Preparation and Identification of ACE Inhibitory Peptides from the Marine Macroalga Ulva intestinalis

Sun, Siqi; Xu, Xiaoting; Sun, Xue; Zhang, Xiaoqian; Chen, Xinping; Xu, Nianjun

doi:10.3390/md17030179

Cited by 140Protein Hydrolysis and Bioactive PeptidesSeaweed-derived Bioactive CompoundsPeptidase Inhibition and Analysis

Preparation and Identification of ACE Inhibitory Peptides from the Marine Macroalga Ulva intestinalis

Open access

Sun, Siqi, Xu, Xiaoting, Sun, Xue, Zhang, Xiaoqian, Chen, Xinping, Xu, Nianjun·2019·Marine Drugs

DOI 10.3390/md17030179PMC PMC6471128

Open this paper in CoChat — free account Open PDF

Abstract

Angiotensin I-converting enzyme (ACE) inhibitory peptides derived from seaweed represent a potential source of new antihypertensive. The aim of this study was to isolate and purify ACE inhibitory peptides (ACEIPs) from the protein hydrolysate of the marine macroalga Ulva intestinalis. U. intestinalis protein was hydrolyzed by five different proteases (trypsin, pepsin, papain, α-chymotrypsin, alcalase) to prepare peptides; compared with other hydrolysates, the trypsin hydrolysates exhibited the highest ACE inhibitory activity. The hydrolysis conditions were further optimized by response surface methodology (RSM), and the optimum conditions were as follows: pH 8.4, temperature 28.5 °C, enzyme/protein ratio (E/S) 4.0%, substrate concentration 15 mg/mL, and enzymolysis time 5.0 h. After fractionation and purification by ultrafiltration, gel exclusion chromatography and reverse-phase high-performance liquid chromatography, two novel purified ACE inhibitors with IC50 values of 219.35 μM (0.183 mg/mL) and 236.85 μM (0.179 mg/mL) were obtained. The molecular mass and amino acid sequence of the ACE inhibitory peptides were identified as Phe-Gly-Met-Pro-Leu-Asp-Arg (FGMPLDR; MW 834.41 Da) and Met-Glu-Leu-Val-Leu-Arg (MELVLR; MW 759.43 Da) by ultra-performance liquid chromatography-tandem mass spectrometry. A molecular docking study revealed that the ACE inhibitory activities of the peptides were mainly attributable to the hydrogen bond and Zn(II) interactions between the peptides and ACE. The results of this study provide a theoretical basis for the high-valued application of U. intestinalis and the development of food-derived ACE inhibitory peptides.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.3390/md17030179

