Journal of Functional Foods 35 (2017) 673–681

Contents lists available at ScienceDirect

Journal of Functional Foods

journal homepage: www.elsevier.com/locate/jff

Health benefits and food applications of bioactive compounds from fish

byproducts: A review
Maryam Atef, Seyed Mahdi Ojagh ⇑
Department of Seafood Science and Technology, Faculty of Fisheries and Environmental Science, Gorgan University of Agricultural Sciences and Natural Resources, Gorgan, Iran

a r t i c l e i n f o a b s t r a c t

Article history: Much attention has recently been paid to natural bioactive compounds from marine organisms as func-
Received 4 October 2016 tional ingredients due to their various beneficial health effects. Marine bioactive compounds have numer-
Received in revised form 10 June 2017 ous applications in food packaging, animal feeding, biodiesel/biogas, natural pigments, cosmetics, and
Accepted 14 June 2017
enzyme isolation, among others. In addition, many studies have reported that marine bioactive com-
Available online 27 June 2017
pounds can be used as antioxidative, antihypertensive, antitumor, anticoagulant, and antimicrobial com-
ponents in functional foods or nutraceuticals and pharmaceuticals due to their health benefits and
Keywords:
therapeutic potentials. This review focuses on the utilization of marine bioactive by-products and their
Marine byproduct
Bioactive compounds
potential application in food and pharmaceutical industries.
Functional properties Ó 2017 Elsevier Ltd. All rights reserved.
Health benefits

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 673
2. The bioactive potential of fish frame protein . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 674
3. Functional properties of fish skin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 675
4. Biomedical and food applications of fish bone. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 676
5. The bioactive potential of fish internal organs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 676
6. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 678
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 678

1. Introduction polysaccharides, minerals, vitamins, antioxidants, enzymes, and

bioactive peptides with valuable nutraceutical, pharmaceutical,
For many years, the identification of bioactive compounds from and cosmeceutical potentials (Barrow & Shahidi, 2008). Further-
marine sources has been a major effort in many research groups. more, various marine materials such as skin, muscle, frame, bone,
Dietary bioactive compounds are food-derived components that, and internal organs are presently utilized to isolate a number of
in addition to their nutritional value, exert a beneficial physiolog- bioactive materials, among which fish bone is a good source of cal-
ical effect in the body (Ryan, Ross, Bolton, Fitzgerald, & Stanton, cium (Ca), fish intestine is a source of crude enzyme, and skin and
2011). Marine organisms serve as a rich source of functional mate- protein remaining on fish frame are inexpensive materials for iso-
rials such as polyunsaturated fatty acids (PUFA), collagen, gelatin, lating bioactive peptides (Barrow & Shahidi, 2008). Bioactive pep-
tides are special protein segments that have numerous potential
physiological functions within the body in addition to acting as
Abbreviations: PUFA, polyunsaturated fatty acids; ACE, angiotensin I converting sources of nitrogen and amino acids (Harnedy & FitzGerald,
enzyme inhibitors; FPH, fish protein hydrolysates; BHA, butylated hydroxyl anisole; 2012). The potential for providing bioactive compounds such as
BHT, butylated hydroxyl toluene; BSE, bovine spongiform encephalopathy; FMD, peptides makes fish proteins important in human nutrition and
foot-and-mouth disease; Ca, calcium; TG, triglyceride; EPA, eicosapentaenoic acid;
DHA, docosahexaenoic acid.
health management (Khora, 2013). The identification of biological
⇑ Corresponding author. properties and extension of nutraceuticals from these bio-
E-mail address: mahdi_ojagh@yahoo.com (S. Mahdi Ojagh). resources have yielded a significant number of drug types in recent

http://dx.doi.org/10.1016/j.jff.2017.06.034
1756-4646/Ó 2017 Elsevier Ltd. All rights reserved.
674 M. Atef, S. Mahdi Ojagh / Journal of Functional Foods 35 (2017) 673–681
years. However, most of these compounds are still at the develop-
mental phase.
This review focuses on the isolation of bioactive compounds
from marine fishery resources and summarized their biological
activities and potential application as ingredients in functional
foods, nutraceuticals, and pharmaceuticals.
2. The bioactive potential of fish frame protein
Fish frame resulting from filleting contains remarkable amounts
of muscle protein and, due to the presence of essential amino acids,
can be regarded as a complete protein source (Larsen, Thilsted,
Kongsbak, & Hansen, 2000). Protein quality is distinguished by
the content of essential amino acids and bioavailability (WHO,
2007). Nevertheless, in addition to utilizing fish protein directly,
the use of fish protein hydrolysates (FPH) has been popular.
Hydrolysis processes not only preserve the high essential amino
acid content, but also produce many improved functions for food
or pharmaceutical applications. Hydrolysis of proteins enhances
physicochemical properties such as solubility (Foh, Wenshui,
Amadou, & Jiang, 2011; Gbogouri, Linder, Fanni, & Parmentier,
2004; Geirsdottir et al., 2011; Thiansilakul, Benjakul, & Shahidi,
2007), emulsifying capacity (Foh et al., 2011; Slizyte, Dauksas,
Falch, Storro, & Rustad, 2005), and oil-binding capacity (Foh
et al., 2011; Geirsdottir et al., 2011; Slizyte et al., 2005) which
are the three most important properties in food formulations
(He, Franco, & Zhang, 2013). In addition, FPH also have good func-
tional properties and can contribute to water holding, texture, gel-
ling, whipping, and emulsification properties when added to food
(Kristinsson, 2007).
One of the important uses of protein hydrolysate is the isolation
of bioactive peptides (Kim & Mendis, 2006), and the peptides so
procured have numerous bioactivities such as antihypertensive
or angiotensin converting enzyme (ACE) inhibition, antiprolifera-
tive (Picot et al., 2006), anticoagulant (Rajapakse, Jung, Mendis,
Moon, & Kim, 2005), immunomodulatory (Kitts & Weiler, 2003),
and chelating (Klompong et al., 2009) effects. Structurally, peptides
are short-chainpeptide segments of a protein molecule. Proteins
are the essential part of tissues in biological organisms (Shahidi
& Zhong, 2008). Bioactive peptides generally include 3–20 amino
acid residues, and their biological activities are based on their
molecular weights and amino acid sequences (Pihlanto-Leppala,
2001). Peptides have antibacterial (Dong, Xu, Huang, Liou, &
Zhou, 2002; Ennaas, Hammami, Beaulieu, & Fliss, 2015; Sila et al.,
2014; Song, Wei, Luo, & Wang, 2012) and antioxidative (Je, Kim,
& Kim, 2005a; Ranathunga, Rajapakse, & Kim, 2006; Wu, Chen, &
Shiau, 2003) activities and can be studied for potential uses as food
additives. Antimicrobial peptides usually have less than 50 amino
acids, of which about 50% are hydrophobic and have a molecular
weight below 10 kDa. Antimicrobial peptides have beneficial
effects in native immunity by directly interacting with bacteria
and killing them. Their mechanism of action is as follows: The pos-
itively charged amino acids of these peptides bind to negatively
charged molecules and substances in the membranes of pathogens,
forming pores which degrade the membranes of bacteria (Najafian
& Babji, 2012; Rajanbabu & Chen, 2011). The antioxidant activity of
proteins and peptides can be the result of specific scavenging of
radicals formed during peroxidation, scavenging of oxygen-
containing compounds, or their metal-chelating ability (Gutierrez
et al., 2003). The radical scavenging activities of peptides can be
influenced by several factors including hydrophobicity/hydrophili
city, amino acid sequences, the degree of hydrolysis, and molecular
weights of peptides (Ambigaipalan & Shahidi, 2017). Under normal
conditions, endogenous antioxidative defense systems can elimi-
nate free radicals, but fail to suppress all the free radicals in
certain situations. This results in cellular damage which, in turn,
initiates diseases such as atherosclerosis, arthritis, diabetes, and
cancer (Sarmadi & Ismail, 2010). FPH made from backbones have
a hydrogen-donating ability. Iron-induced lipid oxidation in lipo-
somes is proposed to occur through the interaction of iron with
lipid peroxides, as a result of which alkoxyl and peroxyl radicals
are formed. The antioxidant activity of FPH is probably due to its
ability to donate hydrogen to the formed alkoxyl and peroxyl rad-
icals, resulting in the formation of more stable alcohols and other
molecules and the reduction of oxidation of liposomes (Slizyte
et al., 2009). Highly reactive molecules generated through these
chemical processes are responsible for producing unpleasant
odours and flavours in rancid foods which may destroy food nutri-
ents (Najafian & Babji, 2012). In this context, Je, Qian, Byun, and
Kim (2007) studied the cytotoxic effects of antioxidant peptides
obtained from tuna backbone protein on human lung fibroblast
and human endothelial cell lines. According to the results, these
peptides did not show any cytotoxic effect on MRC-5 and
ECV304 cells.
On the other hand, synthetic antioxidants agents such as buty-
lated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), tert-
Butylhydroquinone (TBHQ), and propyl gallate (PG) are commonly
employed as additives in food systems. However, because of their
side-effects on human health, induction of DNA damage, and toxi-
city, the use of these chemical compounds as food additives is not
favoured. Nowadays, there is considerable interest in finding
antioxidants from natural resources that have little or no side
effects on human health. These synthetic antioxidants show stron-
ger antioxidant activities than natural antioxidants (Barlow &
Schlatter, 2010; Pezeshk, Ojagh, & Alishahi, 2015; Sila &
Bougatef, 2016). Nevertheless, the beneficial effects of antioxida-
tive compounds on health outcome in humans are currently theo-
retical and some remain to be controversial.
FPH derived from many fish species such as, cod (Guerard &
Sumaya-Martinez, 2003), and mackerel (Wu et al., 2003) have
illustrated antioxidative activities. Antioxidants not only improve
the stability of lipids and lipid-containing foods, but are also used
to protect food products by retarding discoloration and deteriora-
tion resulting from oxidation, and thus extending the shelf-life of
foods (Herpandi et al., 2011). Lipid oxidation leads to the genera-
tion of undesirable off-flavours and potentially toxic reaction prod-
ucts. The antioxidative FPH can also be employed to prolong the
shelf life of food products. For example, Shahidi, Han, and
Synowiecki (1995) indicated that capelin fish protein hydrolysate
added to minced pork muscle reduces the formation of secondary
oxidation products including thiobarbituric acid reactive sub-
stances (TBARS). The FPH of leatherjacket (Salampessy, Phillips,
Seneweera, & Kailasapathy, 2010) and Saurida elongate (Dong,
Sheng, Fu, & Wen, 2005) also showed antimicrobial and anti-
anemia activities, respectively.
In addition, the FPH from many fish species such as blue whit-
ing (Geirsdottir et al., 2011), bonito (Fujita & Yoshikawa, 1999), and
yellowfin sole (Jung, Mendis et al., 2006c) have been found to have
a good antihypertensive activity. Hypertension is a serious con-
temporary concern. To prevent hypertension, synthetic hyperten-
sive drugs (e.g. captopril, enalapril, and lasinopril) are commonly
used. These drugs have numerous side effects on human health
such as dry cough, taste disturbances, and skin rashes. Currently,
naturally safe alternative products with a high ACE-inhibitory
activity are employed for the prevention and treatment of hyper-
tension (Halim, Yusof, & Sarbon, 2016; Kim & Wijesekara, 2010).
Hosomi et al. (2012) compared the anti-hypertensive activity of
FPH and other protein sources such as casein. The results showed
that FPH can provide better health benefits than casein by decreas-
ing the cholesterol content in the blood. Peptides derived from
tuna frame protein hydrolysate demonstrated a strong suppressive
 M. Atef, S. Mahdi Ojagh / Journal of Functional Foods 35 (2017) 673–681 675

