Protective effects of peptides from skate (Okamejei kenojei) skin gelatin against endothelial dysfunction

Seafood processing by-product, skate (Okamejei kenojei) skin, was utilized to isolate active peptides with antihypertensive effect. Two peptides (MVGSAPGVL, 829 Da and LGPLGHQ, 720 Da) were purified from skate skin gelatin. In human endothelial cells, nitric oxide (NO) synthesis was found to be increased and eNOS phosphorylation was upregulated by the peptides. The peptides exhibited inhibitory activities on the production and expression of IL-6. Furthermore, the peptides down-regulated the expression levels of endothelin-1. The peptides inhibited the NF-κB and the phosphorylation of MAPK pathways. In addition, the activation of the PI3K/Akt pathway by the peptides was confirmed. The present study demonstrated that the purified peptides had vasorelaxant effects via endothelium-dependent NO signaling through activation of the PI3K/Akt-eNOS pathway and inhibition of the NF-κB and MAPK pathways. The purified peptides could be used in the food industry as functional ingredients with potent benefits in reducing the risk of cardiovascular diseases.