Screening of Angiotensin-I Converting Enzyme Inhibitory Peptides Derived from Caulerpa lentillifera

Abstract

Peptides with angiotensin-I converting enzyme (ACE) inhibitory activity have received considerable interest due to their potential as antihypertensive agents and consumer concern over the safety of synthetic drugs. The objective of this study was to isolate ACE inhibitory (ACEI) peptides from Caulerpa lentillifera (known commonly as sea grape) protein hydrolysate. In this study, short-chain peptides were obtained after hydrolysis by various enzymes and subsequently by ultrafiltration. Thermolysin hydrolysate showed the highest ACEI activity. Bioassay-guided fractionation was performed using reversed-phase high performance liquid chromatography (RP-HPLC) to uncover the fraction 9 with the highest ACE inhibitory activity from thermolysin hydrolysate. Peptides in this fraction were further identified using liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis coupled with de novo sequencing, which gave two oligopeptides, FDGIP (FP-5) and AIDPVRA (AA-7). The identities and activities of these two peptides were further confirmed using synthetic peptides. Their IC50 values were determined as 58.89 ± 0.68 µM and 65.76 ± 0.92 µM, respectively. Moreover, the inhibition kinetics revealed that both FP-5 and AA-7 are competitive inhibitors. These activities were further explained using molecular docking simulation. The present study is the first report about ACEI peptides derived from Caulerpa lentillifera and it shows the potential for preventing hypertension and for functional food development.

Fish Scale Valorization by Hydrothermal Pretreatment Followed by Enzymatic Hydrolysis for Gelatin Hydrolysate Production

“…The IC 50 value of the gelatin hydrolysate was 0.73 mg/mL. Compared to the captopril (IC 50 = 1.7 ng/mL) [42], the gelatin hydrolysate showed a milder inhibitory activity against ACE. The activity was lower than that of chicken collagen hydrolysate by an Aspergillus species-derived enzyme (IC 50 = 0.26 mg/mL) [43], but higher than that of gelatin hydrolysate obtained from grass carp fish ( Ctenopharyngodon idella ) scale (IC 50 = 1.66 mg/mL) without further purification [44].…”

Seaweed-Derived Proteins and Peptides: Promising Marine Bioactives

“…Another related experiment regarding the use of different proteases to obtain BAPs from C. lentillifera indicated that thermolysin was the most appropriate choice in comparison to α-chymotrypsin, pepsin, and trypsin. In this case, the peptides with the highest ACE inhibitory activity were FDGIP and AIDPVRA [ 101 ]. Among hydrolytic enzymes, pepsin is one of the most used in the last years.…”

“…IC 50 = 0.014 mg/mL [ 115 ] Caulerpa lentillifera Thermolysin; E:S (1:50), 60 °C, pH 8.5, 16 h FDGIP, AIDPVRA In vitro, antihypertensive ACE inhibition. IC 50 (FDGIP)= 0.03 mg/mL, IC 50 (AIDPVRA)= 0.04 mg/mL [ 101 ] Abbreviations: E:S: Enzyme:substrate ( w / w ); IC 50 : Half-inhibitory concentration; TE: Trolox equivalents: BAPs: bioactive peptides; ACE: angiotensin I-converter enzyme; DPPH: 2,2-diphenyl-1-picrylhydrazyl; ABTS: (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)); IL: interleukin; ORAC: oxygen radical absorbance capacity; FRAP: ferric reducing ability of plasma; mTOR: mammalian target of rapamycin. …”

“…Scientific evidence supports the biological effects of seaweed BAPs ( Table 3 ), as it has also been reported with BAPs from other protein sources [ 132 , 133 ]. The main biological effects reported are related to the improvement of hypertension, often described by inhibiting ACE or renin activities [ 52 , 101 , 126 ]. Given that this effect has been verified in various in vivo experiments [ 21 , 112 ] and also reported in human subjects [ 106 ], there is a scientific basis to suggest that seaweed BAPs should be considered as cardioprotective agents.…”

Antihypertensive Effects of Corn Silk Extract and Its Novel Bioactive Constituent in Spontaneously Hypertensive Rats: The Involvement of Angiotensin-Converting Enzyme Inhibition

“…Food peptides with anti-ACE activities have been identified from plants and animals [5,6]. For example, oligopeptides FDGIP and AIDPVRA are ACE inhibitor derived from Caulerpa lentillifera [7]. ACE inhibitory peptides released from alcalase-hydrolyzed amaranth protein exhibit hypotensive effects in spontaneously hypertensive rats (SHRs) [8].…”