Comparison of an angiotensin‐I‐converting enzyme inhibitory peptide from tilapia (Oreochromis niloticus) with captopril: inhibition kinetics, in vivo effect, simulated gastrointestinal digestion and a molecular docking study

Abstract

BACKGROUND: In order to utilize tilapia skin gelatin hydrolysate protein, which is normally discarded as industrial waste in the process of fish manufacture, we study the in vivo and in vitro angiotensin-I-converting enzyme (ACE) inhibitory activity of the peptide Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP). The aim was to provide a pharmacological basis of the development of minimal side effects of ACE inhibitors by comparative analysis with captopril in molecular docking. RESULTS:This peptide from protein-rich wastes showed excellent ACE inhibitory activity (IC 50 = 2.577 mol L −1 ) and exhibited a mixed noncompetitive inhibitory pattern with Lineweaver-Burk plots. Furthermore, LSGYGP and captopril groups both showed significant decreases in blood pressure after 6 h and maintained good digestive stability over 4 h. Molecular bond interactions differentiate competitive captopril upon hydrogen bond interactions and Zn(II) interaction. The C-terminal Pro generates three interactions (hydrogen bonds, hydrophilic interactions and Van der Waals interactions) in the peptide and effectively interactswith the S1 and S2 pockets of ACE. CONCLUSION: LSGYGP, with an IC 50 value of 2.577 mol L −1 , has an antihypertensive effect in spontaneously hypertensive rats. Through comparison with captopril, this study revealed that LSGYGP may be a potential food-derived ACE inhibitory peptide and could act as a functional food ingredient to prevent hypertension.

Current Trends of Bioactive Peptides—New Sources and Therapeutic Effect

“…Molecular docking has shown the potential of these peptides as ACE inhibitors with potential use in preparation of functional food targeted at lowering blood pressure and reducing the risk of CVDs [ 161 ]. The same result was reported for the IVDR, WYK, and VSAVI peptides obtained from olive flounder ( P. olivaceus ) surimi [ 175 ] and the LSGYGP peptide obtained from tilapia ( O. niloticus ) skin gelatin protein hydrolysate [ 176 ]. The LWHTH peptide obtained from the tunicate ( S. clava ) in in silico simulations was found to bind to the active site of ACE, making the ACE–LWHTH complex stable.…”

Purification and characterization of a novel angiotensin I‐converting enzyme‐inhibitory peptide derived from Alaska pollack skins

“…Chen et al. (2020) also separated a novel ACE inhibitory peptide in a sequence of LSGYGP from gelatin hydrolysate protein of tilapia skin, and its IC 50 was 2.577 µmol/L. Lin et al.…”

Ethanolic Extract of Salvia hispanica L. Regulates Blood Pressure by Modulating the Expression of Genes Involved in BP-Regulatory Pathways

“…Hypotensive effects have been observed upon treatment with isolated fractions of plant extracts, mainly associated with the presence of compound antioxidants, saponins and peptides [ 17 , 24 , 30 ]. The mode of action of the inhibitory effect is proposed to be the interaction of antioxidant molecules with different motifs on the ACE catalytic site [ 28 ], specifically, the union of these compounds with the zinc atom present in the catalytic site of ACE, as described by Reeves and Rossow [ 31 ]. EESH has been known to contain a high content of antioxidant compounds (chlorogenic acid, caffeic acid, myricetin, quercetin and kaempferol) [ 18 ], implying that the inhibitory effect of Salvia extracts could be attributed to the presence of antioxidants compounds.…”

“…For example, Steinkamp-Fenske et al [ 21 ] and Zhou et al [ 32 ] analyzed the effect of administration of S. milthiorriza extracts on the regulation and production of NO in a human umbilical endothelium-derived cell line. The authors found a concentration-dependent response besides an over-regulation of eNOS in the treated cells, as compared to control cells [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. We analyzed genes coding for proteins that participate in three different pathways involved in regulation of HT, namely renin–angiotensin system ( Ace and Agtr1a genes), the kallikrein–kinin system ( Bdkrb2 gene) and the nitric oxide ( Nos3 gene) synthesis pathway.…”