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

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

SUBMITTER: Kwon SH 

PROVIDER: S-EPMC4859790 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature