09/04 00:00 [revised]
PHST- 2019/09/08 00:00 [accepted]
PHST- 2019/09/21 06:00 [pubmed]
PHST- 2021/05/21 06:00 [medline]
PHST- 2019/09/21 06:00 [entrez]
AID - S1043-4666(19)30283-2 [pii]
AID - 10.1016/j.cyto.2019.154854 [doi]
PST - ppublish
SO  - Cytokine. 2020 Jan;125:154854. doi: 10.1016/j.cyto.2019.154854. Epub 2019 Sep 17.