ACE-inhibitory Activity Research Articles

Standardised flavonoid extract from Diospyros kaki L.f leaves alleviates high blood pressure and ventricular hypertrophy on cortisone acetate-induced hypertensive rats

The current study was designed to investigate the anti-hypertensive effects of a standardised flavonoid extract from Diospyros kaki L.f leaves (DK extract) on cortisone acetate-induced hypertensive rats. Hypertension was induced in Wistar rats by subcutaneously injecting 2.5 mg cortisone acetate daily and by maintaining the rats on a 1% sodium chloride diet for a period of 28 days. The hypertensive rats were treated daily with DK extract (50 and 100 mg/kg of body weight; p.o.) or captopril (20 mg/kg of body weight; p.o.), a reference drug, for 14 consecutive days. The blood pressure and heart rate of awake rats were measured using a non-invasive tail-cuff method. The heart weight and left ventricular wall thickness of rats were measured. In vitro angiotensin-converting enzyme (ACE) inhibition activity of the DK extract and captopril were analysed. DK extract significantly and dose-dependently reduced systolic and diastolic blood pressure in the hypertensive rats. There were no significant changes observed in heart rate. The cortisone acetate-induced hypertensive rats had increased heart weight and left ventricular wall thickness. These actions were attenuated by the treatment of DK extract (100 mg/kg) and captopril. Moreover, DK extract inhibited ACE activity in vitro with an IC50 of 4.71±0.53 μg/ml. Our findings demonstrate that DK extract exerted anti-hypertensive effects and alleviated ventricular hypertrophy in the cortisone acetate-induced hypertensive rats and these actions occurred at least in part via ACE activity inhibition.

Lactic acid fermentation of guava juice: Evaluation of nutritional and bioactive properties, enzyme (α-amylase, α-glucosidase, and angiotensin-converting enzyme) inhibition abilities, and anti-inflammatory activities.

In the present research, the impact of fermentation with two strains of Lactiplantibacillus plantarum subsp. plantarum (PTCC 1896 and PTCC 1745) on physicochemical properties, antioxidant bioactive compounds, and some health-promoting features of guava juice was investigated. Results showed a significant (p < .05) decrease in pH, total soluble solids, glucose and fructose residues, vitamin C, and total carotenoids after 32 h of fermentation. Total phenolic content, free radical scavenging abilities, and ferrous reducing power were markedly enhanced during the fermentation process. Moreover, fermented juice represented good enzyme inhibition abilities (α-amylase and α-glucosidase) and anti-inflammatory activities. The initial amount of angiotensin-converting enzyme inhibitory activity (26.5%) increased to 72.1% and 66.4% in L. plantarum subsp. plantarum 1896 and L. plantarum subsp. plantarum 1745 treatments, respectively. These findings reveal that guava juice fermentation with the studied Lactobacillus strains can be a promising strategy to augment the functional properties of the fruit-based beverage.

The therapeutic effects of fermented milk with lactic acid bacteria from traditional Daqu on hypertensive mice

Lactic acid bacteria (LAB), a type of microorganism widely used in functional foods, has gained notable research attention in recent years. Certain strains possess the proteolytic ability to release potentially antihypertensive peptides from dairy proteins, which prompted us to explore the LAB strains from an understudied and unique ingredient, Daqu. We screened for 67 strains of LAB strains from traditional Daqu using the calcium dissolution ring method. Sixteen strains exhibiting angiotensin-converting enzyme inhibition (ACE-I) activity exceeding 50% were chosen for 16S rDNA sequencing and safety assessment. It is noteworthy that Enterococcus faecium CP640 and Lacticaseibacillus rhamnosus CP658 exhibited significant ACE-I activity, which was the result of strain fermentation in reconstituted skim milk. These 2 strains did not exhibit hemolytic activity or antibiotic resistance. They also did not produce biogenic amines and showed high survival rates in the gastrointestinal tract. Additionally, Enterococcus faecium CP640 and Lacticaseibacillus rhamnosus CP658 fermented milk exhibited a notable reduction in blood pressure levels in spontaneously hypertensive rats (SHR) compared with negative controls in SHR. Importantly, no adverse effect was observed in normal Wistar-Kyoto rats. Through the analysis of physiological, serum, and urine-related indicators, it was observed that Enterococcus faecium CP640 and Lacticaseibacillus rhamnosus CP658 have the potential to promote weight gain in SHR, alleviate excessive heart rate, improve renal function indicators, and effectively regulate blood sugar and uric acid levels in SHR. These 2 strains showed optimal properties in lowering blood pressure and have the potential to be used in functional dairy products in the future.

