title: Methyl salicylate 2-O-β-D-lactoside, a novel salicylic acid analogue, acts as an anti-inflammatory agent on microglia and astrocytes.
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.
  
  
  RESULTS
  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.
authors.affiliation: Beijing Key Laboratory of Drug Target and Screening Research, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, No,1 Xiannongtan Street, Xicheng District, Beijing 100050, P R China.
authors.forename: Xi
authors.initials: X
authors.lastname: Lan
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.forename: Lan
authors.initials: L
authors.lastname: Sun
authors.forename: Tiantai
authors.initials: T
authors.lastname: Zhang
authors.forename: Guanhua
authors.initials: G
authors.lastname: Du
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D006027:Glycosides / Q000737:chemistry / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D020156:Salicylic Acid / Q000737:chemistry* / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D006027:Glycosides; D053583:Interleukin-1beta; D015850:Interleukin-6; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C008245:lactosides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D020156:Salicylic Acid