Geniposide attenuates oligomeric Aβ(1-42)-induced inflammatory response by targeting RAGE-dependent signaling in BV2 cells.

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.

• Authors: Cui Lv, Lei Wang, Xiaoli Liu, Xiao Cong, Shirley ShiDu Yan, Yongyan Wang, Wensheng Zhang
• Journal: Current Alzheimer research (Curr Alzheimer Res) Vol. 11 Issue 5 Pg. 430-40 ( 2014) ISSN: 1875-5828 [Electronic] United Arab Emirates
• PMID: 24801214 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Interleukin-1beta
• Iridoids
• Peptide Fragments
• RNA, Messenger
• Receptor for Advanced Glycation End Products
• Receptors, Immunologic
• Tumor Necrosis Factor-alpha
• amyloid beta-protein (1-42)
• geniposide
• Green Fluorescent Proteins

Topics

• Amyloid beta-Peptides (pharmacology)
• Animals
• Cell Count
• Cell Line
• Dose-Response Relationship, Drug
• Drug Interactions
• Gene Expression Regulation (drug effects)
• Green Fluorescent Proteins (genetics, metabolism)
• Humans
• Immunoprecipitation
• Interleukin-1beta (metabolism)
• Iridoids (chemistry, pharmacology)
• Mice
• Microglia
• Neuroblastoma (pathology)
• Peptide Fragments (pharmacology)
• RNA, Messenger (metabolism)
• Receptor for Advanced Glycation End Products
• Receptors, Immunologic (genetics, metabolism)
• Signal Transduction (drug effects)
• Transfection
• Tumor Necrosis Factor-alpha (metabolism)