Buffalo yogurt fermented with commercial starter and Lactobacillus plantarum originating from breast milk lowered blood pressure in pregnant hypertensive rats

Nutritional therapy, which may have advantages over medication, is being investigated as a novel treatment for pregnancy-induced hypertension. Several studies have shown that probiotic yogurt supplementation during pregnancy has beneficial effects on maternal and fetal health. In this study, fermented buffalo milk was produced with yogurt culture and Lactobacillus plantarum B, a probiotic isolated from healthy breast milk with high angiotensin-converting enzyme inhibitory activity. The fermentation conditions under which the angiotensin-converting enzyme (ACE) inhibitory activity reached 84.51% were optimized by the response surface method as follows: 2 × 106 cfu/mL of L. plantarum B, yogurt culture 2.5 × 105 cfu/mL, and 8 h at 37°C. The distribution of ACE inhibitory peptides from fermented buffalo milk and fermented cow milk were further analyzed by liquid chromatography-mass spectrometry. By searching according to the structural features of ACE inhibitory peptides, 29 and 11 peptides containing ACE inhibitory peptide features were found in fermented buffalo milk and fermented cow milk, respectively. To investigate the in vivo antihypertensive activity of fermented buffalo milk, 18 pregnant rats were divided into 3 groups (n = 6 in each group) and administered 10 mL of normal saline, yogurt (20 mg/kg), or labetalol hydrochloride (4 mg/kg) daily from the beginning of pregnancy to parturition. To induce hypertension, methyl nitrosoarginine (125 mg/kg) was injected subcutaneously every day from d 15 of pregnancy to the day of delivery. Blood pressure was not significantly changed in the yogurt and labetalol groups after induction of hypertension and was lower compared with the normal saline group, but there was no difference between the yogurt and labetalol groups. This implied that the buffalo yogurt had a preventive and antihypertensive effect in the pregnancy-induced hypertensive rat model. Further studies to determine the mechanism of action, as well as a randomized control trial, are warranted.

α-Glucosidase, Angiotensin-converting Enzyme, and Acetylcholinesterase Inhibitory Activities of a Marine Red Alga Galaxaura oblongata

Seaweeds have gained interest from the pharmaceutical industry due to their diverse secondary metabolites with potential applications in the prevention and treatment of lifestyle diseases. In spite of the abundance of seaweeds in the coastal area of Iligan Bay in the Philippines, there has been limited investigation into their pharmacological properties. Therefore, this study aimed to evaluate the in vitro α-glucosidase inhibition, angiotensin-converting enzyme (ACE) inhibition, and acetylcholinesterase (AChE) inhibition properties of various fractions obtained from the marine red alga Galaxaura oblongata. The methanol extract of G. oblongata was sequentially partitioned into hexane, dichloromethane, ethyl acetate, butanol, and methanol fractions. All assays were performed in vitro and microplate based. The results of α-glucosidase inhibition activity assay showed that the n-hexane fraction and dichloromethane fraction exhibited greater than 50% inhibitory activity at 200 ppm. Furthermore, ACE inhibition activity assay revealed that dichloromethane fraction, ethyl acetate fraction, and butanol fraction displayed ACE inhibition activity above 50% at 250 ppm. In addition, the hexane fraction, dichloromethane fraction, and ethyl acetate fraction demonstrated potent AChE inhibitory activity at 250 ppm. Overall, the findings show that G. oblongata has antidiabetic, anti-hypertensive, and neuroprotective potentials. This is the first report of the in vitro α-Glucosidase, ACE, and AChE inhibition activities of G. oblongata. Further investigation and purification of the highly potent fractions in each assay is highly suggested to identify and characterize the compounds responsible for the observed bioactivities, which could serve as possible leads for drug discovery efforts in the management of various lifestyle diseases.

Investigation of the Elemental Contents, Functional and Nutraceutical Properties of Kefirs Enriched with Spirulina platensis, an Eco-friendly and Alternative Protein Source.

