Identification of Novel Anti-Inflammatory Peptides from Jellyfish Nemopilema nomurai Enzymatic Hydrolysate: An...

Inflammation plays a critical role in host defense and tissue repair; however, excessive or dysregulated inflammatory responses can lead to tissue damage and contribute to the progression of various diseases. Jellyfish-derived peptides have recently emerged as promising marine bioactive compounds with potential anti-inflammatory activity. In this study, three candidate anti-inflammatory peptides were identified from the enzymatic hydrolysate of Nemopilema nomurai through an integrated strategy combining LC-MS/MS-based peptidomics and multi-step in silico screening. The selected peptides (DGIPGMPG, PGFHVPPP, and GPKGYPGP) were prioritized based on predicted bioactivity, non-toxicity, favorable physicochemical properties, and molecular docking with the TLR4/MD-2/LPS complex (PDB ID: 3FXI), with docking scores ranging from -8.4 to -8.3 kcal/mol. Subsequent experimental validation demonstrated that all three peptides exhibited good cytocompatibility and significantly inhibited LPS-induced nitric oxide (NO) production in RAW264.7 macrophages, with GPKGYPGP showing the strongest effect. In addition, these peptides effectively reduced the secretion of pro-inflammatory cytokines, including TNF-α and IL-1β, to varying extents. Collectively, this study identifies three novel anti-inflammatory peptides derived from jellyfish enzymatic hydrolysates and highlights their potential as promising candidates for the development of marine-derived bioactive agents targeting inflammation-related diseases.