Inflammation is a natural immune response to injury, infection, or harmful stimuli. While it is essential for host defense, chronic or excessive inflammation can lead to tissue damage and is implicated in diseases such as inflammatory bowel disease, gout, hyperuricemia nephropathy, and various pulmonary, hepatic, and neurological disorders. Certain oligopeptides, particularly those containing valine and proline, exhibit anti-inflammatory properties. Marine-derived oligopeptides are also known to possess diverse bioactive effects, including anticancer, antioxidative, and anti-inflammatory activities. In this study, an oligopeptide with the sequence CGQCPVS was cyclized via disulfide bond formation using the solid-phase peptide synthesis method. The cyclized peptide was analyzed and compared to its linear form using bioinformatics tools and molecular docking techniques to assess binding efficiency with key inflammatory proteins, including NLRP3, AIM2, Caspase-1, and IL-1β. The cyclized peptide exhibited reduced binding affinity to the NACHT domain of the NLRP3 inflammasome, comparable to MCC950, a known NLRP3 inhibitor. In vitro studies on the HCT116 epithelial cell line demonstrated high cell viability and a reduction in inflammatory markers at a 50 μM concentration. Further, the cyclized peptide downregulated proteins involved in the inflammatory pathway, including pro-inflammatory cytokines, effectively suppressing inflammation. These findings suggest that the cyclized oligopeptide holds potential as a pharmaceutical agent to mitigate NLRP3 inflammasome-associated inflammation and may serve as a promising candidate for developing novel anti-inflammatory therapies.
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