Data Sheet 1_Icariside II protects against neuronal injury by modulating PI3K/AKT-dependent mitochondrial dynamics and apoptosis in Alzheimer’s disease models.docx

Introduction<p>Icariside II (ICS II), a major bioactive flavonoid metabolite from Epimedium, has been reported to exert neuroprotective effects, but its role in regulating mitochondrial dysfunction-related neuronal injury in Alzheimer’s disease (AD) has not been fully clarified.</p>Methods<p>In this study, we administered ICS II to APP/PS1 transgenic mice and to two neuronal cell models of AD-like injury (Aβ-exposed HT22 cells and APP-overexpressing N2a cells).

We evaluated cognitive behaviour, histopathological changes, Aβ burden, neuronal apoptosis, mitochondrial membrane potential (ΔΨm), mitochondrial reactive oxygen species (mtROS) levels, mitochondrial morphology and dynamics (including fragmentation, mitofusin-2 (Mfn2) expression, and dynamin-related protein 1 (Drp1) phosphorylation), as well as cytochrome c (Cyt c) release and caspase-3 activity. RNA-sequencing analysis of hippocampal tissue and pharmacological inhibition with the PI3K inhibitor LY294002 were employed to probe the involvement of the PI3K/AKT signalling pathway.</p>Results and discussion<p>In vivo, ICS II improved cognitive performance, ameliorated hippocampal and cortical histopathological damage, decreased Aβ immunoreactivity, and reduced neuronal apoptosis.