1. Methyl salicylate 2-O-β-D-lactoside, a novel salicylic acid analogue, acts as an anti-inflammatory agent on microglia and astrocytes.
- Author
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Lan, Xi, Liu, Rui, Sun, Lan, Zhang, Tiantai, and Du, Guanhua
- Subjects
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NEUROLOGICAL research , *IMMUNOREGULATION , *CYTOKINES , *ANTI-inflammatory agents , *ALZHEIMER'S disease , *BASAL ganglia diseases , *PROTEIN metabolism , *INTERLEUKINS , *RESEARCH , *CELL culture , *ANIMAL experimentation , *RESEARCH methodology , *SALICYLIC acid , *GLYCOSIDES , *INTERLEUKIN-1 , *MEDICAL cooperation , *EVALUATION research , *CELLULAR signal transduction , *RATS , *COMPARATIVE studies , *CELLS , *TUMOR necrosis factors , *OXIDOREDUCTASES , *MOLECULAR structure , *NITRIC oxide , *PHARMACODYNAMICS - Abstract
Background: Neuroinflammation has been known to play a critical role in the pathogenesis of Alzheimer's 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. Methyl salicylate-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.Findings: Our studies show that DL0309 significantly inhibits lipopolysaccharide (LPS)-induced release of the pro-inflammatory cytokines IL-6, IL-1β, and TNF-α; and the expression of the inflammation-related proteins iNOS, COX-1, and COX-2 by microglia and astrocytes. At a concentration of 10 μM, DL0309 prominently inhibited LPS-induced activation of NF-κB in glial cells by blocking phosphorylation of IKK and p65, and by blocking IκB degradation.Conclusions: We demonstrate here for the first time that DL0309 exerts anti-inflammatory effects in glial cells by suppressing different pro-inflammatory cytokines and iNOS/NO. Furthermore, it also regulates the NF-κB signaling pathway by blocking IKK and p65 activation and IκB degradation. DL0309 also acts as a non-selective COX inhibitor in glial cells. These studies suggest that DL0309 may be effective in the treatment of neuroinflammatory disorders, including AD. [ABSTRACT FROM AUTHOR]- Published
- 2011
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