Antioxidant and angiotensin I-converting enzyme inhibitory activities of northern shrimp (Pandalus borealis) by-products hydrolysate by enzymatic hydrolysis
© The Author(s) 2016
Received: 18 July 2016
Accepted: 19 July 2016
Published: 9 September 2016
In the present study, we investigated to the antioxidant and angiotensin I-converting enzyme (ACE) inhibitory activities of the northern shrimp (Pandalus borealis) by-products (PBB) hydrolysates prepared by enzymatic hydrolysis. The antioxidant and ACE inhibitory activities of five enzymatic hydrolysates (alcalase, protamex, flavourzyme, papain, and trypsin) of PBB were evaluated by the 2, 2′-azino-bis [3-ethylbenzothiazoline-6-sulfonic acid] (ABTS+) radical scavenging and superoxide dismutase (SOD)-like activities, reducing power and Li’s method for ACE inhibitory activity. Of these PBB hydrolysates, the protamex hydrolysate exhibited the most potent ACE inhibitory activity with IC50 value of 0.08 ± 0.00 mg/mL. The PBB protamex hydrolysate was fractionated by two ultrafiltration membranes with 3 and 10 kDa (below 3 kDa, between 3 and 10 kDa, and above 10 kDa). These three fractions were evaluated for the total amino acids composition, antioxidant, and ACE inhibitory activities. Among these fractions, the < 3 kDa and 3–10 kDa fractions showed more potent ABTS+ radical scavenging activity than that of > 10 kDa fraction, while the > 10 kDa fraction exhibited the significant reducing power than others. In addition, 3–10 kDa and > 10 kDa fractions showed the significant ACE inhibitory activity. These results suggested that the high molecular weight enzymatic hydrolysate derived from PBB could be used for control oxidative stress and prevent hypertension.
KeywordsNorthern shrimp Enzymatic hydrolysate Antioxidant Angiotensin I-converting enzyme
Hypertension is one of the primary causes of cardiovascular disease which leads to stroke, coronary artery disease, and sudden cardiac death (Bhuyan and Mugesh 2011). The renin-angiotensin system (RAS) plays a key role in regulating blood volume and hypertension (Hall 1991; Hall et al. 1989). Angiotensin I-converting enzyme (ACE) is important in the functioning of the RAS. Renin converts angiotensinogen to angiotensin I, and ACE catalyzes cleavage of angiotensin I into angiotensin II which is the main active component of hypertension (Paul et al. 2006; Takahashi et al. 2011). The increased angiotensin II causes vasoconstriction along with increased blood volume and water retention (Parish and Miller 1992). Several ACE inhibitors have been tested and developed in order to inhibit angiotensin II-mediated hypertension. Most synthetic ACE inhibitors such as captopril, enalapril, lisinopril, ramipril, and benzapril on the market have been reported with their side effects including skin rash, loss of taste, and dry cough (Dr and Lisa 2012). Moreover, a recent research has found that oxidative stress is a principal factor for hypertension (Bagatini et al. 2011). Excess reactive oxygen species affects cellular functions and reduces the bioavailability of endothelial nitric oxide and enhances low-density lipoprotein oxidation in the vascular system (Ray et al. 2012; Toeroek 2008; Mattson 2009). Therefore, there is a necessity for the development of new ACE inhibitors with potent oxidative stress inhibition and fewer side effects from natural resources.
Northern shrimp (Pandalus borealis), one of the most popular shrimp species in Korea, belongs to family Pandalidae and distributes widely in the deep sea at depths of 20–1330 m with a temperature of 2–14 °C found in the water around the eastern coast of Korea (Bauer 2004). This is rich in nutrients such as proteins, minerals, and vitamins. However, the inedible parts of shrimp by-products including head, shell, and tail portions account for approximately 50 % of the catch and constitute valuable and useful bioactive materials, such as carotenoprotein, pigments, chitin, and chitosan (Chakrabarti 2002; Babu et al. 2008; Younes et al. 2015). Recently, much research has been carried out on the utilization of protein-rich fisheries by-products as nutraceuticals and nutritional supplements with high nutrient (Chae et al. 1998; Guerard et al. 2001; Arvanitoyannis and Kassaveti 2008).
