Geniposide attenuates oligomeric Aβ(1-42)-induced inflammatory response by targeting RAGE-dependent signaling in BV2 cells

Curr Alzheimer Res. 2014;11(5):430-40. doi: 10.2174/1567205011666140514111204.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / pharmacology*
  • Animals
  • Cell Count
  • Cell Line
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Gene Expression Regulation / drug effects
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Immunoprecipitation
  • Interleukin-1beta / metabolism
  • Iridoids / chemistry
  • Iridoids / pharmacology*
  • Mice
  • Microglia
  • Neuroblastoma / pathology
  • Peptide Fragments / pharmacology*
  • RNA, Messenger / metabolism
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / metabolism*
  • Signal Transduction / drug effects*
  • Transfection
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Amyloid beta-Peptides
  • Interleukin-1beta
  • Iridoids
  • Peptide Fragments
  • RNA, Messenger
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • Tumor Necrosis Factor-alpha
  • amyloid beta-protein (1-42)
  • geniposide
  • Green Fluorescent Proteins