In Vivo Action Mechanism Of ACE Inhibitory Peptide From Mizuhopecten Yessoensis Via Metabolomics And Proteomics

In this study,myosin in Mizuhopecten yessoensis was hydrolyzed to identify the novel angiotensin converting enzyme?ACE?inhibitory peptide.And then,the activity of the peptide was evaluated by in vitro and in vivo assay.Moreover,metabolomics and proteomics were used to investigate the in vivo action mechanism of the peptide on the spontaneously hypertension rats?SHR?.The myosin in Mizuhopecten yessoensis was in silico cleaved by gastrointestinal proteases.Subsequently,the ACE was used as the target to screen peptides which were strongly bound to ACE.Next,the in vitro ACE inhibitory activity of these peptides was evaluated using the RP-HPLC method.A novel ACE inhibitory peptide NCW was identified,with the IC₅₀ value of 35.50±1.23?mol/L;Systolic blood pressure?SBP?and diastolic blood pressure?DBP?in SHR were measured to evaluate the in vivo anti-hypertensive effects of the peptide NCW.The SBP and DBP in SHR after long-term administration of the peptide NCW were significantly decreased by 48.09±3.84 and41.63±2.39 mmHg,respectively.The peptide NCW exerted anti-hypertensive activity in vivo;Furthermore,serum changes in SHR after long-term administration of the peptide NCW was investigated using metabolomics approach.Sixty-one known differential metabolites were identified.The KEGG pathway enrichment analysis indicated that the differential metabolites were mainly involved in bile acid biosynthesis,bile secretion,cholesterol metabolism,valine,leucine and isoleucine degradation,and folate biosynthesis;In addition,TMT-LC-Q-TOF-MS-based proteomics was used to analyze serum changes in SHR after long-term administration of the peptide NCW.One hundred and thirty-six differential proteins were identified.The KEGG pathway analysis showed that adrenergic signaling in cardiomyocytes,biosynthesis of amino acids,cardiac muscle contraction,carbon metabolism,pyruvate metabolism,cysteine and methionine metabolism,citrate cycle,glucagon signaling pathway,and estrogen signaling pathway were significantly enriched.