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.
Similar content being viewed by others
References
Bhatia M, Moochhala S (2004) Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome. J Pathol 202:145–156. https://doi.org/10.1002/path.1491
Blackwell TS, Christman JW (1997) The role of nuclear factor-kappa B in cytokine gene regulation. Am J Respir Cell Mol Biol 17:3–9. https://doi.org/10.1165/ajrcmb.17.1.f132
Burnham EL, Taylor WR, Quyyumi AA, Rojas M, Brigham KL, Moss M (2005) Increased circulating endothelial progenitor cells are associated with survival in acute lung injury. Am J Respir Crit Care Med 172:854–860. https://doi.org/10.1164/rccm.200410-1325OC
Cho HY, Jedlicka AE, Reddy SP, Kensler TW, Yamamoto M, Zhang LY, Kleeberger SR (2002) Role of NRF2 in protection against hyperoxic lung injury in mice. Am J Respir Cell Mol Biol 26:175–182. https://doi.org/10.1165/ajrcmb.26.2.4501
Cui YQ, Jia YJ, Zhang T, Zhang QB, Wang XM (2012) Fucoidan protects against lipopolysaccharide-induced rat neuronal damage and inhibits the production of proinflammatory mediators in primary microglia. CNS Neurosci Ther 18:827–833. https://doi.org/10.1111/j.1755-5949.2012.00372.x
Cui YQ, Zhang LJ, Zhang T, Luo DZ, Jia YJ, Guo ZX, Zhang QB, Wang X, Wang XM (2010) Inhibitory effect of fucoidan on nitric oxide production in lipopolysaccharide-activated primary microglia. Clin Exp Pharmacol Physiol 37:422–428. https://doi.org/10.1111/j.1440-1681.2009.05314.x
Islam KN, Mendelson CR (2002) Potential role of nuclear factor kappaB and reactive oxygen species in cAMP and cytokine regulation of surfactant protein-A gene expression in lung type II cells. Mol Endocrinol 16:1428–1440. https://doi.org/10.1210/mend.16.6.0856
Jiang D, Liang J, Fan J, Yu S, Chen S, Luo Y, Prestwich GD, Mascarenhas MM, Garg HG, Quinn DA, Homer RJ, Goldstein DR, Bucala R, Lee PJ, Medzhitov R, Noble PW (2005) Regulation of lung injury and repair by Toll-like receptors and hyaluronan. Nat Med 11:1173–1179. https://doi.org/10.1038/nm1315
Jiang W, Luo T, Li S, Zhou Y, Shen XY, He F, Xu J, Wang HQ (2016) Quercetin protects against okadaic acid-induced injury via MAPK and PI3K/Akt/GSK3beta signaling pathways in HT22 hippocampal neurons. PLoS ONE 11:e0152371. https://doi.org/10.1371/journal.pone.0152371
Karin M, Greten FR (2005) NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol 5:749–759. https://doi.org/10.1038/nri1703
Lee SH, Ko CI, Ahn G, You S, Kim JS, Heu MS, Kim J, Jee Y, Jeon YJ (2012) Molecular characteristics and anti-inflammatory activity of the fucoidan extracted from Ecklonia cava. Carbohydr Polym 89:599–606. https://doi.org/10.1016/j.carbpol.2012.03.056
Lee SH, Ko CI, Jee Y, Jeong Y, Kim M, Kim JS, Jeon YJ (2013) Anti-inflammatory effect of fucoidan extracted from Ecklonia cava in zebrafish model. Carbohydr Polym 92:84–89. https://doi.org/10.1016/j.carbpol.2012.09.066
Liu Y, Wu H, Nie YC, Chen JL, Su WW, Li PB (2011) Naringin attenuates acute lung injury in LPS-treated mice by inhibiting NF-kappaB pathway. Int Immunopharmacol 11:1606–1612. https://doi.org/10.1016/j.intimp.2011.05.022
Matsumoto S, Nagaoka M, Hara H, Kimura-Takagi I, Mistuyama K, Ueyama S (2004) Fucoidan derived from Cladosiphon okamuranus Tokida ameliorates murine chronic colitis through the down-regulation of interleukin-6 production on colonic epithelial cells. Clin Exp Immunol 136:432–439. https://doi.org/10.1111/j.1365-2249.2004.02462.x
