Identification, Characterization and Antihypertensive Effect In Vivo of a Novel ACE-Inhibitory Heptapeptide from Defatted Areca Nut Kernel Globulin Hydrolysates.

Xing Liu,Sang Shen,Guanwen Li,Nan Qin,Xiaomin Wang,Lili Guo,Huimin Wang

doi:10.3390/molecules26113308

Abstract

The areca (Areca catechu L.) nut kernel (ANK) is a good potential protein source for its high protein content of 9.89–14.62 g/100 g and a high yield of around 300,000 tons per year in China. However, utilization of the areca nut kernel is limited. To expand the usage of ANK in pharmaceutical or foods industries, areca nut kernel globulin was extracted and angiotensin-I converting enzyme (ACE) inhibition peptides were prepared and identified using gel chromatography, reversed phase HPLC separation, UPLC-ESI-MS/MS analysis and in silico screening. Finally, a novel ACE-inhibitory heptapeptide (Ala–Pro–Lys–Ile–Glu–Glu–Val) was identified and chemically synthesized. The combination pattern between APKIEEV and ACE, and the inhibition kinetics, antihypertensive effect and endothlein-1 inhibition activity of APKIEEV were studied. The results of the molecular docking demonstrated that APKIEEV could bind to four active sites (not the key active sites) of ACE via short hydrogen bonds and demonstrated high ACE-inhibitory activity (IC50: 550.41 μmol/L). Moreover, APKIEEV exhibited a significantly lowering effect on both the systolic blood pressure and diastolic blood pressure of spontaneously hypertensive rats, and had considerable suppression ability on intracellular endothelin-1. These results highlight the potential usage of APKIEEV as ingredients of antihypertensive drugs or functional foods.

Highlights

Hypertension can induce serious diseases such as vascular sclerosis, stroke and coronary heart disease
The relationship between hypertension and excessive expression of endothelin-1 (ET-1) in the endothelium has been shed lighted by increasing studies [4]
Previous studies have demonstrated that ET-1 inhibition peptides could effectively decrease the systolic and diastolic blood pressure of spontaneously hypertensive rats [5,6]

Summary

Introduction

Hypertension can induce serious diseases such as vascular sclerosis, stroke and coronary heart disease. Hypertension can be induced by many factors including heredity, obesity, stressful life and dietary habits [2]. The angiotensin I-converting enzyme (ACE) plays an important role in increasing blood-pressure through catalyzing the generation of angiotensin-II (a potent vasoconstrictor) and inactivating the bradykinin (a potent vasodilator) [3]. The relationship between hypertension and excessive expression of endothelin-1 (ET-1) in the endothelium has been shed lighted by increasing studies [4]. Previous studies have demonstrated that ET-1 inhibition peptides could effectively decrease the systolic and diastolic blood pressure of spontaneously hypertensive rats [5,6]. ACE inhibitors and ET-1 inhibitors are accepted as reasonable and practical therapy for hypertension

Methods

Results

Conclusion