Regulatory effects of optimized extraction processes for chlorella-derived peptides on key pathological links in rheumatoid arthritis

• Chlorella peptides exert multi-target synergistic regulatory effects on key pathological links of rheumatoid arthritis, including oxidative stress, macrophage polarization, synovial fibroblast invasion, and vascular endothelial dysfunction. • An optimized extraction process using bromelain enzymatic hydrolysis combined with phosphomolybdic acid precipitation was established, achieving high peptide yield with low cost and scalability. • Chlorella peptides exhibit concentration-dependent antioxidant activity and good biocompatibility in the effective concentration range (1-10 μg/mL), supporting their safety for potential clinical translation. • Chlorella peptides promote M2 macrophage polarization, inhibit fibroblast-like synoviocyte migration, proliferation, and invasion, and suppress endothelial cell migration and tube formation, highlighting their therapeutic potential in rheumatoid arthritis.