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. 2020 Aug 4;5(32):19995-20003.
doi: 10.1021/acsomega.0c01340. eCollection 2020 Aug 18.

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

Yijie Yang  1 , Bo Wang  1 , Qi Tian  1 , Bo Li  1   2
Affiliations

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

Yijie Yang et al. ACS Omega. .

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 IC50 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.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
(A) Degree of hydrolysis of Alcalase and Protamex collagen hydrolysates followed by pepsin and pancreatin (PP) digestion at various time points. (B) Molecular weight (MW) distribution of the collagen hydrolysate.
Figure 2
Figure 2
Separation of (A) Alcalase and (B) Protamex collagen hydrolysates after simulated gastrointestinal digestion by a YMC ODS-A C18 column and corresponding inhibition of platelet aggregation induced by ADP of collagen hydrolysate fractions from C18 separation at 2 and 4 mg/mL, respectively. Bars (mean ± SD, n = 3) with different alphabets have mean values that are significantly different (p < 0.05).
Figure 3
Figure 3
ESI mass spectrum of collagen peptides present in (A) AH-PP-F2, (B) AH-PP-F3, (C) PH-PP-F2, and (D) PH-PP-F4. MS/MS spectrum of peptides (E) OGEFG (521.26 Da) and (F) DEGP (416.16 Da).
Figure 4
Figure 4
IC50 values of antiplatelet aggregation effects of CPs induced by (A) ADP and (B) thrombin. The effects of CPs on the release of 5-HT-induced by (C) ADP and (D) thrombin as well as (E) β-TG for ADP and (F) thrombin. Bars (mean ± SD, n = 3) with different alphabets have mean values that are significantly different (p < 0.05). *, **, and *** indicate p < 0.05, p < 0.01, and p < 0.001, respectively, as compared to the control group.
Figure 5
Figure 5
Effects of CPs OGEFG and DEGP on ferric chloride-induced arterial thrombosis model rats. Male Sprague Dawley rats were orally administrated with 0.9% saline, clopidogrel, aspirin, OGEFG, or DEGP at different doses (μmol/kg b.w.), respectively. Bars (mean ± SD, n = 6) with different alphabets have mean values that are significantly different (p < 0.05).
Figure 6
Figure 6
Effects of CPs OGEFG and DEGP on (A) BT and (B) thymus index and spleen index in mice. Male ICR mice were orally administrated with 0.9% saline, clopidogrel, aspirin, OGEFG, or DEGP at different doses (μmol/kg b.w.), respectively. ** and *** indicate p < 0.01 and p < 0.001, respectively, as compared to the vehicle group.
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