Molecular Mechanisms Underlying the Alleviation of Aβ‐Induced Toxicity by Edible Flower Buds of Hemerocallis citrina in Caenorhabditis elegans

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).