title: Paeoniflorin Atttenuates Amyloidogenesis and the Inflammatory Responses in a Transgenic Mouse Model of Alzheimer's Disease.
abstract: Alzheimer's disease (AD) is associated with the inflammatory response in response to amyloid β-peptide (Aβ). Previous studies have suggested that paeoniflorin (PF) shows anti-inflammatory and neuroprotective effects in inflammation-related diseases. However, the impacts of PF on AD have not been investigated. In the present study, we showed that a 4-week treatment with PF could significantly inhibit Aβ burden, Aβ-induced over activation of astrocytes and microglia, downregulation of proinflammatory cytokines, and upregulation of anti-inflammatory cytokines in the brain. In addition, we demonstrated that chronic treatment with PF inhibited the activation of glycogen synthase kinase 3β (GSK-3β) and reversed neuroinflammtory-induced activation of nuclear factor-kappa B (NF-κB) signaling pathways. Moreover, PF exerted inhibitory effects on NALP3 inflammasome, caspase-1, and IL-1β. Collectively, in the present study, we demonstrated that PF exhibits neuroprotective effects in amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic (APP/PS1) mice via inhibiting neuroinflammation mediated by the GSK-3β and NF-κB signaling pathways and nucleotide-binding domain-like receptor protein 3 inflammasome. Thus, these results suggest that PF might be useful to intervene in development or progression of neurodegeneration in AD through its anti-inflammatory and anti-amyloidogenic effects.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital, Henan University of Science and Technology, Luoyang, 471003, Henan, China.
authors.forename: Hong-Ri
authors.initials: HR
authors.lastname: Zhang
authors.forename: Jing-Hua
authors.initials: JH
authors.lastname: Peng
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Cheng
authors.forename: Bao-Zhong
authors.initials: BZ
authors.lastname: Shi
authors.forename: Mao-Ying
authors.initials: MY
authors.lastname: Zhang
authors.forename: Ru-Xiang
authors.initials: RX
authors.lastname: Xu
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D005960:Glucosides / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D039821:Monoterpenes / Q000627:therapeutic use*; D029596:Paeonia; D058225:Plaque, Amyloid / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D053764:Presenilin-1 / Q000235:genetics; D006027:Glycosides
chemical_list: D016564:Amyloid beta-Protein Precursor; D005960:Glucosides; D018836:Inflammation Mediators; D039821:Monoterpenes; D053764:Presenilin-1; C545487:APP protein, human; C015423:peoniflorin; D006027:Glycosides