Title:Geniposide Attenuates Oligomeric Aβ1-42-Induced Inflammatory Response by Targeting RAGE-Dependent Signaling in BV2 Cells
Volume: 11
Issue: 5
Author(s): Cui Lv, Lei Wang, Xiaoli Liu, Xiao Cong, Shirley ShiDu Yan, Yongyan Wang and Wensheng Zhang
Affiliation:
Keywords:
Alzheimer’s disease, geniposide, inflammatory responses, oligomeric Aβ1-42, RAGE, RAGE-dependent signaling
pathway.
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.
