title: Geniposide attenuates oligomeric Aβ(1-42)-induced inflammatory response by targeting RAGE-dependent signaling in BV2 cells.
abstract: The neuroinflammation induced by amyloid-β (Aβ) is one of the key events in Alzheimer's disease (AD) progress in which microglia are the main cells involved. Receptor for advanced glycation end products (RAGE) mediates and enhances Aβ-induced microglial activation and leads to induction of proinflammatory mediators, such as tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Geniposide, a pharmacologically active component purified from gardenia fruit, exhibits a broad spectrum anti-inflammatory effect as well as neurotrophic and neuroprotective properties. However, the effects of geniposide on Aβ-mediated microglial pathways have not been fully discovered. Here, we demonstrate that geniposide treatment significantly blocks Aβ-induced RAGE-dependent signaling (activation of ERK and NF-κB) along with the production of TNF-α and IL-1β in cultured BV2 microglia cells. Notably, based on the data from coimmunoprecipitation assay, we infer that geniposide exerts protective effects on Aβ-induced inflammatroy response through blocking Aβ binding to RAGE and suppressing the RAGE-mediated signaling pathway. Taken together, these findings indicate that geniposide is a potent suppressor of neuroflammation through inhibiting RAGE-dependent signaling pathway. Thus, geniposide may be a potential therapeutic agent for the treatment of neuroinflammation that is involved in neurological diseases such as AD.
authors.forename: Cui
authors.initials: C
authors.lastname: Lv
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Liu
authors.forename: Xiao
authors.initials: X
authors.lastname: Cong
authors.forename: Shirley ShiDu
authors.initials: SS
authors.lastname: Yan
authors.forename: Yongyan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: C Building, Beijing Normal University Science Park, No. 12, Xueyuan Southern Street, Haidian District, Beijing, P.R.China, 100088. zws@bnu.edu.cn.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Zhang
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D002452:Cell Count; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D053583:Interleukin-1beta / Q000378:metabolism; D039823:Iridoids / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D017628:Microglia; D009447:Neuroblastoma / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D053583:Interleukin-1beta; D039823:Iridoids; D010446:Peptide Fragments; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D014409:Tumor Necrosis Factor-alpha; C075222:amyloid beta-protein (1-42); C007835:geniposide; D049452:Green Fluorescent Proteins