In this study, the effect of the use of S. platensis, which is presented as an eco-friendly and alternative protein source, in the production of kefir, a probiotic dairy product, on various physicochemical properties as well as FAA, ACE inhibitory activity, proteolysis, TPC, DPPH, ABTS+, and mineral values was investigated. It was observed that the addition of S. platensis at different ratios to the kefir samples had a statistically very significant (p < 0.01) effect on all physicochemical analyses; L. mesenteroides count; all amino acids except isoleucine, aspartic acid, and glutamic acid; ACE inhibitory activity, TN, TCAN, TCAN/TN, mM Gly, TPC, DPPH, ABTS+, Na, Mg, K, and Fe. In plain kefir samples, mineral contents were determined by order of K > P > Na > Ca > Mg > Zn >> Fe > Cr > Cr > Mn. Furthermore, a general increase was observed in FAA, ACE inhibitory activity, TPC, DPPH, ABTS+, and mineral values, as well as in the counts of Lactococcus spp. and L. mesenteroides in the samples, depending on the proportion of S. platensis added, compared to plain kefir samples. In this context, it was concluded that the addition of S. platensis to kefir at different rates could meet various components required by the body on a daily basis and result in a nutraceutical product.

Natural angiotensin converting enzyme inhibitors: A safeguard against hypertension, respiratory distress syndrome, and chronic kidney diseases.

Hypertension is a serious concern as it is one of the causes of kideny failure and pulmonary fibrosis. An important therapeutic strategy for treating chronic hypertension is to inhibit the angiotensin converting enzyme (ACE). ACE inhibition reduces kidney damage, pulmonary artery pressure, and high blood pressure. Due to their high efficacy and low risk of side effects, natural renin-angiotensin system inhibitors have drawn increasing attention over the past decades. Alkaloids, amino acids, anthocyanidins, flavonoids, glucosinolates, isoflavonoids, phenolic acids, polyphenolics, and triterpenoids are among the bioactive metabolites pocessing an impressive ACE inhibitory activity. Many herbs including Rosmarinus officinalis, Hibiscus sabdariffa, Curcuma longa, Rauwolfia serpentina, Emblica officinalis, Cynara scolymus, Punica granatum, Mucuna pruriens, Capsicum annuum, and Moringa olifera were found having ACE inhibitory activities comparable to captopril and enalpril. These enticing natural ACE inhibitors deserve to be a safeguard medicine against hypertension, respiratory distress syndrome, and chronic kidney diseases. More clinical trials are required before new natural compounds and herbs can be used to treat chronic hypertension and its ramifications, such as respiratory distress syndrome and kidney failure.

Bioactivity of collagen peptides derived from commercial animals: In silico investigation

Collagen peptides (CP) obtained from collagen hydrolysis have drawn much attention for their broad bioactivities, such as antioxidant, anti-inflammatory, angiotensin-converting enzyme (ACE) and dipeptidyl peptidase-IV (DPP-IV) inhibitory activities. This study employed an in silico approach to investigate the bioactivities of CP from fish, chicken, cattle, pig, yak, sheep, and donkey. BLAST analysis of amino acid sequences showed CP from mammals had comparable bioactivities but those from fish and chicken possessed different bioactivity potential due to low protein homology. In silico hydrolysis of collagen with gastrointestinal enzymes, including trypsin, pepsin, and proteinase K showed that the number of bioactive CP from chicken (922) and mammals (737–905) was higher than that from fish (544–675) because of the lower content of proline in fish collagen, but the amount of bioactive peptides percentage to the total peptides generated for tilapia was the highest (86.4%). The most common bioactivities were ACE and DPP-IV inhibitory activities. A molecular docking study showed that Thr-Phe and Gly-Phe had the strongest binding energy to enzymes involved in ACE and DPP-IV, respectively, indicating that collagen was a good source of anti-hypotensive and anti-hypoglycaemic peptides.