Table 1
Biological activity associated with fish by-product derived protein hydrolysates and peptides.

Source Scientific name Origin Bio-activities Peptide(s) sequence Reference

Cod – Frame Antioxidant nd Jeon, Byun, and Kim (1999)
ACE inhibitory
Flounder fish Paralichthys – Antioxidant VCSV, CAAP Ko, Lee, Samarakoon, Kim, and Jeon (2013)
olivaceus
Flounder fish Paralichthys – ACE inhibitory MEVFVP, VSQLTR Ko et al. (2016)
olivaceus
Hoki Johnius Frame Antioxidant GSTVPERTHPACPDFN Kim, Je, and Kim (2007)
belengerii
Hoki Johnius Frame Ca-binding VLSGGTTMYASLYAE Jung and Kim (2007)
belengerii
Lantern fish Benthosema – Neuroprotective Phe-Tyr-Tyr and Asp-Trp Chai, Wu, Yang, Li, and Pan (2016)
pterotum
Leatherjacket Meucheniasp. – ACE inhibitory nd Salampessy, Reddy, Phillips, and Kailasapathy
(2017)
Lizard fish Saurida elongata – ACE inhibitory Arg-Val-Cys-Leu-Pro Wu, Feng, Lan, Xu, and Liao (2015)
Loach Misgurnus – ACE inhibitory nd Li, Zhou, Huang, Sun, and Zeng (2012)
anguillicaudatus
Pollack Theragra Frame ACE inhibitory Phe-Gly-Ala-Ser-Thr-Arg-Gly-Ala Je, Park, Kwon, and Kim (2004)
chalcogramma
Pollack Theragra Frame Antioxidant Leu-Pro-His-Ser-Gly-Tyr Je, Park, & Kim (2005b)
chalcogramma
Pollack Theragra Frame Ca-binding VLSGGTTMAMYTLV Jung, Karawita, Heo, Lee, Kim, and Jeon (2006a)
chalcogramma
Sandfish Arctoscopus – Antioxidant Ala-Thr-Ser-His-His Jang, Liceaga, and Yoon (2016)
japonicus
Sole Limanda aspera Frame Antioxidant N-terminal RPDFDLEPPY Jun, Park, Jung, and Kim (2004)
Sole Limanda aspera Frame Anticoagulant nd Rajapakse, Jung, Mendis, Moon, and Kim, 2005;
Rajapakse, Mendis, Jung, Je, and Kim, 2005
Shark – – ACE inhibitory Cys-Phe, Glu-Tyr, Met-Phe, Phe-Glu Wu et al. (2008)
Tilapia Oreochromis Frame Antioxidant Asp-Cys-Gly-Tyr, Asn-Tyr-Asp-Glu-Tyr Fan, He, Zhuang, and Sun (2012)
niloticus
Tilapia Oreochromis – ACE inhibitory Met, Ile, Leu, Phe Toopcham, Roytrakul, and Yongsawatdigul (2015)
niloticus
Tuna – Frame Antihypertensive Gly-Asp-Leu-Gly-Lys-Thr-Thr-Thr-Val-Ser-Asn- Lee et al. (2010)
Trp-Ser-Pro-Pro-Lys-Try-Lys-Asp-Thr-Pro

nd = not determined.

effect on the systolic blood pressure of hypertensive rats, similar to
the effect of captopril, a commercial antihypertensive drug (Lee,
Qian, & Kim, 2010). Moreover, Suarez-Jimenez, Burgos-
Hernandez, and Ezquerra-Brauer (2012) reviewed bioactive pep-
tides and depsipeptides from marine sources with anticancer
potential. The only anticancer peptide derived described from a
fish source is an anchovy hydrophobic peptide with a molecular
weight of 440.9 Da which is able to induce apoptosis in human
U937 lymphoma cells through increased activity of caspase-3
and caspase-8 (Lee, Kim, Lee, Kim, & Lee, 2003).
There are extensive studies on the biological activity of protein
hydrolysates and peptides from different fish species, as summa-
rized in Table 1.
3. Functional properties of fish skin
Fish processing discards contain a considerable amount of skin
which can be utilized as a potential source for isolating collagen
and gelatin. Collagen is the major structural component of the skin,
bone, fin, scale, tendon, and cartilage of all animals. Traditionally,
collagen has mainly been derived from porcine and bovine sources.
Nevertheless, the utilization of fish skin collagen and gelatin is cur-
rently expected to attract the interest of the industry. This may be
due to the comparative unpopularity of porcine skin collagen and
gelatin because of certain religious reasons, or due to the mad
cow disease, outbreak of bovine spongiform encephalopathy
(BSE), and foot-and-mouth disease (FMD), which have restricted
the use of collagen and gelatin from land-based animals (Helcke,
2000; Kim & Mendis, 2006).
Collagen has numerous applications, e.g. in biomedical and
pharmaceutical industries, especially as a drug carrier as well as
in the treatment of pain associated with osteoarthritis, in the treat-
ment of hypertension, use in tissue engineering, inhibition of
angiogenic diseases (Rehn et al., 2001), cosmetics (Swatschek,
Schatton, Kellermann, Muller, & Kreuter, 2002), production of
wound dressings, vitreous implants, carriers for drug delivery
(Senaratne, Park, & Kim 2006), dermal filler, and hemostat and skin
substitutes (Tanaka, Koyama, & Nomura, 2009). Owing to its
unique physical properties, gelatin has several applications in food
and packaging industries for microencapsulation and light sensi-
tive coatings and in biomedical industries for the encapsulation
of drugs and as a food additive to improve the texture, water-
holding capacity, and stability of several food products
(Borderias, Marti, & Montero, 1994). Collagen and gelatin have
unique proteins compared to fish muscle proteins. Such unique-
ness can be attributed to the presence of amino acid composition
which is rich in non-polar amino acids such as glycine (Gly), ala-
nine (Ala), valine (Val), and proline (Pro) (Kim & Mendis, 2006).
The biological activities of peptides isolated from marine colla-
gen and gelatin have been reported in different studies. In most
studies in the field of food science and technology, the focus has
been on antioxidant and antihypertensive/ACE inhibitory activities
(Fahmi et al., 2004). The antioxidant activities of bioactive peptides
are mainly due to the presence of some aromatic amino acids, and
histidine. Gelatin peptides are rich in hydrophobic amino acids
which result in higher emulsifying ability and, because of the high
percentage of Gly and Pro, marine gelatin peptides possess higher
antioxidant effects than peptides derived from other proteins (Ngo,
Vo, Ngo, Wijesekara, & Kim, 2012). Moreover, the antioxidant
676 M. Atef, S. Mahdi Ojagh / Journal of Functional Foods 35 (2017) 673–681
activities of peptides isolated from Nile tilapia (O. niloticus) scale
gelatin showed r protective effect on DNA damage caused by
hydroxyl radicals and no cytotoxic effect on mouse macrophages
and human lung fibroblasts (Ngo, Qian, Ryu, Park, & Kim, 2010).
Furthermore, collagen- and gelatin-derived peptides represent
numerous other bioactivities such as antimicrobial activity,
mineral-binding capacity, lipid-lowering effect, immunomodula-
tory activity, and beneficial effects on skin, bone, or joint health
(Gómez-Guillén et al., 2010; Hou et al., 2009; Jung, Lee, & Kim,
2006b). Due to dominant presence of hydrophobic amino acids in
gelatin, it exhibits high emulsifying ability for hydrophilic-
hydrophobic partitioning. Also, specific amino acid arrangements
such as Gly, Pro, and hydroxyproline (Hyp) merit special consider-
ation, as the content of Pro residues are able to scavenge free rad-
icals (Mendis, Rajapakse, & Kim, 2005).
In addition, the surface of fish skin is fully covered with scales
(about 30%) that are made up of proteins containing 18 amino
acids. Gly, glutamic acid (Glu), Hyp, arginine (Arg), and aspartic
acid (Asp), which are present in high proportions in fish scale pro-
teins (Nagai, Izumi, & Ishii, 2004), display strong Ca binding affini-
ties (Jung & Kim, 2007). According to Chen et al. (2014), Ca-binding
peptides isolated from tilapia scale protein hydrolysate prevent Ca
deficiency and improve Ca bioavailability.
4. Biomedical and food applications of fish bone
Milk and other dairy products are the major source of Ca; how-
ever, some individuals cannot drink milk due to lactose indigestion
and intolerance (Jung, Lee, & Kim, 2006b). Therefore, many studies
have been performed on supplements containing Ca as alterna-
tives. Among fish processing by-products, fish bone or skeleton is
one of the valuable sources in identifying health-promoting com-
ponents and a potential source of minerals and Ca (Larsen et al.,
2000). In recent years, calcium phosphate bioceramics such as
tetracalcium phosphate, amorphous calcium phosphate, tricalcium
phosphate, and hydroxyl-apatite have also been identified as the
most suitable bone replacement materials (Shahidi & Zhong,
2007). The uptake of Ca across the intestinal mucosa may depend
on the preceding ionization of Ca compounds, since Ca is absorbed
and transported as Ca++. In small fish, Ca is found primarily in
bones as the crystalline compound hydroxyapatite which is insol-
uble at neutral pH. Nevertheless, the gastric acid medium in the
stomach increases the solubility of hydroxyapatite (Larsen et al.,
2000). Approximately 30% of organic components of fish bone is
made of collagen, while its 60–70% of inorganic substances is
mainly composed of calcium phosphate and hydroxyapatite
(Nagai et al., 2004). Therefore, as a potential source of Ca, fish bone
is an essential element for human health (Jung, Shahidi, & Kim,
2009). Ca is important for bone health and, in combination with
vitamin D, improves cardiac health along with a number of dis-
eases including gastrointestinal diseases, diabetes, and hyperten-
sion (Careche, Borderias, Sanchez-Alonso, Lund, & Saarela, 2011).
Larsen et al. (2000) reported that the intake of small fish with
bones can enhance Ca bioavailability in rats. In addition, Jung,
Lee, & Kim, 2006b observed that fish-bone peptides increase Ca
solubility and bioavailability in ovariectomised rats. Fish bone con-
tains hydroxyapatite, thus can be an important Ca dietary supple-
ment, and serves as an alternative for synthetic hydroxyapatite
(Ozawa & Suguru, 2002); accordingly, it can be consumed by peo-
ple with low intakes of milk and dairy products. However, in order
to include fish bone in food, its structure should be changed into an
edible form by different methods such as hot water treatment and
heat acetic acid solution (Ishikawa, Kato, Mihori, Watanabe, &
Sakai, 1990; Jung, Park, Byun, Moon, & Kim, 2005).
5. The bioactive potential of fish internal organs
At present, the appropriate management of fish by-products is a
serious environmental problem as they are highly perishable
(Arvanitoyannis & Kassaveti, 2008). Fish internal organs constitute
approximately 20% of the marine biomass. Nevertheless, if not
used, these compounds are discarded as waste or low-value by-
products, which would generate additional waste disposal and
environmental problems (Bougatef, 2013). Marine fish viscera
include many useful proteins which can be converted into value-
added products, widely applied to improve and promote the nutri-
tional properties of proteins. The viscera of fish contain digestive
tissues such as stomachs, pyloric caeca, intestines, liver, pancreas,
spleen, and gonads. Fish viscera are a potential source for bioactive
materials, enhancing the value of fish processing by-products and
serving as a rich source of different digestive enzymes (Barrow &
Shahidi, 2008). However, the use of fish by-products as sources
of industrial enzymes is associated with some restrictions such
as seasonal availability, variations in the content or activity of
enzymes due to nutritional status, and the highly perishable nature
of the raw material. Among naturally available enzymes from fish
and aquatic invertebrates, proteases constitute a major group and
have been referred to as proteinases and peptidases (Shahidi &
Janak Kamil, 2001). The main enzymes in fish viscera are pepsin,
trypsin, chymotrypsin, and elastase. Even though marine fish-
derived enzymes do not have direct applications in the field of
functional foods and nutraceuticals, they can be utilized to produce
bioactive components in a large scale (Kim & Mendis, 2006). Fur-
thermore, enzymes from fish can be employed for other applica-
tions such as production of fish protein hydrolysate and fish roe,
fish silage, fish sauce; enzymatic removal of fish skin; and as pearl
essence (see Tables 2–5).
By-products from degutting, filleting and other processing oper-
ations are good raw materials for oil production. Fish oil from sal-
mon, tuna, and mackerel is a valuable source of marine lipid.
According to numerous studies, the dietary intake of fish oil
reduces fat. Fish oil supplementation has been suggested to
decrease body fat by affecting appetite, although the underlying
mechanism is still unknown (Hu, Tao, Wang, Xiao, & Wang, 2016).
Marine oils, as a rich source of long-chain omega-3 polyunsatu-
rated fatty acids (PUFA), have attracted considerable attention in
recent years. Omega-3 fatty acids have been known to lower
plasma triacylglycerol (TAG) along with a variety of other drugs
such as fibrates, statins, thiazolidinediones, niacin, and metformin
(Shearer, Savinova, & Harris, 2012). Consumption of fish oil, an
excellent source of PUFA, has been linked to the promotion of
human health against different diseases. Fish oil is mainly com-
posed of two types of fatty acids, namely eicosapentaenoic (EPA)
and docosahexaenoic acids (DHA), and contains different combina-
tions of other fatty acids. The biological effects of EPA and DHA
include effects on lipoproteins, blood pressure, cardiac function,
colon cancer, metal health disorders, endothelial function, vascular
reactivity, and cardiac electrophysiology, as well as potent antipla-
telet and anti-inflammatory effects (Calder, 2004). The TAG-
lowering effect of EPA and DHA has been shown in numerous
experiments, and 3–4 g/day of omega-3 fatty acids has been pro-
ven to reduce plasma TG by about 30% (Harris, Miller, Tighe,
Davidson, & Schaefer, 2008). In addition to their TAG-lowering
effects, fish oils also reduce the risk for a number of cardiovascular
disease (CVD)-related endpoints involving the primary prevention
of major coronary events (Yokoyama et al., 2007); secondary pre-
vention of death or non-fatal myocardial infarction (MI); and all-
cause mortality in heart failure subjects (Tavazzi et al., 2008).
Lipoprotein metabolism is also largely associated with the anti-
obesity effect of fish oil. Plasma levels of TAG are lowered with fish
 M. Atef, S. Mahdi Ojagh / Journal of Functional Foods 35 (2017) 673–681 677

Table 2
Biological activity associated with fish by-product derived fish skin and peptides.

Source Scientific name Origin Bio-activities Peptide(s) sequence Reference

Amur sturgeon Acipenser schrenckii Skin Antioxidant Pro-Ala-Gly-Tyr Nikoo et al. (2014)
Cryoprotective
Bluefin Navodon Skin Antioxidant Gly-Ser-Gly-Gly-Leu, Gly-Pro-Gly-Gly- Chi et al. (2015a)
leatherjacket Septentrionalis Phe-Ile, Phe-Ile-Gly-Pro
Cod Gadus macrocephalus Gelatin Antioxidant Thr-Cys-Ser-Pro, Thr-Gly-Gly-Gly-Asn-Val Ngo et al. (2011)
ACE inhibitory
Hoki Johnius belengerii Skin Antioxidant HGPLGPL Mendis et al. (2005)
Pollack – Skin Antioxidant GE-(Hyp)-GP-(Hyp)-GP-(Hyp)-GP-(Hyp)- Kim et al. (2001)
G, GE-(Hyp)-GP-(Hyp)-GP-(Hyp)-GP-
(Hyp)-GP-(Hyp)-G
Pollack Theragra chalcogramma Skin ACE inhibitory Gly-Pro-Leu, Gly-Pro-Met Byun and Kim (2001)
Salmon Oncorhynchus keta Skin Neurobehavioral nd Xu, Dong, Zhao, and Xu (2015)
Salmon Oncorhynchus keta Skin ACE inhibitory Gly-Leu-Pro-Leu-Asn-Leu-Pro Lee, Jeon, and Byun (2014)
Sea Bream – Scale ACE inhibitory GY, VY, GF, VIY Fahmi et al. (2004)
Snapper Priacanthus Skin Antioxidant nd Phanturat, Benjakul, Visessanguan,
macracanthus and Roytrakul (2010)
Snapper Lutjanus vitta Skin Antioxidant nd Khantaphant and Benjakul (2008)
Sole – Skin Antioxidant nd Gime’nez, Alema’n, Montero, and
Go’mez-Guille’n (2009)
Tilapia Oreochromis niloticus Skin Antioxidant Glu-Gly-Leu, Tyr-Gly-Asp-Glu-Tyr Zhang, Duan, and Zhuang (2012)
Yellowtail – Scale Antioxidant nd Ohba et al. (2003)
ACE inhibitory
Salmon Oncorhynchus keta Skin Long bone Gly, Glu, Pro, Hyd, Asp, Ala, Arg, Lys, Leu, Xu, Han, and Li (2010)
development Ser, Val, Iso, Thr, Phe, His, Met, Tyr
Milkfish Chanos chanos Collagen Iron-binding nd Huang, Wu, Yang, Li, and Kuo (2015)
Salmon Oncorhynchus keta Collagen learning and memory Gly, Glu, Pro, Hyd, Asp, Ala, Arg, Lys, Leu, Pei et al. (2010)
Ser, Val, Iso, Thr, Phe, His, Met, Tyr
Tilapia Oreochromis sp. Collagen Facial Skin Quality nd Chai et al. (2010)

nd = not determined.

Table 3
Biological activity associated with fish by-product derived fish bone and peptides.

Source Scientific name Origin Bio-activities Peptide(s) sequence Reference

Cod Gadus morhua Bone Antioxidant nd Slizyte et al. (2009)
Flying fish Exocoetus volitans Bone Antioxidant nd Naqash and Nazeer (2011)
Antiproliferative
Hoki Johnius belengerii Bone Calcium binding nd Jung et al. (2005)
Yellowtail – Bone Antioxidant nd Morimura et al. (2002)
ACE inhibitory
Yellowtail – Bone Antioxidant nd Ohba et al. (2003)
ACE inhibitory
Tuna – Bone Antioxidant VKAGFAWTANQQLS Je et al. (2007)

nd = not determined.

Table 4
Biological activity associated with fish by-product derived internal organs and peptides.

Source Scientific name Origin Bio-activities Peptide(s) sequence Reference

Herring Clupea harengus Whole, Body, Head, Antioxidant nd Sathivel et al. (2003)
Gonads
Mackerel Magalaspis cordyla viscera Antioxidant Ala–Cys–Phe–Leu Kumar, Nazeer, and Jai ganesh
(2011a)
Black Pomfret Parastromateus Viscera Antioxidant Ala-Met-Thr-Gly-Leu-Glu-Ala Jai ganesh, Nazeer, and Sampath
niger Kumar (2011)
Bluefin Navodon Head Antioxidant Trp-Glu-Gly-Pro-Lys, Gly-Pro-Pro, Chi, Wang, Wang, Zhang, and Deng
leatherjacket septentrionalis Gly-Val-Pro-Leu-Thr (2015b)
Sardinella Sardinella aurita Head/Viscera Antioxidant nd Barkia, Bougatef, Khaled, and Nasri
(2010)
Nile tilapia Oreochromis Viscera / Carcass Antioxidant nd Silva, Ribeiro, Silva, Cahú, and
niloticus Bezerra (2014)
Salmon – Pectoral fin Antioxidant Phe-Leu-Asn-Glu-Phe-Leu-His-Val Ahn, Kim, and Je (2014)
Shark Chiloscyllium Livers Antidiabetic NH2-Met-Leu-Val-Gly-Pro-Ile-Gly- Huang and Wu (2010)
plagiosum Ala-Ala-Lys-Val-Val-Tyr-Glu-Gln
Skate Raja porosa Cartilage Antioxidant Phe-Ile-Met-Gly-Pro-Tyr, Gly-Pro- Pan, Zhao, Hu, and Wang (2016)
Ala-Gly-Asp-Tyr, Ile-Val-Ala-Gly-Pro-
Gln
Sardinella Sardinella aurita Head / viscera ACE inhibitory Phe-Arg-Gly-Leu-Met-His-Tyr Bougatef et al. (2008)
Tuna Thunnus tonggol Dark muscle Human breast Leu-Pro-His-Val-Leu-Thr-Pro-Glu- Hsu, Li-Chan, and Jao (2011)
cancer cell Ala-Gly-Ala-Thr, Pro-Thr-Ala-Glu-
Gly-Gly-Val-Tyr-Met-Val-Thr

nd = not determined.
678 M. Atef, S. Mahdi Ojagh / Journal of Functional Foods 35 (2017) 673–681

Table 5
Biological activity associated with fish oil in human health.

Source Potential health benefit Reference

Fish oil (EPA + DHA) Serum triglycerides Oelrich, Dewell, and Gardner (2013)
LDL cholesterol
LDL sub-fractionsin hypertriglyceridemic adults
Fish oil Reduce Triscylglycerol Levels Capili and Anastasi (2012)
Fish oil Women’s Mental Health Kendall-Tackett (2010)
Fish oil Mouse Gut Microbiota Yu et al. (2014)
Fish oil Plasma Triacylglycerols Moore et al. (2006)
Fish oil Prevents the Adrenal Activation Delarue et al. (2003)
Fish oil Human breast and colorectal tumours Bonatto et al. (2015)
Fish oil supplementation Brain & Systemic Glucose Metabolism Nugent et al. (2011)
Fish oil and multivitamin Reduces oxidative stress Pipingas et al. (2015)
Fish oil and physical exercise Memory Rachetti et al. (2013)
PUFA Breast Milk of Lactating Women Olafsdottir, Thorsdottir, Wagner, and Elmadfa (2006)
PUFA Human atrial electrophysiology Kumar et al., 2011b
PUFA Thrombosis & Vascular disease Harris (2004)
PUFA Metabolic syndrome prevalence Talon, Oliveira, Moreto, Portero-McLellan, and Burini (2015)
Bread containing fish oil Plasma phospholipid fatty acids Liu et al. (2001)
triacylglycerols
HDL-cholesterol
malondialdehyde
Liquid egg product containing fish oil Cardiovascular disease Rose and Holub (2006)

