Scutellarin Mitigates Aβ-Induced Neurotoxicity and Improves Behavior Impairments in AD Mice

Alzheimer's disease (AD) is pathologically characterized by excessive accumulation of amyloid-beta (A beta) within extracellular spaces of the brain. Aggregation of A beta has been shown to trigger oxidative stress, inflammation, and neurotoxicity resulting in cognitive dysfunction. In this study, we use models of cerebral A beta amyloidosis to investigate anti-amyloidogenic effects of scutellarin in vitro and in vivo. Our results show that scutellarin, through binding to A beta 42, efficiently inhibits oligomerization as well as fibril formation and reduces A beta 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 A beta levels in the brain and plasma, decreases A beta plaque associated gliosis and levels of proinflammatory cytokines TNF-alpha and IL-6, attenuates neuroinflammation, displays anti-amyloidogenic effects, and highlights the beneficial effects of intervention on development or progression of AD-like neuropathology.