The aim of the present study was to determine antioxidant and ACE inhibitory activities of enzymatic hydrolysates and its molecular weight cut-off fractions of the P. borealis by-products for prevention of hypertension.
P. borealis was purchased from the market of Yang yang-gun, Gangwon-do, Korea, in May, 2012. Alcalase® 2.4 L, papain, trypsin, serine, o-phthaldialdehyde (OPA), pyrogallol, 2, 2′-azino-bis [3-ethylbenzothiazoline-6-sulfonic acid] (ABTS+), dimethyl sulfoxide (DMSO), ethylenediaminetetraacetic acid (EDTA), potassium ferricyanide (K3Fe(CN)6), trichloroacetic acid (TCA), hippuryl-l-histidyl-l-leucine (HHL), angiotensin I-converting enzyme (ACE), sodium borate, sodium chloride, hydrochloric acid, pyridine, benzene sulfonyl chloride (BSC), captopril, and l-ascorbic acid were purchased from Sigma-Aldrich Chemical Co. (St. Louis, MO, USA) and iron(III) chloride (FeCl3) was obtained from Junsei Chemical Co. (Tokyo, Japan). Protamex and flavourzyme were purchased from Novo Co. (Novozyme Laboratories, Copenhagen, Denmark).
Enzymatic hydrolysis and fractionation of shrimp by-product
The proximate compositions including moisture, crude fat, ash, and crude protein of PBB
Crude fat (%)
Crude protein (%)
21.07 ± 0.22
12.19 ± 0.12
17.18 ± 0.64
44.50 ± 0.35
7.05 ± 0.21
1.12 ± 0.15
18.35 ± 0.21
73.92 ± 0.95
< 3 K
14.04 ± 0.13
4.66 ± 0.21
15.85 ± 0.18
62.07 ± 3.23
7.26 ± 0.17
2.27 ± 0.25
11.75 ± 0.26
69.31 ± 2.11
> 10 K
5.48 ± 0.22
2.30 ± 0.17
12.69 ± 0.31
74.02 ± 2.63
The protamex hydrolysate (38 g) was dissolved in 50 mL deionized water and filtered by two ultrafiltration membranes (Amicon Ultra-filter devices; Millipore, Billerica, MA, USA) with 3 and 10 kDa molecular weight cut-offs (< 3 kDa, 3–10 kDa, and > 10 kDa). The soluble fractions were prepared by centrifuging at 3000×g for 20 min and passed through the membrane sequentially, beginning with the largest molecular weight cut-off membrane cartridge (10 kDa). The retentate and permeate were collected separately, and the retentate was recirculated into the feed until the maximum permeate yield was reached. Permeate from the 10 kDa membrane was then filtered through the 3 kDa membrane with recirculation until the maximum permeate yield was reached.
Degree of hydrolysis (DH)
Total amino acids contents
The total amino acids composition was determined using an amino acid analyzer (S43000; Sykam, Eresing, Germany). Samples were hydrolyzed in hydrochloric acid (6 N) in vacuum-sealed tubes at 110 °C for 24 h.
Tryptophan is measured after alkaline hydrolysis (Sato et al. 1984). Samples (9–10 mg, 0.1 mg precision) were dissolved in 10 mL of 4.2 N sodium hydroxide and hydrolysed in an oven at 110 °C for 20 h. The hydrolysates were filtered using filter paper (ADVANTEC No. 5B) and mass up 50 mL by 0.2 N sodium citrate buffer (pH 4.2). The 1–5 mL of solution was dried in a waterbath at 70 °C. The pH of the hydrolysates was adjusted to 4.2 with 6 N HCl and 0.2 N sodium citrate buffer and mass up 25 mL. The solutions were filtered through 0.2 μm membrane filter and analyzed by amino acid analyzer (Sykam 4300, Sykam, Germany).
ABTS+ radical scavenging activity
The ABTS+ radical scavenging activity was determined using the method of Roberta et al. (1999). The ABTS solution was diluted with water to achieve an absorbance of 0.75 ± 0.03 at 734 nm. Then, 180 μL of ABTS solution was added to 20 μL of different concentrations of samples. The mixture was incubated in the dark for 10 min and measured the absorbance by spectrophotometer (BIO-TEK US/MQX 200, USA) at 734 nm. l-ascorbic acid was used as a positive control and the ABTS+ radical scavenging activity of each sample was expressed as IC50 value.
Superoxide dismutase (SOD)-like activity
The SOD-like activity of the sample was evaluated according to the procedure of Marklund and Marklund (1974) with a slight modification. One hundred microliters of sample solutions were mixed with 100 μL of pyrogallol (7.2 mM) and 100 μL of 50 mM Tris-HCl buffer at pH 8.5 containing 0.2 mM EDTA. After 10 min, 50 μL of 1 N HCl was added to the mixture to stop the reaction and measured the absorbance at 420 nm. l-ascorbic acid was used as a positive control, and the SOD-like activity of the PBB was expressed as IC50 value.
The reducing power of shrimp shell extracts were measured by the method of Oyaizu (1986). Different concentrations of samples in 10 % DMSO were mixed with 50 μL of 0.2 M sodium phosphate buffer (pH 6.6) and 50 μL of potassium ferricyanide (10 mg/mL). The mixtures were incubated at 50 °C for 20 min. Then, 50 μL of TCA (100 mg/mL) was added and centrifuged at 2000×g for 10 min. After centrifugation, 100 μL of the supernatant was mixed with 20 μL of iron(III) chloride (1 mg/mL) and the mixture was measured at 700 nm. Reducing power was expressed as the 0.5 of absorbance (EC50) and l-ascorbic acid was used as a positive control.
ACE inhibitory activity
The inhibitory activity of ACE was monitored according to the method of Li et al. (2005). A 20 μL of sample, 50 μL of 5 mM HHL, and 100 mM of sodium borate buffer (pH 8.3) containing 300 mM NaCl were pre-incubated at 37 °C for 5 min. The reaction was initiated by the addition of 10 μL of ACE solution (100 mU/mL), and the mixture was incubated at 37 °C for 30 min. The reaction was stopped by adding 100 μL of 1 M HCl, and then sodium borate buffer (320 μL), pyridine (600 μL), and BSC (200 μL) were added to the reaction mixture. After incubation at room temperature for 30 min, the absorbance of reaction mixture was measured at 492 nm and the captopril was used as a positive control.
The data were analyzed using analysis of variance through the general linear model procedure (SAS Institute, Cary, NC, USA). Duncan’s multiple range test was applied to determine the significance of the differences between means (P < 0.05).
Results and discussion
Enzymatic hydrolysis and fractionation
Recently, the enzymatic hydrolysates have been studied and utilized as nutraceutical resources. In particular, the interest of many researchers on the enzymatic hydrolysates derived from fish and shrimp processing by-products and the various biological activities such as antioxidant, antibacterial, antiobesity, and antihypertensive activities is growing (Sila et al. 2015; Benoit et al. 2008; Cancre et al. 1999).
The conditions of enzymatic hydrolysis and degree of hydrolysis of the enzymatic hydrolysates of PBB
Crude protein (%)
70.57 ± 2.05
55.96 ± 0.041,d
73.92 ± 0.95
59.85 ± 0.09a
67.40 ± 0.16
55.68 ± 0.08e
69.45 ± 1.33
58.86 ± 0.08b
66.62 ± 0.66
58.31 ± 0.08c
Total amino acids contents
Total amino acids composition for the molecular weight cut-off fractions of protamex hydrolysate (g/100 g)
< 3 kDa
> 10 kDa
Reactive oxygen species (ROS), containing superoxide (O2 −), hydrogen peroxide (H2O2), hydroxyl radical (OH−), and singlet oxygen (O2 ·), can cause the oxidative damage to the important components such as protein, lipid, nucleic acids and have been associated with the occurrence of various diseases including hypertension (Ngo et al. 2011a, b).
