Fucoidan inhibits the production of NO induced by IFN‐γ in C6 glioma cells; Regulation by p38, AP‐1 and scavenger receptor B1

Fucoidan, high‐molecular‐weight sulfated polysaccharides, has various biological activities. Since activated glial cells by neurodegenerative conditions overproduce nitric oxide (NO) which causes neurotoxicity, inhibition of NO production may have beneficial therapeutic effects in the treatment of neurodegenerative diseases. Therefore, we examined the inhibitory effect of fucoidan on NO production induced by a combination of TNF‐α and IFN‐γ in glial cells. Fucoidan inhibited NO production through the inhibition of the AP‐1 activation and p38 pathway, assessed by EMSA and western blot analysis. To further understand the mechanism for the inhibitory effects of fucoidan, C6 cells were treated with TNF‐α or IFN‐γ alone. Interestingly, fucoidan treatment reduced IFN‐γ‐induced NO production but did not affect the production of NO induced by TNF‐α. Moreover, pretreatment with monoclonal antibody against scavenger receptor B1 (SRB1) further increased in the production of NO induced by IFN‐γ, whereas TNF‐α‐induced NO production was not affected. These results suggest that SRB1 activation is responsible for increasing IFN‐γ‐induced NO production. Overall, the data indicate that p38 and AP‐1 play a critical role in fucoidan‐mediated NO inhibition in glial cells and fucoidan inhibits IFN‐γ‐induced NO production that may be subject to regulation by activation of SRB1. Thus fucoidan may be useful for the prevention of both NO and glial cell‐mediated neurodegenerative disorders.