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

Archives of Pharmacal Research 2020년 43권 6호 p.646 ~ 654
 ( Zhu De-Zhang ) - Qingdao University Affiliated Hospital Department of Anesthesiology

 ( Wang Yan-Ting ) - Qingdao University Affiliated Hospital Department of Anesthesiology
 ( Zhuo Yan-Li ) - Qingdao University Affiliated Hospital Department of Anesthesiology
 ( Zhu Kong-Juan ) - Qingdao University Affiliated Hospital Department of Anesthesiology
 ( Wang Xiang-Zhen ) - Qingdao University Affiliated Hospital Department of Anesthesiology
 ( Liu Ai-Jie ) - Qingdao University Affiliated Hospital Department of Anesthesiology

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 80 mg/kg) groups. LPS was given by intracheal instillation and fucoidan was given 1 h 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.

키워드

LPS; Fucoidan; Lung injury; Nrf2
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