Antioxidant and ACE inhibitory activities for the enzymatic hydrolysates of PBB
ACE inhibitory activity
0.16 ± 0.023, c
2.82 ± 0.72a
9.42 ± 0.82a
0.11 ± 0.01b
0.17 ± 0.00b, c
2.04 ± 0.15a
6.75 ± 0.94b
0.08 ± 0.00c
0.20 ± 0.00a, b
3.13 ± 0.51a
4.63 ± 0.15c
0.11 ± 0.00b
0.21 ± 0.03a
2.59 ± 0.48a
4.46 ± 0.31c
0.11 ± 0.01b
0.22 ± 0.02a
2.44 ± 0.13a
6.62 ± 0.06b
0.13 ± 0.00a
0.004 ± 0.000d
0.02 ± 0.00b
0.04 ± 0.00d
0.00002 ± 0.00000d
SOD, an important antioxidant defense enzyme, catalyzes the dismutation of the superoxide anion (O2 −) into oxygen (O2) and hydrogen peroxide (H2O2). The SOD-like activity is widely used for assay to measure the inhibition of pyrogallol autoxidation. The results of SOD-like activity of the five enzymatic hydrolysates were shown in Table 4. The protamex hydrolysate exerted the greatest SOD-like activity (2.04 ± 0.15 mg/mL) among hydrolysates, while the alcalase hydrolysate exhibited moderate activity.
The reducing power is the ability to donate an electron or hydrogen (Dorman et al. 2003). The electron donation capacity of the five PBB enzymatic hydrolysates were evaluated and showed in Table 4. All the PBB hydrolysates exhibited moderate reducing power.
Antioxidant and ACE inhibitory activities for the molecular weight cut-off fractions of the protamex hydrolysate
ABTS+ scavenging activity
ACE inhibitory activity
< 3 K
0.22 ± 0.013, b
20.14 ± 0.39a
0.06 ± 0.00a
0.22 ± 0.00b
13.84 ± 0.16b
0.03 ± 0.00b
> 10 K
0.24 ± 0.01a
7.04 ± 0.83c
0.03 ± 0.00b
0.005 ± 0.000c
0.07 ± 0.00d
0.04 ± 0.00d
0.00001 ± 0.0000c
ACE inhibitory activity
The inhibition of ACE, a key enzyme regulating the blood pressure, has been recognized as the most effective therapy for the treatment of hypertension. However, many synthetic ACE inhibitors including captopril, enalapril, alacepril, fosinopril, and lisinopril cause side effects such as cough, taste alterations, skin rashes, and angioneurotic edema (Alderman 1996; Cicoira et al. 2001; Vyssoulis et al. 2001). Therefore, it is necessary to develop safe and effective ACE inhibitors from natural products.
The ACE inhibitory activity of the enzymatic hydrolysates of PBB was shown in Table 4. Among the five PBB hydrolysates, the protamex hydrolysate exhibited the most potent ACE inhibitory activity with IC50 value of 0.08 ± 0.00 mg/mL, followed by flavourzyme (IC50 = 0.11 ± 0.00 mg/mL) > alcalase (IC50 = 0.11 ± 0.01 mg/mL) > papain (IC50 = 0.11 ± 0.00 mg/mL) > trypsin (IC50 = 0.13 ± 0.00 mg/mL).
The ACE inhibitory activity of the three MWCO fractions of protamex hydrolysate was measured and shown in Table 5. Among the MWCO fractions, the > 3 kDa fraction including 3–10 kDa and > 10 kDa fractions showed significant ACE inhibitory activity with IC50 value of 0.03 ± 0.00 mg/mL. This result also indicated that high molecular weight fraction, 3–10 kDa and > 10 kDa, exhibited potent ACE inhibitory activity compared with protamex enzymatic hydrolysate.
