Purification and Characterization of Novel Collagen Peptides against Platelet Aggregation and Thrombosis from Salmo salar

Abstract

Collagen is a rich source of bioactive peptides and is widely distributed in the skin and bone tissue. In this study, collagen from Salmo salar skin was hydrolyzed with Alcalase or Protamex followed by simulated digestion, YMC ODS-A C18 separation, and ESI-MS/MS analysis. A total of 19 peptides were identified and synthesized for investigation of their antiplatelet activities. Hyp-Gly-Glu-Phe-Gly (OGEFG) and Asp-Glu-Gly-Pro (DEGP) exhibited the most potent activity against ADP-induced platelet aggregation among them with IC 50 values of 277.17 and 290.00 μM, respectively, and inhibited the release of β-TG and 5-HT in a dose-dependent manner significantly. Single oral administration of OGEFG and DEGP also inhibited thrombus formation in a ferric chloride-induced arterial thrombosis model at a dose of 200 μmol/kg body weight and did not prolong the bleeding time or cause an immune response in mice. Therefore, our findings indicated that collagen peptides had a potential to be developed into an effective specific medical food in the prevention of thrombotic diseases.

A Collagen‐Derived Oligopeptide from Salmo salar Collagen Hydrolysates Restrains Atherogenesis in ApoE–/– Mice via Targeting P2Y12 Receptor

“…Notably, the coagulation parameters were not altered when treated with OG‐5 in effective dosage (Figure 1D), which is consistent with the result of tail bleeding assay that OG‐5 (200 µmol kg −1 bw) would not prolong the bleeding time. [ 6 ] These results suggest that OG‐5 effectively inhibits thrombus formation without causing bleeding complication.…”

“…Our previous study also showed that OG‐5 exhibits the most potent activity against ADP‐induced platelet aggregation with IC 50 values of 277.17 µM and inhibits the granule release of β‐TG and 5‐HT. [ 6 ] Antithrombosis ability in vivo of OG‐5 was further evaluated in carrageenan‐induced mouse tail thrombosis model by using aspirin as a positive control. As shown in Figure 1C, OG‐5 inhibited thrombus formation by 30% at an oral dosage of 50 mg kg −1 bw, approximately.…”

“…Similar results were also observed in a ferric chloride‐induced arterial thrombosis model. [ 6 ] Furthermore, oral administration of OG‐5 did not prolong the coagulation parameters including PT, APTT, and TT (Figure 1D). These results suggest that OG‐5 could inhibit platelet activation in vitro, and significantly attenuated thrombosis formation in mice without bleeding risks.…”

“…OG‐5 is one of the most potent antiplatelet peptides among them and also inhibited thrombus formation in a ferric chloride‐induced arterial thrombosis model. [ 6 ] In this study, we performed in vitro and in vivo studies to demonstrate that collagen peptide OG‐5 could be an attractive agent in the prevention of atherogenesis. Actually, OG‐5 was firstly identified as an antiplatelet aggregation peptide especially for 2MeS‐ADP‐induced platelet activation (Figure 1B).…”

“…The peptide OG‐5 is one of the most potent antiplatelet peptides among them and also inhibited thrombus formation in a ferric chloride‐induced arterial thrombosis model without bleeding risks. [ 6 ] However, the target and antiplatelet activation mechanism of OG‐5 remained unknown. The data present here clarified the precise mechanism and P 2 Y 12 receptor was identified as the target of OG‐5.…”