Bioactive angiotensin converting enzyme inhibitory activity and antihypertensive activity derived from fish protein hydrolysate: a systematic review

In the fish processing sector, fish have been processed in large quantities, are generated and discarded into the sea or dumped into the oceans. However, by employing effective strategies, this fishery waste can be utilized and converted into fish protein hydrolysate (FPH). FPH is a rich source of amino acids and peptides that have biological properties such as angiotensin-converting enzyme (ACE) inhibition, antimicrobial, antioxidant, and anticancer activity. The FPH has been used as a functional food perspective related to improving human health, primarily by maintaining blood pressure and normal heart function as measured by antihypertensive activity. FPH can be produced by various fish species, parts, and hydrolysis methods. Several studies have been published on the acceptability of FPH in obtaining bioactive properties from various fish, each using a different method to obtain bioactive properties. FPH is commonly produced by fish species such as Atlantic Cod, Lizard Fish, Atlantic Chub Mackerel, Atlantic Horse Mackerel, and Kawakawa (Mackerel Tuna). Furthermore, we summarized the various methodologies used by various researchers based on raw material data collection, method of production, ACE-inhibitory assay, ACE-inhibitory activity, degree of hydrolysis, molecular weight, purification method, and ACE-I peptide structure in this review.

Variation of bioactive potentials during the production of enzyme-modified cheese

Milk proteins are a known source of bioactive peptides released through proteolysis. Enzyme-modified cheese (EMC), produced with high proteolysis levels, has the potential to provide such peptides. This study aimed to explore the bioactive potentials (antioxidant, antihypertensive, antidiabetic, antimicrobial, and antiproliferative potentials) of EMC during production stages and after in vitro digestion. Results showed remarkable increases in antioxidant activities and sustained ACE inhibition activity values with each production stage. The samples inhibited α-amylase activity before in vitro digestion, while significant inhibition of α-glucosidase activity was observed after digestion. Furthermore, antimicrobial effects on Staphylococcus aureus were observed after digestion, with limited antiproliferative effects on various cancer cells. The study demonstrates the potential of EMC to positively impact body functions through its bioactive properties. Further research is needed to investigate the components formed during the production stages in detail.

Purification and Molecular Docking Study on the Angiotensin I-Converting Enzyme (ACE)-Inhibitory Peptide Isolated from Hydrolysates of the Deep-Sea Mussel Gigantidas vrijenhoeki.

The objective of this study was to prepare an angiotensin I-converting enzyme (ACE)-inhibitory peptide from the hydrothermal vent mussel, Gigantidas vrijenhoeki. The G. vrijenhoeki protein was hydrolyzed by various hydrolytic enzymes. The peptic hydrolysate exhibited the highest ACE-inhibitory activity and was fractionated into four molecular weight ranges by ultrafiltration. The <1 kDa fraction exhibited the highest ACE inhibitory activity and was found to have 11 peptide sequences. Among the analyzed peptides, KLLWNGKM exhibited stronger ACE inhibitory activity and an IC50 value of 0.007 μM. To investigate the ACE-inhibitory activity of the analyzed peptides, a molecular docking study was performed. KLLWNGKM exhibited the highest binding energy (-1317.01 kcal/mol), which was mainly attributed to the formation of hydrogen bonds with the ACE active pockets, zinc-binding motif, and zinc ion. These results indicate that G. vrijenhoeki-derived peptides can serve as nutritional and pharmacological candidates for controlling blood pressure.

Effects of coagulants on peptide profiles and ACE-inhibitory activity in ultrafiltered white (Beyaz) cheese

The present study aimed to evaluate the effects of two different enzymes, one derived from microbial sources and the other from animal sources, on the peptide profile with low molecular weight (<3 kDa) and ACE-inhibitory activity of White (Beyaz) cheese produced from ultrafiltered (UF) milk. The control group's cheeses were produced using pasteurized milk. Throughout the 90-day ripening period, the coagulating enzyme demonstrated no significant effects on the dry matter and protein values (p > 0.05). The protein content of < 3 kDa peptide extracts changed ripening, with no statistically significant effects attributed to the enzyme variation (p > 0.05). ACE inhibition increased in all cheeses by the end of the ripening process (p < 0.05). The ACE-inhibitory activity of < 3 kDa peptide extracts obtained from the UF White cheese produced using the microbial enzyme exhibited an increase corresponding to the observed increase in the total area of RP-HPLC peaks. The LC-MS/MS analysis revealed that the animal-sourced control group yielded the highest number of β-casein and αS1-casein peptides. Many < 3 kDa peptides described in the present possessed proline and positively charged amino acids at their C-terminal, contributing to ACE inhibition.

Application of plant-based proteins for fortification of oat yogurt storage stability and bioactivity.

