Microglial activation plays a pivotal role in the pathogenesis of
neurodegenerative diseases by producing various proinflammatory
cytokines and
nitric oxide (NO). In the present study, the anti-inflammatory and subsequent
neuroprotective effects of
catechol and its derivatives including
3-methylcatechol,
4-methylcatechol, and
4-tert-butylcatechol were investigated in microglia and
neuroblastoma cells in culture. The four
catechol compounds showed anti-inflammatory effects with different potency. The
catechols significantly decreased
lipopolysaccharide (LPS)-induced NO and
tumor necrosis factor (
TNF)-alpha production in BV-2 microglia cells. The
catechols also inhibited the expression of
inducible nitric oxide synthase (iNOS) and
TNF-alpha at
mRNA or
protein levels in the LPS-stimulated BV-2 cells. In addition, the
catechols inhibited LPS-induced nuclear translocation of p65 subunit of nuclear factor (
NF)-kappaB, IkappaB degradation, and phosphorylation of
p38 mitogen-activated protein kinase (MAPK) in BV-2 cells. Moreover, the
catechols attenuated the cytotoxicity of LPS-stimulated BV-2 microglia toward co-cultured rat B35
neuroblastoma cells. The
catechols, however, did not protect B35 cells against H(2)O(2) toxicity, indicating that the compounds exerted the
neuroprotective effect by inhibiting the inflammatory activation of microglia in the co-culture. The anti-inflammatory and neuroprotective properties of the
catechols in cultured microglia and
neuroblastoma cells suggest a therapeutic potential of these compounds for the treatment of
neurodegenerative diseases that are associated with an excessive microglial activation.