PMID- 23747519
OWN - NLM
STAT- MEDLINE
DCOM- 20140328
LR  - 20161125
IS  - 1089-8611 (Electronic)
IS  - 1089-8603 (Linking)
VI  - 33
DP  - 2013 Sep 1
TI  - PG201 downregulates the production of nitrite by upregulating heme oxygenase-1 
      expression through the control of phosphatidylinositol 3-kinase and NF-E2-related 
      factor 2.
PG  - 42-55
LID - S1089-8603(13)00154-7 [pii]
LID - 10.1016/j.niox.2013.05.003 [doi]
AB  - PG201 is an ethanol extract prepared from a specially designed botanical 
      formulation and has previously been shown to contain strong anti-arthritic 
      activities by controlling inflammation and cartilage destruction in two animal 
      models [1,2]. In the present study, we evaluated the effects of PG201 on the 
      expression of heme oxygenase-1 (HO-1). The treatment of Raw264.7 cells (a murine 
      macrophage cell line) and bone marrow-derived macrophages (BMDMs) with PG201 
      increased the protein and RNA levels of HO-1. The results from a reporter plasmid 
      assay indicated that PG201 induced HO-1 promoter activity through the stress 
      response element present in the two enhancers of the HO-1 promoter. The treatment 
      of cells with PG201 increased the total amount and the nuclear level of 
      NF-E2-related factor 2 (Nrf2). Protein analysis using BMDMs from Nrf2 knockout 
      mice showed that Nrf2 was necessary for the PG201-mediated induction of HO-1 
      expression. The PG201-mediated induction of these anti-oxidative stress factors 
      was inhibited by a specific inhibitor of phosphatidylinositol 3-kinase (PI3K), 
      but not by inhibitors of p38, ERK and JNK mitogen-activated protein kinases. 
      Furthermore, the results from an experiment involving a specific siRNA and 
      chemical inhibitors for HO-1 showed that the PG201-mediated increase of the HO-1 
      protein contributed to the suppression of inducible nitric oxide synthase (iNOS) 
      and nitrite production stimulated by lipopolysaccharide. Taken together, these 
      results suggest that PG201 activates Nrf2 through the PI3K signal transduction 
      pathway, increases the expression of HO-1, and subsequently decreases the 
      production of iNOS and nitrite, eventually exerting anti-inflammatory activities.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Choi, Jinyong
AU  - Choi J
AD  - School of Biological Sciences, Seoul National University, Seoul 151-742, South 
      Korea.
FAU - Lee, Junsub
AU  - Lee J
FAU - Lee, Junghun
AU  - Lee J
FAU - Kim, Seon-Hee
AU  - Kim SH
FAU - Kim, Jiyoung
AU  - Kim J
FAU - Kim, Sunyoung
AU  - Kim S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130606
PL  - United States
TA  - Nitric Oxide
JT  - Nitric oxide : biology and chemistry
JID - 9709307
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nitrites)
RN  - 0 (Plant Extracts)
RN  - 0 (herbal extract PG201)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Cell Line
MH  - Down-Regulation/drug effects
MH  - Gene Expression Regulation/drug effects
MH  - Heme Oxygenase-1/*biosynthesis/genetics/metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - NF-E2-Related Factor 2/genetics/*metabolism
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Nitrites/*metabolism
MH  - Phosphatidylinositol 3-Kinases/genetics/*metabolism
MH  - Plant Extracts/*pharmacology
MH  - Promoter Regions, Genetic/drug effects
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - Heme oxygenase-1
OT  - Inducible nitric oxide synthase
OT  - Nitrite
OT  - Nrf2
OT  - PG201
OT  - Phosphatidylinositol 3-kinase
EDAT- 2013/06/12 06:00
MHDA- 2014/03/29 06:00
CRDT- 2013/06/11 06:00
PHST- 2012/12/22 00:00 [received]
PHST- 2013/05/07 00:00 [revised]
PHST- 2013/05/29 00:00 [accepted]
PHST- 2013/06/11 06:00 [entrez]
PHST- 2013/06/12 06:00 [pubmed]
PHST- 2014/03/29 06:00 [medline]
AID - S1089-8603(13)00154-7 [pii]
AID - 10.1016/j.niox.2013.05.003 [doi]
PST - ppublish
SO  - Nitric Oxide. 2013 Sep 1;33:42-55. doi: 10.1016/j.niox.2013.05.003. Epub 2013 Jun 
      6.