The purpose of this study was to evaluate the addition of plant-based peanut protein isolate (PNP) and commercial pea protein (CPP) on the quality of oat yogurt (OY). PNP and CPP were partially characterized for techno-functional properties. PNP had higher solubility (acidic and basic regions) and emulsifying activity than CPP. The water absorption capacity of CPP is significantly (p<0.05) higher than PNP. Amino acid profiles of PNP and CPP were promising for the nutritional enhancement of OYs. OYs with PNP or CPP (0.5, 1, 2% w/v) were stored for 21 days and compared to the control group with no protein. On the 21st day of storage, (i) PNP- or CPP-added OYs were found to be comparable to the control with respect to post-acidification and viscosity, (ii) syneresis was more evident in PNP-added OYs than in CPP-added ones, (iii) total color change of 1% CPP-added OY was equal to the control, and (iv) hardnesses of control, 2% PNP, and 2% CPP-added OYs were 0.29±0.00, 0.39±0.01, and 0.45±0.00N, respectively. No adverse sensory effects were detected for CPP or PNP addition. Both proteins increased the total phenolic, soluble protein, antioxidant, antihypertensive, and α-glucosidase inhibition activity of oat milk and OYs, with PNP superior to CPP overall. Compared to oat milk, the fermentation process increased ACE inhibition activity in in vitro digested samples, whereas it reduced digested yogurts' antioxidant activity. Utilization of PNP in OY can solve the waste problem of peanut producers and the texture problem of the OY producers while formulating a functional product. PRACTICAL APPLICATION: Plant-based (PB) yogurts have a growing consumer demand. The low-protein content of PB yogurts results in low acceptance with respect to their undesirable textural and sensorial attributes. This study provided a technical basis for the PB yogurt manufacturers focusing on the addition of commercial pea protein and isolated peanut protein into oat yogurt formulation without any thickeners or flavors. In vitro digestion of protein-added oat milk and oat yogurts showed the benefits of fermentation on bioactivity to the consumers.

PLM4ACE: A protein language model based predictor for antihypertensive peptide screening

Angiotensin-I converting enzyme (ACE) regulates the renin-angiotensin system and is a drug target in clinical treatment for hypertension. This study aims to develop a protein language model (pLM) with evolutionary scale modeling (ESM-2) embeddings that is trained on experimental data to screen peptides with strong ACE inhibitory activity. Twelve conventional peptide embedding approaches and five machine learning (ML) modeling methods were also tested for performance comparison. Among the 65 classifiers tested, logistic regression with ESM-2 embeddings showed the best performance, with balanced accuracy (BACC), Matthews correlation coefficient (MCC), and area under the curve of 0.883 ± 0.017, 0.77 ± 0.032, and 0.96 ± 0.009, respectively. Multilayer perceptron and support vector machine also exhibited great compatibility with ESM-2 embeddings. The ESM-2 embeddings showed superior performance in enhancing the prediction model compared to the 12 traditional embedding methods. A user-friendly webserver (https://sqzujiduce.us-east-1.awsapprunner.com) with the top three models is now freely available.

Identification and In Silico Analysis of ACE-Inhibitory Peptides Derived from Milk Fermented by Lacticaseibacillus paracasei.

Inhibition of angiotensin I-converting enzyme (ACE) activity is an effective way to treat hypertension. In the present study, the ability to produce ACE-inhibitory peptides during fermentation of skimmed milk by the Lacticaseibacillus paracasei M3 strain was evaluated, and the inhibitory mechanism and stability were studied by bioinformatics analysis. The results showed that the ACE inhibition activity of fermented milk was 71.94 ± 1.39%. After digestion with gastric juice and pancreatic juice, the ACE inhibitory activities of the fermented milk were 78.40 ± 1.93 and 74.96 ± 1.73%, respectively. After the fermented milk was purified using ultrafiltration and gel chromatography, 11 peptides from milk proteins were identified and sequenced by Nano LC-MS/MS. Molecular docking displayed that peptide PWIQPK had a high affinity, with ACE showing a binding energy of -6.10 kcal/mol. Hydrogen bonds were formed between PWIQPK and Glu384 in the S1 active pocket of ACE and Asp358. In addition, van der Waals forces were observed. In silico proteolysis suggested that PWIQPK could resist the digestion of pepsin and trypsin, indicating that it is relatively stable in the digestive tract. All results indicate that milk fermented by L. paracasei M3 has the potential to be used as a functional food having antihypertensive effects.

