Biomol Ther.  2016 May;24(3):268-282. 10.4062/biomolther.2015.150.

The Anti-Inflammatory Activity of Eucommia ulmoides Oliv. Bark. Involves NF-κB Suppression and Nrf2-Dependent HO-1 Induction in BV-2 Microglial Cells

• Kwon SH
• Ma SX
• Hwang JY
• Ko YH
• Seo JY
• Lee BR
• Lee SY
• Jang CG

• KMID: 2164219
• DOI: http://doi.org/10.4062/biomolther.2015.150

Abstract

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-3β (GSK-3β), and their downstream transcription factor, nuclear factor-kappa B (NF-κB). EUE also blocked the nuclear translocation of NF-κB 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 PGE2 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-3β, consequently suppressing NF-κB activation and inducing Nrf2-dependent HO-1 activation.

Keyword

Eucommia ulmoides Oliv. Bark.; Pro-inflammatory responses; Nuclear factor-kappa B; Nuclear factor erythroid 2-related factor 2; Heme oxygenase-1; BV-2 microglial cells

MeSH Terms

Cytokines
Dinoprostone
DNA
Eucommiaceae*
Glycogen Synthase
Heme Oxygenase-1
Mitogen-Activated Protein Kinases
Phosphorylation
Reactive Oxygen Species
Transcription Factors
Up-Regulation
Zinc
Cytokines
DNA
Dinoprostone
Glycogen Synthase
Heme Oxygenase-1
Mitogen-Activated Protein Kinases
Reactive Oxygen Species
Transcription Factors
Zinc