Multilevel Assessment of the Antioxidant Potential of Two Edible Insects Following In Vitro Simulated Gastrointestinal Digestion

In recent years, insect-derived peptides have attracted attention for their potential biological activities, particularly antioxidant properties. This study assessed the antioxidant activity of two widely consumed edible insects, <i>T. molitor</i> and <i>A. diaperinus</i> larvae, using cell-free and cell-based approaches. Whole lyophilized larvae, digestion products from the oral, gastric, and intestinal phases, as well as the <3 kDa permeate fraction (D-P3) derived from the intestinal digestion phase, were evaluated using biochemical antioxidant assays. Overall, digested samples exhibited higher antioxidant capacity than their undigested counterparts. At the cellular level, treatment of LPS-stimulated, PMA-differentiated THP-1 macrophages with <i>A. diaperinus</i> D-P3 was associated with increased mRNA expression of genes related to antioxidant defense, including NFE2-like bZIP transcription factor 2 (<i>NFE2L2</i>, also known as Nrf2), glutathione-disulfide reductase (<i>GSR</i>), superoxide dismutase 1 (<i>SOD1</i>), and catalase (<i>CAT</i>), whereas <i>T. molitor</i> D-P3 preferentially modulated nuclear factor kappa B p50 subunit (<i>NFKB1</i>) and nuclear factor kappa B p65 subunit (<i>RELA</i>). Overall, these findings indicate that gastrointestinal digestion enhances the bioaccessibility of antioxidant components in both edible insect species while revealing species-specific transcriptional responses under in vitro inflammatory conditions. This multilevel assessment provides mechanistic insight into the antioxidant-related biological activity of digestion-derived insect peptides and supports their further investigation as functional ingredients in food and feed systems.