College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, China.
School of Health Science and Engineering, National Grain Industry (Urban Grain and Oil Security) Technology Innovation Center, University of Shanghai for Science and Technology, Shanghai, China.
J Food Sci. 2022 Jul;87(7):3279-3293. doi: 10.1111/1750-3841.16215. Epub 2022 Jun 15.
Platelet activation is involved in cardiovascular thrombosis. Our previous study demonstrated that oral administration of collagen peptides (CPs) inhibited platelet activation, but the mechanism of action of CPs remained to be elucidated. As a continued effort, the objective of this study was to identify the active ingredient of CPs and clarify its molecular mechanism. Simulated absorbate of CPs was prepared by simulated gastrointestinal digestion and intestinal absorption system, and then separated by C18 column. The fraction with the highest antiplatelet activity was subjected to NanoUPLC-ESI-MS/MS for peptide sequencing. Novel tripeptide Hyp-Asp-Gly (ODG) was identified. It had a broad-spectrum inhibition of platelet activation induced by collagen, thrombin, and adenosine diphosphate (ADP). ODG could survive simulated gastrointestinal digestion and be absorbed intact. Furthermore, it showed good stability in plasma. ODG had no significant effect on the PLC-PKC-Ca pathway, but it inhibited the PI3K/Akt-MAPK/ERK1/2 signaling. At a dosage of 200 µmol/kg body weight, ODG had an in vivo anti-thrombosis activity without bleeding risk. The present study provides one of the mechanisms of action of CPs and highlights its potential use as a functional component to combat cardiovascular thrombosis. PRACTICAL APPLICATION: This study has suggested that tripeptide Hyp-Asp-Gly(ODG) derived from collagen have potent activities. This novel collagen peptide had a greatpotential to be applied to combat cardiovascular thrombosis in the foodindustry. Meanwhile, this work is expected to provide a theoretical basis forthe development of safe and effective anti-platelet and anti-thrombosis peptides.
血小板活化参与心血管血栓形成。我们之前的研究表明，口服胶原蛋白肽（CPs）可抑制血小板活化，但 CPs 的作用机制仍需阐明。作为进一步的努力，本研究的目的是确定 CPs 的有效成分并阐明其分子机制。通过模拟胃肠道消化和肠吸收系统制备 CPs 的模拟吸收物，然后用 C18 柱分离。具有最高抗血小板活性的部分用 NanoUPLC-ESI-MS/MS 进行肽测序。鉴定出新型三肽 Hyp-Asp-Gly（ODG）。它对胶原蛋白、凝血酶和二磷酸腺苷（ADP）诱导的血小板活化具有广谱抑制作用。ODG 可以耐受模拟胃肠道消化并完整吸收。此外，它在血浆中表现出良好的稳定性。ODG 对 PLC-PKC-Ca 途径没有明显影响，但它抑制了 PI3K/Akt-MAPK/ERK1/2 信号通路。在 200µmol/kg 体重的剂量下，ODG 具有体内抗血栓形成活性而没有出血风险。本研究提供了 CPs 的作用机制之一，并强调了其作为功能性成分用于对抗心血管血栓形成的潜力。实际应用：本研究表明源自胶原蛋白的三肽 Hyp-Asp-Gly（ODG）具有很强的活性。这种新型胶原蛋白肽具有很大的潜力在食品工业中用于对抗心血管血栓形成。同时，这项工作有望为开发安全有效的抗血小板和抗血栓肽提供理论基础。
