Geniposide Attenuates Oligomeric Aβ1-42-Induced Inflammatory Response by Targeting RAGE-Dependent Signaling in BV2 Cells

The neuroinflammation induced by amyloid-beta (A beta) 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 beta -induced microglial activation and leads to induction of proinflammatory mediators, such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). 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 beta-mediated microglial pathways have not been fully discovered. Here, we demonstrate that geniposide treatment significantly blocks A beta-induced RAGE-dependent signaling (activation of ERK and NF-kappa B) along with the production of TNF-alpha and IL-1 beta in cultured BV2 microglia cells. Notably, based on the data from coimmunoprecipitation assay, we infer that geniposide exerts protective effects on A beta-induced inflammatroy response through blocking A beta 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.