Novel Targets and Potential Mechanisms of Mizuhopecten yessoensis-Derived Tripeptide NCW as Antihypertensive Peptides.

ABSTRACT

SCOPE Mizuhopecten yessoensis-derived tripeptide Asn-Cys-Trp (NCW) exhibits a potent antihypertensive effect in vivo. However, a lack of knowledge of the antihypertensive mechanism of tripeptide NCW limits its application for functional foods industrialization. The purpose of this study is to elucidate the corresponding targets and mechanisms of tripeptide NCW in hypertension regulation. METHODS AND RESULTS: Administration of tripeptide NCW for 3 weeks, the blood pressure of spontaneously hypertensive rats (SHRs) is significantly decreased. After sacrifice, the serum sample is analyzed using tandem mass tag (TMT)-based liquid chromatography with tandem mass spectrometry to identify differentially expressed proteins. The proteomic analysis indicates that tripeptide NCW administration alters serum protein profiles in SHR rats, significantly upregulating 106 proteins and downregulating 30 proteins. These proteins enhance the glycolysis, glucose, and TCA cycle, improve amino metabolism, trigger the cAMP/PKA, cGMP/PKG, PI3K/AKT, and AMPK signal pathways, and inhibit Ras-regulated JNK activation, TGF-ß/MAPK, and TGF-ß/ RhoA/ROCK pathways. CONCLUSION: Tripeptide NCW supplementation is demonstrated to regulate signal pathways involved in the control of blood pressure and regulate the energy and amino acids metabolic processes in serum, providing important insights into the protective effects of tripeptide NCW on hypertension.