Lunasin and lunasin-like peptides inhibit inflammation through suppression of NF-κB pathway in the macrophage

Inflammation is part of the host defense mechanism against harmful matters and injury; however, aberrant inflammation is associated to the development of chronic diseases such as cancer. Lunasin is a novel peptide that demonstrates potential anticancer activity against mammalian cancer cell lines and may play a role in inflammation. The objective of this study was to determine the mechanism of action by which lunasin and lunasin-like peptides exert their anti-inflammatory properties using RAW 264.7 macrophage cell line as an in vitro model. We purified three peptides (5, 8, and 14 kDa) from defatted soybean flour with a positive immunoreactivity towards lunasin mouse monoclonal antibody. Treatment with these peptides (10-50 μM) resulted in the inhibition of pro-inflammatory markers in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. The 5 kDa peptide inhibited most potently pro-inflammatory markers including interleukin-6 production (IC₅₀ = 2 μM), interleukin-1β production (IC₅₀ = 13 μM), nuclear factor-kappa B (NF-κB) transactivation (IC₅₀ = 21 μM), cyclooxygenase-2 expression (IC₅₀ = 25 μM), nitric oxide production (IC₅₀ = 28 μM), inducible nitric oxide synthase expression (IC₅₀ = 37 μM), prostaglandin E₂ production (IC₅₀ = 41 μM), p65 nuclear translocation (IC₅₀ = 48 μM) and p50 nuclear translocation (IC₅₀ = 77 μM). In conclusion, lunasin and lunasin-like peptides purified from defatted soybean flour inhibited inflammation in LPS-induced RAW 264.7 macrophage by suppressing NF-κB pathway.