earticle

영어

Cardiovascular diseases, principally myocardial infarction, stroke and atherosclerosis, are a significant public health problem worldwide. In this study, skin gelatin of skate (Okamejei kenojei) was sequentially hydrolyzed using Alcalase and protease and was separately using a 1 kDa molecular weight cut-off membrane. Antihypertensive effect in spontaneously hypertensive rats revealed that oral administration of hydrolysate below 1 kDa can decrease systolic blood pressure significantly. Vascularity, muscularization and cellular proliferation in rat lung tissues were detected by immunohistochemical staining. Finally, two peptides responsible for ACE inhibitory activity were identified to be MVGSAPGVL (829 Da) (SP1) and LGPLGHQ (720 Da) (SP2) with IC50 values of 3.09 μM and 4.22 μM, respectively. The purified peptides are found to attenuate reactive oxygen species production and increase antioxidative enzymes in EA.hy926 cells. The purified peptides augmented the production of nitric oxide by activating endothelial nitric oxide synthase (eNOS) expression in EA.hy926 cells. The peptides significantly suppressed angiotensin II-induced release and the expression levels of endothelin-1, pro-inflammatory products and cytokines; tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6 and IL-8 in EA.hy926 cells. Molecular signaling pathway studies showed that the peptides inhibited the nuclear factor kappa B (NF-κB) p65 and p50 subunits and the phosphorylation of mitogen activated protein kinase (MAPK) pathway molecules in EA.hy926 cells. These results suggested that the cardioprotective mechanism of hydrolysate and peptides isolated from skate skin gelatin may be partly due to improvement of endothelial function associated with eNOS and oxidative stress pathway. In conclusion, the purified hydrolysate and peptides would be beneficial ingredients for nutraceuticals and pharmaceuticals against cardiovascular diseases.