Lipopolysaccharide (LPS)-induced activation of microglia triggers the release of neuroinflammatory molecules, contributing to the progression of neurodegenerative diseases. Targeting these neuroinflammatory molecules could serve as a potential therapeutic strategy. Given the evidence supporting the immune-boosting properties of curcumin (Curc) and the protective effects of mono- phosphoryl lipid A (MPL) in the central nervous system (CNS) related to Alzheimer’s disease (AD), this study aimed to assess the anti-inflammatory effects of these compounds on primary rat microglial cells, which are crucial in the response to neuroinflam- mation. This in vitro study investigated the effects of Curc, MPL, and their coadministration (Curc + MPL) on inflammatory cytokine levels in activated microglial cells. Primary microglial cells were isolated from 1-day-old rats and treated with various concentrations of Curc, MPL, and Curc + MPL prior to LPS stimulation. Cell viability was assessed using the MTT assay, followed by the Griess assay to evaluate nitric oxide (NO) production. The levels of inflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), as well as the gene expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), were analyzed via real-time PCR. Additionally, enzyme-linked immunosorbent assay (ELISA) was employed to quantify the protein levels of IL-1β, TNF-α, and IL-6. Our findings demonstrate that Curc and MPL possess antineuroinflammatory properties in LPS-stimulated microglial cells. Notably, the coadministration of Curc and MPL (Curc + MPL) significantly inhibited the production of pro-inflammatory cytokines IL-1β, TNF-α, and IL-6. Furthermore, Curc + MPL suppressed the expression of iNOS and COX-2. These results strongly suggest that Curc + MPL is a promising neuroprotective agent for the treatment of neurodegenerative disorders by mitigating neuroinflammatory responses.

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