Characterization of fermented pomegranate juice: ACE inhibitory activity under in vitro digestion, antioxidant capacity, phenolics composition, chemical properties and sensory evaluation.

The online version contains supplementary material available at 10.1007/s10068-023-01388-w.

A screening strategy for identifying umami peptides with multiple bioactivities from Stropharia rugosoannulata using in silico approaches and SPR sensing

Umami peptides from natural resources have garnered considerable attention for their potential bioactivities and flavor-enhancing characteristics. In this study, we constructed a database comprising 123 peptides from Stropharia rugosoannulata and screened for umami peptides with both angiotensin I-converting enzyme (ACE) and dipeptidyl peptidase-4 (DPP-IV) inhibitory activities using online prediction tools and molecular docking, and further confirmed by SPR sensing, intelligent sensory and activities test. Five peptides with varying chain lengths were synthesized and by evaluations analyses they exhibited strong umami, with thresholds ranging from 0.105 mmol/L to 0.547 mmol/L. According to the targeted SPR molecular interaction analysis, umami peptides and hT1R3 receptor exhibited a “fast-on/fast-off” binding mode with stronger intensity and persistence than MSG. Furthermore, in vitro experiments revealed that five peptides showed potent ACE and DPP-IV inhibitory activities. Notably, the EAF inhibitory activity was the most significant among the peptides. This comprehensive screening strategy provides a rapid approach for identifying high-sensitivity umami peptides with bioactivities.

Isolation, identification, and structure-activity relationship of novel ACE inhibitory peptides from earthworm protein in vitro gastrointestinal digestion product

Earthworms are a good protein resources with several health-promoting effects, particularly for antihypertensive activity. However, the active components remain unknown. In the present study, earthworms’ protein in vitro gastrointestinal digestion product (EWP-GI) was prepared and purified by ultrafiltration and column chromatography. The potential angiotensin-converting enzyme (ACE) inhibitory peptides were identified using UPLC-MS/MS and screened using in silico tools and molecular docking. Finally, seven novel ACEI peptides (SSPLWER, RFFGP, LERWP, MFPGIADR, FPGIADR, SADRISHGF and ADRYSSWP) were obtained. The two most active peptides, SSPLWER and RFFGP, presented ACE inhibitory activity with IC50 values of 14.30 ± 0.81 and 117.63 ± 0.36 μM respectively, and both acted as competitive inhibitors. The peptides occupied the active sites of ACE to generate steric hindrance, which weakened the catalytic reaction. Moreover, the tryptophan residue in SSPLWER and the arginine residue in RFFGP played an important role in the ACE inhibitory effects of peptides. Thus, these results indicated that peptides were the active ingredients of earthworms that exerted ACE inhibitory activity after gastrointestinal digestion, offering a new perspective to further enlighten the hypotensive activity of earthworm.

A novel angiotensin-converting enzyme (ACE) inhibitory peptide from tilapia skin: Preparation, identification and its potential antihypertensive mechanism

To obtain food-derived peptides with high ACE inhibitory activity, tilapia skin was pretreated with steam explosion prior to enzymatic hydrolysis. The results showed that steam explosion pretreatment improved the hydrolysis efficiency and ACE inhibitory activity of fish skin hydrolysates. A novel ACE inhibitory peptide VGLFPSRSF (1009.17 Da) was obtained from steam-exploded fish skin hydrolysates. VGLFPSRSF had an IC50 value of 61.43 μM for ACE inhibitory activity, showing a non-competitive binding mode and gastrointestinal enzyme hydrolysis resistance. Molecular docking results showed that VGLFPSRSF interacted with ACE receptor protein through hydrogen bonding and hydrophobic interactions. Based on the results of network pharmacological analysis and molecular docking, VGLFPSRSF might regulate blood pressure through interaction with hypertensive targets such as AKT1, ACE, CD4, REN, and MMP9. Steam-exploded tilapia skin peptides had potential antihypertension activity and might be promising to achieve high-value utilization of fish skin by-products.

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

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: 102.75μmol/L) and Zn-chelating capacity (11.69mg/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.