Digestion Products from Oxidized Rice Bran Protein Exacerbate Oxidative Stress and Inflammation via Nrf2/NF-κB Crosstalk

To comprehensively elucidate the structure-activity relationship of oxidation on rice bran protein (RBP) nutrition, a hepatic metabolism model was established to evaluate the cellular impacts of RBP digestion products (RBPDP). Chromatography and multivariate analyses revealed oxidation-dependent changes in RBPDP profiles, marked by the loss of native protective peptides and formation of enzyme-resistant aggregates, identified as nutritional deterioration and oxidation markers, respectively. Compared to native RBP, digestion products from oxidized RBP elevated oxidation products and suppressed antioxidant capacity despite Nrf2 activation while increasing pro-inflammatory cytokines via the MyD88/NF-κB pathway. The NF-κB inhibitor pyrrolidine dithiocarbamate partially attenuated damage, though its efficacy diminished with increasing RBP oxidation. Results demonstrated that oxidation-induced protective peptide depletion and aggregate formation synergistically drove oxidative damage and an inflammatory response via activated Keap1-Nrf2/ARE and MyD88/NF-κB pathways. Critically, Nrf2/NF-κB crosstalk served as a key regulatory node, providing molecular targets to optimize the nutrition of RBP-based functional foods under oxidative stress.