PMID- 27261558
OWN - NLM
STAT- MEDLINE
DCOM- 20170417
LR  - 20170417
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 38
DP  - 2016 Sep
TI  - Resokaempferol-mediated anti-inflammatory effects on activated macrophages via 
      the inhibition of JAK2/STAT3, NF-kappaB and JNK/p38 MAPK signaling pathways.
PG  - 104-14
LID - S1567-5769(16)30197-7 [pii]
LID - 10.1016/j.intimp.2016.05.010 [doi]
AB  - The excessive or prolonged production of inflammatory mediators can result in 
      numerous chronic diseases, such as rheumatoid arthritis, atherosclerosis, 
      diabetes, and cancer. Therefore, for many inflammatory-related diseases, 
      pharmaceutical intervention is required to restrain the excessive release of such 
      inflammatory mediators. Novel therapeutics and mechanistic insight are sought for 
      the management of chronic inflammatory diseases. Resokaempferol (RES) is a type 
      of flavonoid recently reported to demonstrate anti-cancer properties. However, 
      the anti-inflammatory capacity of RES has not been studied to date. Therefore, 
      this study investigated whether RES is capable of suppressing the inflammatory 
      response to lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and the 
      mechanism by which this is achieved. We found that RES attenuated the LPS-induced 
      production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), 
      cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), interleukin (IL)-1beta, tumor 
      necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein 1 (MCP-1) and IL-6. RES 
      also inhibited the nuclear translocation of signal transducer and activator of 
      transcription (STAT) 3 and reduced the LPS-mediated phosphorylation of Janus 
      kinase (JAK) 2 and STAT3 at the sites of Ser727 and Tyr705. RES also inhibited 
      the activation of NF-kappaB and JNK/p38 MAPK signaling pathways in LPS-induced 
      RAW264.7 cells. Additionally, RES inhibited the activation of the JAK2/STAT3 
      pathway in exogenous IL-6-activated RAW264.7 macrophages. We conclude that RES 
      inhibits the inflammatory response in activated macrophages by blocking the 
      activation of the JAK2/STAT3 pathway by both LPS and IL-6 signaling.
CI  - Copyright (c) 2016 Elsevier B.V. All rights reserved.
FAU - Yu, Qian
AU  - Yu Q
AD  - Research Studio of Integration of Traditional and Western Medicine, First 
      Hospital, Peking University, Beijing 100034, China.
FAU - Zeng, KeWu
AU  - Zeng K
AD  - State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical 
      Sciences, Peking University, Beijing 100191, China.
FAU - Ma, XiaoLi
AU  - Ma X
AD  - State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical 
      Sciences, Peking University, Beijing 100191, China.
FAU - Song, FangJiao
AU  - Song F
AD  - Research Studio of Integration of Traditional and Western Medicine, First 
      Hospital, Peking University, Beijing 100034, China.
FAU - Jiang, Yong
AU  - Jiang Y
AD  - State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical 
      Sciences, Peking University, Beijing 100191, China.
FAU - Tu, PengFei
AU  - Tu P
AD  - State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical 
      Sciences, Peking University, Beijing 100191, China. Electronic address: 
      pengfeitu@vip.163.com.
FAU - Wang, XueMei
AU  - Wang X
AD  - Research Studio of Integration of Traditional and Western Medicine, First 
      Hospital, Peking University, Beijing 100034, China. Electronic address: 
      wangxuemeibjmu@163.com.
LA  - eng
PT  - Journal Article
DEP - 20160601
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (5-deoxykaempferol)
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cytokines)
RN  - 0 (Flavonoids)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-6)
RN  - 0 (Kaempferols)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, mouse)
RN  - EC 2.7.10.2 (Jak2 protein, mouse)
RN  - EC 2.7.10.2 (Janus Kinase 2)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Cytokines/metabolism
MH  - Flavonoids/*pharmacology
MH  - Inflammation Mediators/metabolism
MH  - Interleukin-6/immunology
MH  - Janus Kinase 2/*metabolism
MH  - Kaempferols/*pharmacology
MH  - Lipopolysaccharides/immunology
MH  - MAP Kinase Kinase 4/metabolism
MH  - Macrophages/*drug effects/immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred ICR
MH  - NF-kappa B/metabolism
MH  - RAW 264.7 Cells
MH  - STAT3 Transcription Factor/*metabolism
MH  - Signal Transduction/drug effects
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
OTO - NOTNLM
OT  - Inflammation
OT  - JAK2/STAT3
OT  - MAPK
OT  - NF-kappaB
OT  - Resokaempferol
EDAT- 2016/06/05 06:00
MHDA- 2017/04/18 06:00
CRDT- 2016/06/05 06:00
PHST- 2015/11/27 00:00 [received]
PHST- 2016/05/16 00:00 [revised]
PHST- 2016/05/16 00:00 [accepted]
PHST- 2016/06/05 06:00 [entrez]
PHST- 2016/06/05 06:00 [pubmed]
PHST- 2017/04/18 06:00 [medline]
AID - S1567-5769(16)30197-7 [pii]
AID - 10.1016/j.intimp.2016.05.010 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2016 Sep;38:104-14. doi: 10.1016/j.intimp.2016.05.010. Epub 
      2016 Jun 1.