PMID- 25969626
OWN - NLM
STAT- MEDLINE
DCOM- 20160212
LR  - 20181113
IS  - 1466-1861 (Electronic)
IS  - 0962-9351 (Print)
IS  - 0962-9351 (Linking)
VI  - 2015
DP  - 2015
TI  - Punicalagin Induces Nrf2/HO-1 Expression via Upregulation of PI3K/AKT Pathway and 
      Inhibits LPS-Induced Oxidative Stress in RAW264.7 Macrophages.
PG  - 380218
LID - 10.1155/2015/380218 [doi]
LID - 380218
AB  - Reactive oxygen species (ROS) and oxidative stress are thought to play a central 
      role in potentiating macrophage activation, causing excessive inflammation, 
      tissue damage, and sepsis. Recently, we have shown that punicalagin (PUN) 
      exhibits anti-inflammatory activity in LPS-stimulated macrophages. However, the 
      potential antioxidant effects of PUN in macrophages remain unclear. Revealing 
      these effects will help understand the mechanism underlying its ability to 
      inhibit excessive macrophage activation. Hemeoxygenase-1 (HO-1) exhibits 
      antioxidant activity in macrophages. Therefore, we hypothesized that HO-1 is a 
      potential target of PUN and tried to reveal its antioxidant mechanism. Here, PUN 
      treatment increased HO-1 expression together with its upstream mediator nuclear 
      factor-erythroid 2 p45-related factor 2 (Nrf2). However, specific inhibition of 
      Nrf2 by brusatol (a specific Nrf2 inhibitor) dramatically blocked PUN-induced 
      HO-1 expression. Previous research has demonstrated that the PI3K/Akt pathway 
      plays a critical role in modulating Nrf2/HO-1 protein expression as an upstream 
      signaling molecule. Here, LY294002, a specific PI3K/Akt inhibitor, suppressed 
      PUN-induced HO-1 expression and led to ROS accumulation in macrophages. 
      Furthermore, PUN inhibited LPS-induced oxidative stress in macrophages by 
      reducing ROS and NO generation and increasing superoxide dismutase (SOD) 1 mRNA 
      expression. These findings provide new perspectives for novel therapeutic 
      approaches using antioxidant medicines and compounds against oxidative stress and 
      excessive inflammatory diseases including tissue damage, sepsis, and endotoxemic 
      shock.
FAU - Xu, Xiaolong
AU  - Xu X
AD  - CAU-BUA TCVM Teaching and Researching Team, College of Veterinary Medicine, China 
      Agricultural University (CAU), No. 2 West Yuanmingyuan Road, Beijing 100193, 
      China.
FAU - Li, Hongquan
AU  - Li H
AD  - College of Animal Science and Veterinary Medicine, Shanxi Agricultural 
      University, Taigu, Shanxi 030801, China.
FAU - Hou, Xiaolin
AU  - Hou X
AD  - College of Animal Science and Technology, Beijing University of Agriculture 
      (BUA), Beijing 102206, China.
FAU - Li, Deyin
AU  - Li D
AD  - College of Animal Science and Technology, Beijing University of Agriculture 
      (BUA), Beijing 102206, China.
FAU - He, Shasha
AU  - He S
AD  - CAU-BUA TCVM Teaching and Researching Team, College of Veterinary Medicine, China 
      Agricultural University (CAU), No. 2 West Yuanmingyuan Road, Beijing 100193, 
      China.
FAU - Wan, Changrong
AU  - Wan C
AD  - CAU-BUA TCVM Teaching and Researching Team, College of Veterinary Medicine, China 
      Agricultural University (CAU), No. 2 West Yuanmingyuan Road, Beijing 100193, 
      China.
FAU - Yin, Peng
AU  - Yin P
AUID- ORCID: 0000-0002-9824-4964
AD  - CAU-BUA TCVM Teaching and Researching Team, College of Veterinary Medicine, China 
      Agricultural University (CAU), No. 2 West Yuanmingyuan Road, Beijing 100193, 
      China.
FAU - Liu, Mingjiang
AU  - Liu M
AD  - CAU-BUA TCVM Teaching and Researching Team, College of Veterinary Medicine, China 
      Agricultural University (CAU), No. 2 West Yuanmingyuan Road, Beijing 100193, 
      China.
FAU - Liu, Fenghua
AU  - Liu F
AD  - College of Animal Science and Technology, Beijing University of Agriculture 
      (BUA), Beijing 102206, China ; Beijing Key Laboratory for Dairy Cow Nutrition, 
      Beijing 102206, China.
FAU - Xu, Jianqin
AU  - Xu J
AUID- ORCID: 0000-0002-7941-573X
AD  - CAU-BUA TCVM Teaching and Researching Team, College of Veterinary Medicine, China 
      Agricultural University (CAU), No. 2 West Yuanmingyuan Road, Beijing 100193, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150419
PL  - United States
TA  - Mediators Inflamm
JT  - Mediators of inflammation
JID - 9209001
RN  - 0 (Hydrolyzable Tannins)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NFE2L2 protein, human)
RN  - 65995-63-3 (punicalagin)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Cell Line
MH  - Heme Oxygenase-1/genetics/*metabolism
MH  - Humans
MH  - Hydrolyzable Tannins/*pharmacology
MH  - Macrophages/drug effects/metabolism
MH  - NF-E2-Related Factor 2/genetics/*metabolism
MH  - Oxidative Stress/drug effects
MH  - Phosphatidylinositol 3-Kinases/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-akt/genetics/*metabolism
PMC - PMC4417599
EDAT- 2015/05/15 06:00
MHDA- 2016/02/13 06:00
PMCR- 2015/04/19
CRDT- 2015/05/14 06:00
PHST- 2014/07/26 00:00 [received]
PHST- 2014/10/12 00:00 [revised]
PHST- 2014/10/17 00:00 [accepted]
PHST- 2015/05/14 06:00 [entrez]
PHST- 2015/05/15 06:00 [pubmed]
PHST- 2016/02/13 06:00 [medline]
PHST- 2015/04/19 00:00 [pmc-release]
AID - 10.1155/2015/380218 [doi]
PST - ppublish
SO  - Mediators Inflamm. 2015;2015:380218. doi: 10.1155/2015/380218. Epub 2015 Apr 19.