Isolation of novel ACE-inhibitory peptide from naked oat globulin hydrolysates in silico approach: Molecular docking, in vivo antihypertension and effects on renin and intracellular endothelin-1

J Food Sci. 2020 Apr;85(4):1328-1337. doi: 10.1111/1750-3841.15115. Epub 2020 Mar 27.

Abstract

Naked oat globulin was hydrolyzed by alcalase, flavourzyme, pepsin, and trypsin in sequence. The hydrolysates (NOGH) were purified using gel chromatography, reversed-phase high performance liquid chromatography (RP-HPLC). Finally, fraction D7d with the highest ACE-inhibitory was subjected to liquid chromatography-mass spectrometry analysis and 14 peptides were identified. Of which, peptide SSYYPFK (890.4 Da) was chose to synthesize based on in silico analysis. The SSYYPFK demonstrated high ACE-inhibitory activity (IC50 : 91.82 µM) with competitive inhibition mode, and could effectively (P < 0.05) lower the systolic blood pressure and diastolic pressure of spontaneously hypertensive rats at the concentration of 100 to 150 mg/kg body weight. Molecular docking simulation demonstrated that SSYYPFK could bind with the active site S1 of ACE via short hydrogen bonds. It could remain the ACE-inhibitory activity after simulated gastrointestinal hydrolysis. Moreover, SSYYPFK showed acceptable renin and endothelin-1 suppressing capacity (47.59% and 27.88% at 1.5 mg/mL, respectively). These results indicated that SSYYPFK may have similar antihypertensive mechanism with captopril, and could be develop to natural antihypertensive products. PRACTICAL APPLICATION: One novel ACE-inhibitory peptide SSYYPFK (890.4 Da) was identified from naked oat globulin hydrolysates. It exhibited relatively high renin and intracellular endothelin-1 suppressing capacity, and could effectively (P < 0.05) lower the systolic blood pressure and diastolic pressure of spontaneously hypertensive rats. This peptide could be used as natural and safe nutraceuticals and/or functional ingredients.

Keywords: Naked oat globulin; angiotensin-I converting enzyme; endothelin-1; molecular docking; renin.