A Collagen‐Derived Oligopeptide from Salmo salar Collagen Hydrolysates Restrains Atherogenesis in ApoE –/– Mice via Targeting P 2 Y 12 Receptor

• Published in: Molecular Nutrition & Food Research
• Main Authors: Yang, Yijie, Liu, Hui, Cui, Liyuan, Liu, Yibo, Fu, Lulu, Li, Bo
• Other Authors: National Key Research and Development Program of China
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2022
• Subjects: Salmo salar
• Online Access: http://dx.doi.org/10.1002/mnfr.202200166; https://onlinelibrary.wiley.com/doi/pdf/10.1002/mnfr.202200166; https://onlinelibrary.wiley.com/doi/full-xml/10.1002/mnfr.202200166

Scope Collagen hydrolysates have been reported with a variety of biological activities. The previous study has separated and identified a series of Hyp‐Gly containing antiplatelet peptides from collagen hydrolysates from Salmo salar . But the target and underlying mechanism in platelets remains unknown. Methods and results In this study, peptide OGEFG (OG‐5) inhibits platelet aggregation especially induced by 2MeS‐ADP and attenuates tail thrombosis formation by 30% in a dose‐dependent manner, via apparent antagonism effects on P 2 Y 12 receptors to regulate Gβγi‐PI3K‐Akt signaling and Gαi‐cAMP‐VASP signaling is demonstrated. The molecular docking results also reveal a strong binding energy with the P 2 Y 12 receptor of peptide OG‐5 (−10.70 kcal mol −1 ). In vitro study suggests that OG‐5 inhibited the release of inflammatory cytokines in endothelial cells and macrophage cells, migration of vascular smooth muscle cell induced by ADP, which is highly released in ApoE –/– mice. Long‐term administration of OG‐5 significantly reduces atherosclerotic plaque formation without side effects in ApoE –/– mice, exhibiting a comparable effect with aspirin. Conclusion These results reveal that collagen hydrolysates with OG‐containing peptides have potential to be developed as an effective diet supplement to prevent the occurrence of atherogenesis and thrombotic disease.