Abstract
BACKGROUND: Activated microglia induced by amyloid-beta (Aβ) release proinflammatory cytokines that can induce neurotoxicity. High-mobility group box 1 protein (HMGB1) and HMGB1-mediated inflammatory responses have been attributed with memory impairment in patients with Alzheimer's disease (AD). There is accumulating evidence to suggest curcumin is a potent anti-inflammatory polyphenol. However, whether curcumin could effectively inhibit inflammation through the suppression of HMGB1 production or HMGB1-mediated inflammatory responses in Aβ-activated microglia is still unclear. METHODS: Primary microglia were prepared from the cerebral cortices of one- to three-day-old Sprague Dawley rats. The microglia were cultured and treated with Aβ(25-35) 50 µM for 24 h to prove a toxic effect. Curcumin 10 µM was administrated 1 h before Aβ(25-35) treatment. The levels of HMGB1, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the culture medium were analyzed by ELISA. Western blotting was conducted to assess the expression level of toll-like receptor 4 (TLR4) and the receptor for advanced glycation end products (RAGE). In addition, PC12 cells were treated with conditioned medium from microglia treated with Aβ(25-35) or Aβ(25-35) and curcumin, and cell viability was subsequently assessed by MTT. RESULTS: Curcumin was found to significantly inhibit HMGB1 expression and release in Aβ(25-35)-stimulated microglia. Pretreatment with curcumin reduced TLR4 and RAGE expression. Proinflammatory cytokines such as IL-1β and TNF-α were also remarkably reduced by curcumin. In addition, curcumin protected neurons from indirect toxicity mediated by Aβ(25-35)-treated microglia. CONCLUSIONS: Curcumin effectively inhibits Aβ(25-35)-induced neuroinflammation in microglia, partly by suppressing the expression of HMGB1, TLR4, and RAGE.