Cites

50 of 50 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Peptides from Gracilariopsis lemaneiformis, Mazzaella japonica, and Ulva intestinalis contribute to ACE inhibition and cardiovascular health.
“Other promising peptides have been identified from Gracilariopsis lemaneiformis, Mazzaella japonica (Rhodophyta), and Ulva intestinalis (Chlorophyta), each contributing to ACE inhibition and cardiovascular health [58–60].”
From Navigating the potential of algal peptides: health effects, market applications, and scientific challenges (2026) · cites this paper as [60]
For this paper, the relevant part of the multi-citation sentence concerns Ulva intestinalis. The Conclusions (page unavailable in our copy) report two peptides from that species with measured ACE-inhibitory activity, but say that antihypertensive experiments in mice are still needed. The paper therefore supports ACE inhibition and potential cardiovascular relevance, not an established cardiovascular-health benefit. (LLM, conf=0.86)
Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Fish Protein Hydrolysates: Production, Biochemical, and Functional Properties
Kristinsson, H. G., & Rasco, B. A. (2000) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408690091189266 · Cited by 1,243 · cited 1× · see citing works
“Different proteases affect the composition and size of the polypeptides produced, which can affect their biological activities [26].”
Background
Hypotensive Peptides from Milk Proteins
Fitzgerald, R. J., Murray, B. A., & Walsh, D. J. (2004) · Journal of Nutrition · doi:10.1093/jn/134.4.980s · Cited by 725 · cited 1× · see citing works
“captopril, and lisinopril, are widely used in hypertension treatments, synthetic ACEIs have a series of negative effects, including hypotension, cough, increased potassium levels and, angioedema [5,6].”
Background
Bioactive Peptides from Muscle Sources: Meat and Fish
Ryan, J. T., Ross, R., Bolton, D., Fitzgerald, G., & Stanton, C. (2011) · Nutrients · doi:10.3390/nu3090765 · Cited by 493 · cited 2× · see citing works
“According to previous studies, most ACEIPs are small peptides of 2–12 residues and molecular weights less than 3000 Da [33], which may more easily fit in the ACE active site and thus assert inhibitory activity [34].”
Background
Physiological, chemical and technological aspects of milk-protein-derived peptides with antihypertensive and ACE-inhibitory activity
López‐Fandiño, R., Otte, J., & Camp, J. V. (2006) · International Dairy Journal · doi:10.1016/j.idairyj.2006.06.004 · Cited by 385 · cited 1× · see citing works
“To date, ACEIPs derived from a variety of products such as milk [7], bovine collagen [8], mushrooms [9], rice [10], and marine sources including fish, shellfish, and macroalgae [11,12], have been reported.”
Background
Characterization of inhibition and stability of soy-protein-derived angiotensin I-converting enzyme inhibitory peptides
Wu, J., & Ding, X. (2002) · Food Research International · doi:10.1016/s0963-9969(01)00131-4 · Cited by 344 · cited 1× · see citing works
“After gastrointestinal digestion, some food-derived ACEIPs do not exhibit (or exhibit fewer than) the expected hypotensive effects [38,39].”
Background
Health benefits of marine foods and ingredients
Larsen, R., Eilertsen, K., & Elvevoll, E. O. (2011) · Biotechnology Advances · doi:10.1016/j.biotechadv.2011.05.017 · Cited by 294 · cited 1× · see citing works
“According to previous studies, many unique bioactive compounds, including peptides, fats, and carbohydrates, have been isolated from macroalgae [13,14].”
Background
Isolation and characterisation of a novel angiotensin I-converting enzyme (ACE) inhibitory peptide from the algae protein waste
Sheih, I.-C., Fang, T. J., & Wu, T.-K. (2009) · Food Chemistry · doi:10.1016/j.foodchem.2008.12.019 · Cited by 280 · cited 1× · see citing works
“Proteases are necessary to release ACEIPs from inactive forms [25].”
Background
Antihypertensive effects of Undaria pinnatifida (wakame) peptide on blood pressure in spontaneously hypertensive rats
Suetsuna, K., Maekawa, K., & Chen, J.-R. (2004) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2003.11.004 · Cited by 249 · cited 1× · see citing works
“5 μM), and Tyr-Asn-Lys-Leu (IC50 = 21 μM) from Undaria pinnatifida [15] and Ile-Tyr (IC50 = 2.”
Purification and identification of a ACE inhibitory peptide from oyster proteins hydrolysate and the antihypertensive effect of hydrolysate in spontaneously hypertensive rats
Wang, J., Hu, J., Cui, J., Bai, X., Du, Y., Miyaguchi, Y., & Lin, B. (2008) · Food Chemistry · doi:10.1016/j.foodchem.2008.03.059 · Cited by 212 · cited 1× · see citing works
“Hypertension seriously affects human health and is a causative factor of cardiovascular diseases, stroke, and renal diseases, among others [1,2].”
Background
A novel angiotensin-І converting enzyme (ACE) inhibitory peptide from gastrointestinal protease hydrolysate of silkworm pupa (Bombyx mori) protein: Biochemical characterization and molecular docking study
Wu, Q., Jia, J., Yan, H. H., Du, J., & Gui, Z. (2014) · Peptides · doi:10.1016/j.peptides.2014.07.026 · Cited by 193 · see citing works
Angiotensin converting enzyme-inhibitory activity of peptides isolated from Manchego cheese. Stability under simulated gastrointestinal digestion
Ruiz, J. Á. G., Ramos, M., & Recio, I. (2004) · International Dairy Journal · doi:10.1016/j.idairyj.2004.04.007 · Cited by 193 · cited 2× · see citing works
“The Cterminal amino acids of the two peptides in our study (FGMPLDR and MELVLR) were Arg, which was consistent with the results of a previous study [36].”
Result
Antihypertensive and antimicrobial bioactive peptides from milk proteins
., E. M. H., & Chand, R. (2007) · European Food Research and Technology · doi:10.1007/s00217-007-0689-6 · Cited by 182 · see citing works
Purification and identification of an angiotensin I-converting enzyme inhibitory peptide from fermented soybean extract
Rho, S. J., Lee, J.-S., Chung, Y. I., Kim, Y.-W., & Lee, H. G. (2009) · Process Biochemistry · doi:10.1016/j.procbio.2008.12.017 · Cited by 170 · cited 1× · see citing works
“It has been reported that peptides with molecular weights <3 kDa generally possess high ACE inhibitory activity [29,30].”
Background
Production of antioxidant and ACE-inhibitory peptides from Kluyveromyces marxianus protein hydrolysates: Purification and molecular docking
Mirzaei, M., Mirdamadi, S., Ehsani, M. R., & Aminlari, M. (2017) · Journal of Food and Drug Analysis · doi:10.1016/j.jfda.2017.07.008 · Cited by 169 · cited 1× · see citing works
“It has been reported that hydrogen bond interactions play an irreplaceable role in stabilizing the structure of the complex as well as the ACE reaction [41,42].”
Background
Heart Health Peptides from Macroalgae and Their Potential Use in Functional Foods
Fitzgerald, C., Gallagher, E., Taşdemir, D., & Hayes, M. (2011) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf201114d · Cited by 160 · cited 1× · see citing works
“According to previous studies, many unique bioactive compounds, including peptides, fats, and carbohydrates, have been isolated from macroalgae [13,14].”
Background
ACE-inhibitory peptides identified from the muscle protein hydrolysate of hard clam (Meretrix lusoria)
Tsai, J., Chen, J.-L., & Pan, B. S. (2008) · Process Biochemistry · doi:10.1016/j.procbio.2008.02.019 · Cited by 152 · cited 1× · see citing works
“To date, ACEIPs derived from a variety of products such as milk [7], bovine collagen [8], mushrooms [9], rice [10], and marine sources including fish, shellfish, and macroalgae [11,12], have been reported.”
Background
Characteristics and antioxidant of Ulva intestinalis sulphated polysaccharides extracted with different solvents
Peasura, N., Laohakunjit, N., Kerdchoechuen, O., & Wanlapa, S. (2015) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2015.09.030 · Cited by 149 · cited 1× · see citing works
“1%), and other bioactive compounds [23,24], and the high content of crude proteins in U.”
Background
Performance of two commonly used angiotensin-converting enzyme inhibition assays using FA-PGG and HHL as substrates
Shalaby, S. M., Zakora, M., & Otte, J. (2006) · Journal of Dairy Research · doi:10.1017/s0022029905001639 · Cited by 148 · see citing works
Production of angiotensin I converting enzyme inhibitory (ACE-I) peptides during milk fermentation and their role in reducing hypertension
Rai, A. K., Sanjukta, S., & Jeyaram, K. (2015) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2015.1068736 · Cited by 147 · cited 1× · see citing works
“1, ACE), a peptidase belonging to the zinc metalloenzyme family, plays an important role in RAS and KKS, inactivating angiotensin I to the potent vasoconstrictor angiotensin II and also inactivating the vasodilator bradykinin to raise blood pressure [3].”
Background
Angiotensin-I converting enzyme (ACE) inhibitory tripeptides from rice protein hydrolysate: Purification and characterization
Chen, J., Liu, S., Ye, R., Cai, G., Ji, B., & Wu, Y. (2013) · Journal of Functional Foods · doi:10.1016/j.jff.2013.07.013 · Cited by 127 · cited 1× · see citing works
“To date, ACEIPs derived from a variety of products such as milk [7], bovine collagen [8], mushrooms [9], rice [10], and marine sources including fish, shellfish, and macroalgae [11,12], have been reported.”
Background
Colorimetric, High-Throughput Assay for Screening Angiotensin I-Converting Enzyme Inhibitors
Jimsheena, V. K., & Gowda, L. R. (2009) · Analytical Chemistry · doi:10.1021/ac901775h · Cited by 124 · cited 1× · see citing works
“Previous studies have shown that the amino acid composition of a peptide has a significant effect on its ACE inhibitory activity [31], and it has been reported that ACE prefers to bind to a polypeptide with a high content of hydrophobic amino acids [32].”
Background
Purification and identification of angiotensin I-converting enzyme inhibitory peptide from buckwheat ( Moench)
MA, M., Bae, I. Y., Lee, H. G., & YANG, C. (2005) · Food Chemistry · doi:10.1016/j.foodchem.2005.01.052 · Cited by 123 · see citing works
Revalorisation of bovine collagen as a potential precursor of angiotensin I-converting enzyme (ACE) inhibitory peptides based on in silico and in vitro protein digestions
Fu, Y., Young, J. F., Løkke, M. M., Lametsch, R., Aluko, R. E., & Therkildsen, M. (2016) · Journal of Functional Foods · doi:10.1016/j.jff.2016.03.026 · Cited by 112 · cited 1× · see citing works
“To date, ACEIPs derived from a variety of products such as milk [7], bovine collagen [8], mushrooms [9], rice [10], and marine sources including fish, shellfish, and macroalgae [11,12], have been reported.”
Background
Antihypertensive effect of novel angiotensin I converting enzyme inhibitory peptide from chum salmon (Oncorhynchus keta) skin in spontaneously hypertensive rats
Lee, J. K., Jeon, J.-K., & Byun, H. (2014) · Journal of Functional Foods · doi:10.1016/j.jff.2014.01.021 · Cited by 109 · cited 1× · see citing works
