title: Xanthoceraside inhibits pro-inflammatory cytokine expression in Aβ25-35/IFN-γ-stimulated microglia through the TLR2 receptor, MyD88, nuclear factor-κB, and mitogen-activated protein kinase signaling pathways.
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 β25-35 (Aβ25-35)/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-1β and tumor necrosis factor-α in a concentration-dependent manner. Reverse transcriptase-polymerase chain reaction and western blotting analyses showed that xanthoceraside decreased the Aβ25-35/IFN-γ-induced production of cyclooxygenase-2 and inducible NO synthase. These effects were accompanied by inhibited activities of nuclear 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.
authors: Department of Pharmacology, Life Science and Biopharmaceutics School, Shenyang Pharmaceutical University, Shenyang, PR China.
authors: Yue
authors: Y
authors: Qi
authors: Li-Bo
authors: LB
authors: Zou
authors: Li-Hua
authors: LH
authors: Wang
authors: Ge
authors: G
authors: Jin
authors: Jin-Jin
authors: JJ
authors: Pan
authors: Tian-Yan
authors: TY
authors: Chi
authors: Xue-Fei
authors: XF
authors: Ji
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents; D002478:Cells, Cultured; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D007371:Interferon-gamma / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000378:metabolism*; D051379:Mice; D017628:Microglia; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D058990:Molecular Targeted Therapy; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology*; D018696:Neuroprotective Agents; D010446:Peptide Fragments / Q000494:pharmacology*; D012503:Saponins / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology*; D051195:Toll-Like Receptor 2 / Q000502:physiology*; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D012503:Saponins; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C074636:amyloid beta-protein (25-35); C548611:xanthoceraside; D007371:Interferon-gamma; D020928:Mitogen-Activated Protein Kinases