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.