“Various factors such as temperature, pH, and substrate concentration affect protein extraction from marine sources [27], and the effect of pH on the ACE inhibition rate of the hydrolysates was significant, as shown in Figure 2A.”
Background
Optimization of a green process for the extraction of lutein and chlorophyll from spinach by-products using response surface methodology (RSM)
Derrien, M., Badr, A., Gosselin, A., Desjardins, Y., & Angers, P. (2017) · LWT · doi:10.1016/j.lwt.2017.01.010 · Cited by 109 · cited 1× · see citing works
“9560), indicating that this model may be used to analyze and predict changes in ACE inhibitory activity under different enzymatic hydrolysis conditions [28].”
Method
Effect of angiotensin I converting enzyme inhibitory peptide purified from skate skin hydrolysate
Lee, J. K., Jeon, J.-K., & Byun, H. (2010) · Food Chemistry · doi:10.1016/j.foodchem.2010.09.039 · Cited by 108 · see citing works
Angiotensin- I- converting enzyme (ACE) inhibitory peptides from Pacific cod skin gelatin using ultrafiltration membranes
Ngo, D., Vo, T., Ryu, B., & Kim, S. (2016) · Process Biochemistry · doi:10.1016/j.procbio.2016.07.006 · Cited by 106 · cited 1× · see citing works
“This is a reference for assessing the binding between proteins and peptides [38,40].”
Background
Isolation of an Antihypertensive Peptide from Alcalase Digest of Spirulina platensis
Lu, J., Ren, D., Xue, Y. Y., Sawano, Y., Miyakawa, T., & Tanokura, M. (2010) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf100193f · Cited by 99 · cited 1× · see citing works
“Some peptides have exhibited powerful antihypertensive effects comparable to those of pharmaceutical drugs in spontaneously hypertensive rats (SHRs) [16,18].”
Background
Investigations into Inhibitor Type and Mode, Simulated Gastrointestinal Digestion, and Cell Transport of the Angiotensin I-Converting Enzyme–Inhibitory Peptides in Pacific Hake (Merluccius productus) Fillet Hydrolysate
Cinq-Mars, C. D., Hu, C., Kitts, D. D., & Li‐Chan, E. C. Y. (2007) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf072277p · Cited by 98 · see citing works
Angiotensin-I converting enzyme inhibitory peptides from antihypertensive skate (Okamejei kenojei) skin gelatin hydrolysate in spontaneously hypertensive rats
Ngo, D., Kang, K., Ryu, B., Vo, T., Jung, W., Byun, H., & Kim, S. (2014) · Food Chemistry · doi:10.1016/j.foodchem.2014.11.013 · Cited by 95 · see citing works
Novel angiotensin I-converting enzyme inhibitory peptides derived from edible mushroom Agaricus bisporus (J.E. Lange) Imbach identified by LC–MS/MS
Lau, C. C., Abdullah, N., Shuib, A. S., & Aminudin, N. (2013) · Food Chemistry · doi:10.1016/j.foodchem.2013.10.053 · Cited by 92 · cited 1× · see citing works
“To date, ACEIPs derived from a variety of products such as milk [7], bovine collagen [8], mushrooms [9], rice [10], and marine sources including fish, shellfish, and macroalgae [11,12], have been reported.”
Background
Purification and identification of a novel ACE inhibitory peptide from marine alga Gracilariopsis lemaneiformis protein hydrolysate
Cao, D., Lv, X., Xu, X., Hong, Y., Sun, X. K., & Xu, N. (2017) · European Food Research and Technology · doi:10.1007/s00217-017-2886-2 · Cited by 92 · cited 2× · see citing works
“To date, ACEIPs derived from a variety of products such as milk [7], bovine collagen [8], mushrooms [9], rice [10], and marine sources including fish, shellfish, and macroalgae [11,12], have been reported.”
BackgroundSelf-citation
Production of reducing sugar from Enteromorpha intestinalis by hydrothermal and enzymatic hydrolysis
Kim, D., Lee, S.-B., & Jeong, G. (2014) · Bioresource Technology · doi:10.1016/j.biortech.2014.03.078 · Cited by 85 · cited 1× · see citing works
“1%), and other bioactive compounds [23,24], and the high content of crude proteins in U.”
Background
A Model for the Growth of Opportunistic Macroalgae (Enteromorpha sp.) in Tidal Estuaries
Martins, I., & Marques, J. C. (2002) · Estuarine Coastal and Shelf Science · doi:10.1006/ecss.2001.0900 · Cited by 81 · see citing works
A HPLC-UV method for the determination of angiotensin I-converting enzyme (ACE) inhibitory activity
Lahogue, V., Vallée‐Rehel, K., Taupin, L., Haras, D., & Allaume, P. (2009) · Food Chemistry · doi:10.1016/j.foodchem.2009.05.080 · Cited by 81 · cited 1× · see citing works
“Therefore, inhibition of ACE activity is effective for maintaining blood pressure within a normal range [4].”
Background
Optimization of ACE inhibitory peptides from black soybean by microwave-assisted enzymatic method and study on its stability
Li, M., Xia, S., Zhang, Y., & Li, X. (2018) · LWT · doi:10.1016/j.lwt.2018.08.045 · Cited by 80 · cited 2× · see citing works
“According to previous studies, most ACEIPs are small peptides of 2–12 residues and molecular weights less than 3000 Da [33], which may more easily fit in the ACE active site and thus assert inhibitory activity [34].”
Background
Purification and identification of angiotensin I-converting enzyme inhibitors from the red alga Porphyra yezoensis.
Suetsuna, K. (1998) · PubMed · Cited by 78 · see citing works
A novel angiotensin converting enzyme inhibitory peptide derived from proteolytic digest of Chinese soft-shelled turtle egg white proteins
Rawendra, R. D. S., Aisha, Chang, C., Aulanni’am, A., Chen, H., Huang, T., & Hsu, J. (2013) · Journal of Proteomics · doi:10.1016/j.jprot.2013.10.006 · Cited by 76 · cited 1× · see citing works
“Furthermore, the lisinopril, an ACE inhibitor, was found to share interactions at Ala354, His383, Glu384, and Lys511, showing that those residues might play major roles in ACE binding [44,45].”
Background
Isolation and characterization of angiotensin I-converting enzyme (ACE) inhibitory peptides from Ulva rigida C. Agardh protein hydrolysate
Paiva, L., Lima, E., Isabel, A., & Baptista, J. (2016) · Journal of Functional Foods · doi:10.1016/j.jff.2016.07.006 · Cited by 76 · cited 1× · see citing works
“8 μM were purified from an Ulva rigida protein hydrolysate [17].”
Method
Mass occurrence of unattached Enteromorpha intestinalis on the Finnish Baltic Sea coast
Bäck, S., Lehvo, A., & Blomster, J. (2000) · GRO · Cited by 74 · see citing works
Biochemical characterization of a novel antioxidant and angiotensin I-converting enzyme inhibitory peptide from Struthio camelus egg white protein hydrolysis
Asoodeh, A., Tabrizi, M. H., Shabestarian, H., Emtenani, S., & Emtenani, S. (2016) · Journal of Food and Drug Analysis · doi:10.1016/j.jfda.2015.11.010 · Cited by 67 · cited 1× · see citing works
“Previous studies have shown that the amino acid composition of a peptide has a significant effect on its ACE inhibitory activity [31], and it has been reported that ACE prefers to bind to a polypeptide with a high content of hydrophobic amino acids [32].”
Background
Measuring Angiotensin-I Converting Enzyme Inhibitory Activity by Micro Plate Assays: Comparison Using Marine Cryptides and Tentative Threshold Determinations with Captopril and Losartan
Henda, Y. B., Labidi, A., Fruitier‐Arnaudin, I., Bridiau, N., Delatouche, R., Maugard, T., Piot, J., Sannier, F., Thiéry, V., & Bordenave-Juchereau, S. (2013) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf403004e · Cited by 64 · see citing works
In silico analysis and antihypertensive effect of ACE-inhibitory peptides from smooth-hound viscera protein hydrolysate: Enzyme-peptide interaction study using molecular docking simulation
Abdelhedi, O., Nasri, R., Jridi, M., Mora, L., Oseguera-Toledo, M. E., Aristoy, M., Amara, I. B., Toldrá, F., & Nasri, M. (2017) · Process Biochemistry · doi:10.1016/j.procbio.2017.04.032 · Cited by 62 · cited 1× · see citing works
“Furthermore, the lisinopril, an ACE inhibitor, was found to share interactions at Ala354, His383, Glu384, and Lys511, showing that those residues might play major roles in ACE binding [44,45].”
Background
Identification and Molecular Docking Study of a Novel Angiotensin-I Converting Enzyme Inhibitory Peptide Derived from Enzymatic Hydrolysates of Cyclina sinensis
Yu, F., Zhang, Z., Luo, L., Zhu, J., Huang, F., Yang, Z., Tang, Y., & Ding, G. (2018) · Marine Drugs · doi:10.3390/md16110411 · Cited by 56 · cited 3× · see citing works
“After gastrointestinal digestion, some food-derived ACEIPs do not exhibit (or exhibit fewer than) the expected hypotensive effects [38,39].”
Background
The molecular mechanisms of interactions between bioactive peptides and angiotensin-converting enzyme
Pan, D., Guo, H., Zhao, B., & Cao, J. (2011) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2011.05.033 · Cited by 42 · cited 1× · see citing works
“Furthermore, as ACE is a metalloenzyme with a zinc ion coordinated in the active site with His348, Glu372, and His344 [38], the presence of Zn(II) plays an important role in ACE inhibition [46].”
Background
Differential effects of oral trandolapril and enalapril on rat tissue angiotensin-converting enzyme
Chevillard, C., Brown, N. L., Mathieu, M.-N., Laliberté, F., & Worcel, M. (1988) · European Journal of Pharmacology · doi:10.1016/0014-2999(88)90629-2 · Cited by 42 · cited 1× · see citing works
“captopril, and lisinopril, are widely used in hypertension treatments, synthetic ACEIs have a series of negative effects, including hypotension, cough, increased potassium levels and, angioedema [5,6].”
Background
Hydrolysis and purification of ACE inhibitory peptides from the marine microalga Isochrysis galbana
Wu, H., Xu, N., Sun, X. K., Hong, Y., & Zhou, C. (2014) · Journal of Applied Phycology · doi:10.1007/s10811-014-0347-x · Cited by 40 · cited 1× · see citing works
“Freeze-thaw with the frequency ultrasonic method [47] was used to extract protein from U.”
MethodSelf-citation
Effect of varying chain length between P1 and P1′ position of tripeptidomimics on activity of angiotensin-converting enzyme inhibitors
Chaudhary, S., Vats, I. D., Chopra, M., Biswas, P., & Pasha, S. (2009) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2009.05.079 · Cited by 33 · cited 1× · see citing works
“It has been reported that hydrogen bond interactions play an irreplaceable role in stabilizing the structure of the complex as well as the ACE reaction [41,42].”
Background
Seasonal variation in the mode of reproduction of Ulva intestinalis in a brackish water environment
Alström-Rapaport, C., Leskinen, E., & Pamilo, P. (2010) · Aquatic Botany · doi:10.1016/j.aquabot.2010.08.003 · Cited by 27 · cited 1× · see citing works
“intestinalis can quickly occupy the littoral zone [20], and it is among the species that cause green tides, which can affect the growth of other coastal organisms [21,22].”
Background
In vitro antimicrobial activities of methanolic extract from marine alga Enteromorpha intestinalis
Ibrahim, D., & Lim, S.-H. (2015) · Asian Pacific Journal of Tropical Biomedicine · doi:10.1016/j.apjtb.2015.07.012 · Cited by 26 · see citing works

