Cricket‐Enriched Pasta Attenuates Oxidative and Inflammatory Stress in Intestinal Cells: Molecular and Proteomic Insights

The growing demand for sustainable food sources has led to increasing interest in edible insects such as house cricket ( Acheta domesticus ) as functional ingredients. This study evaluated the anti‐inflammatory and antioxidant potential of cricket powder–enriched (10%) durum wheat pasta subjected to a simulated gastrointestinal digestion followed by the application of bioaccessible fraction (BF) to a Caco‐2 intestinal inflammation model. Differentiated Caco‐2 cells were pretreated for 24 h with BF (diluted 1/30, v/v) before lipopolysaccharide (LPS) stimulation (10 μg/mL, 24 h). Bioactivity was evaluated by assessing inflammatory and oxidative stress markers, including nitric oxide (NO), reactive oxygen species (ROS), pro‐inflammatory cytokines (IL‐6 and IL‐8), and NF‐κB p65 nuclear translocation. Intestinal barrier integrity was assessed via transepithelial electrical resistance (TEER). Pretreatment with the BF from cricket‐enriched pasta significantly reduced LPS‐induced NO (15.7%) and ROS (27.3%) levels, inhibited IL‐6 (39.6%) and IL‐8 (52.1%) secretion, and blocked NF‐κB p65 nuclear translocation (54.7%), indicating an anti‐inflammatory and antioxidant activity. In contrast, BF from conventional wheat (100%) pasta showed no significant protective effects. However, neither pasta type improved LPS‐induced barrier disruption, with TEER values remaining at approximately 250 Ω·cm 2 compared to 522.5 Ω·cm 2 in the control. LC‐MS/MS analysis identified nine low‐molecular‐weight cricket‐derived peptides. Subsequent molecular docking simulations demonstrated their capacity to interact with oxidative stress (Keap‐1, MPO, and iNOS) and inflammation‐related (NF‐κB and its p65 subunit) targets, with several peptides showing superior binding affinities compared to positive controls (e.g., GGGSGLGGGGGLGGGSG to iNOS: −9.2 vs. −6.8 kcal/mol; GGGIGGGSGLGGG to Keap‐1: −6.3 vs. −0.3 kcal/mol; SPQQPGQGQQPGQGQ to p65: −6.4 vs. −5.7 kcal/mol; and PQQPQLPFPQQPQ to NF‐κB: −6.0 vs. −6.6 kcal/mol). These findings suggest cricket‐enriched pasta may support intestinal health, although further in vivo research is needed.