Isoorientin Inhibits Amyloid beta(25-35)-Induced Neuronal Inflammation in BV2 Cells by Blocking the NF-kappa B Signaling Pathway

Abstract

Alzheimer's disease (AD) is a severe neurodegenerative disorder. AD is pathologically characterized by the formation of intracellular neurofibrillary tangles, and extracellular amyloid plaques which were comprised of amyloid-beta (A beta) peptides. A beta induces neurodegeneration by activating microglia, which triggers neurotoxicity by releasing various inflammatory mediators and reactive oxygen species (ROS). Nuclear factor-kappa B (NF-kappa B) is expressed in human tissues including the brain and plays an important role in A beta-mediated neuronal inflammation. Thus, the identification of molecules that inhibit the NF-kappa B pathway is considered an attractive strategy for the treatment and prevention of AD. Isoorientin (3 & PRIME;,4 & PRIME;,5,7-Tetrahydroxy-6-C-glucopyranosyl flavone; ISO), which can be extracted from several plant species, such as Philostachys and Patrinia is known to have various pharmacological activities such as anticancer, antioxidant, and antibacterial activity. However, the effect of ISO on A beta-mediated inflammation and apoptosis in the brain has yet to be elucidated. In the present study, we investigated whether ISO regulated A beta-induced neuroinflammation in microglial cells and further explored the underlying mechanisms. Our results showed that ISO inhibited the expression of iNOS and COX-2 induced by A beta(25-35.) And, it inhibited the secretion of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). In addition, ISO reduced the ROS production in A beta(25-35)-induced BV2 cells and inhibited NF-kappa B activation. Furthermore, ISO blocked A beta(25-35)-induced apoptosis of BV2 cells. Based on these findings, we suggest that ISO represents a promising therapeutic drug candidate for the treatment and prevention of AD.