Fucoidan protects against lipopolysaccharide-induced rat neuronal damage and inhibits the production of proinflammatory mediators in primary microglia.

ABSTRACT

BACKGROUND: Fucoidan, a sulfated polysaccharide extracted from brown algae, possesses potent antiinflammatory effects. AIMS: To examine the effect of fucoidan treatment on inflammation-mediated dopaminergic neuronal damage and its potential mechanisms. METHODS: Microglial activation and injury of dopaminergic neurons were induced by intranigral injection of lipopolysaccharide (LPS), and the effects of fucoidan treatment on animal behavior, microglial activation and survival ratio of dopaminergic neurons were investigated. We further observed the efficacy of fucoidan on tumor necrosis factor-alpha (TNF-α) and the production of reactive oxygen species (ROS) in LPS-activated primary microglia. RESULTS: Fucoidan significantly improved the behavioral manifestation, prevented the loss of dopaminergic neurons and inhibited the deleterious activation of microglia in the substantia nigra pars compacta of LPS-treated rats. Further in vitro experiments indicated that the excessive production of TNF-α and ROS in LPS-induced primary microglia were significantly inhibited by fucoidan administration. CONCLUSION: This is the first study to demonstrate that fucoidan possesses neuroprotective effects on injured dopaminergic neurons in a LPS-induced animal model of Parkinson's disease. The mechanisms underlying these effects may include its potent down-regulation of intracellular ROS and subsequent proinflammatory cytokine release in LPS-activated microglia.