Flagged first, then by citations

Sorted by citations

Seaweeds as a Source of Functional Proteins
Thiviya, P., Gamage, A., Gama-Arachchige, N. S., Merah, O., & Madhujith, T. (2022) · Phycology · doi:10.3390/phycology2020012 · Cited by 170 · see citing works
Seaweed Protein Hydrolysates and Bioactive Peptides: Extraction, Purification, and Applications
Echave, J., Fraga‐Corral, M., García-Pérez, P., Popović‐Djordjević, J. B., Avdović, E., Radulović, M. Đ., Xiao, J., Prieto, M. A., & Simal‐Gándara, J. (2021) · Marine Drugs · doi:10.3390/md19090500 · Cited by 154 · see citing works
“5 ◦C FGMPLDR, MELVLR ACE inhibition [84]”
Development of animal/ plant-based protein hydrolysate and its application in food, feed and nutraceutical industries: State of the art
Etemadian, Y., Ghaemi, V., Shaviklo, A. R., Pourashouri, P., Mahoonak, A. S., & Rafipour, F. (2020) · Journal of Cleaner Production · doi:10.1016/j.jclepro.2020.123219 · Cited by 148 · see citing works
Seaweed-Derived Proteins and Peptides: Promising Marine Bioactives
Echave, J., Otero, P., Garcia‐Oliveira, P., Munekata, P. E. S., Pateiro, M., Lorenzo, J. M., Simal‐Gándara, J., & Prieto, M. A. (2022) · Antioxidants · doi:10.3390/antiox11010176 · Cited by 143 · see citing works
“Again, trypsin produced the extract with the highest ACE inhibitory activity, and two peptides were indicated as the most active (FGMPLDR and MELVLR) [53].”
BackgroundInfluential
Current knowledge on the extraction, purification, identification, and validation of bioactive peptides from seaweed
Cermeño, M., Kleekayai, T., Amigo‐Benavent, M., Harnedy‐Rothwell, P. A., & Fitzgerald, R. J. (2020) · Electrophoresis · doi:10.1002/elps.202000153 · Cited by 139 · see citing works
Seventeen novel angiotensin converting enzyme (ACE) inhibitory peptides from the protein hydrolysate of Mytilus edulis : isolation, identification, molecular docking study, and protective function on HUVECs
Suo, S., Zhao, Y., Wang, Y., Pan, X.-Y., Chi, C., & Wang, B. (2022) · Food & Function · doi:10.1039/d2fo00275b · Cited by 134 · see citing works
Screening and mechanisms of novel angiotensin-I-converting enzyme inhibitory peptides from rabbit meat proteins: A combined in silico and in vitro study
Chen, J., Yu, X., Chen, Q., Wu, Q., & He, Q. (2021) · Food Chemistry · doi:10.1016/j.foodchem.2021.131070 · Cited by 122 · see citing works
Bioactivity of Marine-Derived Peptides and Proteins: A Review
Shahidi, F., & Saeid, A. (2025) · Marine Drugs · doi:10.3390/md23040157 · Cited by 112 · see citing works
Proteins and bioactive peptides from algae: insights into antioxidant, anti-hypertensive, anti-diabetic and anti-cancer activities
Leong, Y. K., & Chang, J.-S. (2024) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2024.104352 · Cited by 109 · see citing works
Bioactive Compounds of Marine Algae and Their Potential Health and Nutraceutical Applications: A Review
Cadâr, E., Popescu, A., Dragan, A.-M.-L., Pesterau, A.-M., Pascale, C., Anuța, V., Prasacu, I., Velescu, B. Ș., Tomescu, C. L., Bogdan-Andreescu, C. F., et al. (2025) · Marine Drugs · doi:10.3390/md23040152 · Cited by 123 · see citing works
Macroalgal Proteins: A Review
Brien, R. O. O., Hayes, M., Sheldrake, G. N., Tiwari, B. K., & Walsh, P. J. (2022) · Foods · doi:10.3390/foods11040571 · Cited by 100 · see citing works
Macroalgal-derived protein hydrolysates and bioactive peptides: Enzymatic release and potential health enhancing properties
Pimentel, F. B., Alves, R. C., Harnedy, P. A., FitzGerald, R. J., & Oliveira, M. B. P. P. (2019) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2019.09.006 · Cited by 81 · see citing works
Bioactive Peptides from Algae: Traditional and Novel Generation Strategies, Structure-Function Relationships, and Bioinformatics as Predictive Tools for Bioactivity
O’Connor, J., Garcia-Vaquero, M., Meaney, S., & Tiwari, B. K. (2022) · Marine Drugs · doi:10.3390/md20050317 · Cited by 81 · see citing works
Preparation, Identification, Molecular Docking Study and Protective Function on HUVECs of Novel ACE Inhibitory Peptides from Protein Hydrolysate of Skipjack Tuna Muscle
Zheng, S.-L., Luo, Q.-B., Suo, S., Zhao, Y., Chi, C., & Wang, B. (2022) · Marine Drugs · doi:10.3390/md20030176 · Cited by 79 · see citing works
“Molecular size and amino acid sequence are two critical factors influencing the ACEi ability of antihypertensive peptides [49,50].”
Background
A Review on Nutrients, Phytochemicals, and Health Benefits of Green Seaweed, Caulerpa lentillifera
Syakilla, N., George, R., Chye, F. Y., Pindi, W., Mantihal, S., Wahab, N. A., Fadzwi, F. M., Gu, P. H., & Matanjun, P. (2022) · Foods · doi:10.3390/foods11182832 · Cited by 88 · see citing works
Understanding the Mechanism for the Structure-Activity Relationship of Food-Derived ACEI Peptides
Ding, Q., Sheikh, A. R., Chen, Q., Hu, Y., Sun, N., Su, X., Luo, L., Ma, H., & He, R. (2021) · Food Reviews International · doi:10.1080/87559129.2021.1936005 · Cited by 69 · see citing works
Protein Recovery from Underutilised Marine Bioresources for Product Development with Nutraceutical and Pharmaceutical Bioactivities
Nguyễn, T. T., Heimann, K., & Zhang, W. Y. (2020) · Marine Drugs · doi:10.3390/md18080391 · Cited by 66 · see citing works
Bioactive peptides in fermented foods and their application: a critical review
Chourasia, R., Phukon, L. C., Abedin, M. M., Padhi, S., Singh, S. P., & Kumar, A. (2022) · Systems Microbiology and Biomanufacturing · doi:10.1007/s43393-022-00125-4 · Cited by 65 · see citing works
Oyster-Derived Zinc-Binding Peptide Modified by Plastein Reaction via Zinc Chelation Promotes the Intestinal Absorption of Zinc
Li, J., Chen, G., Wang, Z., Gao, R., Ren, J., Zhou, X., Wang, H., Xu, H. J., Xiao, F., Cao, Y., et al. (2019) · Marine Drugs · doi:10.3390/md17060341 · Cited by 64 · see citing works
“pH can affect the binding efficiency of enzyme molecules and substrates [20].”
Background
Considerations for Docking of Selective Angiotensin-Converting Enzyme Inhibitors
Caballero, J. (2020) · Molecules · doi:10.3390/molecules25020295 · Cited by 63 · see citing works
Efficacy of a Novel ACE-Inhibitory Peptide from Sargassum maclurei in Hypertension and Reduction of Intracellular Endothelin-1
Zheng, Y., Zhang, Y., & San, S. (2020) · Nutrients · doi:10.3390/nu12030653 · Cited by 63 · see citing works
“35 μM) isolated from the marine macroalga Ulva intestinalis [8,38]; but higher than that of peptides QAGLSPVR (63.”
Comprehensive review on some food-derived bioactive peptides with anti-hypertension therapeutic potential for angiotensin-converting enzyme (ACE) inhibition
Olalere, O. A., Yap, P., & Gan, C. (2023) · Journal of Proteins and Proteomics · doi:10.1007/s42485-023-00106-8 · Cited by 59 · see citing works
Chemical composition of a hot water crude extract (HWCE) from Ulva intestinalis and its potential effects on growth performance, immune responses, and resistance to white spot syndrome virus and yellowhead virus in Pacific white shrimp (Litopenaeus vannamei)
Klongklaew, N., Praiboon, J., Tamtin, M., & Srisapoome, P. (2021) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2021.02.004 · Cited by 53 · see citing works
Research progress in the preparation and structure-activity relationship of bioactive peptides derived from aquatic foods
Mao, Z., Jiang, H., Sun, J., Zhao, Y., Gao, X., & Mao, X. (2024) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2024.104443 · Cited by 53 · see citing works
Production and characterization of bioactive peptides in novel functional soybean chhurpi produced using Lactobacillus delbrueckii WS4
Chourasia, R., Phukon, L. C., Abedin, M. M., Sahoo, D., & Rai, A. K. (2022) · Food Chemistry · doi:10.1016/j.foodchem.2022.132889 · Cited by 50 · see citing works
Potential of Seaweeds to Mitigate Production of Greenhouse Gases during Production of Ruminant Proteins
Bhowmick, G. D., & Hayes, M. (2023) · Global Challenges · doi:10.1002/gch2.202200145 · Cited by 50 · see citing works
Therapeutic Potential of Seaweed-Derived Bioactive Compounds for Cardiovascular Disease Treatment
Cho, C. H., Lu, Y., Kim, M., Jeon, Y., & Lee, S. (2022) · Applied Sciences · doi:10.3390/app12031025 · Cited by 46 · see citing works
Bioactive peptides with antioxidant and ACE inhibitory properties in goat milk protein hydrolysates: Peptidomics and molecular docking study
Zhang, W., Abubaker, M. A., Li, Z., He, Y., Qin, S., Li, L., & Liu, Y. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.140286 · Cited by 43 · see citing works
Identification and Antihypertension Study of Novel Angiotensin I-Converting Enzyme Inhibitory Peptides from the Skirt of Chlamys farreri Fermented with Bacillus natto
Gao, J., Liu, Q., Zhao, L., Yu, J., Wang, S., Cao, T., Gao, X., & Wei, Y. (2020) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.0c04232 · Cited by 42 · see citing works
Characterization of ACE Inhibitory Peptides Prepared from Pyropia pseudolinearis Protein
Kumagai, Y., Toji, K., Katsukura, S., Morikawa, R., Uji, T., Yasui, H., Shimizu, T., & Kishimura, H. (2021) · Marine Drugs · doi:10.3390/md19040200 · Cited by 42 · see citing works
Targeting Protein–Protein Interfaces with Peptides: The Contribution of Chemical Combinatorial Peptide Library Approaches
Monti, A., Vitagliano, L., Caporale, A., Ruvo, M., & Doti, N. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24097842 · Cited by 40 · see citing works
“As an example, Sun et al. (2019) identified new small inhibitory peptides of the Angiotensin I-converting enzyme (ACE), a prominent target for treating hypertension and cardiovascular diseases, from the hydrolysate of proteins obtained from the Marine Macroalga Ulva intestinalis [134].”
BackgroundInfluential
From Sea to Lab: Angiotensin I-Converting Enzyme Inhibition by Marine Peptides—Mechanisms and Applications
Jo, D., Khan, F., Park, S., Ko, S., Kim, K. W., Yang, D., Kim, J.-Y., Oh, G., Choi, G., Lee, D.-S., et al. (2024) · Marine Drugs · doi:10.3390/md22100449 · Cited by 38 · see citing works
A novel angiotensin-converting enzyme inhibitory peptide from rabbit meat protein hydrolysate: identification, molecular mechanism, and antihypertensive effect in vivo
Chen, J., Yu, X., Huang, W., Wang, C., & He, Q. (2021) · Food & Function · doi:10.1039/d1fo02830h · Cited by 37 · see citing works
A Novel Angiotensin-I-Converting Enzyme (ACE) Inhibitory Peptide from Takifugu flavidus
Su, Y., Chen, S., Cai, S., Liu, S., Pan, N., Su, J., Qiao, K., Xu, M., Chen, B., Yang, S., et al. (2021) · Marine Drugs · doi:10.3390/md19120651 · Cited by 37 · see citing works
“Different types of proteases yield polypeptides of different compositions and sizes, which can affect their biological activities [21].”
Nutritional Composition and Functional Properties of A. platensis-Derived Peptides: A Green and Sustainable Protein-Rich Supplement
Begum, N., Qi, F., Yang, F., Khan, Q. U., Faizan, Fu, Q., Li, J., Xiu, W., Wang, X., Wang, J., et al. (2024) · Processes · doi:10.3390/pr12112608 · Cited by 38 · see citing works
“…residues (Leu, Ile, Ala, and Met) inhibit ACE by competitive effect, while peptides with positively charged residues (His, Arg, and Lys) and branched side chain (Leu, Ile, and Val), or with aromatic amino acids at c-terminal (Trp, Tyr, Pro, and Phe), inhibit ACE in a non-competitive manner [85,86].”
Isolation, identification, and molecular docking analysis of novel ACE inhibitory peptides from Spirulina platensis
