Screening and characterization of a novel cupin-like polypeptide from Oyster (Ostrea gigas) and its anti-inflammatory effect via TAK1 mediated NF-κB pathway

Inflammation is a natural host defense response to injury or infection, and seafood-derived polypeptides exhibit prominent anti-inflammatory potential with promising therapeutic applications. Here, we report the screening, characterization and anti-inflammatory evaluation of a novel cupin-like polypeptide OGP1-1 from Ostrea gigas . OGP1-1 exerted significant anti-inflammatory effects in RAW264.7 macrophages in vitro and in a transgenic zebrafish model in vivo. Chemical proteomics identified transforming growth factor-β-activated kinase 1 (TAK1) as the direct molecular target, and molecular docking and dynamics simulations confirmed stable binding within TAK1's activation loop. Mechanistic studies demonstrated that OGP1-1 exerts its anti-inflammatory effects by suppressing the TAK1-mediated NF-κB signaling pathway. Collectively, these findings position OGP1-1 as a novel cupin-like polypeptide with potent anti-inflammatory activity and high potential for development as a functional food ingredient in inflammation management.