Identification, molecular docking, and kinetic studies of six novel angiotensin-I-converting enzyme (ACE) inhibitory peptides derived from Kenaf (Hibiscus cannabinus L.) seed

Zaharuddin, Nurul Dhania; Barkia, Ines; Ibadullah, Wan Zunairah Wan; Zarei, Mohammad; Saari, Nazamid

doi:10.1016/j.ijbiomac.2022.09.142

Cited by 18 publications

(17 citation statements)

References 24 publications

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“…We found that the smaller the molecular weight of the hydrolysate, the higher the ACE inhibitory activity. The results are similar to the kenaf ( Hibiscus cannabinus L. ) seed studied by Nurul Dhania et al ( 50 ). Therefore, we used Flavourzyme to hydrolyze HMP.…”

Section: Discussionsupporting

confidence: 89%

“…Among the five hydrolysates, the one with the highest ACE inhibition activity was chosen for further optimization. The feed liquid ratio (w/v, 1: 15, 1: 20, 1: 25, 1: 30, and 1:35), enzyme to substrate ratios (E/S, 1,000 U, 2,000 U, 3,000 U, 4,000 and 5,000 U/g), enzymatic hydrolyses times (1.0, 2.0, 3.0, 4.0, and 5.0 h); temperatures (35,40,45,50,55, and 60 • C), and pH (5.0, 6.0, 7.0, 8.0, and 9.0) on the inhibitory activity of ACE were further studied. The supernatant was collected and lyophilized, prepare 5 mg/mL solution, and measure the ACE inhibition rate.…”

Section: Single Factor Testmentioning

confidence: 99%

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Preparation and activity evaluation of angiotensin-I converting enzyme inhibitory peptides from protein hydrolysate of mulberry leaf

Chen

et al. 2023

Front. Nutr.

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Angiotensin-I converting enzyme (ACE) inhibitory peptides drew wide attention in the food industry because of their natural reliability, non-toxicity, and safety. However, the characteristics of ACE inhibitory peptides obtained from protein hydrolysate of mulberry leaf prepared by Flavourzyme were still unclear. Based on the single-factor test, the Plackett–Burman test and response surface test were used to determine the key factors affecting the ACE inhibition rate in mulberry leaf protein hydrolysate and the optimum conditions of enzymatic hydrolysis. The results showed that the optimum technical parameters were as follows: the ratio of material to liquid is 1: 25 (w / v, g/mL), the Flavourzyme to substrate ratio was 3,000 U/g, the temperature of enzymatic hydrolysis was 50°C, pH was 6.3, and the time of enzymatic hydrolysis was 2.9 h. The ACE inhibitory peptides in the mulberry leaf protein hydrolysates were purified by ultrafiltration and gel filtration, aiming to obtain the highest active component. The 12 peptide sequences were identified by reverse liquid chromatography-mass spectrometry, and then, they were docked to the crystal structure of human angiotensin-I converting enzyme (1O8A), and the interaction mechanisms of 12 peptide sequences and 1O8A were analyzed. The docking results showed that among the 12 peptide sequences, ERFNVE (792.37 Da), TELVLK (351.72 Da), MELVLK (366.72 Da), and FDDKLD (376.67 Da), all had the lowest docking energy, and inhibition constant. The chemosynthetic ERFNVE (IC50: 2.65 mg/mL), TELVLK (IC50: 0.98 mg/mL), MELVLK (IC50:1.90 mg/mL) and FDDKLD (IC50:0.70 mg/mL) demonstrated high ACE-inhibitory activity with competitive inhibition mode. These results indicated that the ACE-inhibiting peptides from mulberry leaf protein hydrolyzed (FHMP) had the potential activities to inhibit ACE and could be used as functional food or drugs to inhibit ACE. This work provides positive support for mining the biological activity of mulberry leaves in the treatment of hypertension.

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Section: Discussionsupporting

confidence: 89%

Section: Single Factor Testmentioning

confidence: 99%

Preparation and activity evaluation of angiotensin-I converting enzyme inhibitory peptides from protein hydrolysate of mulberry leaf

Chen

et al. 2023

Front. Nutr.

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“…Within the QSAR-predicted peptides, YNL has been determined to have ACE-inhibitory activity, which has not been reported for the other peptides generated in this investigation. Therefore, based on the inverse relationship between the activity of ACE-inhibitory peptides and IC 50 values [ 29 ], six peptides with IC 50 values less than 10 μM were selected for further study. Standards of these six peptides were synthesized by analysis and injected according to the liquid-phase conditions and mass spectrometry parameters.…”

Section: Resultsmentioning

confidence: 99%

Biodirected Screening and Preparation of Larimichthys crocea Angiotensin-I-Converting Enzyme-Inhibitory Peptides by a Combined In Vitro and In Silico Approach

