title: Xylocoside G reduces amyloid-β induced neurotoxicity by inhibiting NF-κB signaling pathway in neuronal cells.
abstract: Amyloid-β (Aβ) 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 Aβ-induced toxicity in SH-SY5Y cells and primary neurons. Pretreatment with XG significantly attenuated the cell viability reduction induced by Aβ 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 Aβ on Bax and Bcl-2 expression and repressed Aβ-induced caspase-3 activation, suggesting that the neuroprotective effect of XG is associated with apoptosis regulation. Neuroinflammation has been implicated in Aβ-induced neuronal death. XG significantly attenuated Aβ-stimulated release of inflammatory factors such as tumor necrosis factor-α, interleukin-1β, and prostaglandin E2. It also downregulated the expression of cyclooxygenase-2 in SH-SY5Y cells. Further molecular mechanism studies demonstrated that XG inhibited Aβ-induced NF-κB 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 Aβ-induced inflammation and apoptosis by down-regulating NF-κB signaling pathways.
authors.affiliation: Neuroscience Research Institute, Department of Neurobiology, Key Laboratory for Neuroscience, Ministry of Education and Ministry of Public Health, Health Science Center, Peking University, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.forename: Miao
authors.initials: M
authors.lastname: Sun
authors.forename: Ting
authors.initials: T
authors.lastname: Zhou
authors.forename: Kaiyin
authors.initials: K
authors.lastname: Zhong
authors.forename: Hecheng
authors.initials: H
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.forename: Xinying
authors.initials: X
authors.lastname: Liu
authors.forename: Ruizhong
authors.initials: R
authors.lastname: Xiao
authors.forename: Jia
authors.initials: J
authors.lastname: Ge
authors.forename: Pengfei
authors.initials: P
authors.lastname: Tu
authors.forename: Dong Sheng
authors.initials: DS
authors.lastname: Fan
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lan
authors.forename: Chen
authors.initials: C
authors.lastname: Hui
authors.forename: Dehua
authors.initials: D
authors.lastname: Chui
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D045744:Cell Line, Tumor; D002540:Cerebral Cortex / Q000166:cytology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D004660:Encephalitis / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009447:Neuroblastoma; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000378:metabolism; D011247:Pregnancy; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D004365:Drugs, Chinese Herbal; D053583:Interleukin-1beta; D016328:NF-kappa B; D009498:Neurotoxins; D014409:Tumor Necrosis Factor-alpha; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone