PMID- 18549674
OWN - NLM
STAT- MEDLINE
DCOM- 20081028
LR  - 20161124
IS  - 0022-3573 (Print)
IS  - 0022-3573 (Linking)
VI  - 60
IP  - 7
DP  - 2008 Jul
TI  - Activation of the Nrf2-antioxidant system by a novel cyclooxygenase-2 inhibitor 
      furan-2-yl-3-pyridin-2-yl-propenone: implication in anti-inflammatory function by 
      Nrf2 activator.
PG  - 879-87
LID - 10.1211/jpp.60.7.0009 [doi]
AB  - Furan-2-yl-3-pyridin-2-yl-propenone (FPP-3) is a novel synthetic compound and has 
      demonstrated anti-inflammatory activity by inhibiting cyclooxygenase-2 (COX-2). 
      It is widely accepted that reactive oxygen species (ROS) generated by activated 
      inflammatory cells can exacerbate inflammation. In this study, the potential 
      antioxidative efficacy of FPP-3 has been investigated in murine cells. FPP-3 
      increased the expression of multiple antioxidative enzymes, including 
      NAD(P)H:quinone oxidoreductase 1 (Nqo1), gamma-glutamylcysteine ligase (GCL) and 
      heme oxygenase-1 (HO-1), by facilitating the nuclear translocation of nuclear 
      factor-erythroid 2-p45-related factor 2 (Nrf2). Inducibility of antioxidant 
      proteins such as HO-1 were lost in nrf2-deficient murine fibroblasts. As a result 
      of enhanced cellular antioxidative capacity, elevation of NF-kappaB-driven 
      reporter gene expression by lipopolysaccharide was attenuated by FPP-3 treatment 
      in murine fibroblasts. Furthermore, FPP-3 treatment inhibited UVA-mediated 
      induction of COX-2 in murine keratinocytes. Our current study suggests that 
      FPP-3, which has been developed as a novel COX-2 inhibitor, has antioxidative 
      properties by activating the Nrf2-ARE pathway. The dual function of this compound 
      may provide a better strategy to block/attenuate the inflammation process and to 
      alleviate ROS-associated inflammatory complications.
FAU - Manandhar, Sarala
AU  - Manandhar S
AD  - College of Pharmacy, Yeungnam University, 214-1 Dae-dong, Gyeongsan-si, 
      Gyeongsangbuk-do 712-749, South Korea.
FAU - You, Aram
AU  - You A
FAU - Lee, Eung-Seok
AU  - Lee ES
FAU - Kim, Jung-Ae
AU  - Kim JA
FAU - Kwak, Mi-Kyoung
AU  - Kwak MK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Pharm Pharmacol
JT  - The Journal of pharmacy and pharmacology
JID - 0376363
RN  - 0 (1-furan-2-yl-3-pyridin-2-yl-propenone)
RN  - 0 (Antioxidants)
RN  - 0 (Cyclooxygenase 2 Inhibitors)
RN  - 0 (Furans)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, mouse)
RN  - 0 (Pyridines)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - T75W9911L6 (Propane)
SB  - IM
MH  - Animals
MH  - Antioxidants/*metabolism
MH  - Cells, Cultured
MH  - Cyclooxygenase 2 Inhibitors/*pharmacology
MH  - Furans/*pharmacology
MH  - Heme Oxygenase-1/physiology
MH  - Lipopolysaccharides/pharmacology
MH  - MAP Kinase Signaling System
MH  - Mice
MH  - NF-E2-Related Factor 2/*physiology
MH  - Propane/*analogs & derivatives/pharmacology
MH  - Pyridines/*pharmacology
MH  - Reactive Oxygen Species/metabolism
MH  - Response Elements
EDAT- 2008/06/14 09:00
MHDA- 2008/10/29 09:00
CRDT- 2008/06/14 09:00
PHST- 2008/06/14 09:00 [pubmed]
PHST- 2008/10/29 09:00 [medline]
PHST- 2008/06/14 09:00 [entrez]
AID - 10.1211/jpp.60.7.0009 [doi]
PST - ppublish
SO  - J Pharm Pharmacol. 2008 Jul;60(7):879-87. doi: 10.1211/jpp.60.7.0009.