Zhang, N., Li, F., Zhang, T., Li, C., Zhu, L., & Yan, S. (2022) · European Food Research and Technology · doi:10.1007/s00217-021-03949-x · Cited by 37 · see citing works
A novel angiotensin I-converting enzyme inhibitory peptide derived from the trypsin hydrolysates of salmon bone proteins
Kaewsahnguan, T., Noitang, S., Sangtanoo, P., Srimongkol, P., Saisavoey, T., Reamtong, O., Choowongkomon, K., & Karnchanatat, A. (2021) · PLoS ONE · doi:10.1371/journal.pone.0256595 · Cited by 35 · see citing works
“[61] determined the most potent amino sequences for ACEinhibitory peptides derived from the marine macroalga, Ulva intestinalis, to be Phe-Gly-MetPro-Leu-Asp-Arg (834.”
Background
Seaweed Proteins as a Source of Bioactive Peptides
Alboofetileh, M., Hamzeh, A., & Abdollahi, M. (2021) · Current Pharmaceutical Design · doi:10.2174/1381612827666210208153249 · Cited by 34 · see citing works
Green seaweed Ulva lactuca, a potential source of bioactive peptides revealed by in silico analysis
Amin, M. A., Chondra, U., Mostafa, E., & Alam, M. M. (2022) · Informatics in Medicine Unlocked · doi:10.1016/j.imu.2022.101099 · Cited by 33 · see citing works
Microalgae-Derived Peptides: Exploring Bioactivities and Functional Food Innovations
Ashraf, A., Guo, Y., Yang, T., ud Din, A. S., Ahmad, K., Li, W., & Hou, H. (2025) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.4c06800 · Cited by 32 · see citing works
Marine-Derived Compounds Applied in Cardiovascular Diseases: Submerged Medicinal Industry
Akram, W., Rihan, M., Ahmed, S., Arora, S., Ahmad, S., & Vashishth, R. (2023) · Marine Drugs · doi:10.3390/md21030193 · Cited by 31 · see citing works
Preparation and purification of an immunoregulatory peptide from Stolephorus chinensis of the East Sea of China
Xu, B., Ye, L., Tang, Y., Zheng, J., Tian, X., Yang, Y., & Yang, Z. (2020) · Process Biochemistry · doi:10.1016/j.procbio.2020.08.011 · Cited by 30 · see citing works
Angiotensin-I-Converting Enzyme Inhibitory Activity of Protein Hydrolysates Generated from the Macroalga Laminaria digitata (Hudson) JV Lamouroux 1813
Purcell, D., Packer, M. A., & Hayes, M. (2022) · Foods · doi:10.3390/foods11121792 · Cited by 30 · see citing works
“179 mg/mL when assessed previously [32].”
Background
Purification and molecular docking of angiotensin converting enzyme-inhibitory peptides derived from corn gluten meal hydrolysate and from in silico gastrointestinal digestion
Wongngam, W., Hamzeh, A., Tian, F., Roytrakul, S., & Yongsawatdigul, J. (2023) · Process Biochemistry · doi:10.1016/j.procbio.2023.03.006 · Cited by 29 · see citing works
Bioactive peptides of marine organisms: Roles in the reduction and control of cardiovascular diseases
Du, J., Xiao, M., Sudo, N., & Liu, Q. (2024) · Food Science & Nutrition · doi:10.1002/fsn3.4183 · Cited by 27 · see citing works
“…Palmaria palmata , the microalga Chlorella vulgaris , Ulva intestinalis , and Gracilariopsis lemaneiformis all showed in vitro ACE inhibitory activity (Deng et al., 2018; Fitzgerald et al., 2012; Sheih, Fang, et al., 2009; Sheih, Wu, et al., 2009; Suetsuna & Nakano, 2000; Sun et al., 2019).”
Background
Angiotensin I-converting enzyme inhibitory peptide: an emerging candidate for vascular dysfunction therapy
Wu, Q., Luo, F., Wang, X., Lin, Q., & Liu, G. (2021) · Critical Reviews in Biotechnology · doi:10.1080/07388551.2021.1948816 · Cited by 25 · see citing works
“FGMPLDR and MELVLR obtained from the marine macroalga Ulva intestinalis are bound to the active center of ACE via hydrogen bond and Zn(II) interactions [64].”
How Healthy Are Non-Traditional Dietary Proteins? The Effect of Diverse Protein Foods on Biomarkers of Human Health
Bull, C. F., Belobrajdic, D. P., Hamzelou, S., Jones, D., Leifert, W. R., Reyes, R. P., Terefe, N. S., Williams, G., & Colgrave, M. L. (2022) · Foods · doi:10.3390/foods11040528 · Cited by 24 · see citing works
“The identification of angiotensin Iconverting enzyme (ACE) inhibitory peptides in the protein hydrolysate of the macroalga Ulva intestinalis, which are stable during gastrointestinal digestion [9], as well as the ACE inhibitory properties of Ulva compressa and Ulva rigida [10] make Ulva sp.”
Background
A screening strategy for bioactive peptides from enzymolysis extracts of Lentinula edodes based on molecular docking and molecular dynamics simulation
Chen, D., XueXiang, S., Chen, W., Wu, D., Zhang, Z., Liu, P., Liu, Y., Li, W., & Yang, Y. (2024) · Journal of Future Foods · doi:10.1016/j.jfutfo.2024.07.017 · Cited by 23 · see citing works
Rational design of mimetic peptides based on the interaction between Inga laurina inhibitor and trypsins for Spodoptera cosmioides pest control
Meriño‐Cabrera, Y., Castro, J. S., Díez, J. D. R., Macedo, M. L. R., Mendes, T. A. D. O., & Oliveira, M. G. D. A. (2020) · Insect Biochemistry and Molecular Biology · doi:10.1016/j.ibmb.2020.103390 · Cited by 22 · see citing works
Identification of angiotensin‐converting enzyme inhibitory peptides from peanut meal ( Arachis hypogaea Linn) fermented by Lactobacillus pentosus using MALDI‐TOF–MS and LC–MS/MS
Li, W., Guan, Y., Shi, L., Chen, Y., Huang, H., Zhen, H., Wu, P., Wang, C., Wu, Q., & Li, W. (2024) · Food Frontiers · doi:10.1002/fft2.352 · Cited by 22 · see citing works
In vitro immunomodulation activity of protein hydrolysate from spirulina (Arthrospira platensis): the ingredient of future foods
Htoo, N. Y. M., Kraseasintra, O., Buncharoen, W., Kaewkod, T., Pekkoh, J., Tragoolpua, Y., Khoo, K. S., Chaipoot, S., Srinuanpan, S., & Pumas, C. (2024) · Frontiers in Marine Science · doi:10.3389/fmars.2024.1303025 · Cited by 23 · see citing works
An update on the effects of food-derived active peptides on the intestinal microecology
Mu, J., Lin, Q., & Liang, Y. (2022) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2022.2094889 · Cited by 21 · see citing works
“…FDAPs, most of them focused on the acquisition of FDAPs and their physiological functions in the nervous system, digestive system, immune sys-tem, or other organ systems (Chalamaiah, Yu, and Wu 2018; Cheng et al. 2019; Liu and Udenigwe 2019; Panya et al. 2019; Sun et al. 2019; Xiang et al. 2021).”
Background
Purification and Molecular Docking Study on the Angiotensin I-Converting Enzyme (ACE)-Inhibitory Peptide Isolated from Hydrolysates of the Deep-Sea Mussel Gigantidas vrijenhoeki
Heo, S., Kang, N., Kim, E.-A. L., Kim, J., Lee, S., Ahn, G., Oh, J. H., Shin, A. Y., Kim, D., & Heo, S. (2023) · Marine Drugs · doi:10.3390/md21080458 · Cited by 21 · see citing works
Unlocking the potential of chicken liver byproducts: Identification of antioxidant peptides through in silico approaches and anti-aging effects of a selected peptide in Caenorhabditis elegans
Chen, Q., Nie, X., Huang, W., Wang, C., Lai, R., Lu, Q., He, Q., & Yu, X. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.132833 · Cited by 21 · see citing works
Eco-friendly nutrient from ocean: Exploring Ulva seaweed potential as a sustainable food source
Khan, N., Sudhakar, K., & Mamat, R. (2024) · Journal of Agriculture and Food Research · doi:10.1016/j.jafr.2024.101239 · Cited by 26 · see citing works
Study on the Interaction of Algal Peptides on Virulence Factors of Helicobacter pylori: In Silico Approach
MubarakAli, D., Akshaya, T., Raghunathan, S., & Navabshan, I. (2021) · Applied Biochemistry and Biotechnology · doi:10.1007/s12010-021-03716-4 · Cited by 21 · see citing works
Exploration of cyclooxygenase-2 inhibitory peptides from walnut dreg proteins based on in silico and in vitro analysis
Hong, Z., Xie, J., Tao, L., Dai, J., Li, T., Zhang, L., Bai, Y., Hu, X., Chen, J., Sheng, J., et al. (2024) · Food Science and Human Wellness · doi:10.26599/fshw.2022.9250143 · Cited by 20 · see citing works
Study on the domain selective inhibition of angiotensin‐converting enzyme (ACE) by food‐derived tyrosine‐containing dipeptides
Song, C., Qiao, B., Zhang, Q., Wang, C., Fu, Y., & Zhu, B. (2021) · Journal of Food Biochemistry · doi:10.1111/jfbc.13779 · Cited by 20 · see citing works
Enhancing microalgal proteins for nutraceutical and functional food applications
Kaur, M., Bhatia, S., Bagchi, D., Tak, Y., Kaur, G., Kaur, C., Kaur, A., & Sharma, N. (2025) · Future Foods · doi:10.1016/j.fufo.2025.100564 · Cited by 19 · see citing works
Isolation, identification, and in vivo evaluation of the novel antihypertensive peptide, VSKRLNGDA, derived from chicken blood cells
Wongngam, W., Roytrakul, S., Mitani, T., Katayama, S., Nakamura, S., & Yongsawatdigul, J. (2022) · Process Biochemistry · doi:10.1016/j.procbio.2022.02.011 · Cited by 19 · see citing works
Fractionation and identification of bioactive peptides from red macroalgae protein hydrolysates: In silico analysis and in vitro bioactivities
Dhaouafi, J., Romdhani, M., Deracinois, B., Flahaut, C., Nedjar, N., & Balti, R. (2024) · Biocatalysis and Agricultural Biotechnology · doi:10.1016/j.bcab.2024.103211 · Cited by 18 · see citing works
Algae as a source of peptides inhibitors of the angiotensin-converting enzyme: a systematic review
de Amorim, A. P., SILVA, G. H. D., Costa, R. M. P. B., Porto, A. L. F., & Bezerra, R. P. (2022) · Anais da Academia Brasileira de Ciências · doi:10.1590/0001-3765202220201636 · Cited by 18 · see citing works
“With the purpose to separate the peptides based on their molecular weight, one of the methods to fractionation is the UF, which consists to separate the peptide according to its size using membrane with different cut-off (Cao et al. 2017, Sun et al. 2019).”
Method
First Report of Screening of Novel Angiotensin-I Converting Enzyme Inhibitory Peptides Derived from the Red Alga Acrochaetium sp.
Windarto, S., Lee, M., Nursyam, H., & Hsu, J. (2022) · Marine Biotechnology · doi:10.1007/s10126-022-10152-w · Cited by 20 · see citing works
“2018), Ulva intestinalis (Sun et al. 2019), and Pyropia pseudolinearis (Kumagai et al.”
Background
The Ocean’s Pharmacy: Health Discoveries in Marine Algae
Silva, M., Avni, D., Varela, J. C. S., & Barreira, L. A. (2024) · Molecules · doi:10.3390/molecules29081900 · Cited by 18 · see citing works
Marine Natural Products in Inflammation‐Related Diseases: Opportunities and Challenges
Zhang, T., Ouyang, Z., Zhang, Y., Sun, H., Kong, L., Xu, Q., Qu, J., & Sun, Y. (2025) · Medicinal Research Reviews · doi:10.1002/med.22109 · Cited by 18 · see citing works
Identification of novel ACE inhibitory peptides from Nannochloropsis oculata through peptidomics, in silico screening and molecular docking
Lin, L., Yuan, W., Xiao, J., Jia, J., Xie, Y., Cai, Q., Dai, C., Li, Q., & Wang, B. (2025) · Food Chemistry · doi:10.1016/j.foodchem.2025.145073 · Cited by 18 · see citing works
Screening and Molecular Mechanisms of Novel ACE-Inhibitory Peptides from Gracilariopsis lemaneiformis
Su, Y., Chen, S., Shen, J., Yi, Z., Liu, S., Cai, S., Pan, N., Qiao, K., Chen, X., Chen, B., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232314850 · Cited by 17 · see citing works
“isolated ACE-inhibitory peptides from the marine macroalga Ulva intestinalis by ultra-filtration, gel chromatography, and HPLC methods [16].”
MethodSelf-citation
Discovery of ACE Inhibitory Peptides Derived from Green Coffee Using In Silico and In Vitro Methods
Dai, H., He, M., Hu, G., Li, Z., Al-Romaima, A., Wu, Z., Liu, X., & Qiu, M. (2023) · Foods · doi:10.3390/foods12183480 · Cited by 17 · see citing works
