Amentoflavone suppresses amyloid β1–42 neurotoxicity in Alzheimer's disease through the inhibition of pyroptosis

Abstract

BackgroundThe accumulation of Amyloid β (Aβ) plays key roles in Alzheimer's disease (AD) by inducing intracellular reactive oxygen species (ROS) and neuronal cell death. In this study, we aimed to identify the neuroprotective mechanisms of amentoflavone (AF) in Aβ-induce neuronal cell injury. Materials and methodsThe animal model was established by injecting Aβ1-42 into the bilateral hippocampus. The effect of AF on Aβ1-42-induced neurological dysfunction was examined using the Y-maze and radical maze tests. The hippocampal neuron viability was examined using Nissl staining and TUNEL assay. On the other hand, in vitro studies were conducted using SH-SY5Y cells. The expression level of marker proteins was measured using western blot. The activity of caspase-1 and the levels of pro-inflammatory cytokines were determined using ELISA assay. AMPKα knock down was carried out by transfecting SH-SY5Y cells with siRNA against AMPK transcript. ResultsNeurological tests showed that AF significantly attenuated Aβ1-42-induced neurological dysfunction. AF suppressed Aβ1-42-induced pyroptosis in the hippocampal region of the rat model, which was associated with the modulation of AMPK/GSK3β signaling. Similar results were obtained in vitro in SH-SY5Y cells exposed to Aβ1-42, showing that the neuroprotective activity of AF is mediated by suppressing pyroptosis through AMPK/GSK3β signaling. ConclusionAF inhibits Aβ1-42-induced neurotoxicity in animal and cellular models through AMPK/GSK3β-mediated pyroptosis suppression. Our results highlight AF as a clinical compound for the prevention and treatment of AD.