Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Arctigenin Increases Hemeoxygenase-1 Gene Expression by Modulating PI3K/AKT Signaling Pathway in Rat Primary Astrocytes

  • Jeong, Yeon-Hui (Department of Molecular Medicine, Tissue Injury Defense Research Center, Ewha Womans University Medical School) ;
  • Park, Jin-Sun (Department of Molecular Medicine, Tissue Injury Defense Research Center, Ewha Womans University Medical School) ;
  • Kim, Dong-Hyun (Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University) ;
  • Kim, Hee-Sun (Department of Molecular Medicine, Tissue Injury Defense Research Center, Ewha Womans University Medical School)
  • Received : 2014.10.17
  • Accepted : 2014.11.05
  • Published : 2014.11.30
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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.

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References

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