Recently, many researchers have reported that various bioactive peptides derived from fisheries processing by-products including crab shell (Yoon et al. 2013), Pacific cod skin (Ngo et al. 2011a, b), squid skin and muscle (Mendis et al. 2005; Rajapakse et al. 2005), and tuna (Qian et al. 2007; Je et al. 2005; Lee et al. 2010). In the present study, PBB protamex hydrolysate showed notable ABTS+ radical scavenging and ACE inhibitory activities. In addition, its MWCO fractions exerted potent ACE inhibitory activities. Therefore, more detailed investigations are necessary to isolate and identify the peptides from active enzymatic hydrolysate and to clarify the mechanism of active peptides.
In this study, the five enzymatic hydrolysates of PBB derived from fisheries processing by-products were investigated on the antioxidant and ACE inhibitory activities. The PBB Protamex hydrolysate which showed the most potent ACE inhibitory activity than other fractions was fractionated as the below 3 kDa, between 3 and 10 kDa, and above 10 kDa fractions respectively to isolate the active materials. But these fractions showed lower antioxidant activities than those of enzymatic hydrolysate, while these fractions showed the significant ACE inhibitory activity. In addition, 3-10 kDa and >10 kDa fractions showed the better ACE inhibitory activity than <3 kDa fraction. These results suggested that the high molecular weight enzymatic hydrolysate derived from PBB could be used for prevent hypertension.
Angiotensin I converting enzyme
Pandalus borealis by-products
- ABTS+ :
Renin angiotensin system
- K3Fe(CN)6 :
Benzene sulfonyl chloride
- FeCl3 :
Iron (III) chloride
Molecular weight cut-offs
Reactive oxygen species
This work was supported by a grant from the National Institute of Fisheries Science (NIFS), (R2016064/RP-2016-EC-002).
SB carried out the anti-oxidant and ACE inhibitory activities assay. NY performed the enzymatic hydrolysis and fractionation. KB analyzed the total amino acids composition. CW participated in the design of the study and performed the statistical analysis. All authors read and approved the final manuscript.
The authors have no pecuniary or other personal interest, direct or indirect, in any matter that raises or may raise a conflict with our duties.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Adler-Nissen, J. 1986. Enzymic hydrolysis of food protein. Baking, UK Elsevier 9–56, 110–169
- Alderman CP. Adverse effects of the angiotensin-converting enzyme inhibitors. Ann Pharmacother. 1996;30:55–61.PubMedGoogle Scholar
- AOAC. 2000. Association of Official Analytical Chemists. 17th Edn., Official Method of Analysis, Washington D.C., USA.
- Arvanitoyannis I, Kassaveti A. Fish industry waste: treatments, environmental impacts, current and potential uses. Int J Food Sci Tech. 2008;43:726–45.View ArticleGoogle Scholar
- Babu CM, Chakrabarti R, Sambasivarao KRS. Enzymatic isolation of carotenoid-protein complex from shrimp head waste and its use as a source of carotenoids. LWT-Food Sci Tech. 2008;41:227–35.View ArticleGoogle Scholar
- Bagatini MD, Martins CC, Battisti V, Gasparetto D, da Rosa CS, Spanevello RM, Ahmed M, Schmatz R, Rosa M, Schetinger C, Morsch VM. Oxidative stress versus antioxidant defenses in patients with acute myocardial infarction. Heart Vessels. 2011;26:55–63.View ArticlePubMedGoogle Scholar
- Bauer R. 2004. Remarkable shrimps, adaptations and natural history of the carideans. Animal Natural History Series. University of Oklahoma Press 7, 296.
