Fucoidan inhibits LPS-induced acute lung injury in mice through regulating GSK-3β-Nrf2 signaling pathway.

Abstract

The purpose of this study was to investigate the protective effects of fucoidan on Lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. The mice were divided into the control, LPS, and LPS + fucoidan (20, 40, or 80mg/kg) groups. LPS was given by intracheal instillation and fucoidan was given 1h before LPS treatment. Myeloperoxidase (MPO) activity, malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS), glutathione (GSH) contents, and inflammatory cytokine production were detected. The results showed that LPS-induced TNF-α, IL-1β, and IL-6 production, lung wet/dry (W/D) ratio, ROS, MDA content, and MPO activity were suppressed by fucoidan. The levels of SOD and GSH were increased by fucoidan. Meanwhile, LPS-induced nuclear factor kappa-B (NF-κB) activation was dose-dependently attenuated by fucoidan. Furthermore, fucoidan increased the expression of nuclear factor erythroid-2 related factor 2 (Nrf2), Glycogen synthase kinase3β (GSK-3β), and heme oxygenase (HO-1). In vitro, the results demonstrated that fucoidan or GSK-3β inhibitor significantly inhibited LPS-induced TNF-α production in A549 cells. And the inhibition of fucoidan on TNF-α production was blocked by Nrf2 siRNA. This study showed fucoidan protected mice against LPS-induced ALI through inhibiting inflammatory and oxidative responses via regulating GSK-3β-Nrf2 signaling pathway.