Excessive microglial activation and subsequent
neuroinflammation lead to synaptic loss and dysfunction as well as neuronal cell death, which are involved in the pathogenesis and progression of several
neurodegenerative diseases. Thus, the regulation of microglial activation has been evaluated as effective therapeutic strategies. Although
dieckol (DEK), one of the phlorotannins isolated from marine brown alga Ecklonia cava, has been previously reported to inhibit microglial activation, the molecular mechanism is still unclear. Therefore, we investigated here molecular mechanism of DEK via
extracellular signal-regulated kinase (ERK), Akt and
nicotinamide adenine dinuclelotide
phosphate (
NADPH) oxidase-mediated pathways. In addition, the neuroprotective mechanism of DEK was investigated in microglia-mediated neurotoxicity models such as neuron-microglia co-culture and microglial
conditioned media system. Our results demonstrated that treatment of
anti-oxidant DEK potently suppressed phosphorylation of ERK in
lipopolysaccharide (LPS, 1 µg/ml)-stimulated BV-2 microglia. In addition, DEK markedly attenuated Akt phosphorylation and increased expression of gp91 (
phox) , which is the catalytic component of
NADPH oxidase complex responsible for microglial
reactive oxygen species (ROS) generation. Finally, DEK significantly attenuated neuronal cell death that is induced by treatment of microglial
conditioned media containing neurotoxic secretary molecules. These
neuroprotective effects of DEK were also confirmed in a neuron-microglia co-culture system using
enhanced green fluorescent protein (EGFP)-transfected B35
neuroblastoma cell line. Taken together, these results suggest that DEK suppresses excessive microglial activation and microglia-mediated neuronal cell death via downregulation of ERK, Akt and
NADPH oxidase-mediated pathways.