Yang,

Wang,

Huang

et al. 2024

Molecules

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Food-derived angiotensin-I-converting enzyme (ACE)-inhibitory peptides have gained attention for their potent and safe treatment of hypertensive disorders. However, there are some limitations of conventional methods for preparing ACE-inhibitory peptides. In this study, in silico hydrolysis, the quantitative structure–activity relationship (QSAR) model, LC-MS/MS, inhibition kinetics, and molecular docking were used to investigate the stability, hydrolyzability, in vitro activity, and inhibition mechanism of bioactive peptides during the actual hydrolysis process. Six novel ACE-inhibitory peptides were screened from the Larimichthys crocea protein (LCP) and had low IC50 values (from 0.63 ± 0.09 µM to 10.26 ± 0.21 µM), which were close to the results of the QSAR model. After in vitro gastrointestinal simulated digestion activity of IPYADFK, FYEPFM and NWPWMK were found to remain almost unchanged, whereas LYDHLGK, INEMLDTK, and IHFGTTGK were affected by gastrointestinal digestion. Meanwhile, the inhibition kinetics and molecular docking results were consistent in that ACE-inhibitory peptides of different inhibition forms could effectively bind to the active or non-central active centers of ACE through hydrogen bonding. Our proposed method has better reproducibility, accuracy, and higher directivity than previous methods. This study can provide new approaches for the deep processing, identification, and preparation of Larimichthys crocea.

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“…In addition, the trinitrobenzenesulfonic acid method was used to determine the hydrolysis degree (Adler-Nissen, 1979). fractions were collected and lyophilized, and their ACE inhibitory activity and Zn-chelating ability were determined (Udechukwu et al, 2018;Zaharuddin et al, 2022). The subfraction with the highest ACE-inhibitory activity was further separated using reversephase high performance liquid chromatography (RP-HPLC) on a Kromasil 100-5 C 18 column (4.6 × 250 mm, 5 μm; Eka Chemicails, Sweden) with deionized water containing 0.1% (v/v) trifluoroacetate as the elution solution A.…”

Section: Preparation Of Dopkghmentioning

confidence: 99%

Oil palm kernel globulin antihypertensive peptides: isolation and characterization, ACE inhibition mechanisms, zinc-chelating activity, security and stability

et al. 2023

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Introduction: The oil palm kernel (OPK) expeller is the main byproduct of palm oil, but its utilization is limited.Methods: To obtain angiotensin-I-converting enzyme (ACE) inhibition peptides with Zn-chelating capacity, defatted oil palm kernel globulin hydrolysates (DOPKGH) were subjected to Sephadex G-15 gel electrophoresis, reverse-phase high liquid performance chromatography, and UPLC-ESI-MS/MS analysis.Results and discussion: Five representative oligopeptides, including Gln-Arg-Leu-Asp-Arg-Cys-Lys (QRLERCK), Leu-Leu-Leu-Gly-Val-Ala-Asn-Tyr-Arg (LLLGVANYR), Arg-Ala-Asp-Val-Phe-Asn-Pro-Arg (RADVFNPR), Arg-Val-Ile-Lys-Tyr-Asn-Gly-Gly-Gly-Ser-Gly (RVIKYNGGGSG), and Glu-Val-Pro-Gln-Ala-Tyr-Ile-Pro (EVPQAYIP), without potential toxicity and allergenicity, were identified in DOPKGH. Of these, only EVPQAYIP showed both ACE-inhibitory activity (IC50: 102.75 μmol/L) and Zn-chelating capacity (11.69 mg/g). Molecular docking and inhibition kinetics showed that EVPQAYIP was a competitive inhibitor of ACE because it could bind to Glu384, Lys511, and Gln281 (belonging to the central S1 and S2 pockets, respectively) of ACE. Moreover, EVPQAYIP affects zinc tetrahedral coordination in ACE by binding to Glu411; the amino and carboxyl groups of EVPQAYIP chelate with zinc ions. During gastrointestinal digestion, the ACE inhibitory activity of EVPQAYIP was relatively stable. Additionally, EVPQAYIP enhanced zinc stability in the intestine and exerted antihypertensive effects in spontaneous hypertensive rats. These results suggest the potential application of OPK peptides as ingredients in antihypertensive agents or zinc fortification.

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Identification, molecular docking, and kinetic studies of six novel angiotensin-I-converting enzyme (ACE) inhibitory peptides derived from Kenaf (Hibiscus cannabinus L.) seed

Cited by 18 publications

References 24 publications

Preparation and activity evaluation of angiotensin-I converting enzyme inhibitory peptides from protein hydrolysate of mulberry leaf

Preparation and activity evaluation of angiotensin-I converting enzyme inhibitory peptides from protein hydrolysate of mulberry leaf

Biodirected Screening and Preparation of Larimichthys crocea Angiotensin-I-Converting Enzyme-Inhibitory Peptides by a Combined In Vitro and In Silico Approach

Oil palm kernel globulin antihypertensive peptides: isolation and characterization, ACE inhibition mechanisms, zinc-chelating activity, security and stability

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