Geniposide Attenuates Oligomeric Aβ_1-42-Induced Inflammatory Response by Targeting RAGE-Dependent Signaling in BV2 Cells

Title:Geniposide Attenuates Oligomeric Aβ_1-42-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 Aβ_1-42, 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.

Cite this article as:

Lv Cui, Wang Lei, Liu Xiaoli, Cong Xiao, Yan ShiDu Shirley, Wang Yongyan and Zhang Wensheng, Geniposide Attenuates Oligomeric Aβ_1-42-Induced Inflammatory Response by Targeting RAGE-Dependent Signaling in BV2 Cells, Current Alzheimer Research 2014; 11 (5) . https://dx.doi.org/10.2174/1567205011666140514111204