“Moreover, a variety of bioactive peptides obtained from the protein of marine organisms including fish [8], mollusks [9,10], seaweed [11,12], and microbial fermentation products [13,14] have been confirmed to have an ACE inhibitory function.”
Background
Noncompetitive tight‐binding inhibition of Anticarsia gemmatalis trypsins by Adenanthera pavonina protease inhibitor affects larvae survival
Meriño‐Cabrera, Y., Mendes, T. A. D. O., Castro, J. S., Barbosa, S. L., Macedo, M. L. R., & Oliveira, M. G. D. A. (2020) · Archives of Insect Biochemistry and Physiology · doi:10.1002/arch.21687 · Cited by 16 · see citing works
Complementation of reducing power for 5-hydroxyvaleric acid and 1,5-pentanediol production via glucose dehydrogenase in Escherichia coli whole-cell system
Kim, B., Oh, S. J., Hwang, J. H., Kim, H., Shin, N., Joo, J. C., Choi, K., Park, S., Park, K., Bhatia, S. K., et al. (2023) · Enzyme and Microbial Technology · doi:10.1016/j.enzmictec.2023.110305 · Cited by 15 · see citing works
Preparation, identification, activity prediction, and protective effects on IR-HepG2 cells of five novel DPP-IV inhibitory peptides from protein hydrolysate of skipjack tuna dark muscles
Meng, L., Song, Y., Zheng, B., Zhao, Y., Hong, B. S., Ma, M., Wen, Z., Miao, W., & Xu, Y. (2023) · Food & Function · doi:10.1039/d3fo02948d · Cited by 15 · see citing works
Targeted Affinity Purification and Mechanism of Action of Angiotensin-Converting Enzyme (ACE) Inhibitory Peptides from Sea Cucumber Gonads
Wang, Y., Chen, S., Shi, W., Liu, S., Chen, X., Pan, N., Wang, X., Su, Y., & Liu, Z. (2024) · Marine Drugs · doi:10.3390/md22020090 · Cited by 15 · see citing works
“Its two novel ACE inhibitors, FGMPLDR and MELVLR, which were prepared in Ulva intestinalis , also had low IC values of 219.4 µ M and 236.9 µ M, respectively [32].”
BackgroundInfluentialSelf-citation
Angiotensin-I-converting enzyme inhibitory peptides from eel (Anguilla japonica) bone collagen: preparation, identification, molecular docking, and protective function on HUVECs
Xiang, H., Huang, H., Shao, Y., Hao, S., Li, L., Wei, Y., Chen, S., & Zhao, Y. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1462656 · Cited by 15 · see citing works
Marine-derived protein: peptide bioresources for the development of nutraceuticals for improved athletic performance
Penggalih, M. H. S. T., Praditya, G. N., Rizqiansyah, C. Y., Setyawardani, A., Purnomo, A. F., Maulana, R. A., Gunawan, W. B., Subali, D., Kurniawan, R., Mayulu, N., et al. (2023) · Frontiers in Sports and Active Living · doi:10.3389/fspor.2023.1281397 · Cited by 14 · see citing works
Pharmacoinformatics and cellular studies of algal peptides as functional molecules to modulate type-2 diabetes markers
Kurniawan, R., Taslim, N. A., Hardinsyah, H., Syauki, A. Y., Idris, I., Aman, A. M., Permatasari, H. K., Wiyarta, E., Surya, R., Mayulu, N., et al. (2024) · Future Foods · doi:10.1016/j.fufo.2024.100354 · Cited by 14 · see citing works
Moringa leaf extract and green algae improve the growth and physiological attributes of Mentha species under salt stress
Al-Taisan, W. A., Alabdallah, N. M., & Almuqadam, L. (2022) · Scientific Reports · doi:10.1038/s41598-022-18481-5 · Cited by 14 · see citing works
Concentration and purification of seaweed extracts using membrane technologies
Díaz-Reinoso, B. (2020) · Elsevier eBooks · doi:10.1016/b978-0-12-817943-7.00014-7 · Cited by 14 · see citing works
In vitro enzyme inhibitory effects of green and brown Australian seaweeds and potential impact on metabolic syndrome
Shannon, E., Conlon, M. A., & Hayes, M. (2023) · Journal of Applied Phycology · doi:10.1007/s10811-022-02900-1 · Cited by 12 · see citing works
Molecular binding mechanism and novel antidiabetic and anti-hypertensive bioactive peptides from fermented camel milk with anti-inflammatory activity in raw macrophages cell lines
Shukla, P., Sakure, A. A., Basaiawmoit, B., Khakhariya, R., Maurya, R., Bishnoi, M., Kondepudi, K. K., Liu, Z., Padhi, S., Rai, A. K., et al. (2023) · Amino Acids · doi:10.1007/s00726-023-03335-9 · Cited by 12 · see citing works
“Sun et al. (2019) investigated the peptides with molecular weights below 3 kDa can effectively stop the ACE activity.”
Background
Alaria esculenta, Ulva lactuca, and Palmaria palmata as Potential Functional Food Ingredients for the Management of Metabolic Syndrome
Shannon, E., & Hayes, M. (2025) · Foods · doi:10.3390/foods14020284 · Cited by 12 · see citing works
“Other mechanisms have been attributed to zinc and hydrogen bond interactions [16].”
Molecular modeling in cardiovascular pharmacology: Current state of the art and perspectives
Lagoutte‐Renosi, J., Allemand, F., Ramseyer, C., Yesylevskyy, S. O., & Davani, S. (2021) · Drug Discovery Today · doi:10.1016/j.drudis.2021.11.026 · Cited by 11 · see citing works
Purification, Identification, and In Silico Analysis of Anti-Obesity and Antidiabetic Peptides from the Red Seaweed Palmaria palmata
Ghelichi, S., Hajfathalian, M., Helalat, S. H., Svensson, B., & Jacobsen, C. (2025) · Marine Drugs · doi:10.3390/md23100392 · Cited by 13 · see citing works
“Several studies have supported its use for producing protein hydrolysates with high yields and desirable functional properties from various seaweed biomasses [24–27].”
Angiotensin-I converting enzyme (ACE) inhibitory bioaccessible peptides obtained from protein extracts of Macrocystis pyrifera and Chondracanthus chamissoi seaweeds
Vásquez, V., Martínez, R., Rodríguez-Núñez, K., & Bernal, C. (2024) · Algal Research · doi:10.1016/j.algal.2024.103575 · Cited by 10 · see citing works
Advances in analytical techniques coupled to in vitro bioassays in the search for new peptides with functional activity in effect-directed analysis
Guerra-Fajardo, L. D., Pavón-Pérez, J., Vallejos‐Almirall, A., & Jorquera-Pereira, D. (2022) · Food Chemistry · doi:10.1016/j.foodchem.2022.133784 · Cited by 11 · see citing works
Hydrolysate protein from brown macroalgae ( Sargassum ilicifolium ): Antioxidant, antitumor, antibacterial, and ACE inhibitory activities
Mousaie, M., Khodadadi, M., & Tadayoni, M. (2022) · Journal of Food Processing and Preservation · doi:10.1111/jfpp.17020 · Cited by 10 · see citing works
The Molecular Docking and Inhibition Kinetics of Angiotensin I-Converting Enzyme Inhibitory Peptides Derived from Soft-Shelled Turtle Yolk
Nong, N. T. P., Sutopo, C. C. Y., Hung, W., Wu, P., & Hsu, J. (2022) · Applied Sciences · doi:10.3390/app122312340 · Cited by 10 · see citing works
Ameliorative effect of mussel-derived ACE inhibitory peptides on spontaneous hypertension rats
You, Q., Sun, X., Chen, J., Yu, J., & Wei, Y. (2023) · European Journal of Nutrition · doi:10.1007/s00394-023-03222-9 · Cited by 10 · see citing works
Self-citation
Characterization of Proteins Extracted from Ulva sp., Padina sp., and Laurencia sp. Macroalgae Using Green Technology: Effect of In Vitro Digestion on Antioxidant and ACE-I Inhibitory Activity
Şensu, E., Ayar, E. N., Okudan, E. Ş., Özçelik, B., & Yücetepe, A. (2023) · ACS Omega · doi:10.1021/acsomega.3c05041 · Cited by 10 · see citing works
Purification of angiotensin converting enzyme inhibitory peptides and antihypertensive effect generated from Indonesian traditional fermented beef (Cangkuk)
Mirdhayati, I., Zain, W. N. H., Fatah, A., Yokoyama, I., & Arihara, K. (2024) · Animal Bioscience · doi:10.5713/ab.23.0433 · Cited by 10 · see citing works
“Factors determining ACE-inhibitory activity are amino acid composition, propensity to bind hydrophobic amino acids, small peptides, and molecular weights 3,000 Da [24].”
Background
Valorization of Hakka Huangjiu lees: Optimization of ultrasound-assisted enzymatic extraction and identification of angiotensin I-converting enzyme inhibitory peptides
Yang, S., Wang, H., Bai, W., Zhao, W., Liu, G., & Liu, X. (2024) · Food and Bioproducts Processing · doi:10.1016/j.fbp.2024.05.010 · Cited by 9 · see citing works
Abalone Viscera Fermented with Aspergillus oryzae 001 Prevents Pressure Elevation by Inhibiting Angiotensin Converting Enzyme
Iwamoto, N., Sasaki, A., Maizawa, T., & Hamada‐Sato, N. (2023) · Nutrients · doi:10.3390/nu15040947 · Cited by 9 · see citing works
Bioactive peptide production and determination of functional properties using crude water extracts of Ulva lactuca (Chlorophyta) and Sargassum crassifolium (Phaeophyceae) collected from Sri Lanka
Hamit, C. S., Nam, K., & Abeyrathne, E. D. N. S. (2022) · Applied Phycology · doi:10.1080/26388081.2022.2063758 · Cited by 9 · see citing works
“…antihypertensive, anticoagulant, anti-diabetic, and anti-HIV, depending on their structural properties (Admassu et al., 2018; Bondu et al., 2015; Cian, Garzón, Ancona, Guerrero, & Drago, 2016; Harnedy & FitzGerald, 2011, 2013; Sarmadi & Ismail, 2010; Sun et al., 2019; tePimentel et al., 2019).”
Synergistic Effect of Surfactant on Disperser Energy and Liquefaction Potential of Macroalgae (Ulva intestinalis) for Biofuel Production
Veettil, R. P., Rabia, R., Kumar, M. D., Gondi, R., Sankarapandian, K., Kannan, M., Kumar, G., Al-Qaradawi, S. Y., & Jeyakumar, R. B. (2023) · Fermentation · doi:10.3390/fermentation9010055 · Cited by 9 · see citing works
Neuroprotective peptides isolated from flavourzyme-pea protein hydrolysate protect human SH-SY5Y cells from Aβ1-42 induced apoptosis
Hsieh, L., Hsu, Y.-C., & Chiang, W. (2023) · Journal of Functional Foods · doi:10.1016/j.jff.2023.105755 · Cited by 8 · see citing works
GRU4ACE : Enhancing ACE inhibitory peptide prediction by integrating gated recurrent unit with multi‐source feature embeddings
Ahmad, S., Schaduangrat, N., Chumnanpuen, P., & Shoombuatong, W. (2025) · Protein Science · doi:10.1002/pro.70026 · Cited by 8 · see citing works
“Similarly, glutamic acid (E) shows a marked contrast, being present in 5.35% of active peptides versus only 1.15% in inactive ones, underscoring its beneficial effect on inhibitory activity (Sun et al., 2019; Wang et al., 2021).”
Influential
Identification of Novel Nonapeptides from Sipunculus nudus L. and Comparing Its ACEI Activities Mechanism by Molecular Docking
Qi, Y., Tang, X., Liu, H., Lin, Q., Lu, Y., & Luo, H. (2021) · International Journal of Peptide Research and Therapeutics · doi:10.1007/s10989-021-10328-3 · Cited by 8 · see citing works
A Perspective on Enzyme Inhibitors from Marine Organisms
Tischler, D. (2020) · Marine Drugs · doi:10.3390/md18090431 · Cited by 8 · see citing works
“For example, the algae Ulva intestinalis was used to generate a protein hydrolysate containing potential bioactives [11].”
Method
Nanoliposomal Encapsulation and Purification of Angiotensin-Converting Enzyme Inhibitor Peptides from Ulva rigida
Şensu, E., Koku, H., Demircan, E., Şişman, S., Gülseren, İ., Karaduman, T., Çakır, B., Okudan, E. Ş., Duruksu, G., Özçelik, B., et al. (2025) · ACS Omega · doi:10.1021/acsomega.5c00780 · Cited by 7 · see citing works
Green Seaweeds as a Potential Source of Biomolecules and Bioactive Peptides: Recent Progress and Applications – A Review
Das, S., Behera, M., Das, S. R., Behera, K. C., & Singh, L. (2024) · Chemistry & Biodiversity · doi:10.1002/cbdv.202401695 · Cited by 7 · see citing works
Antioxidant, antidiabetic, and antihypertensive activities of defatted pigmented rice bran protein hydrolysates
Mojumder, M. N., Mahmud, Z., Khan, I. M., Tamanna, S., Rahman, M. A., Ferdous, N., Alauddin, M., & Howlader, M. Z. H. (2024) · Discover Applied Sciences · doi:10.1007/s42452-024-06304-3 · Cited by 7 · see citing works
“[58].”

