Multi-faced neuroprotective effects of geniposide depending on the RAGE-mediated signaling in an Alzheimer mouse model

Neuropharmacology. 2015 Feb:89:175-84. doi: 10.1016/j.neuropharm.2014.09.019. Epub 2014 Sep 28.

Abstract

The receptor for advanced glycation end products (RAGE)-mediated signaling pathway is related to Aβ-induced pathogenic responses. Geniposide, a pharmacologically active component purified from gardenia fruit, could attenuate the oligomeric Aβ(1-42)-induced inflammatory response by blocking the ligation of Aβ to RAGE and suppressing the RAGE-mediated signaling in vitro. Here, we investigated whether geniposide can exert protective effects on the neuroinflammation and memory deficits in an Alzheimer's disease (AD) mouse model. The results indicate that geniposide treatment significantly suppresses RAGE-dependent signaling (activation of ERK and IκB/NF-κB), the production of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and cerebral Aβ accumulation in vivo. Furthermore, we demonstrate that geniposide augments synaptic plasticity by attenuating the Aβ-induced reduction of long-term potentiation and increasing the miniature excitatory postsynaptic current (mEPSC) amplitude and frequency in hippocampal neurons. In addition, the intragastric administration of geniposide improves learning and memory in APP/PS1 mice. Taken together, these studies indicate that geniposide has profound multifaceted neuroprotective effects in an AD mouse model. Geniposide demonstrates its neuroprotection by inhibiting inflammation, ameliorating amyloid pathology and improving cognition. Thus, geniposide may be a potential therapeutic agent for halting and preventing AD progression.

Keywords: APP/PS1 transgenic mice; Alzheimer's disease; Amyloid-β; Geniposide; Receptor for advanced glycation end products.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Alzheimer Disease / prevention & control*
  • Animals
  • Cells, Cultured
  • Disease Models, Animal*
  • Iridoids / pharmacology
  • Iridoids / therapeutic use*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / physiology*
  • Treatment Outcome

Substances

  • Iridoids
  • Neuroprotective Agents
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • geniposide