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
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概要
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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 B<span style="font-variant: small-caps;">unge</span>, 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.
著者
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Zou Li-bo
Department Of Life Science And Biopharmaceutics Shenyang Pharmaceutical University
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Chi Tian-yan
Department Of Life Science And Biopharmaceutics Shenyang Pharmaceutical University
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Ji Xue-fei
Department Of Life Science And Biopharmaceutics Shenyang Pharmaceutical University
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Qi Yue
Department Of Epidemiology Beijing An Zhen Hospital Capital Medical University Beijing Institute Of Heart Lung And Blood Vessel Diseases
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Zou Li-Bo
Department of Pharmacology, Life Science and Biopharmaceutics School, Shenyang Pharmaceutical University, China
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Wang Li-Hua
Shenyang Institute of Applied Ecology, Chinese Academy of Sciences, China
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Jin Ge
Department of Pharmacology, Life Science and Biopharmaceutics School, Shenyang Pharmaceutical University, China
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Pan Jin-Jin
Department of Pharmacology, Life Science and Biopharmaceutics School, Shenyang Pharmaceutical University, China
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Chi Tian-Yan
Department of Pharmacology, Life Science and Biopharmaceutics School, Shenyang Pharmaceutical University, China
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Ji Xue-Fei
Department of Pharmacology, Life Science and Biopharmaceutics School, Shenyang Pharmaceutical University, China
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- 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