Biomol Ther.  2014 Nov;22(6):497-502. 10.4062/biomolther.2014.121.

Arctigenin Increases Hemeoxygenase-1 Gene Expression by Modulating PI3K/AKT Signaling Pathway in Rat Primary Astrocytes

• Jeong YH
• Park JS
• Kim DH
• Kim HS

• KMID: 2170590
• DOI: http://doi.org/10.4062/biomolther.2014.121

Abstract

In the present study, we found that the natural compound arctigenin inhibited hydrogen peroxide-induced reactive oxygen species (ROS) production in rat primary astrocytes. Since hemeoxygenase-1 (HO-1) plays a critical role as an antioxidant defense factor in the brain, we examined the effect of arctigenin on HO-1 expression in rat primary astrocytes. We found that arctigenin increased HO-1 mRNA and protein levels. Arctigenin also increases the nuclear translocation and DNA binding of Nrf2/c-Jun to the antioxidant response element (ARE) on HO-1 promoter. In addition, arctigenin increased ARE-mediated transcriptional activities in rat primary astrocytes. Further mechanistic studies revealed that arctigenin increased the phosphorylation of AKT, a downstream substrate of phosphatidylinositol 3-kinase (PI3K). Treatment of cells with a PI3K-specific inhibitor, LY294002, suppressed the HO-1 expression, Nrf2 DNA binding and ARE-mediated transcriptional activities in arctigenin-treated astrocyte cells. The results collectively suggest that PI3K/AKT signaling pathway is at least partly involved in HO-1 expression by arctigenin via modulation of Nrf2/ARE axis in rat primary astrocytes.

Keyword

Arctigenin; Astrocyte; Hemeoxygenase-1; PI3K/AKT; Nrf2/ARE axis

MeSH Terms

Animals
Antioxidant Response Elements
Astrocytes*
Axis, Cervical Vertebra
Brain
DNA
Gene Expression*
Hydrogen
Phosphatidylinositol 3-Kinase
Phosphorylation
Rats*
Reactive Oxygen Species
RNA, Messenger
DNA
Hydrogen
Phosphatidylinositol 3-Kinase
RNA, Messenger
Reactive Oxygen Species