Screening and Molecular Mechanisms of Novel ACE-Inhibitory Peptides from Gracilariopsis lemaneiformis

Abstract

Candidate peptides with novel angiotensin-I-converting enzyme (ACE) inhibitor activity were obtained from hydrolysates of Gracilariopsis lemaneiformis by virtual screening method. Our results showed that G. lemaneiformis peptides (GLP) could significantly lower blood pressure in spontaneously hypertensive rats (SHR). At least 101 peptide sequences of GLP were identified by LC-MS/MS analysis and subjected to virtual screening. A total of 20 peptides with the highest docking score were selected and chemically synthesized in order to verify their ACE-inhibitory activities. Among them, SFYYGK, RLVPVPY, and YIGNNPAKG showed good effects with IC50 values of 6.45 ± 0.22, 9.18 ± 0.42, and 11.23 ± 0.23 µmoL/L, respectively. Molecular docking studies revealed that three peptides interacted with the active center of ACE by hydrogen bonding, hydrophobic interactions, and electrostatic forces. These peptides could form stable complexes with ACE. Furthermore, SFYYGK, RLVPVPY, and YIGNNPAKG significantly reduced systolic blood pressure (SBP) in SHR. YIGNNPAKG exhibited the highest antihypertensive effect, with the largest decrease in SBP (approximately 23 mmHg). In conclusion, SFYYGK, RLVPVPY, and YIGNNPAKG can function as potent therapeutic candidates for hypertension treatment.

Angiotensin-Converting Enzyme 2 Activation Is Not a Common Feature of Angiotensin-Converting Enzyme Inhibitory Peptides

“…About 200 ACEi tripeptides were selected from the established database as tripeptides usually possess the highest ACEi activity. , Considering the possible discrepancies in the results obtained by different researchers via various methods, selected ACEi peptides were all subjected to molecular docking to predict their interactions with ACE. ACEi activity is usually positively correlated with the binding affinity between ACE and ACEi peptides, , based on which potent ACEi peptides were determined using the binding score. Accordingly, 20 peptides with the highest binding score were selected to determine their in vitro ACE2a activity.…”

Gut microbiota and hypertension: a bibliometric analysis of recent research (2014–2023)

“…Antihypertensive Peptides (ACEIPs) are bioactive peptides generated through fermentation by specific GM, exhibiting antioxidant, anti-inflammatory, and blood pressure-lowering properties ( 54 ). ACEIPs achieve their antihypertensive effects through the inhibition of the angiotensin-converting enzyme and the stimulation of angiotensin-converting enzyme 2 pathways ( 55 , 56 ). As shown in Figure 6B , ACEIP, depicted by the red cluster, is closely tied to keywords like HTN, metabolic syndrome, and insulin resistance.…”