Xanthoceraside inhibits pro-inflammatory cytokine expression in Aß25-35/IFN-γ-stimulated microglia through the TLR2 receptor, MyD88, nuclear factor-κB, and mitogen-activated protein kinase signaling pathways.
J Pharmacol Sci
; 122(4): 305-17, 2013.
Article
em En
| MEDLINE
| ID: mdl-23966052
ABSTRACT
An accumulating body of evidence suggests that Alzheimer's disease (AD) is associated with microglia-mediated neuroinflammation and pro-inflammatory cytokine expression. Therefore, the suppression of neuroinflammation and pro-inflammatory cytokine might theoretically slow down the progression of AD. Xanthoceraside, a novel triterpenoid saponin extracted from the husks of Xanthoceras sorbifolia Bunge, has potent antiinflammatory and neuroprotective effects. However, the molecular mechanism underlying its anti-inflammatory action remains unclear. In the present study, we attempted to determine the effects of xanthoceraside on the production of pro-inflammatory mediators in amyloid ß25-35 (Aß25-35)/interferon-γ (IFN-γ)-stimulated microglia. Our results indicated that xanthoceraside (0.01 and 0.1 µM) significantly inhibited the release of nitric oxide (NO) and pro-inflammatory cytokines interleukin-1ß and tumor necrosis factor-α in a concentration-dependent manner. Reverse transcriptase-polymerase chain reaction and western blotting analyses showed that xanthoceraside decreased the Aß25-35/IFN-γ-induced production of cyclooxygenase-2 and inducible NO synthase. These effects were accompanied by inhibited activities of nuclearâ
factor-κB and mitogen-activated protein kinase through Toll-like receptor 2 in a myeloid differentiation protein 88-dependent manner. Our results provide support for the therapeutic potential of xanthoceraside in AD.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
/
Saponinas
/
Triterpenos
/
Transdução de Sinais
/
Peptídeos beta-Amiloides
/
NF-kappa B
/
Interferon gama
/
Fator de Necrose Tumoral alfa
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Fármacos Neuroprotetores
/
Proteínas Quinases Ativadas por Mitógeno
Limite:
Animals
Idioma:
En
Revista:
J Pharmacol Sci
Ano de publicação:
2013
Tipo de documento:
Article