Effects of Red Onion Peel Extracts on Oxidative Stress in Caenorhabditis elegans

Polyphenols are natural compounds with antioxidant properties that help prevent chronic diseases. Red onion (Allium cepa) peels are an underutilized source of polyphenols, offering a sustainable opportunity for the valorization of agricultural by-products. Polyphenol-rich extracts were obtained from red onion peels using subcritical water extraction and adsorption resin chromatography. Their biological effects were evaluated in Caenorhabditis elegans under oxidative stress conditions. A multi-omics approach integrating transcriptomics, metabolomics, and lipidomics was applied to assess molecular responses. The extract exhibited a high total phenolic content (>400 mg GAE/g) and strong antioxidant capacity, supporting a highly enriched polyphenolic profile. Survival assays confirmed the absence of toxicity at 100 µg/mL GAE. Transcriptomic analysis revealed 158 differentially expressed genes associated with stress response and metabolic regulation. Metabolomic profiling indicated a systematic reduction in amino acid levels alongside an increase in betaine in treated worms, suggesting adaptive metabolic reprogramming. Lipidomic analysis revealed significant lipid remodeling, characterized by decreased triglycerides, increased diacylglycerols, and changes in membrane phospholipids, indicating alterations in membrane composition and cellular responses associated with oxidative stress adaptation. Together, these results support a model in which red onion peel extracts induce coordinated transcriptional and metabolic adaptations associated with cellular resilience and stress adaptation. This study highlights the potential of agro-industrial by-products as functional bioactive ingredients and demonstrates the value of multi-omics approaches for uncovering system-level responses.