PMID- 26298161
OWN - NLM
STAT- MEDLINE
DCOM- 20160614
LR  - 20181113
IS  - 1420-908X (Electronic)
IS  - 1023-3830 (Linking)
VI  - 64
IP  - 10
DP  - 2015 Oct
TI  - NZ suppresses TLR4/NF-kappaB signalings and NLRP3 inflammasome activation in 
      LPS-induced RAW264.7 macrophages.
PG  - 799-808
LID - 10.1007/s00011-015-0863-4 [doi]
AB  - OBJECTIVE: The purpose of the present study was to evaluate the potential 
      therapeutic effects of NZ on lipopolysaccharide (LPS)-induced RAW264.7 cells and 
      explore its underlying mechanisms. METHODS: The effect of NZ on NO generation in 
      LPS-activated macrophage was measured by Griess assay. The concentrations of 
      TNF-alpha, IL-18, IL-1beta were analyzed with ELISA kits. The LPS-induced production of 
      reactive oxygen species (ROS) was determined by flow cytometry. The protein 
      expressions of TLR4, NF-kappaB and NLRP3 signaling pathway were investigated with 
      Western blot analysis. RESULTS: It was shown that NZ significantly reduced the 
      production of NO and the generation of pro-inflammatory cytokines in LPS-induced 
      RAW264.7 cells. In addition, NZ markedly inhibited the up-regulation of toll-like 
      receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and the activation 
      of nuclear factor kappa B (NF-kappaB) in LPS-stimulated RAW 264.7 macrophages. Of 
      note, NZ suppressed the expression of the inflammasome component such as NOD-like 
      receptor 3(NLRP3), apoptosis-associated speck-like protein containing CARD(ASC), 
      as well as the levels of cytokines including Interleukin-18(IL-18) and 
      Interleukin-1beta(IL-1beta). CONCLUSION: These results indicated that NZ inhibited the 
      generations of NO and pro-inflammatory cytokines by suppressing TLR4/MyD88/NF-kappaB 
      pathway, suggesting that NZ could be an effective candidate for ameliorating 
      LPS-induced inflammatory responses.
FAU - Xiang, Pengjun
AU  - Xiang P
AD  - State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 
      24 Tongjiaxiang, Nanjing, 210009, China.
FAU - Chen, Tong
AU  - Chen T
AD  - State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 
      24 Tongjiaxiang, Nanjing, 210009, China.
FAU - Mou, Yi
AU  - Mou Y
AD  - State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 
      24 Tongjiaxiang, Nanjing, 210009, China.
FAU - Wu, Hui
AU  - Wu H
AD  - State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 
      24 Tongjiaxiang, Nanjing, 210009, China.
FAU - Xie, Peng
AU  - Xie P
AD  - State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 
      24 Tongjiaxiang, Nanjing, 210009, China.
FAU - Lu, Guo
AU  - Lu G
AD  - State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 
      24 Tongjiaxiang, Nanjing, 210009, China.
FAU - Gong, Xiaojian
AU  - Gong X
AD  - State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 
      24 Tongjiaxiang, Nanjing, 210009, China.
FAU - Hu, Qinghua
AU  - Hu Q
AD  - State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 
      24 Tongjiaxiang, Nanjing, 210009, China.
FAU - Zhang, Yihua
AU  - Zhang Y
AD  - State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 
      24 Tongjiaxiang, Nanjing, 210009, China.
FAU - Ji, Hui
AU  - Ji H
AD  - State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 
      24 Tongjiaxiang, Nanjing, 210009, China. huijicpu@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150823
PL  - Switzerland
TA  - Inflamm Res
JT  - Inflammation research : official journal of the European Histamine Research 
      Society ... [et al.]
JID - 9508160
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cytokines)
RN  - 0 (Inflammasomes)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (NF-kappa B)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, mouse)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (olean-28-13beta-olide-2)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 6SMK8R7TGJ (Oleanolic Acid)
RN  - EC 3.4.22.36 (Caspase 1)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
MH  - Carrier Proteins/*drug effects
MH  - Caspase 1/metabolism
MH  - Cell Survival/drug effects
MH  - Cytokines/metabolism
MH  - Inflammasomes/*drug effects
MH  - Lipopolysaccharides/pharmacology
MH  - Mice
MH  - Myeloid Differentiation Factor 88/biosynthesis
MH  - NF-kappa B/*antagonists & inhibitors
MH  - NLR Family, Pyrin Domain-Containing 3 Protein
MH  - Nitric Oxide/metabolism
MH  - Oleanolic Acid/analogs & derivatives/pharmacology
MH  - RAW 264.7 Cells
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction/*drug effects
MH  - Toll-Like Receptor 4/*antagonists & inhibitors
OTO - NOTNLM
OT  - LPS
OT  - NF-kappaB
OT  - NLRP3
OT  - NO
OT  - NZ
OT  - RAW264.7
EDAT- 2015/08/25 06:00
MHDA- 2016/06/15 06:00
CRDT- 2015/08/24 06:00
PHST- 2015/06/28 00:00 [received]
PHST- 2015/07/30 00:00 [accepted]
PHST- 2015/07/29 00:00 [revised]
PHST- 2015/08/24 06:00 [entrez]
PHST- 2015/08/25 06:00 [pubmed]
PHST- 2016/06/15 06:00 [medline]
AID - 10.1007/s00011-015-0863-4 [pii]
AID - 10.1007/s00011-015-0863-4 [doi]
PST - ppublish
SO  - Inflamm Res. 2015 Oct;64(10):799-808. doi: 10.1007/s00011-015-0863-4. Epub 2015 
      Aug 23.