AIM Methyl salicylate 2-0-β-D-lactoside (MSL) is a novel NSAIDs of molecule chemically related to salicylic acid.It is isolated from a kind of traditional Chinese medicine, Gaultheria yunnanensis (FRANCH) Rehder.The roles of MSL in Aβ intracerebroventrical (i.c.v) injected mice model is studied to explore the effects of MSL on learning and memory functions and further study the mechanisms of neuroirdlammation in AD.METHODS ICR mice were pre-oral garaged with MSL (75, 150 and 300 mg·kg-1)for 4 weeks, and then intracerebroventrical (i.c.v) injected with Aβ1-42 peptide.Morris water maze and step-through passive avoidance behavior experiments were carried out to test the learning and memory functions of mice.Furthermore, Aβ secreting and GFAP,which represented for glial activation, were measured by immunohistochemistry.Besides, proteins of mice brain were collected to test the APP, iNOS, COX1/2 expression and the activation of NF-κB and MAPK signaling pathway by western blotting.Other proteins were used to study the release of pro-inflammatory cytokines level (IL-6, IL-1β, and TNF-α) by ELISA.RESULTS MSL ameliorates learning and memory deficits in Aβ treated mice at the dose of 300 rag· kg-1.Moreover, Aβ40/42 and APP expression are decreased significantly by the same dose of MSL.In addition, pre-administrating with the dosage of 300 mg·kg-1, MSL not only suppresses the expression of GFAP in cortex and hippocampus, also shows a non-selective COX inhibitor activity in Aβ injected mice brains.Furthermore, it inhibits the phosphorylation of IKK, p38/MAPK and ERK42/44/MAPK and blocks the degradation of IκB,which causes the down regulation of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) release and iNOS expression.CONCLUSION Pretreatment of MSL improves learning and memory in an Aβ injected mouse model and clear Aβ accumulation by inhibiting neuroinflammatory responses in central nervous system, including glia cells activation, COX1/2 expression and the transduction of NF-κB/MAPK signaling pathway.