Paeoniflorin ameliorates A beta-stimulated neuroinflammation via regulation of NF-kappa B signaling pathway and A beta degradation in C6 glial cells

초록

BACKGROUND/OBJECTIVES: Alzheimer's disease is common age-related neurodegenerative condition characterized by amyloid beta (A beta) accumulation that leads cognitive impairment. In the present study, we investigated the protective effect of paeoniflorin (PF) against A beta-induced neuroinflammation and the underlying mechanism in C6 glial cells. MATERIALS/METHODS: C6 glial cells were treated with PF and A beta(25-35), and cell viability, nitric oxide (NO) production, and pro-inflammatory cytokine release were measured. Furthermore, the mechanism underlying the effect of PF on inflammatory responses and A beta degradation was determined by Western blot. RESULTS: A beta(2)(5-)(35) significantly reduced cell viability, but this reduction was prevented by the pretreatment with PF. In addition, PF significantly inhibited A beta(2)(5-)(35)-induced NO production in C6 glial cells. The secretion of interleukin (IL)-6, IL-1 beta, and tumor necrosis factor-alpha was also significantly reduced by PF. Further mechanistic studies indicated that PF suppressed the production of these pro-inflammatory cytokines by regulating the nuclear factor-kappa B (NF-kappa B) pathway. The protein levels of inducible NO synthase and cyclooxygenase-2 were downregulated and phosphorylation of NF-kappa B was blocked by PF. However, PF elevated the protein expression of inhibitor kappa B-alpha and those of A beta degrading enzymes, insulin degrading enzyme and neprilysin. CONCLUSIONS: These findings indicate that PF exerts protective effects against A beta-mediated neuroinflammation by inhibiting NF-kappa B signaling, and these effects were associated with the enhanced activity of A beta degradation enzymes.

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