oil consumption by suppressing the synthesis of very-low-density
lipoproteins (VLDL) and hepatic lipogenesis (Hu et al., 2016). Fish
oil also improves hepatic lipid metabolism and inhibits liver sterol
regulatory element-binding protein (SREBP)-1c proteolytic cas-
cade, suggesting a decrease in lipogenesis, as well as activating
peroxisome proliferator-activated receptor (PPAR) a-mediated fat
oxidation (Nakatani, Kim, Kaburagi, Yasuda, & Ezaki, 2003).
Moreover, fish oil is a good source of dietary vitamin D. The
importance of vitamin D in relation to a wide range of health
aspects such as prevention of cancer, heart disease, and inflamma-
tory conditions, as well as mental and bone health is well recog-
nized (Hayes, 2010; Mulligan, Felton, Riek, & Bernal-Mizrachi,
2010). UK food tables (Anonymous, 2002) suggest that cod liver
oil and herring at high levels, and huss and mackerel to a limited
extent, can supply considerable amounts of vitamin D (Ashwell,
Stone, Stolte, Cashman, & MacDonald, 2010).
A wide range of dairy and nondairy foods such as bakery prod-
ucts (Liu, Wallin, & Saldeen, 2001; Saldeen, Wallin, & Marklinder,
1998; Yep, Li, Mann, Bode, & Sinclair, 2002;), biscuit and cracker
(Harrison et al. 2004), pasta (Iafelice et al., 2008; Verardo et al.,
2009), eggs (Kassis, Drake, Beamer, Matak, & Jaczynski, 2010), dairy
products including milk and yogurt (Estrada, Boeneke, Bechtel, &
Sathivel, 2011), juices (Ilyasoglu & Nehir, 2014); and nutrition bars
has been enriched with omega-3 oils.
6. Conclusion
In recent years, much attention has been paid to natural bioac-
tive compounds as functional ingredients. Bioactive peptides
derived from marine by-products have potentials in the develop-
ment of functional foods and pharmaceutical products. The antiox-
idative properties of marine-derived bioactive peptides have a vast
potential for use as nutraceuticals and pharmaceuticals and can be
a better substitute for synthetic antioxidants. Moreover, antimicro-
bial peptides from marine by-products can be used in antimicro-
bial drugs and as vaccines to inactivate specific pathogens in
food preservation and supplementation. In addition, bioactive
compounds derived from marine organisms improve health and
reduce disease risk. Therefore, evidence suggests that marine-
derived bioactive peptides have potentials as active ingredients
for preparing various functional foods, nutraceuticals and pharma-
ceutical products due to their valuable biological functions and
beneficial health effects. Based on the evidence demonstrating
their beneficial health effects, fish-derived bioactive peptides have
antioxidative and antimicrobial potential in order to be employed
as active ingredients in functional foods, food supplements, and by
the pharmaceutical industry.
References
Ahn, C. B., Kim, J. G., & Je, J. Y. (2014). Purification and antioxidant properties of
octapeptide from salmon byproduct protein hydrolysate by gastrointestinal
digestion. Food Chemistry, 147, 78–83.
Ambigaipalan, P., & Shahidi, F. (2017). Bioactive peptides from shrimp shell
processing discards: Antioxidant and biological activities. Journal of Functional
Foods, 34, 7–17.
Anonymous (2002). McCance & Widdowson’s The Composition of Foods. Integrated
Dataset. <http://www.food.gov.uk/science/dietarysurveys/dietsurveys/>.
Arvanitoyannis, I. S., & Kassaveti, A. (2008). Fish industry waste: Treatments,
environmental impacts, current and potential uses. International Journal of Food
Science & Technology, 43, 726–745.
Ashwell, M., Stone, E. M., Stolte, H., Cashman, K. D., & MacDonald, H. (2010). UK
Food Standards Agency Workshop Report: An investigation of the relative
contributions of diet and sunlight to vitamin D status. The British Journal of
Nutrition, 104, 603–611.
Barkia, A., Bougatef, A., Khaled, H. B., & Nasri, M. (2010). Antioxidant activities of
sardinelle heads and/or viscera protein hydrolysates prepared by enzymatic
treatment. Journal of Food Biochemistry, 34, 303–320.
Barlow, S., & Schlatter, J. (2010). Risk assessment of carcinogens in food. Toxicology
and Applied Pharmacology, 2, 180–190.
Barrow, C., & Shahidi, F. (2008). Marine nutraceuticals and functional foods. New York,
USA: CRC Press.
Bonatto, S. J. R., Yamaguchi, A. A., Coelho, I., Nunes, E. A., Iagher, F., Fukushima, J. I., ...
Fernandes, L. C. (2015). Fish oil reduces the proliferation of cells cultured from
human breast and colorectal tumours: An in vitro study. Journal of Functional
Foods, 19, 941–948.
Borderias, J., Marti, M. A., & Montero, P. (1994). Influence of collagenous material
during frozen storage when added to minced cod (Gadus morhua). Zeitschrift für
Lebensmittel-Untersuchung und-Forschung, 199, 255–261.
Bougatef, A. (2013). Trypsins from fish processing waste: Characteristics and
biotechnological applications-comprehensive review. Journal of Cleaner
Production, 57, 257–265.
Bougatef, A., Nedjar-Arroume, N., Ravallec-Plé, R., Leroy, Y., Guillochon, D., Barkia,
A., & Nasri, M. (2008). Angiotensin I-converting enzyme (ACE) inhibitory
activities of sardinelle (Sardinella aurita) by-products protein hydrolysates
obtained by treatment with microbial and visceral fish serine proteases. Food
Chemistry, 111, 350–356.
Byun, H. G., & Kim, S. K. (2001). Purification and characterization of angiotensin I
converting enzyme (ACE) inhibitory peptides from Alaska pollack (Theragra
chalcogramma) skin. Process Biochemistry, 36, 1155–1162.
Calder, P. C. (2004). N 3 Fatty acids and cardiovascular disease: Evidence explained
and mechanisms explored. Clinical Science, 107, 1–11.
Capili, B., & Anastasi, J. K. (2012). Exploratory study: Evaluating the effects of fish oil
and controlled diet to reduce triglyceride levels in HIV. Journal of the Association
of Nurses in AIDS Care, 24, 276–282.
Careche, M., Borderias, A. J., Sanchez-Alonso, I., Lund, E. K., & Saarela, M. (2011).
Functional seafood products. Functional foods: Concept to product, 557–581.
 M. Atef, S. Mahdi Ojagh / Journal of Functional Foods 35 (2017) 673–681
Chai, H. J., Li, J. H., Huang, H. N., Li, T. L., Chan, Y. L., Shiau, C. Y., & Wu, C. J. (2010).
Effects of sizes and conformations of fish-scale collagen peptides on facial skin
qualities and transdermal penetration efficiency. Journal of Biomedicine and
Biotechnology, 10, 1–9.
Chai, H. J., Wu, C. J., Yang, S. H., Li, T. L., & Pan, B. S. (2016). Peptides from hydrolysate
of lantern fish (Benthosema pterotum) proved neuroprotectivein vitro and
in vivo. Journal of Functional Foods, 24, 438–449.
Chen, D., Mu, X., Huang, H., Nie, R., Liu, Z., & Zeng, M. (2014). Isolation of a calcium-
binding peptide from tilapia scale protein hydrolysate and its calcium
bioavailability in rats. Journal of Functional Foods, 6, 575–584.
Chi, C. F., Wang, B., Hu, F. Y., Wang, Y. M., Zhang, B., Deng, S. G., & Wu, C. W. (2015a).
Purification and identification of three novel antioxidant peptides from protein
hydrolysate of bluefin leatherjacket (Navodon septentrionalis) skin. Food
Research International, 73, 124–139.
Chi, C. F., Wang, B., Wang, Y. M., Zhang, B., & Deng, S. G. (2015b). Isolation and
characterization of three antioxidant peptides from protein hydrolysate of
bluefin leatherjacket (Navodon septentrionalis) heads. Journal of Functional Foods,
12, 1–10.
Delarue, J., Matzinger, O., Binnert, C., Schneiter, P., Chioléro, R., & Tappy, L. (2003).
Fish oil prevents the adrenal activation elicited by mental stress in healthy men.
Diabetes & Metabolism, 29, 289–295.
Dong, Y., Sheng, G., Fu, J., & Wen, K. (2005). Chemical characterization and anti-
anaemia activity of fish protein hydrolysate from Saurida elongate. Journal of the
Science of Food and Agriculture, 85, 2033–2039.
Dong, X. Z., Xu, H. B., Huang, K. X., Liou, Q., & Zhou, J. (2002). The preparation and
characterization of an antimicrobial polypeptide from the loach, Misgurnus
anguillicaudatus. Protein Expression and Purification, 26, 235–242.
Ennaas, N., Hammami, R., Beaulieu, L., & Fliss, I. (2015). Purification and
characterization of four antibacterial peptides from protamex hydrolysate of
Atlantic mackerel (Scomber scombrus) by-products. Biochemical and Biophysical
Research Communications, 462, 195–200.
Estrada, J. D., Boeneke, C., Bechtel, P., & Sathivel, S. (2011). Developing a strawberry
yogurt fortified with marine fish oil. American Dairy Science Association, 94,
5760–5769.
Fahmi, A., Morimura, S., Guob, H. C., Shigematsu, T., Kida, K., & Uemura, Y. (2004).
Production of angiotensin I converting enzyme inhibitory peptides from sea
bream scale. Process Biochemistry, 39, 1195–1200.
Fan, J., He, J., Zhuang, Y., & Sun, L. (2012). Purification and identification of
antioxidant peptides from enzymatic hydrolysates of Tilapia (Oreochromis
niloticus) Frame Protein. Molecules, 17, 12836–12850.
Foh, M. B. K., Wenshui, X., Amadou, I., & Jiang, Q. (2011). Influence of pH
shift on functional properties of protein isolated of Tilapia (Oreochromis
niloticus) muscles and of soy protein isolate. Food and Bioprocess Technology,
1–9.
Fujita, H., & Yoshikawa, M. (1999). LKPNM: A prodrug-type ACE-inhibitory peptide
derived from fish protein. Immunopharmacology, 44, 123–127.
Gbogouri, G. A., Linder, M., Fanni, J., & Parmentier, M. (2004). Influence of hydrolysis
degree on the functional properties of salmon byproducts hydrolysates. Journal
of Food Science, 69, 615–622.
Geirsdottir, M. S., Sigurgisladottir, S., Hamaguchi, P. Y., Thorkelsson, G., Johannsson,
R., Kristinsson, H. G., & Kristjansson, M. M. (2011). Enzymatic hydrolysis of Blue
whiting (Micromesistius poutassou); functional and bioactive properties. Journal
of Food Science, 76, 14–20.
Giménez, Alemán, A., Montero, P., & Gómez-Guillén, M. C. (2009). Antioxidant and
functional properties of gelatin hydrolysates obtained from skin of sole and
squid. Food Chemistry, 114, 976–983.
Gómez-Guillén, M. C., López-Caballero, M. E., López de Lacey, A., Alemán, A.,
Giménez, B., & Montero, P. (2010). Antioxidant and antimicrobial peptide
fractions from squid and tuna skin gelatin. In E. Le Bihan & N. Koueta (Eds.), Sea
by-products as a real material: New ways of application (pp. 89–115). Kerala,
India: Transworld Research Network Signpost.
Guerard, F., & Sumaya-Martinez, M. T. (2003). Antioxidant effects of protein
hydrolysates in the reaction with glucose. Journal of the American Oil Chemists’
Society, 80, 467–470.
Gutierrez, M. E., Garcia, A. F., de Madariaga, M. A., Sagrista, M. L., Casado, F. J., &
Mora, M. (2003). Interaction of tocopherols and phenolic compounds with
membrane lipid components. Evaluation of their antioxidant activity in a
liposomal model system. Life Sciences, 72, 2337–2360.
Halim, N. R. A., Yusof, H. M., & Sarbon, N. M. (2016). Functional and bioactive
properties of fish protein hydolysates and peptides: A comprehensive review.
Trends in Food Science & Technology, 51, 24–33.
Harnedy, P. A., & FitzGerald, R. J. (2012). Bioactive peptides from marine processing
waste and shellfish: A review. Journal of Functional Foods, 4, 6–24.
Harris, W. S. (2004). Omega-3 fatty acids, thrombosis and vascular disease.
International Congress Series, 1262, 380–383.
Harris, W. S., Miller, M., Tighe, A. P., Davidson, M. H., & Schaefer, E. J. (2008). Omega-
3 fatty acids and coronary heart disease risk: Clinical and mechanistic
perspectives. Atherosclerosis, 197, 12–24.
Harrison, R. A., Sagara, M., Rajpura, A., Armitage, L., Birt, N., & Birt, C. A. (2004). Can
foods with added soya-protein or fish-oil reduce risk factors for coronary
disease? A factorial randomized controlled trial. Nutrition, Metabolism, and
Cardiovascular Diseases, 14, 344–350.
Hayes, D. P. (2010). Vitamin D and ageing. Biogerontology, 11, 1–16.
He, Sh., Franco, Ch., & Zhang, W. (2013). Functions, applications and production of
protein hydrolysates fromfish processing co-products (FPCP). Food Research
International, 50, 289–297.
679
Helcke, T. (2000). Gelatin. The food technologist’s friend or foe? International Food
Ingredients, 1, 6–8.
Herpandi, N. H., Rosma, A., & Wan Nadiah, W. A. (2011). The tuna fishing industry: a
new outlook on fish protein hydrolysates. Comprehensive Reviews in Food Science
and Food Safety, 10, 195–207.
Hosomi, R., Fukunaga, K., Arai, H., Kanda, S., Nishiyama, T., & Yoshida, M. (2012).
Fish protein hydrolysates affect cholesterol metabolism in rats fed non-
cholesterol and high-cholesterol diets. Journal of Medicinal Food, 15, 299–306.
Hou, H., Li, B., Zhao, X., Zhuang, Y., Ren, G., & Yan, M. (2009). The effect of pacific cod
(Gadus macrocephalus) skin gelatin polypeptides on UV radiation induced skin
photoaging in ICR mice. Food Chemistry, 115, 945–950.
Hsu, K. C., Li-Chan, E. C. Y., & Jao, C. L. (2011). Antiproliferative activity of peptides
prepared from enzymatic hydrolysates of tuna dark muscle on human breast
cancer cell line MCF-7. Food Chemistry, 126, 617–622.
Hu, X., Tao, N., Wang, X., Xiao, J., & Wang, M. (2016). Marine-derived bioactive
compounds with anti-obesity effect: A review. Journal of Functional Foods, 21,
372–387.
Huang, F. J., & Wu, W. T. (2010). Purification and characterization of a new peptide
(S-8300) from shark liver. Journal of Food Biochemistry, 34, 962–970.
Huang, C. Y., Wu, C. H., Yang, J. I., Li, Y. H., & Kuo, J. M. (2015). Evaluation of iron-
binding activity of collagen peptides prepared from the scales of four cultivated
fishes in Taiwan. Journal of Food and Drug Analysis, 23, 671–678.
Iafelice, G., Caboni, M. F., Cubadda, R., Di Criscio, T., Trivisonno, M. C., & Marconi, E.
(2008). Development of functional spaghetti enriched with long chain Omega-3
fatty acids. Cereal Chemistry, 85, 146–151.
Ilyasoglu, H., & Nehir, El. S. (2014). Nanoencapsulation of EPA/DHA with sodium
caseinate gum Arabic complex and its usage in the enrichment of fruit juice.
LWT - Food Science and Technology, 56, 461–468.
Ishikawa, M., Kato, M., Mihori, T., Watanabe, H., & Sakai, Y. (1990). Effect of vapor
pressure on the rate of softening of fish bone by super-heated steam cooking.
Nippon Suisan Gakkaishi, 56, 1687–1691.
Jai ganesh, R., Nazeer, R. A., & Sampath Kumar, N. S. (2011). Purification and
identification of antioxidant peptide from black pomfret, Parastromateus niger
(Bloch, 1975) viscera protein hydrolysate. Food Science and Biotechnology, 20,
1087–1094.
Jang, H. L., Liceaga, A. M., & Yoon, K. Y. (2016). Purification, characterization and
stability of an antioxidant peptide derived from sandfish (Arctoscopus japonicus)
protein hydrolysates. Journal of Functional Foods, 20, 433–442.
Je, J. Y., Kim, S. Y., & Kim, S. K. (2005a). Preparation and antioxidative activity of hoki
frame protein hydrolysate using ultrafiltration membranes. European Food
Research and Technology, 62, 157–221.
Je, J. Y., Park, P. J., & Kim, S. K. (2005b). Antioxidant activity of a peptide isolated
from Alaska pollack (Theragra chalcogramma) frame protein hydrolysate. Food
Research International, 38, 45–50.
Je, J. Y., Park, P. J., Kwon, J. Y., & Kim, S. K. (2004). A novel angiotensin I converting
enzyme inhibitory peptide from Alaska pollack (Theragra chalcogramma) frame
protein hydrolysate. Journal of Agricultural and Food Chemistry, 52, 7842–7845.
Je, J. Y., Qian, Z. J., Byun, H. G., & Kim, S. K. (2007). Purification and characterization
of an antioxidant peptide obtained from tuna backbone protein by enzymatic
hydrolysis. Process Biochemistry, 42, 840–846.
Jeon, Y. J., Byun, H. G., & Kim, S. K. (1999). Improvement of functional properties of
cod frame protein hydrolysates using ultrafiltration membranes. Process
Biochemistry, 35, 471–478.
Jun, S. Y., Park, P. J., Jung, W. K., & Kim, S. K. (2004). Purification and characterization
of an antioxidative peptide from enzymatic hydrolysates of yellowfin sole
(Limanda aspera) frame protein. European Food Research and Technology, 219,
20–26.
Jung, W. K., Karawita, R., Heo, S. J., Lee, B. J., Kim, S. K., & Jeon, Y. J. (2006a). Recovery
of a novel Ca-binding peptide from Alaska pollack (Theragra chalcogramma)
backbone by pepsinolytic hydrolysis. Process Biochemistry, 41, 2097–2100.
Jung, W. K., & Kim, S. K. (2007). Calcium-binding peptide derived from pepsinolytic
hydrolysates of hoki (Johnius belengerii) frame. European Food Research and
Technology, 224, 763–767.
Jung, W. K., Lee, B. J., & Kim, S. K. (2006b). Fish-bone peptide increases calcium
solubility and bioavailability in ovariectomised rats. British Journal of Nutrition,
95, 124–128.
Jung, W., Mendis, E., Je, J., Park, P., Son, B. W., Kim, H. C., ... Kim, S. K. (2006c).
Angiotensin I-converting enzyme inhibitory peptide from yellow fins sole
(Limmanda aspera) frame protein and its antihypertensive effect in
spontaneously hypertensive rats. Food Chemistry, 94, 26–32.
Jung, W. K., Park, P. J., Byun, H. G., Moon, S. H., & Kim, S. K. (2005). Preparation of
hoki (Johnius belengerii) bone oligophosphopeptide with a high affinity to
calcium by carnivorous intestine crude proteinase. Food Chemistry, 91, 333–340.
Jung, W. K., Shahidi, F., & Kim, S. K. (2009). Calcium from fish bone and other marine
resources. In C. Barrow & F. Shahidi (Eds.), Marine nutraceuticals and functional
foods (pp. 419–426). CRC Press.
Kassis, N., Drake, S. R., Beamer, S. K., Matak, K. E., & Jaczynski, J. (2010). Development
of nutraceutical egg products with omega-3-rich oils. LWT - Food Science and
Technology, 43, 777–783.
Kendall-Tackett, K. (2010). Long-chain Omega-3 fatty acids and women’s mental
health in the perinatal period and beyond. Journal of Midwifery & Women’s
Health, 55, 561–567.
Khantaphant, S., & Benjakul, S. (2008). Comparative study on the proteases from fish
pyloric caeca and the use for production of gelatin hydrolysate with
antioxidative activity. Comparative Biochemistry and Physiology. Part B,
Biochemistry and Molecular Biology, 151, 410–419.
680 M. Atef, S. Mahdi Ojagh / Journal of Functional Foods 35 (2017) 673–681
Khora, S. (2013). Marine fish-derived bioactive peptides and proteins for human
therapeutics. International Journal of Pharmacy and Pharmaceutical Sciences, 5,
31–37.
Kim, S. Y., Je, J. Y., & Kim, S. K. (2007). Purification and characterization of
antioxidant peptide from hoki (Johnius belengerii) frame protein by
gastrointestinal digestion. The Journal of Nutritional Biochemistry, 18,
31–38.
