ABSTRACT
Alzheimer's disease (AD) is pathologically characterized by excessive accumulation of amyloid-beta (Aß) within extracellular spaces of the brain. Aggregation of Aß has been shown to trigger oxidative stress, inflammation, and neurotoxicity resulting in cognitive dysfunction. In this study, we use models of cerebral Aß amyloidosis to investigate anti-amyloidogenic effects of scutellarin in vitro and in vivo. Our results show that scutellarin, through binding to Aß42, efficiently inhibits oligomerization as well as fibril formation and reduces Aß oligomer-induced neuronal toxicity in cell line SH-SY5Y. After nine months of treatment in APP/PS1 double-transgenic mice, scutellarin significantly improves behavior, reduces soluble and insoluble Aß levels in the brain and plasma, decreases Aß plaque associated gliosis and levels of proinflammatory cytokines TNF-α and IL-6, attenuates neuroinflammation, displays anti-amyloidogenic effects, and highlights the beneficial effects of intervention on development or progression of AD-like neuropathology.
