Protective effects of curcumin against neuroinflammation induced by Aβ25-35 in primary rat microglia: modulation of high-mobility group box 1, toll-like receptor 4 and receptor for advanced glycation end products expression

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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.