Abstract

Dried daylily flower buds, rich in polyphenols, are an edible vegetable renowned for their nutritional and health benefits. This study employed Caenorhabditis elegans ( C. elegans ) as a model organism to investigate the protective effects of the ethyl acetate fraction from the ethanol extract of Hemerocallis citrina (HC-EA) against amyloid-beta (Aβ) toxicity and elucidate its underlying mechanisms The results demonstrated that HC-EA significantly alleviated Aβ-induced paralysis and extended lifespan in C. elegans , while exhibiting no observable toxicity at concentrations ranging from 0.1 to 1 mg/mL. Mechanistically, HC-EA reduced Aβ transcription and protein levels, decreased reactive oxygen species (ROS) accumulation, and enhanced glutathione peroxidase (GPx) and proteasome activities in Alzheimer's disease (AD) C. elegans models. Furthermore, HC-EA upregulated the expression of antioxidant-related genes ( gst-4 , skn-1 ) and proteasome subunit genes ( rpt-3 , pbs-1 , pbs-2 , pbs-5 ), and conferred resistance to paraquat-induced oxidative stress via the SKN-1 pathway in wild-type nematodes. Notably, the proteasome inhibitor MG132 partially reversed HC-EA's anti-paralysis effect, suggesting that its action depends on proteasome activation and SKN-1-mediated oxidative stress mitigation. Collectively, HC-EA may attenuate Aβ toxicity by enhancing proteasome activity and antioxidant pathways, offering a potential protective effect against Alzheimer's disease (AD). Graphical