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Mediators Inflamm. 2015;2015:380218. doi: 10.1155/2015/380218. Epub 2015 Apr 19.

Punicalagin Induces Nrf2/HO-1 Expression via Upregulation of PI3K/AKT Pathway and Inhibits LPS-Induced Oxidative Stress in RAW264.7 Macrophages.

Author information

1
CAU-BUA TCVM Teaching and Researching Team, College of Veterinary Medicine, China Agricultural University (CAU), No. 2 West Yuanmingyuan Road, Beijing 100193, China.
2
College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, China.
3
College of Animal Science and Technology, Beijing University of Agriculture (BUA), Beijing 102206, China.
4
College of Animal Science and Technology, Beijing University of Agriculture (BUA), Beijing 102206, China ; Beijing Key Laboratory for Dairy Cow Nutrition, Beijing 102206, China.

Abstract

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.

PMID:
25969626
PMCID:
PMC4417599
DOI:
10.1155/2015/380218
[Indexed for MEDLINE]
Free PMC Article

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