Kim, S., Kim, Y., Byun, H., Nam, K., Joo, D., & Shahidi, F. (2001). Isolation and
characterization of antioxidative peptides from gelatin hydrolysate of Alaska
Pollack skin. Journal of Agricultural and Food Chemistry, 49, 1984–1989.
Kim, S., & Mendis, E. (2006). Bioactive compounds from marine processing
byproducts – A review. Food Research International, 39, 383–393.
Kim, S. K., & Wijesekara, I. (2010). Development and biological activities of marine-
derived bioactive peptides: A review. Journal of Functional Foods, 2, 1–9.
Kitts, D. D., & Weiler, K. (2003). Bioactive proteins and peptides from food sources.
Applications of bioprocesses used in isolation and recovery. Current
Pharmaceutical Design, 9, 1309–1323.
Klompong, V., Benjakul, S., Yachai, M., Visessanguan, W., Shahidi, F., & Hayes, K. D.
(2009). Amino acid composition and antioxidative peptides from protein
hydrolysates of yellow stripe trevally (Selaroides leptolepis). Journal of Food
Science, 74, 126–133.
Ko, J. Y., Kang, N., Lee, J., Kim, J. S., Kim, W. S., Park, S. J., ... Jeon, Y. J. (2016).
Angiotensin I-converting enzyme inhibitory peptides from an enzymatic
hydrolysate of flounder fish (Paralichthys olivaceus) muscle as a potent anti-
hypertensive agent. Process Biochemistry, 51, 535–541.
Ko, J. Y., Lee, J. H., Samarakoon, K., Kim, J. S., & Jeon, Y. J. (2013). Purification and
determination of two novel antioxidant peptides from flounder fish
(Paralichthys olivaceus) using digestive proteases. Food and Chemical
Toxicology, 52, 113–120.
Kristinsson, H. G. (2007). Aquatic food protein hydrolysates. In F. Shahidi (Ed.),
Maximising the value of marine by-products. Cambridge, UK: Woodhead
Publishing Ltd.
Kumar, N. S., Nazeer, R. A., & Jai ganesh, R. (2011a). Purification and biochemical
characterization of antioxidant peptide from horse mackerel (Magalaspis
cordyla) viscera protein. Peptides, 32, 149–156.
Kumar, S., Sutherland, F., Rosso, R., Teh, A. W., Lee, G., Heck, P. M., ... Sparks, P. B.
(2011b). Effects of chronic omega-3 polyunsaturated fatty acid
supplementation on human atrial electrophysiology. Heart Rhythm, 8, 562–568.
Larsen, T., Thilsted, S. H., Kongsbak, K., & Hansen, M. (2000). Whole small fish as a
rich calcium source. British Journal of Nutrition, 83, 191–196.
Lee, J. K., Jeon, J. K., & Byun, H. G. (2014). Antihypertensive effect of novel
angiotensin I converting enzyme inhibitory peptide from chum salmon
(Oncorhynchus keta) skin in spontaneously hypertensive rats. Journal of
Functional Foods, 7, 381–389.
Lee, Y. G., Kim, J. Y., Lee, K. W., Kim, K. H., & Lee, H. J. (2003). Peptides from anchovy
sauce induce apoptosis in a human lymphoma cell (U937) through the increase
of caspase-3 and -8 activities. Annals of the New York Academy of Sciences, 1010,
399–404.
Lee, S., Qian, Z., & Kim, S. (2010). A novel angiotensin I converting enzyme inhibitory
peptide from tuna frame protein hydrolysate and its antihypertensive effect in
spontaneously hypertensive rats. Food Chemistry, 118, 96–102.
Li, Y., Zhou, J., Huang, K., Sun, Y., & Zeng, X. (2012). Purification of a novel
angiotensin I-converting enzyme (ACE) inhibitory peptide with an
antihypertensive effect from loach (Misgurnus anguillicaudatus). Journal of
Agricultural and Food Chemistry, 60, 1320–1325.
Liu, M., Wallin, R., & Saldeen, T. (2001). Effect of bread containing fish oil on plasma
phospholipid fatty acids, triglycerides, HDL-cholesterol, and malondialdehyde
in subjects with hyperlipidemia. Nutrition Research, 21, 1403–1410.
Mendis, E., Rajapakse, N., & Kim, S. K. (2005). Antioxidant properties of a radicals
scavenging peptide purified from enzymatically prepared fish skin gelatin
hydrolysate. Journal of Agriculture and Food Chemistry, 53, 581–587.
Moore, C. S., Bryant, S. P., Mishra, G. D., Krebs, J. D., Browning, L. M., Miller, G. J., ...
Jebb, S. A. (2006). Oily fish reduces plasma triacylglycerols: A primary
prevention study in overweight men and women. Nutrition, 22, 1012–1024.
Morimura, S., Nagata, H., Uemura, Y., Fahmi, A., Shigematsu, T., & Kida, K. (2002).
Development of an effective process for utilization of collagen from livestock
and fish waste. Process Biochemistry, 37, 1403–1412.
Mulligan, M. L., Felton, S. K., Riek, A. E., & Bernal-Mizrachi, C. (2010). Implications of
vitamin D deficiency in pregnancy and lactation. American Journal of Obstetrics
and Gynecology, 202(429), 1–9.
Nagai, T., Izumi, M., & Ishii, M. (2004). Fish scale collagen. Preparation and partial
characterization. International Journal of Food Science and Technology, 39,
239–244.
Najafian, L., & Babji, A. S. (2012). A review of fish-derived antioxidant and
antimicrobial peptides: Their production, assessment, and applications.
Peptides, 33, 178–185.
Nakatani, T., Kim, H.-J., Kaburagi, Y., Yasuda, K., & Ezaki, O. (2003). A low fish oil
inhibits SREBP-1 proteolytic cascade, while a high-fish-oil feeding decreases
SREBP-1 mRNA in mice liver relationship to anti-obesity. Journal of Lipid
Research, 44, 369–379.
Naqash, S. Y., & Nazeer, R. A. (2011). Evaluation of bioactive properties of peptide
isolated from Exocoetus volitans backbone. International Journal of Food Science
and Technology, 46, 37–43.
Ngo, D., Qian, Z., Ryu, B., Park, J. W., & Kim, S. (2010). In vitro antioxidant activity of a
peptide isolated from Nile tilapia (Oreochromis niloticus) scale gelatin in free
radical-mediated oxidative systems. Journal of Functional Foods, 2, 107–117.
Ngo, D. H., Ryu, B., Vo, T. S., Himaya, S. W. A., Wijesekara, I., & Kim, S. K. (2011). Free
radical scavenging and angiotensin-I converting enzyme inhibitory peptides
from Pacific cod (Gadus macrocephalus) skin gelatin. International Journal of
Biological Macromolecules, 49, 1110–1116.
Ngo, D. H., Vo, T. S., Ngo, D. N., Wijesekara, I., & Kim, S. K. (2012). Biological activities
and potential health benefits of bioactive peptides derived from marine
organisms. International Journal of Biological Macromolecules, 51, 378–383.
Nikoo, M., Benjakul, S., Ehsani, A., Li, J., Wu, F., Yang, N., ... Xu, X. (2014). Antioxidant
and cryoprotective effects of a tetrapeptide isolated from Amur sturgeon skin
gelatin. Journal of Functional Foods, 7, 609–620.
Nugent, S., Croteau, E., Pifferi, F., Fortier, M., Tremblay, S., Turcotte, E., & Cunnane, S.
C. (2011). Brain and systemic glucose metabolism in the healthy elderly
following fish oil supplementation. Prostaglandins, Leukotrienes and Essential
Fatty Acids (PLEFA), 85, 287–291.
Oelrich, B., Dewell, A., & Gardner, C. D. (2013). Effect of fish oil supplementation on
serum triglycerides, LDL cholesterol and LDL subfractions in
hypertriglyceridemic adults. Nutrition, Metabolism & Cardiovascular Diseases,
23, 350–357.
Ohba, R., Deguchi, T., Kishikawa, M., Arsyad, F., Morimura, S., & Kida, K. (2003).
Physiological functions of enzymatic hydrolysates of collagen or keratin
contained in livestock and fish waste. Food Science and Technology Research, 9,
91–93.
Olafsdottir, A. S., Thorsdottir, I., Wagner, K. H., & Elmadfa, I. (2006). Polyunsaturated
fatty acids in the diet and breast milk of lactating Icelandic women with
traditional fish and cod liver oil consumption. Annals of Nutrition & Metabolism,
50, 270–276.
Ozawa, M., & Suguru, S. (2002). Microstructural development of natural
hydroxyapatite originated from fish-bone waste through heat treatment.
Journal of the American Ceramists Society, 85, 1315–1317.
Pan, X., Zhao, Y., Hu, F., & Wang, B. (2016). Preparation and identification of
antioxidant peptides from protein hydrolysate of skate (Raja porosa) cartilage.
Journal of Functional Foods, 25, 220–230.
Pei, X., Yang, R., Zhang, Z., Gao, L., Wang, J., Xu, Y., ... Li, Y. (2010). Marine collagen
peptide isolated from Chum Salmon (Oncorhynchus keta) skin facilitates
learning and memory in aged C57BL/6J mice. Food Chemistry, 118, 333–340.
Pezeshk, S., Ojagh, S. M., & Alishahi, A. (2015). Effect of plant antioxidant and
antimicrobial compounds on the shelf-life of seafood – a review. Czech Journal of
Food Sciences, 33, 195–203.
Phanturat, P., Benjakul, S., Visessanguan, W., & Roytrakul, S. (2010). Use of pyloric
caeca extract from bigeye snapper (Priacanthus macracanthus) for the
production of gelatin hydrolysate with antioxidative activity. LWT-Food
Science and Technology, 43, 86–97.
Picot, L., Bordenave, S., Didelot, S., Fruitier-Arnaudin, I., Sannier, F., Thorkelsson, G.,
... Piot, J. M. (2006). Antiproliferative activity of fish protein hydrolysates on
human breast cancer cell lines. Process Biochemistry, 41, 1217–1222.
Pihlanto-Leppala, A. (2001). Bioactive peptides derived from bovine proteins:
Opioid and ACE-inhibitory peptides. Trends in Food Science and Technology, 11,
347–356.
Pipingas, A., Sinclair, A., Croft, K. D., Januszewski, A. J., Jenkins, A. J., Mori, T. A., ...
Pase, M. P. (2015). Fish oil and multivitamin supplementation reduces oxidative
stress but not inflammation in healthy older adults: A randomized controlled
trial. Journal of Functional Foods, 19, 949–957.
Rachetti, A. L. F., Arida, R. M., Patti, C. L., Zanin, K. A., Fernades-Santos, L., Frussa-
Filho, R., ... Cysneiros, R. M. (2013). Fish oil supplementation and physical
