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Background: Amyloidogenesis is linked to neuroinflammation. The tyrosine-fructose Maillard reaction product, 2,4-bis(p-hydroxyphenyl)-2-butenal, possesses anti-inflammatory properties in cultured macrophages, and in an arthritis animal model. Because astrocytes and microglia are responsible for amyloidogenesis and inflammatory reactions in the brain, we investigated the anti-inflammatory and anti-amyloidogenic effects of 2,4-bis(p-hydroxyphenyl)-2-butenal in lipopolysaccharide (LPS)-stimulated astrocytes and microglial BV-2 cells.Methods: Cultured astrocytes and microglial BV-2 cells were treated with LPS (1 μg/ml) for 24 h, in the presence (1, 2, 5 μM) or absence of 2,4-bis(p-hydroxyphenyl)-2-butenal, and harvested. We performed molecular biological analyses to determine the levels of inflammatory and amyloid-related proteins and molecules, cytokines, Aβ, and secretases activity. Nuclear factor-kappa B (NF-κB) DNA binding activity was determined using gel mobility shift assays.Results: We found that 2,4-bis(p-hydroxyphenyl)-2-butenal (1, 2, 5 μM) suppresses the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) as well as the production of nitric oxide (NO), reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in LPS (1 μg/ml)-stimulated astrocytes and microglial BV-2 cells. Further, 2,4-bis(p-hydroxyphenyl)-2-butenal inhibited the transcriptional and DNA binding activity of NF-κB--a transcription factor that regulates genes involved in neuroinflammation and amyloidogenesis via inhibition of IκB degradation as well as nuclear translocation of p50 and p65. Consistent with the inhibitory effect on inflammatory reactions, 2,4-bis(p-hydroxyphenyl)-2-butenal inhibited LPS-elevated Aβ42 levels through attenuation of β- and γ-secretase activities. Moreover, studies using signal transducer and activator of transcription 3 (STAT3) siRNA and a pharmacological inhibitor showed that 2,4-bis(p-hydroxyphenyl)-2-butenal inhibits LPS-induced activation of STAT3.Conclusions: These results indicate that 2,4-bis(p-hydroxyphenyl)-2-butenal inhibits neuroinflammatory reactions and amyloidogenesis through inhibition of NF-κB and STAT3 activation, and suggest that 2,4-bis(p-hydroxyphenyl)-2-butenal may be useful for the treatment of neuroinflammatory diseases like Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Background: Chungsim-Yeunja-Tang (CYT) has been used as a medicine for cerebral infarction (CI) patients in Korea. The objective of this study was to determine precisely the effect of CYT on CI patients using peripheral blood mononuclear cells (PBMCs).Methods: For a clinical study, 47 CI patients were identified who had taken CYT (0.01 g/kg) 3 times a day after meals for 2 weeks by oral administration. For ex vivo experiments, peripheral blood mononuclear cells (PBMCs) were isolated from CI patients. We analyzed the effect of CYT and its main components on lipopolysaccharide (LPS)-induced cytokine production and mechanism on PBMCs of CI patients by using ELISA, western blot analysis, transcription factor enzyme-linked immunoassay, and caspase assay.Results: Clinical signs of CI significantly disappeared about 2 weeks after oral administration of CYT to CI patients (P < 0.05). CYT and quercetin, an active compound of CYT, significantly inhibited LPS-induced interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α production and expression in PBMCs. CYT and quercetin also inhibited LPS-induced nuclear translocation and DNA binding activities of nuclear factor-κB and degradation of IκBα. In addition, CYT and quercetin inhibited LPS-induced IL-32 expression and caspase-1 activation.Conclusion: These results suggest a mechanism that might explain the beneficial effect of CYT in treating CI patients. Taken together, our findings indicate that inhibition of IL-32 expression and caspase-1 activation may be a novel biomarker and potential therapeutic target in CI. [ABSTRACT FROM AUTHOR]