2026-10-13T06:56:19Z https://api.figshare.com/v2/oai

oai:figshare.com:article/33950320 2026-09-21T05:48:33Z category_19 portal_316 item_type_3 month_year_09_2026

Data Sheet 3_Icariside II protects against neuronal injury by modulating PI3K/AKT-dependent mitochondrial dynamics and apoptosis in Alzheimer’s disease models.xlsx Si-Yu Shan (21179222) Jia-Ming Bai (21179210) Yu Tian (367745) Yu-Feng Shen (2258335) Ye-Xin Zhang (1777012) Yu-Han Cheng (808412) Yang Liu (4829) Hong-Yang Ning (25080724) Dong-Yu Min (21179219) Lu Ren (836410) Hong-He Xiao (21179228) Pharmacology Alzheimer’s disease apoptosis Icariside II mitochondrial dynamics PI3K/AKT signaling pathway 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. RNA-sequencing analysis suggested the involvement of PI3K/AKT signaling in the response to ICS II treatment. In vitro, ICS II increased cell viability, reduced oxidative stress, and inhibited apoptosis. These effects were associated with increased PI3K expression and AKT phosphorylation, restoration of ΔΨm, reduced mtROS accumulation, restored mitochondrial morphology (e.g., alleviated fragmentation, reduced punctate fragments, and increased mitochondrial length), decreased Cyt c release, increased Mfn2 expression, and decreased Drp1 phosphorylation at Ser616 and caspase-3 levels. Notably, co-treatment with LY294002 largely abolished these protective effects, indicating that PI3K/AKT signaling is functionally involved in this process. Taken together, our findings suggest that ICS II protects against AD-related neuronal injury are closely associated with PI3K/AKT-dependent regulation of mitochondrial dynamics and apoptosis, thereby providing a mechanistic foundation for further exploration of ICS II as a natural product-derived candidate for AD intervention.</p> 2026-09-21T05:48:33Z Dataset Dataset 10.3389/fphar.2026.1911518.s001 https://figshare.com/articles/dataset/Data_Sheet_3_Icariside_II_protects_against_neuronal_injury_by_modulating_PI3K_AKT-dependent_mitochondrial_dynamics_and_apoptosis_in_Alzheimer_s_disease_models_xlsx/33950320 CC BY 4.0