College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China.
Key Laboratory of Functional Dairy, Ministry of Education, Beijing, 100083, China.
Mol Nutr Food Res. 2022 Jul;66(13):e2200166. doi: 10.1002/mnfr.202200166. Epub 2022 May 8.
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.
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 Y 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 Y receptor of peptide OG-5 (-10.70 kcal mol ). 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.
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.
胶原蛋白水解物具有多种生物学活性。先前的研究已经从鲑鱼胶原蛋白水解物中分离和鉴定了一系列含有 Hyp-Gly 的抗血小板肽。但血小板中的靶点和潜在机制仍不清楚。
在这项研究中，肽 OGEFG（OG-5）通过明显的 P Y 受体拮抗作用，调节 Gβγi-PI3K-Akt 信号和 Gαi-cAMP-VASP 信号，以剂量依赖的方式抑制由 2MeS-ADP 诱导的血小板聚集，尤其对血小板聚集有抑制作用，并能将血栓尾巴形成减少 30%。分子对接结果也表明肽 OG-5 与 P Y 受体具有很强的结合能（-10.70 kcal/mol）。体外研究表明，OG-5 抑制了内皮细胞和巨噬细胞中炎症细胞因子的释放，以及 ADP 诱导的血管平滑肌细胞迁移，而 ApoE 小鼠中 ADP 高度释放。在 ApoE 小鼠中，长期给予 OG-5 可显著减少动脉粥样硬化斑块的形成，且无副作用，与阿司匹林的效果相当。
这些结果表明，含有 OG 的胶原蛋白水解物肽具有作为有效饮食补充剂的潜力，可预防动脉粥样硬化形成和血栓性疾病的发生。
