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
Activated microglia induced by amyloid-beta (Aβ) release pro-inflammatory cytokines that can induce neurotoxicity. High mobility group box-1 protein 1 (HMGB1) and HMGB1-mediated inflammatory responses are regulated mainly through the toll-like receptor 4 (TLR4) and the receptor for advanced glycation end products (RAGE), which have been implicated in memory impairments in Alzheimer’s disease (AD). Preventing the production of HMGB1 and HMGB1-mediated inflammatory responses may function as a therapeutic target for AD. Curcumin, a polyphenol isolated from the curcuma longa, has potent anti- inflammatory properties. However, whether curcumin could be an effective agent for inhibiting inflammation by suppressing the production of HMGB1 or HMGB1-mediated inflammatory responses in Aβ-activated microglia is still unclear. In the present study, we found that curcumin could significantly inhibit HMGB1 expression and release in Aβ25-35-stimulated microglia. Pretreated with curcumin reduced the TLR4 and RAGE expression. Proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin- 1β (IL-1β) were also remarkably reduced by curcumin. In addition, curcumin protected neurons from indirect toxicity mediated by Aβ25-35-treated microglia. The present study supplies evidence that curcumin effectively inhibits neuroinflammation induced by Aβ25-35 in microglia in part through suppressing the expression of HMGB1, TLR4, and RAGE.