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논문 기본 정보

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학술저널
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Kwon, Seung-Hwan (Department of Pharmacology, School of Pharmacy, Sungkyunkwan University) Ma, Shi-Xun (Department of Pharmacology, School of Pharmacy, Sungkyunkwan University) Hwang, Ji-Young (Department of Pharmacology, School of Pharmacy, Sungkyunkwan University) Ko, Yong-Hyun (Department of Pharmacology, School of Pharmacy, Sungkyunkwan University) Seo, Ji-Yeon (Department of Pharmacology, School of Pharmacy, Sungkyunkwan University) Lee, Bo-Ram (Department of Pharmacology, School of Pharmacy, Sungkyunkwan University) Lee, Seok-Yong (Department of Pharmacology, School of Pharmacy, Sungkyunkwan University) Jang, Choon-Gon (Department of Pharmacology, School of Pharmacy, Sungkyunkwan University)
저널정보
한국응용약물학회 Biomolecules & Therapeutics(구 응용약물학회지) Biomolecules & therapeutics 제24권 제3호
발행연도
2016.1
수록면
268 - 282 (15page)

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In the present study, we investigated the anti-inflammatory properties of Eucommia ulmoides Oliv. Bark. (EUE) in lipopolysaccharide (LPS)-stimulated microglial BV-2 cells and found that EUE inhibited LPS-mediated up-regulation of pro-inflammatory response factors. In addition, EUE inhibited the elevated production of pro-inflammatory cytokines, mediators, and reactive oxygen species (ROS) in LPS-stimulated BV-2 microglial cells. Subsequent mechanistic studies revealed that EUE suppressed LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs), phosphoinositide-3-kinase (PI3K)/Akt, glycogen synthase $kinase-3{\beta}$ ($GSK-3{\beta}$), and their downstream transcription factor, nuclear factor-kappa B ($NF-{\kappa}B$). EUE also blocked the nuclear translocation of $NF-{\kappa}B$ and inhibited its binding to DNA. We next demonstrated that EUE induced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated heme oxygenase-1 (HO-1) expression. We determined that the significant up-regulation of HO-1 expression by EUE was a consequence of Nrf2 nuclear translocation; furthermore, EUE increased the DNA binding of Nrf2. In contrast, zinc protoporphyrin (ZnPP), a specific HO-1 inhibitor, blocked the ability of EUE to inhibit NO and $PGE_2$ production, indicating the vital role of HO-1. Overall, our results indicate that EUE inhibits pro-inflammatory responses by modulating MAPKs, PI3K/Akt, and $GSK-3{\beta}$, consequently suppressing $NF-{\kappa}B$ activation and inducing Nrf2-dependent HO-1 activation.

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