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Background/objectives: Atherosclerosis is a chronic inflammatory disease of the arterial wall, which involves multiple cell types. Peptide OG-5 is identified from collagen hydrolysates derived from Salmo salar and exhibits an inhibitory effect on early atherosclerosis. The primary objective of this study was to investigate the impact of OG-5 on advanced atherosclerotic lesions as well as its stability during absorption., Methods: In this study, the ApoE-/- mice were employed to establish advanced atherosclerosis model to investigate the treatment effect of peptide OG-5., Results: The results showed that oral administration of OG-5 at a dosage of 150 mg/kg bw resulted in a 30% reduction in the aortic plaque formation area in ApoE -/- mice with few bleeding risks. Specifically, intervention with a low dose of OG-5 (50 mg/kg bw), initiated in the early stage of atherosclerosis, continues to provide benefits into the middle and late stages without bleeding risks. Furthermore, treatment of OG-5 increased expression levels of contractile phenotype markers and reduced the accumulation of lipoprotein in VSMCs induced by ox-LDL. Peptide OG-5 could ensure transport across Caco-2 cell monolayers, exhibiting a P app value of 1.80 × 10 -5 cm/s, and exhibited a robust stability in plasma with remaining content >70% after 8 h incubation. In vivo studies revealed that OG-5 reached maximum concentration in blood after 120 min., Conclusion: The present results demonstrate the potential efficacy of peptide OG-5 as a promising agent for intervention in anti-atherogenesis strategies.

Atherosclerosis (AS) is the underlying condition in most cardiovascular diseases, which is blood vessel inflammation participated by many factors. Collagen hydrolysate from salmo salar skin (SCH) obtained in this study showed strong anti-inflammatory activity, protection of endothelial cell injury, antioxidant activity, and anti-platelet aggregation activity in vitro, exhibiting a great potential of attenuating AS. In this study, multifunctional peptides FAGPPGGDGQPGAK and IAGPAGPRGPSGPA, which mainly showed strong anti-inflammatory activity, were identified from SCH after separation of ultrafiltration and column chromatography. Moreover, SCH (contained anti-platelet peptides and anti-inflammatory peptides) was observed to inhibit arterial intima thickening and plaques formation in apolipoprotein E-deficient (ApoE -/- ) mice fed with high-fat diets without side effects, exhibiting a comparable effect with aspirin. SCH showed combined effect on regulating serum biomarkers of inflammation (IL-6 and TNF-α), endothelial injury (MCP-1), platelet activation (TXB 2 and PF4) and oxidative stress (MDA and CAT). This research suggested SCH as a potential dietary supplement for the primary prevention of AS., (Copyright © 2022. Published by Elsevier Ltd.)

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., (© 2022 Wiley-VCH GmbH.)

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‐Ca2+ 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. [ABSTRACT FROM AUTHOR]

Increasing evidence has shown that collagen peptides had various biological activities. In this study, a novel antiplatelet peptide Met‐Glu (ME) was separated and identified from silver carp skin by YMC ODS‐A C18 separation and ESI‐MS/MS analysis. Peptide ME inhibited platelet aggregation and secretion of platelet granules induced by ADP, thrombin and collagen, and significantly attenuated ferric chloride‐induced thrombus formation in rats. It did not prolong the bleeding time in mice even at the dose of 300 μmol/kg body weight that showed potent anti‐thrombosis effects. Additionally, peptide ME targeted at Gq‐protein to downregulate the phosphorylation of PLCβ, an important upstream effector of PI3K/Akt and Erk/MAPK signaling to inhibit intracellular calcium ion mobilization. These results suggest that peptide ME inhibited thrombosis in vivo and inhibited Gq‐mediated signaling in platelets, indicating the possibility that ME could potentially be developed as a novel therapeutic agent in the prevention and treatment of thrombotic diseases. Practical applications: Cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity worldwide. The proximal cause of CVDs is intravascular thrombosis formation, which mostly results from platelet activation, aggregation, and granules secretion. Traditional drugs in the prevention of thrombotic disease, such as aspirin and clopidogrel, are still limited for their side effects, especially bleeding complications. Collagen is a natural source for bioactive peptides and our previous study has shown that collagen peptides could inhibit platelet aggregation in vitro. Understanding the mechanism of collagen peptides on regulation of platelet activation and their in vivo anti‐thrombosis activities were important for the development of novel‐specific medical food in the prevention of thrombotic diseases. [ABSTRACT FROM AUTHOR]