Nanoencapsulation of phycocyanin peptides enhances anti‐inflammatory activity and alleviates ulcerative colitis

BACKGROUND: Ulcerative colitis (UC) is a prevalent inflammatory bowel disease, and current medications have considerable side effects. Phycocyanin peptides (PCPs) have demonstrated anti-inflammatory potential; however, their clinical application is limited by poor stability and low bioavailability. This study prepared highly active PCPs via ultrasound-assisted enzymatic hydrolysis and used chitosan-sodium tripolyphosphate nanoencapsulation to improve their application performance. RESULTS: PCPs significantly inhibited nitric oxide release in lipopolysaccharide-induced RAW264.7 cells. The encapsulation efficiency of phycocyanin peptide nanoparticles (PCP-NPs) reached 91.33%, with markedly enhanced gastrointestinal stability and bioavailability. In mouse experiments, PCP-NPs reduced the disease activity index of ulcerative colitis mice, repaired colonic injury, down-regulated pro-inflammatory cytokines, and up-regulated anti-inflammatory cytokines and intestinal tight junction proteins. Three core anti-inflammatory peptides, YAINA, FPYTT, and YVTYA, were isolated and identified. CONCLUSION: Nanoencapsulation strengthens the anti-inflammatory activity and intestinal barrier repair capacity of PCPs, which hold promising application potential as functional food ingredients for ulcerative colitis prevention. © 2026 Society of Chemical Industry.