Mei SH, McCarter SD, Deng Y, Parker CH, Liles WC, Stewart DJ (2007) Prevention of LPS-induced acute lung injury in mice by mesenchymal stem cells overexpressing angiopoietin 1. PLoS Med 4:e269. https://doi.org/10.1371/journal.pmed.0040269
Nguyen T, Nioi P, Pickett CB (2009) The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem 284:13291–13295. https://doi.org/10.1074/jbc.R900010200
Park J, Cha JD, Choi KM, Lee KY, Han KM, Jang YS (2017) Fucoidan inhibits LPS-induced inflammation in vitro and during the acute response in vivo. Int Immunopharmacol 43:91–98. https://doi.org/10.1016/j.intimp.2016.12.006
Parsons PE, Eisner MD, Thompson BT, Matthay MA, Ancukiewicz M, Bernard GR, Wheeler AP, Nhlbi Acute Respiratory Distress Syndrome Clinical Trials Network (2005) Lower tidal volume ventilation and plasma cytokine markers of inflammation in patients with acute lung injury. Crit Care Med 33:1–6. (discussion 230-232)
Reddy NM, Kleeberger SR, Kensler TW, Yamamoto M, Hassoun PM, Reddy SP (2009) Disruption of Nrf2 impairs the resolution of hyperoxia-induced acute lung injury and inflammation in mice. J Immunol 182:7264–7271. https://doi.org/10.4049/jimmunol.0804248
Rojas M, Woods CR, Mora AL, Xu J, Brigham KL (2005) Endotoxin-induced lung injury in mice: structural, functional, and biochemical responses. Am J Physiol Lung Cell Mol Physiol 288:L333–341. https://doi.org/10.1152/ajplung.00334.2004
Ruffmann R (1998) Reactive oxygen species in acute lung injury. Eur Respir J 12:1486
Schmidt EP, Yang Y, Janssen WJ, Gandjeva A, Perez MJ, Barthel L, Zemans RL, Bowman JC, Koyanagi DE, Yunt Z, Smith LP, Cheng SS, Overdier KH, Thompson KR, Geraci MW, Douglas IS, Pearse DB, Tuder RM (2012) The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis. Nat Med 18:1217–1223. https://doi.org/10.1038/nm.2843
Soler-Cataluna JJ, Martinez-Garcia MA, Roman Sanchez P, Salcedo E, Navarro M, Ochando R (2005) Severe acute exacerbations and mortality in patients with chronic obstructive pulmonary disease. Thorax 60:925–931. https://doi.org/10.1136/thx.2005.040527
Xiao M, Zhu T, Zhang W, Wang T, Shen YC, Wan QF, Wen FQ (2014) Emodin ameliorates LPS-induced acute lung injury, involving the inactivation of NF-kappaB in mice. Int J Mol Sci 15:19355–19368. https://doi.org/10.3390/ijms151119355
Yan YJ, Li Y, Lou B, Wu MP (2006) Beneficial effects of ApoA-I on LPS-induced acute lung injury and endotoxemia in mice. Life Sci 79:210–215. https://doi.org/10.1016/j.lfs.2006.02.011
Zhu T, Wang DX, Zhang W, Liao XQ, Guan X, Bo H, Sun JY, Huang NW, He J, Zhang YK, Tong J, Li CY (2013) Andrographolide protects against LPS-induced acute lung injury by inactivation of NF-kappaB. PLoS ONE 8:e56407. https://doi.org/10.1371/journal.pone.0056407
Zhu T, Li C, Zhang X, Ye C, Tang S, Zhang W, Sun J, Huang N, Wen F, Wang D, Deng H, He J, Qi D, Deng W, Yang T (2018) GLP-1 Analogue liraglutide enhances SP-A expression in LPS-induced acute lung injury through the TTF-1 signaling pathway. Mediat Inflamm 2018:3601454. https://doi.org/10.1155/2018/3601454
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
All authors declare that they have no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Zhu, DZ., Wang, YT., Zhuo, YL. et al. Fucoidan inhibits LPS-induced acute lung injury in mice through regulating GSK-3β-Nrf2 signaling pathway. Arch. Pharm. Res. 43, 646–654 (2020). https://doi.org/10.1007/s12272-020-01234-1
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12272-020-01234-1