PMID- 25091623
OWN - NLM
STAT- MEDLINE
DCOM- 20150609
LR  - 20211203
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 22
IP  - 2
DP  - 2014 Oct
TI  - The anti-inflammatory effect of 3-deoxysappanchalcone is mediated by inducing 
      heme oxygenase-1 via activating the AKT/mTOR pathway in murine macrophages.
PG  - 420-6
LID - S1567-5769(14)00302-6 [pii]
LID - 10.1016/j.intimp.2014.07.025 [doi]
AB  - 3-Deoxysappanchalcone (3-DSC), isolated from Caesalpinia sappan (Leguminosae), is 
      a chalcone that exerts a variety of pharmacological activities. In the present 
      study, we demonstrated that 3-DSC exerts anti-inflammatory activity in murine 
      macrophages by inducing heme oxygenase-1 (HO-1) expression at the translational 
      level. Treatment of RAW264.7 cells with 3-DSC induced HO-1 protein expression in 
      a dose- and time-dependent manner without affecting HO-1 mRNA expression. 
      Mitogen-activated protein kinase inhibitors or actinomycin D, a transcriptional 
      inhibitor, did not block 3-DSC-mediated HO-1 induction. However, 3-DSC-mediated 
      HO-1 induction was completely blocked by treatment with cycloheximide, a 
      translational inhibitor, or rapamycin, an inhibitor of the mammalian target of 
      rapamycin (mTOR). Strikingly, 3-DSC increased the phosphorylation level of mTOR 
      downstream target molecules such as eukaryotic translation initiation factor 
      4E-binding protein 1 (4E-BP1) and S6 kinase 1 (S6K1), as well as AKT in a dose- 
      and time-dependent manner, suggesting that the 3-DSC induces HO-1 expression by 
      activating the AKT/mTOR pathway. Consistent with the notion that HO-1 has 
      anti-inflammatory properties, 3-DSC inhibited the production of nitric oxide (NO) 
      and interleukin (IL)-6 in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. 
      Inhibition of HO-1 activity by treatment with tin protoporphyrin IX, a specific 
      HO-1 inhibitor, abrogated the inhibitory effects of 3-DSC on the production of NO 
      and IL-6 in LPS-stimulated RAW264.7 cells. Taken together, 3-DSC may be an 
      effective HO-1 inducer at the translational level that has anti-inflammatory 
      effects, and a valuable compound for modulating inflammatory conditions.
CI  - Copyright (c) 2014 Elsevier B.V. All rights reserved.
FAU - Kim, Jun-Hyeong
AU  - Kim JH
AD  - Department of Biochemistry, College of Natural Sciences, Kangwon National 
      University, Chuncheon, Gangwon-Do 200-701, Republic of Korea.
FAU - Choo, Young-Yeon
AU  - Choo YY
AD  - Department of Biochemistry, College of Natural Sciences, Kangwon National 
      University, Chuncheon, Gangwon-Do 200-701, Republic of Korea.
FAU - Tae, Nara
AU  - Tae N
AD  - Department of Biochemistry, College of Natural Sciences, Kangwon National 
      University, Chuncheon, Gangwon-Do 200-701, Republic of Korea.
FAU - Min, Byung-Sun
AU  - Min BS
AD  - College of Pharmacy, Catholic University of Daegu, Gyeongsan 712-702, Republic of 
      Korea.
FAU - Lee, Jeong-Hyung
AU  - Lee JH
AD  - Department of Biochemistry, College of Natural Sciences, Kangwon National 
      University, Chuncheon, Gangwon-Do 200-701, Republic of Korea. Electronic address: 
      jhlee36@kangwon.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140801
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Chalcones)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Membrane Proteins)
RN  - 0 (RNA, Messenger)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 1.14.14.18 (Hmox1 protein, mouse)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - LHE9JFQ1U8 (3-deoxysappanchalcone)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Caesalpinia
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Chalcones/*pharmacology
MH  - Heme Oxygenase-1/genetics/*metabolism
MH  - Lipopolysaccharides
MH  - Macrophages/*drug effects/metabolism
MH  - Membrane Proteins/genetics/*metabolism
MH  - Mice, Inbred C57BL
MH  - Nitric Oxide/metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
OTO - NOTNLM
OT  - 3-Deoxysappanchalcone
OT  - Anti-inflammatory effect
OT  - Heme oxygenase-1
OT  - Translation
OT  - mTOR
EDAT- 2014/08/06 06:00
MHDA- 2015/06/10 06:00
CRDT- 2014/08/06 06:00
PHST- 2014/02/17 00:00 [received]
PHST- 2014/06/09 00:00 [revised]
PHST- 2014/07/22 00:00 [accepted]
PHST- 2014/08/06 06:00 [entrez]
PHST- 2014/08/06 06:00 [pubmed]
PHST- 2015/06/10 06:00 [medline]
AID - S1567-5769(14)00302-6 [pii]
AID - 10.1016/j.intimp.2014.07.025 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2014 Oct;22(2):420-6. doi: 10.1016/j.intimp.2014.07.025. 
      Epub 2014 Aug 1.