Alzheimers disease (AD) is the chronic progressive neurodegenerative disorder that affects the elderly.Clinical studies have found that the amyloid deposits in the brain are aggravated along with the deterioration of the AD pathology as the chronic progressive neurodegenerative diseases.Indeed,Aβ peptides change particularly significantly early in the preclinical stage AD (PCAD),indicating that Aβ clearance could be a potent target for the treatment of PCAD.The efficacy is further enhanced when hippocampal transplantation is combined with acupuncture.Therapeutic acupuncture regulates the cytokine levels associated with survival,proliferation,and differentiation of neural stem cells,modified neural activity,and repair of damaged cells,resulting in improved cognitive function.When the acupuncture needle was inserted into the acupoint and rotated,mechanical signal was transmitted into cells with subsequent cellular response and downstream effects,such as cell secretion,modification of extracellular matrix,amplification and propagation of the signal,and modulation of afferent sensory.Nerve transmission might be another possible mechanism for the observed neuroprotective effects of acupuncture,as also observed in a recent acupuncture study in treating inflammation of neuronal system.Xylocoside G (XG) is an active compound isolated from a traditional Chinese medicinal plant,Itoa orientalis.We have previously reported that XG has neuroprotective effects,with the mechanism yet unknown.In this study,we investigated the possible mechanisms underlying neuroprotection of XG against Aβ induced toxicity in primary neurons.Pretreatment with XG significantly attenuateded the cell viability reduction induced by Aβ exposure in a dose dependent manner which was testified by MTT and LDH release assay.Neuroinflammation has been implicated in Aβ induced neuronal death.XG significantly attenuated Aβ stimulated release of inflammatory factors such as TNFα,IL1β and PGE2.It also downregulated the expression of COX2 in cells.Further molecular mechanism studies demonstrated that XG inhibited Aβ induced NFκB p65 translocation,which was probably the result of inhibition of JNK phosphorylation but not ERK or p38 MAPK pathway by XG.This is the first study to demonstrate that XG protects cells against Aβ induced inflammation and apoptosis through down regulating NF κB signaling pathways.The most opportune time for preventive intervention in AD is early in its PCAD.