Identification of pyrocatechol, a coffee ingredient that exerts antineuroinflammatory effects by inhibiting NF-kappaB

Abstract

Abstract Although epidemiological studies have suggested that the frequency of coffee consumption negatively correlates with the incidence of neurodegenerative diseases, its causality based on molecular mechanisms remains unclear. Since neuroinflammation is closely associated with the pathogenesis of neurodegenerative diseases, we hypothesized that the consumption of coffee prevents the onset of neurodegenerative diseases by suppressing neuroinflammation. Coffee and decaffeinated coffee decoctions significantly attenuated the lipopolysaccharide (LPS)-induced production of nitric oxide by inhibiting the expression of inducible nitric oxide synthase (iNOS) in the murine microglia cell line, BV-2. Both decoctions also attenuated the LPS-induced expression of pro-inflammatory cytokines and chemokines, such as interleukin (IL)-6, tumor necrosis factor (TNF) α, CCL2, and CXCL1, in BV-2 cells. In addition, both decoctions inhibited the LPS-induced nuclear translocation and transcriptional activation of nuclear factor-κB (NF-κB), a major transcription factor in inflammation, suggesting that coffee ingredients other than caffeine prevent neuroinflammation by inhibiting NF-κB. Pyrocatechol, a component of roasted coffee produced by the thermal decomposition of chlorogenic acid, exhibited anti-inflammatory activity by inhibiting the LPS-induced activation of NF-κB, similar to the coffee decoctions. The intake of pyrocatechol also significantly inhibited the accumulation of microglia and the expression of iNOS, IL-6, TNFα, CCL2, and CXCL1 in murine brains injected with LPS, similar to the coffee decoctions. These results indicate that the anti-inflammatory activity of pyrocatechol contributes to the suppressive effects of coffee on the onset of neurodegenerative diseases.