Affiliation: C Building, Beijing Normal University Science Park, No. 12, Xueyuan Southern Street, Haidian District, Beijing, P.R.China, 100088.
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 A β-induced microglial activation and leads to induction of proinflammatory mediators, such as tumor necrosis factor- α (TNF-α ) and interleukin-1β (IL-1 β). 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 A β-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-κ B) 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 A β-induced inflammatroy response through blocking A β 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.