Xylocoside G reduces amyloid-? induced neurotoxicity by inhibiting NF-?B signaling pathway in neuronal cells.

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Xylocoside G reduces amyloid-? induced neurotoxicity by inhibiting NF-?B signaling pathway in neuronal cells.

J Alzheimers Dis. 2012;30(2):263-75

Authors: Yu Y, Zhou L, Sun M, Zhou T, Zhong K, Wang H, Liu Y, Liu X, Xiao R, Ge J, Tu P, Fan DS, Lan Y, Hui C, Chui D

Abstract
Amyloid-? (A?) peptide, which can invoke a cascade of inflammatory responses, is considered to play a causal role in the development and progress of Alzheimer's disease (AD). 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, of which the mechanism is yet unknown. In this study, we investigated the possible mechanisms underlying neuroprotection of XG against A?-induced toxicity in SH-SY5Y cells and primary neurons. Pretreatment with XG significantly attenuated the cell viability reduction induced by A? exposure in a dose dependent manner which was testified by 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase release assay. In addition, pretreatment with XG countered the effect of A? on Bax and Bcl-2 expression and repressed A?-induced caspase-3 activation, suggesting that the neuroprotective effect of XG is associated with apoptosis regulation. Neuroinflammation has been implicated in A?-induced neuronal death. XG significantly attenuated A?-stimulated release of inflammatory factors such as tumor necrosis factor-?, interleukin-1?, and prostaglandin E2. It also downregulated the expression of cyclooxygenase-2 in SH-SY5Y cells. Further molecular mechanism studies demonstrated that XG inhibited A?-induced NF-?B 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 SH-SY5Y cells against A?-induced inflammation and apoptosis by down-regulating NF-?B signaling pathways.

PMID: 22430528 [PubMed - indexed for MEDLINE]

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