Isolation and characterization of angiotensin I-converting enzyme (ACE) inhibitory peptides from Ulva rigida C. Agardh protein hydrolysate
Paiva, L., Lima, E., Isabel, A., & Baptista, J. (2016) · Journal of Functional Foods · doi:10.1016/j.jff.2016.07.006 · Cited by 76 · see citing works
Screening of Angiotensin-I Converting Enzyme Inhibitory Peptides Derived from Caulerpa lentillifera
Joel, C. H., Sutopo, C. C. Y., Prajitno, A., Su, J.-H., & Hsu, J.-L. (2018) · Molecules · doi:10.3390/molecules23113005 · Cited by 48 · see citing works
Purification identification and function analysis of ACE inhibitory peptide from Ulva prolifera protein
Li, Z., He, Y., He, H., Zhou, W., Li, M., Lu, A., Che, T., & Shen, S. (2022) · Food Chemistry · doi:10.1016/j.foodchem.2022.134127 · Cited by 52 · see citing works
In Vitro and In Silico Approaches to Generating and Identifying Angiotensin-Converting Enzyme I Inhibitory Peptides from Green Macroalga Ulva lactuca
García‐Vaquero, M., Mora, L., & Hayes, M. (2019) · Marine Drugs · doi:10.3390/md17040204 · Cited by 82 · see citing works
Purification and identification of antihypertensive peptides from seaweed pipefish (Syngnathus schlegeli) muscle protein hydrolysate
Wijesekara, I., Qian, Z., Ryu, B., Ngo, D., & Kim, S. (2010) · Food Research International · doi:10.1016/j.foodres.2010.12.022 · Cited by 113 · see citing works

