Bitter Almond Albumin ACE-Inhibitory Peptides: Purification, Screening, and Characterization In Silico, Action Mechanisms, Antihypertensive Effect In Vivo, and Stability

Abstract

Almond expeller is an undeveloped reservoir of bioactive peptides. In the current study, a zinc ion ligand Arg-Pro-Pro-Ser-Glu-Asp-Glu-Asp-Gln-Glu (RPPSEDEDQE) offering a noncompetitive inhibitory effect on ACE (IC50: 205.50 μmol·L‒1) was identified from almond albumin hydrolysates via papain and thermolysin hydrolysis, subsequent chromatographic separation, and UPLC-Q-TOF-MS/MS analysis. Molecular docking simulated the binding modes of RPPSEDEDQE to ACE and showed the formation of hydrogen bonds between RPPSEDEDQE and seven active residues of ACE. Moreover, RPPSEDEDQE could bind to fifteen active sites of ACE by hydrophobic interactions, and link with the His387 and zinc ions of the zinc tetrahedral coordination. Ultraviolet wavelength scanning and Fourier-transformed infrared spectroscopy analysis revealed that RPPSEDEDQE can provide multiple binding sites for zinc ions. However, RPPSEDEDQE cannot bind with any central pocket of ACE, which was evidenced by an inhibition kinetics experiment. Additionally, the zinc-chelating capacity and inhibiting ability against ACE of RPPSEDEDQE were both not significantly reduced by the hydrolysis of gastrointestinal enzymes. A moderate to high dose of RPPSEDEDQE (100–150 mg·kg bw‒1) significantly reduced the systolic and diastolic blood pressure of spontaneous hypertensive rats, but chelation with zinc ions decreased its antihypertensive efficiency. These results indicate that bitter almond albumin peptides may be used for lowering blood pressure.

Armeniacae semen amarum: a review on its botany, phytochemistry, pharmacology, clinical application, toxicology and pharmacokinetics

“…Additionally, it has exhibited positive antihypertensive effects on spontaneously hypertensive rats at concentrations of 100 and 150 mg/mL. Although not as effective as 10 mg/kg captopril, this polypeptide has led to a significant decrease in systolic and diastolic blood pressure ( Qin et al, 2023 ). These findings suggest that the polypeptide holds the potential for anti-DM effects and could be utilized in the development of anti-DM drugs.…”

“…Moreover, a polypeptide extracted from ASA water extract has displayed the ability to form a complex with zinc ions, exhibiting remarkablely lowering blood pressure effect. This polypeptide shows promise for further development as an antihypertensive drug ( Qin et al, 2023 ).…”

Bioactive Peptides from Ruditapes philippinarum Attenuate Hypertension and Cardiorenal Damage in Deoxycorticosterone Acetate–Salt Hypertensive Rats

“…In addition, the use of antihypertensive drugs in therapy is associated with mild (hyperkalemia, hypotension) and severe adverse events (acute kidney injury, syncope) [6]. As a promising alternative, numerous bioactive peptides have exhibited antihypertensive effects with fewer side effects compared with traditional drugs [7][8][9].…”