Isovitexin Attenuates Aβ-Induced Neurotoxicity by Activating SKN-1/Nrf2 Signaling and Suppressing Ferroptosis in Caenorhabditis elegans Models of Alzheimer’s Disease
TL;DR
Results showed that isovitexin significantly extended lifespan, reduced Aβ accumulation, and improved neuromuscular function, demonstrating marked neuroprotective effects, and support further investigation of isovitexin as a candidate for mitigating Aβ-induced neurodegeneration.
Abstract
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by β-amyloid (Aβ) deposition, oxidative stress, ferroptosis, and mitochondrial dysfunction, while effective therapeutic interventions remain limited. Epidemiological evidence indicates that tea and flavonoids with antiaging properties lower AD risk. In this study, untargeted metabolomic profiling identified isovitexin as a differentially abundant flavonoid in postfermented dark tea (DT), and Caenorhabditis elegans (C. elegans) AD models were employed to evaluate its anti-AD potential and elucidate the underlying molecular mechanisms. The results showed that isovitexin significantly extended lifespan, reduced Aβ accumulation, and improved neuromuscular function, demonstrating marked neuroprotective effects. Mechanistically, isovitexin mitigated Aβ-triggered toxicity through SKN-1 signaling, accompanied by the attenuation of Aβ-evoked ferroptosis and mitochondrial dysfunction. Collectively, these results broaden the therapeutic potential of dark tea flavonoids and support further investigation of isovitexin as a candidate for mitigating Aβ-induced neurodegeneration.