The MHLWAAK peptide derived from C-phycocyanin ameliorated ulcerative colitis by regulating the PPAR pathway in vivo and in vitro

Ulcerative colitis (UC) is a chronic, relapsing inflammatory disease of the colon. Compared with current therapeutic drugs, bioactive peptides are safer and more promising for UC prevention and treatment. Our previous studies demonstrated that the MHLWAAK peptide derived from C-phycocyanin exhibited excellent antioxidant and anti-inflammatory effects. However, its potential therapeutic effects on UC remain unexplored. In the present study, we aimed to evaluate the therapeutic potency of MHLWAAK in UC and its underlying mechanism using in vivo and in vitro experiments. The in vivo results showed that MHLWAAK effectively alleviated the inflammatory responses and intestinal tissue damage in the zebrafish model with UC induced by dextran sulfate sodium. An RNA-seq analysis revealed that MHLWAAK regulated the peroxisome proliferator-activated receptor (PPAR) pathway at the transcriptional level. The qRT-PCR results consistently indicated that lipid-related genes were upregulated after peptide administration. Additionally, in vitro studies demonstrated that MHLWAAK exerted potent anti-inflammatory effects on lipopolysaccharide-induced inflammatory responses by suppressing the expression of inflammatory genes and proteins. Additionally, western blotting revealed that PPARγ activation inhibited the NF-κB signaling pathways at the protein level after MHLWAAK administration. In summary, this study highlighted the anti-inflammatory activities of MHLWAAK in vitro and in vivo . MHLWAAK peptide development represents a novel and promising strategy for UC prevention and treatment. • MHLWAAK peptide ameliorated DSS-induced UC in zebrafish. • MHLWAAK suppressed the expression of inflammatory genes and proteins. • MHLWAAK ameliorated UC by activating the PPAR signaling pathway.