Anti-inflammatory effects of fucoidan through inhibition of NF-κB, MAPK and Akt activation in lipopolysaccharide-induced BV2 microglia cells

• Published in: Food and chemical toxicology 2011-08, Vol.49 (8), p.1745-1752
• Main Authors: Park, Hye Young, Han, Min Ho, Park, Cheol, Jin, Cheng-Yun, Kim, Gi-Young, Choi, Il-Whan, Kim, Nam Deuk, Nam, Taek-Jeong, Kwon, Taeg Kyu, Choi, Yung Hyun
• Format: Article
• Language: English
• Subjects: Akt; Animals; anti-inflammatory activity; Anti-Inflammatory Agents - pharmacology; Biological and medical sciences; Cells, Cultured; chemokine CCL2; Chemokine CCL2 - genetics; Chemokine CCL2 - metabolism; Cyclooxygenase 2 - genetics; Cyclooxygenase 2 - metabolism; Dinoprostone - antagonists & inhibitors; Dinoprostone - metabolism; Down-Regulation; Fucoidan; Fucus - chemistry; inducible nitric oxide synthase; interleukin-1beta; Interleukin-1beta - genetics; Interleukin-1beta - metabolism; JNK Mitogen-Activated Protein Kinases - genetics; JNK Mitogen-Activated Protein Kinases - metabolism; lipopolysaccharides; Lipopolysaccharides - adverse effects; MAPK; Medical sciences; Mice; Microglia - cytology; Microglia - drug effects; Microglia - metabolism; mitogen-activated protein kinase; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - genetics; Mitogen-Activated Protein Kinases - metabolism; neurodegenerative diseases; neuroglia; NF-kappa B - antagonists & inhibitors; NF-kappa B - genetics; NF-kappa B - metabolism; NF-κB; nitric oxide; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; p38 Mitogen-Activated Protein Kinases - genetics; p38 Mitogen-Activated Protein Kinases - metabolism; PGE2; Phaeophycophyta; Plant Extracts - pharmacology; Polysaccharides - pharmacology; prostaglandin synthase; prostaglandins; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Rabbits; Toxicology; transcription factor NF-kappa B; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2011.04.020

► The inhibitory effects of fucoidan on LPS-induced pro-inflammatory mediators in BV2 microglia were investigated. ► Fucoidan inhibited production of NO and PGE2, and levels of iNOS, COX-2, and pro-inflammatory cytokines. ► Moreover, fucoidan exhibited anti-inflammatory properties by suppression of NF-κB, MAPK, and AKT pathways. ► We conclude that fucoidan could be used for development of nutraceuticals for inflammatory and neurodegenerative disorders. Fucoidan, a sulfated polysaccharide extracted from brown seaweed, displays a wide variety of internal biological activities; however, the cellular and molecular mechanisms underlying fucoidan’s anti-inflammatory activity remain poorly understood. In this study, we investigated the inhibitory effects of fucoidan on production of lipopolysaccharide (LPS)–induced pro-inflammatory mediators in BV2 microglia. Our data indicated that fucoidan treatment significantly inhibited excessive production of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-stimulated BV2 microglia. It also attenuated expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, monocyte chemoattractant protein-1 (MCP-1), and pro-inflammatory cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor (TNF)-α. Moreover, fucoidan exhibited anti-inflammatory properties by suppression of nuclear factor-kappa B (NF-κB) activation and down-regulation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and AKT pathways. These finding suggest that fucoidan may offer substantial therapeutic potential for treatment of neurodegenerative diseases that are accompanied by microglial activation.