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 (Aβ)
peptides. Aβ induces neurodegeneration by activating microglia, which triggers neurotoxicity by releasing various inflammatory mediators and
reactive oxygen species (ROS).
Nuclear factor-kappa B (NF-κB) is expressed in human tissues including the brain and plays an important role in Aβ-mediated neuronal
inflammation. Thus, the identification of molecules that inhibit the NF-κB pathway is considered an attractive strategy for the treatment and prevention of AD.
Isoorientin (3',4',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 Aβ-mediated
inflammation and apoptosis in the brain has yet to be elucidated. In the present study, we investigated whether ISO regulated Aβ-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 Aβ25-35. And, it inhibited the secretion of pro-inflammatory
cytokines such as
tumor necrosis factor-α (TNF-α) and
interleukin-6 (IL-6). In addition, ISO reduced the ROS production in Aβ25-35-induced BV2 cells and inhibited NF-κB activation. Furthermore, ISO blocked Aβ25-35-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.