Study on antioxidant synergistic anti-inflammatory peptide from Giant Salamander ( <em>Andrias davidianus</em>): functional mechanism and delivery by nano-starch

In this study, we explored the anti-inflammatory and antioxidant characteristics of the giant salamander peptide P3. We found that P3 enhances the resistance of RAW264.7 cells to Lipopolysaccharide (LPS)&nbsp;by modulating the Mitogen-Activated Protein Kinase / Nuclear Factor kappa-light-chain-enhancer of activated B cells (MAPK/NF-κB)&nbsp;signaling pathway. Specifically, P3 boosted the activation of mitogen-activated protein kinase, interleukin-6&nbsp;(IL-6), and tumor necrosis factor alpha, while decreasing levels of inflammatory factors like Interleukin-1β&nbsp;(IL-1β)&nbsp;and nitric oxide&nbsp;(NO). Given its potent antioxidant properties, we further examined impact of P3 in the Keap1-ARE-Nrf2&nbsp;signaling pathway and its products. P3 increased the levels of antioxidant enzymes such as glutathione peroxidase and superoxide dismutase, while reducing the concentrations of oxidation products like malondialdehyde and catalase.&nbsp;During <em>in vitro</em>&nbsp;digestion, the functional efficacy of P3 diminished. However, when combined with nano-starch (NS), NS-P3 demonstrated preserved functionality. Our findings indicate that P3 not only exhibits anti-inflammatory effects but also mitigates chronic oxidative stress damage. NS-P3 effectively safeguards the antioxidant capabilities of P3 during simulated digestion.