- Benoit C, Rozenn RP, Elisa C, Martine FP. Peptides from fish and crustacean by-products hydrolysates stimulate cholecystokinin release in STC-1 cells. Food Chem. 2008;111:970–5.View ArticleGoogle Scholar
- Bhuyana BJ, Mugesh G. Effect of peptide-based captopril analogues on angiotensin converting enzyme activity and peroxynitrite-mediated tyrosine nitration. Org Biomol Chem. 2011;9:5185–92.View ArticleGoogle Scholar
- Cancre I, Ravallec R, Wormhoudt AV, Stenberg E, Gildberg A, Gal YL. Secretagogues and growth factors in fish and crustacean protein hydrolysates. Mar Biotechnol. 1999;1:489–94.View ArticlePubMedGoogle Scholar
- Chae H, In M, Kim M. Process development for the enzymatic hydrolysis of food protein: effects of pre-treatment and post-treatments on degree of hydrolysis and other product characteristics. Biotechnol Bioproc E. 1998;3:35–9.View ArticleGoogle Scholar
- Chakrabarti R. Carotenoprotein from tropical brown shrimp shell waste by enzymatic process. Food Biotechnol. 2002;16:81–90.View ArticleGoogle Scholar
- Cicoira M, Zanolla L, Rossi A, Golia G, Franceschini L, Cabrini G, Bonizzato A, Graziani M, Anker SD, Coats AJS, Zardini P. Failure of aldosterone suppression despite angiotensin-converting enzyme (ACE) inhibitor administration in chronic heart failure is associated with ACE DD genotype. J Am Coll Cardiol. 2001;37:1808–12.View ArticlePubMedGoogle Scholar
- Dorman HJD, Peltoketo A, Hiltunen R, Tikkanen MJ. Characterization of the antioxidant properties of de-odorized aqueous extracts from selected Lamiaceae herbs. Food Chem. 2003;83:255–62.View ArticleGoogle Scholar
- Dr RCP, Lisa JM. Adverse effects of angiotensin converting enzyme (ACE) inhibitors. Drug Saf. 2012;7:14–31.Google Scholar
- Guerard F, Dufosse L, Broise D, Binet A. Enzymatic hydrolysis of proteins from yellowfin tuna (Thunnus albacares) wastes using alcalase. J Mol Catal B: Enzym. 2001;11:1051–9.View ArticleGoogle Scholar
- Hall JE, Coleman TG, Guyton AC. The renin-angiotensin system, normal physiology and changes in older hypertensives. J Am Geriatr Soc. 1989;37:801–13.View ArticlePubMedGoogle Scholar
- Hall JE. Control of blood pressure by the renin-angiotensin-aldosterone system. Clin Cardiol. 1991;14:6–21.View ArticleGoogle Scholar
- Je YJ, Park PJ, Kim SK. Antioxidant activity of a peptide isolated from Alaska Pollack (Theragra chalcogramma) frame protein hydrolysate. Food Res Int. 2005;38:45–50.View ArticleGoogle Scholar
- Kristinsson HG, Rasco BA. Biochemical and functional properties of Atlantic salmon (Salmo salar) muscle hydrolyzed with various alkaline protease. J Agric Food Chem. 2000;48:657–66.View ArticlePubMedGoogle Scholar
- Lee SH, Qian ZJ, Kim SK. A novel angiotensin I converting enzyme inhibitory peptide from tuna frame protein hydrolysate and its antihypertensive effect in spontaneously hypertensive rats. Food Chem. 2010;118:96–102.View ArticleGoogle Scholar
- Li GH, Liu H, Shi YH, Le GW. Direct spectrophotemetric measurement of angiotensin I-converting enzyme inhibitory activity for screening bioactive peptides. J Pharm Biomed Anal. 2005;37:219–24.View ArticlePubMedGoogle Scholar
- Marklund S, Marklund G. Involvement of the superoxide anion radical in the auto oxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem. 1974;47:469–74.View ArticlePubMedGoogle Scholar
- Mattson MP. Roles of the lipid peroxidation product 4-hydroxynonenal in obesity, the metabolic syndrome, and associated vascular and neurodegenerative disorders. Exp Geront. 2009;44:625–33.View ArticleGoogle Scholar
