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OBJECTIVE Neuroinflammation has been known to play a critical role in the pathogenesis of alzheimers disease (AD).Activation of microglia and astrocytes is a characteristic of brain inflammation.Epidemiological studies have shown that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) delays the onset of AD and suppresses its progression.Methylsalicylate-2-O-β-D-lactoside (DL0309) is a new molecule chemically related to salicylic acid.The present study aimed to evaluate the anti-inflammatory effects of DL0309.METHODS Cells were pre-treated for 1 h with DL0309 at the concentration of 0.1, 1 and 10 μmol·L-1 respectively, and then stimulated by lipopolysaccharide (LPS, 0.5 μg· ml-1) for 24 h.Pro-inflammatory cytokines (IL-6, IL-1 β and TNFα) levels, NO production and COX1/2 expression were measured.After exposing to LPS (0.5μg·ml-1) for 10min or 45 min, the activation of NF-κB signal pathway was measured by western blotting.RESULTS Our studies showed that DL0309 significantly inhibited LPS-induced the release of pro-inflammatory cytokines (IL-6, IL-1 β, and TNF-α) and the expression of inflammatory related proteins (iNOS, COX-1, and COX-2) in microglia and astrocytes.At the concentration of 10 μmol·L-1 , DL0309 prominently inhibited LPS-induced the activation of NF-κB in glia cells via blocking the phosphorylation of IKK, p65 and IκB degradation.CONCLUSION We have first demonstrated that DL0309 exerts anti-inflammatory effects in glia cells by inhibiting different pro-inflammatory cytokines and iNOS/NO.Furthermore, it also regulates the NF-κB signaling pathway by blocking IKK, IκB and p65 activation.It also acts as a non-selective COX inhibitor in glia cells.These studies suggest that DL0309 may be effective in the treatment of neuroinflammatory disorders including AD.