Proteomics-Driven Mechanistic Insights into the Anti-Inflammatory Potential of Thinned Apple Polyphenols in a DNBS-Induced Colitis Model in Mice

Ulcerative colitis (UC) is a multifactorial inflammatory bowel disease (IBD) with increasing incidence worldwide. Current treatments, including NSAIDs and corticosteroids, provide partial symptom relief but are associated with significant side effects, highlighting the need for novel therapies with improved safety profiles. Given the role of oxidative stress and inflammation in driving tissue damage during colitis, natural compounds with antioxidant and anti-inflammatory properties represent promising therapeutic candidates. Thinned apples (TA), an agricultural byproduct, were identified as a valuable source of polyphenols (TAP) with demonstrated anti-inflammatory and antioxidant activities in a cell-based inflammation model. This study evaluates TAP's therapeutic potential in a DNBS-induced colitis mouse model using label-free quantitative proteomics. Proteomic analysis revealed modulation of key pathways affected by TAP treatment, including: (i) activation of antioxidant defense mechanisms; (ii) reversal of DNBS-induced alterations, specifically ferroptosis and heme-toxicity; (iii) suppression of immune responses; and (iv) attenuation of ulcerative features, with downregulation of proteins involved in coagulation, inflammation, and angiogenesis. Overall, TAP showed significant therapeutic effects by targeting oxidative stress and inflammation, supporting its use as a polyphenol-rich extract in health products for UC. Moreover, repurposing TA as a bioactive extract offers an innovative strategy for industrial applications in therapeutic development.