Authors: Sun, S., Xu, X., Sun, X., Zhang, X., Chen, X., & Xu, N.
Affiliations: Ningbo University (CN)
Vanderbilt University Medical Center (US)
Corresponding author: Xu, Nianjun
ORCID: Sun, Siqi
Sun, Xue
Zhang, Xiaoqian
Chen, Xinping
Xu, Nianjun
Venue: Marine Drugs
Publisher: MDPI AG
Published: 2019-03-19
Volume: 17
Issue: 3
Pages: 179
ISSN: 1660-3397 (ISSN-L)
DOI: 10.3390/md17030179
PMC: PMC6471128
OpenAlex: W2922600776
Cited by: 140
References: 50
Citations by year: 2026: 9 · 2025: 21 · 2024: 29 · 2023: 22 · 2022: 27 · 2021: 15 · 2020: 14 · 2019: 3
FWCI: 4.88
Type: journal article
Language: en
Open access: gold
dx.doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Marine Drugs (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Discover Archive (Vanderbilt University) (submittedVersion, cc-by)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders: Natural Science Foundation of Zhejiang Province (LZ17D060001)
Ningbo International Cooperation Program (2017D10019)
Ningbo Municipal Bureau of Science and Technology (2016C10034)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Hydrolysis and Bioactive Peptides
Life Sciences › Agricultural and Biological Sciences › Aquatic Science › Seaweed-derived Bioactive Compounds
Health Sciences › Medicine › Oncology › Peptidase Inhibition and Analysis
Keywords: ACE inhibitory peptides, Ulva intestinalis, seaweed, protein hydrolysates, trypsin hydrolysis, enzymatic hydrolysis optimization, peptide purification, antihypertensive peptides, food-derived bioactive peptides, zinc binding
MeSH terms: Angiotensin-Converting Enzyme Inhibitors, Antihypertensive Agents, Drug Stability, Hydrolysis, Hypertension, Peptidyl-Dipeptidase A, Peptide Hydrolases, Peptides, Protein Hydrolysates, Seaweed, Inhibitory Concentration 50, Ulva, Enzyme Assays, Molecular Docking Simulation

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Preparation and Identification of ACE Inhibitory Peptides from the Marine Macroalga Ulva intestinalis

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks