Preparation and Identification of ACE Inhibitory Peptides from the Marine Macroalga Ulva intestinalis.

Siqi Sun,Xinping Chen,Nianjun Xu,Xue Sun,Xiaoting Xu,Xiaoqian Zhang

doi:10.3390/md17030179

Abstract

Angiotensin I-converting enzyme (ACE) inhibitory peptides derived from seaweed represent a potential source of new antihypertensive. The aim of this study was to isolate and purify ACE inhibitory peptides (ACEIPs) from the protein hydrolysate of the marine macroalga Ulva intestinalis. U. intestinalis protein was hydrolyzed by five different proteases (trypsin, pepsin, papain, α-chymotrypsin, alcalase) to prepare peptides; compared with other hydrolysates, the trypsin hydrolysates exhibited the highest ACE inhibitory activity. The hydrolysis conditions were further optimized by response surface methodology (RSM), and the optimum conditions were as follows: pH 8.4, temperature 28.5 °C, enzyme/protein ratio (E/S) 4.0%, substrate concentration 15 mg/mL, and enzymolysis time 5.0 h. After fractionation and purification by ultrafiltration, gel exclusion chromatography and reverse-phase high-performance liquid chromatography, two novel purified ACE inhibitors with IC50 values of 219.35 μM (0.183 mg/mL) and 236.85 μM (0.179 mg/mL) were obtained. The molecular mass and amino acid sequence of the ACE inhibitory peptides were identified as Phe-Gly-Met-Pro-Leu-Asp-Arg (FGMPLDR; MW 834.41 Da) and Met-Glu-Leu-Val-Leu-Arg (MELVLR; MW 759.43 Da) by ultra-performance liquid chromatography-tandem mass spectrometry. A molecular docking study revealed that the ACE inhibitory activities of the peptides were mainly attributable to the hydrogen bond and Zn(II) interactions between the peptides and ACE. The results of this study provide a theoretical basis for the high-valued application of U. intestinalis and the development of food-derived ACE inhibitory peptides.

Highlights

Hypertension, a common, serious chronic disease, affects approximately 25% of the adult population worldwide
Angiotensin I-converting enzyme (E.C.3.4.15.1, ACE), a peptidase belonging to the zinc metalloenzyme family, plays an important role in renin–angiotensin system (RAS) and KKS, inactivating angiotensin I to the potent vasoconstrictor angiotensin II and inactivating the vasodilator bradykinin to raise blood pressure [3]
Trypsin was chosen for the production of ACE inhibitory peptides (ACEIPs)

Summary

Introduction

Hypertension, a common, serious chronic disease, affects approximately 25% of the adult population worldwide. Hypertension seriously affects human health and is a causative factor of cardiovascular diseases, stroke, and renal diseases, among others [1,2]. The renin–angiotensin system (RAS) and kallikrein–kinin system (KKS) are crucial for regulating blood pressure in the human body. Angiotensin I-converting enzyme (E.C.3.4.15.1, ACE), a peptidase belonging to the zinc metalloenzyme family, plays an important role in RAS and KKS, inactivating angiotensin I to the potent vasoconstrictor angiotensin II and inactivating the vasodilator bradykinin to raise blood pressure [3]. Inhibition of ACE activity is effective for maintaining blood pressure within a normal range [4]. ACE inhibitors (ACEIs) inhibit ACE activity and reduce blood pressure by inhibiting the synthesis of angiotensin II or promoting the release of bradykinin.

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