- Mendis E, Rajapakse M, Byun HG, Kim SK. Investigation of jumbo squid (Dosidicus gigas) skin gelatin peptides for their in vitro antioxidant effects. Life Sci. 2005;77:2166–78.View ArticlePubMedGoogle Scholar
- Nielsen PM, Petersen D, Dambmann C. Improved method for determining food protein degree of hydrolysis. J Food Sci. 2001;66:642–6.View ArticleGoogle Scholar
- Ngo DH, Ryu BM, Vo TS, Himaya SWA, Wijesekara I, Kim SW. Free radical scavenging and angiotensin-I converting enzyme inhibitory peptides from Pacific cod (Gadus macrocephalus) skin gelatin. Int J Biol Macromol. 2011a;49:1110–6.View ArticlePubMedGoogle Scholar
- Ngo DH, Wijesekara I, Vo TS, Ta QV, Kim SW. Marine food-derived functional ingredients as potential antioxidants in the food industry: an overview. Food Res Int. 2011b;44:523–9.View ArticleGoogle Scholar
- Oyaizu M. Studies on product of browning reaction prepared from glucose amine. Jpn J Nutr. 1986;44:307–15.View ArticleGoogle Scholar
- Qian ZJ, Je JY, Kim SK. Antihypertensive effect of angiotensin I converting enzyme-inhibitory peptide from hydrolysates of bigeye tuna dark muscle, Thunnus obesus. J Agric Food Chem. 2007;55:8398–403.View ArticlePubMedGoogle Scholar
- Parish RC, Miller LJ. Adverse effects of angiotensin converting enzyme (ACE) inhibitors. Drug Saf. 1992;7:14–31.View ArticlePubMedGoogle Scholar
- Paul M, Poyan Mehr A, Kreutz R. Physiology of local rennin-angiotensin systems. Physiol Rev. 2006;86:747–803.View ArticlePubMedGoogle Scholar
- Rajapakse N, Mendis E, Byun HG, Kim SK. Purification and in vitro antioxidative effects of giant squid muscle peptides on free radical-mediated oxidative systems. J Biochem. 2005;16:562–9.Google Scholar
- Ray PD, Huang BW, Tsuji Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal. 2012;24:981–90.View ArticlePubMedPubMed CentralGoogle Scholar
- Roberta R, Nicoletta P, Anna P, Ananth P, Min Y, Catherine RE. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med. 1999;26:1231–7.View ArticleGoogle Scholar
- Sato D, Seino T, Kobayashi T, Murai A, Yugari Y. Determination of the tryptophan content of feed and foodstuffs by ion exchnages liquid chromatography. Agric Biol Chem. 1984;48:2961–9.View ArticleGoogle Scholar
- Sila A, Kamoun Z, Chlissi Z, Makni M, Moncef N, Sahnoun Z, Nedjar-Arroume N, Bougatef A. Ability of natural astaxanthin from shrimp by-products to attenuate liver oxidative stress in diabetic rats. Pharmacol Rep. 2015;67:310–6.View ArticlePubMedGoogle Scholar
- Takahashi H, Yoshika M, Komiyama Y, Nishimura M. The central mechanism underlying hypertension: a review of the roles of sodium ions, epithelial sodium channels, the rennin-angiotensin-aldosterone system, oxidative stress and endogenous digitalis in the brain. Hypertens Res. 2011;34:1147–60.View ArticlePubMedPubMed CentralGoogle Scholar
- Toeroek J. Participation of nitric oxide in different models of experimental hypertension. Physiol Res. 2008;57:813–25.Google Scholar
- Vyssoulis GP, Karpanou EA, Papavassiliou MV, Belegrinos DA, Giannakopoulou AE, Toutouzas PK. Side effects of antihypertensive treatment with ACE inhibitors. Am J Hypertens. 2001;14:114–5.View ArticleGoogle Scholar
- Yoon NY, Shim KB, Lim CW, Kim SB. Antioxidant and angiotensin I converting enzyme inhibitory activities of red snow crab Chionoecetes japonicas shell hydrolysate by enzymatic hydrolysis. Fish Aquat Sci. 2013;16:237–42.Google Scholar
- Younes I, Nasri R, Bkhairia I, Jellouli K, Nasri M. New proteases extracted from red scorpion fish (Scorpaena scrofa) viscera: characterization and application as a detergent additive and for shrimp waste deproteinization. Food Bioprod Process. 2015;94:453–62.View ArticleGoogle Scholar