Other Effects of Peptides

Antihypertensive Activity

Hypertension is a cardiovascular disease that affects approximately one quarter of the world’s population and is a controllable risk factor that plays a role in related complications. The angiotensin I-converting enzyme (ACE) is a dipeptityl carboxy- peptitase and has the role of turning angiotensin I to angiotensin II. Angiotensin II has a general vasoconstriction impact. It plays an important physiological role in controlling blood pressure, liquid, and salt balance in vertebrates (Hartmann and Meisel 2007; Hayes et al. 2016) and peptides that repress the ACE enzyme are

TABLE 12.1 Antioxidant Peptides

Peptide Source

Hydrolysis Method

Amino Acid Sequence




Alcalase Neutrase

Thr-Gln-Val-Tyr Arg-Pro-Asn-Tyr-Thr-Asp-Ala, