The Anti-Inflammatory Activity of Eucommia ulmoides Oliv. Bark. Involves NF-κB Suppression and Nrf2-Dependent HO-1 Induction in BV-2 Microglial Cells.
10.4062/biomolther.2015.150
- Author:
Seung Hwan KWON
1
;
Shi Xun MA
;
Ji Young HWANG
;
Yong Hyun KO
;
Ji Yeon SEO
;
Bo Ram LEE
;
Seok Yong LEE
;
Choon Gon JANG
Author Information
1. Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea. jang@skku.edu
- Publication Type:Original Article
- Keywords:
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:
Cytokines;
Dinoprostone;
DNA;
Eucommiaceae*;
Glycogen Synthase;
Heme Oxygenase-1;
Mitogen-Activated Protein Kinases;
Phosphorylation;
Reactive Oxygen Species;
Transcription Factors;
Up-Regulation;
Zinc
- From:Biomolecules & Therapeutics
2016;24(3):268-282
- CountryRepublic of Korea
- Language:English
-
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.