exercise program: Distinct effects on different memory tasks. Behavioural Brain
Research, 237, 283–289.
Rajanbabu, V., & Chen, J. C. (2011). Applications of antimicrobial peptides from fish
and perspectives for the future, review. Peptides, 32, 415–420.
Rajapakse, N., Jung, W. K., Mendis, E., Moon, S. H., & Kim, S. K. (2005a). A novel
anticoagulant purified from fish protein hydrolysate inhibits factor XIIa and
platelet aggregation. Life Sciences, 76, 2607–2619.
Rajapakse, N., Mendis, E., Jung, W. K., Je, J. Y., & Kim, S. K. (2005b). Purification of a
radical scavenging peptide from fermented mussel sauce and its antioxidant
properties. Food Research International, 38, 175–182.
Ranathunga, S., Rajapakse, N., & Kim, S. K. (2006). Purification and characterization
of antioxidantative peptide derived from muscle of conger eel (Conger
myriaster). European Food Research and Technology, 222, 310–315.
Rehn, M., Veikkola, T., Kukk-valdre, E., Nakamura, H., Ilmonen, M., Lombardo, C., ...
Vuori, K. (2001). Interaction of endostain with integrins implicated in
angiogenesis. Proceedings of the National Academy of Sciences of the United
States of America, 98, 1024–1029.
Rose, E. L., & Holub, B. J. (2006). Effects of a liquid egg product containing fish oil on
selected cardiovascular disease risk factors: A randomized crossover trial. Food
Research International, 39, 910–916.
Ryan, J. T., Ross, R. P., Bolton, D., Fitzgerald, G. F., & Stanton, C. (2011). Bioactive
peptides from muscle sources: Meat and fish, review. Nutrients, 3, 765–791.
Salampessy, J., Phillips, M., Seneweera, S., & Kailasapathy, K. (2010). Release of
antimicrobial peptides through bromelain hydrolysis of leatherjacket
(Meucheniasp.) insoluble proteins. Food Chemistry, 120, 556–560.
Salampessy, J., Reddy, N., Phillips, M., & Kailasapathy, K. (2017). Isolation and
characterization of nutraceutically potential ACE-Inhibitory peptides from
leatherjacket (Meuchenia sp.) protein hydrolysates. LWT – Food Science and
Technology, 80, 430–436.
Saldeen, T., Wallin, R., & Marklinder, I. (1998). Effects of a small dose of stable fish
oil substituted for margarine in bread on plasma phospholipid fatty acids and
serum triglycerides. Nutrition Research, 18, 1483–1492.
 M. Atef, S. Mahdi Ojagh / Journal of Functional Foods 35 (2017) 673–681
Sarmadi, B. H., & Ismail, A. (2010). Antioxidative peptides from food proteins: A
review. Peptide, 31, 1949–1956.
Sathivel, S., Bechtel, P. J., Babbitt, J., Smiley, S., Crapo, C., Reppond, K. D., &
Prinyawiwatkul, W. (2003). Biochemical and functional properties of herring
(Clupea harengus) byproduct hydrolysates. Journal of Food Science, 68,
2196–2200.
Senaratne, L. S., Park, P., & Kim, S. (2006). Isolation and characterization of collagen
from brown backed toadfish (Lagocephalus gloveri) skin. Bioresource Technology,
97, 191–197.
Shahidi, F., Han, X. Q., & Synowiecki, J. (1995). Production and characteristics of
protein hydrolysates from capelin (Mallotus villosus). Food Chemistry, 53,
285–293.
Shahidi, F., & Janak Kamil, Y. V. A. (2001). Enzymes from fish and aquatic
invertebrates and their application in the food industry. Trends in Food Science
& Technology, 12, 435–464.
Shahidi, F., & Zhong, Y. (2008). Bioactive peptides. Journal of AOAC International, 91,
914–931.
Shahidi, F., & Zhong, Y. (2007). Antioxidants from marine by-products. In F. Shahidi
(Ed.), Maximizing the value of marine by-products (pp. 397–412). Cambridge, UK:
Woodhead Publishing.
Shearer, G. C., Savinova, O. V., & Harris, W. S. (2012). Fish oil – How does it reduce
plasma triglycerides? Biochimica et Biophysica Acta, 1821, 843–851.
Sila, A., & Bougatef, A. (2016). Antioxidant peptides from marine by-products:
Isolation, identification and application in food systems. A review. Journal of
Functional Foods, 21, 10–26.
Sila, A., Hedhili, K., Przybylski, R., Ellouz-Chaabouni, S., Dhulster, P., Bougatef, A., &
Nedjar-Arroume, N. (2014). Antibacterial activity of new peptides from barbel
protein hydrolysates and mode of action via a membrane damage mechanism
against Listeria monocytogenes. Journal of Functional Foods, 11, 322–329.
Silva, J. F. X., Ribeiro, K., Silva, J. F., Cahú, T. B., & Bezerra, R. S. (2014). Utilization of
tilapia processing waste for the production of fish protein hydrolysate. Animal
Feed Science and Technology, 196, 96–106.
Slizyte, R., Dauksas, E., Falch, E., Storro, I., & Rustad, T. (2005). Characteristics of
protein fractions generated from hydrolysed cod (Gadus morhua) by-products.
Process Biochemistry, 40, 2021–2033.
Slizyte, R., Mozuraityte, R., Martınez-Alvarez, O., Falch, E., Fouchereau-Peronb, M., &
Rustad, T. (2009). Functional, bioactive and antioxidative properties of
hydrolysates obtained from cod (Gadus morhua) backbones. Process
Biochemistry, 44, 668–677.
Song, R., Wei, R., Luo, H., & Wang, D. (2012). Isolation and characterization of an
antibacterial peptide fraction from the pepsin hydrolysate of half-fin anchovy
(Setipinna taty). Molecules, 17, 2980–2991.
Suarez-Jimenez, G., Burgos-Hernandez, A., & Ezquerra-Brauer, J. (2012). Bioactive
peptides and depsipeptides with anticancer potential: Sources from marine
animals. Marine Drugs, 10, 963–986.
Swatschek, D., Schatton, W., Kellermann, J., Muller, W. E. G., & Kreuter, J. (2002).
Marine sponge collagen: Isolation, characterization and effects on the skin
parameters surface-pH, moisture and sebum. European Journal of Pharmaceutics
and Biopharmaceutics, 53, 107–113.
Talon, L. C., Oliveira, E. P., Moreto, F., Portero-McLellan, K. C., & Burini, R. C. (2015).
Omega-3 fatty acids supplementation decreases metabolic syndrome
681
prevalence after lifestyle modification program. Journal of Functional Foods, 19,
922–928.
Tanaka, M., Koyama, Y. I., & Nomura, Y. (2009). Effects of collagen peptide ingestion
on UV-B-induced skin damage. Bioscience, Biotechnology, and Biochemistry, 73,
930–932.
Tavazzi, L., Maggioni, A. P., Marchioli, R., Barlera, S., Franzosi, M. G., Latini, R., ...
Tognoni, G. (2008). Effect of n-3 polyunsaturated fatty acids in patients with
chronic heart failure (the GISSI-HF trial): A randomized, double-blind, placebo-
controlled trial. Lancet, 372, 1223–1230.
Thiansilakul, Y., Benjakul, S., & Shahidi, F. (2007). Compositions, functional
properties and anti-oxidative activity of protein hydrolysates prepared from
round scad (Decapterus maruadsi). Food Chemistry, 103, 1385–1394.
Toopcham, T., Roytrakul, S., & Yongsawatdigul, J. (2015). Characterization and
identification of angiotensin I-converting enzyme (ACE) inhibitory peptides
derived from tilapia using Virgibacillus halodenitrificans SK1-3-7 proteinases.
Journal of Functional Foods, 14, 435–444.
Verardo, V., Ferioli, F., Riciputi, Y., Iafelice, G., Marconi, E., & Caboni, M. F. (2009).
Evaluation of lipid oxidation in spaghetti pasta enriched with long chain n-3
polyunsaturated fatty acids under different storage conditions. Food Chemistry,
114, 472–477.
WHO (2007). Protein and amino acid requirements in human nutrition: Report of the
joint WHO/FAO/UNU expert consultation. Geneva: World Health Organization.
Wu, C. H., Chen, H. M., & Shiau, C. Y. (2003). Free amino acids and peptides as related
to antioxidant properties in protein hydrolysates of mackerel (Scomber
austriasicus). Food Research International, 36, 949–957.
Wu, S., Feng, X., Lan, X., Xu, Y., & Liao, D. (2015). Purification and identification of
Angiotensin-I Converting Enzyme (ACE) inhibitory peptide from lizard fish
(Saurida elongata) hydrolysate. Journal of Functional Foods, 13, 295–299.
Wu, H., He, H. L., Chen, X. L., Sun, C. Y., Zhang, Y. Z., & Zhou, B. C. (2008). Purification
and identification of novel angiotensin-I-converting enzyme inhibitory peptides
from shark meat hydrolysate. Process Biochemistry, 43, 457–461.
Xu, L., Dong, W., Zhao, J., & Xu, Y. (2015). Effect of marine collagen peptides on
physiological and neurobehavioral development of male rats with perinatal
asphyxia. Marine Drugs, 13, 3653–3671.
Xu, Y., Han, X., & Li, Y. (2010). Effect of marine collagen peptides on long bone
development in growing rats. Journal of the Science of Food and Agriculture, 90,
1485–1491.
Yep, Y., Li, D., Mann, N., Bode, O., & Sinclair, A. (2002). Bread enriched with
microencapsulated tuna oil increases plasma docosahexaenoic acid and total
omega-3 fatty acids in humans. Asia Pacific Journal of Clinical Nutrition, 11,
285–291.
Yokoyama, M., Origasa, H., Matsuzaki, M., Matsuzawa, Y., Saito, Y., Ishikawa, Y., ...
Shirato, K. (2007). Effects of eicosapentaenoic acid on major coronary events in
hypercholesterolaemic patients (JELIS): A randomised open-label, blinded
endpoint analysis. Lancet, 369, 1090–1098.
Yu, H., Zhu, J., Pan, W., Shen, S., Shan, W., & Das, U. N. (2014). Effects of fish oil with a
high content of n-3 polyunsaturated fatty acids on mouse gut microbiota.
Archives of Medical Research, 45, 195–202.
Zhang, Y. F., Duan, X., & Zhuang, Y. L. (2012). Purification and characterization of
novel antioxidant peptides from enzymatic hydrolysates of tilapia (Oreochromis
niloticus) skin gelatin. Peptides, 38, 13–21.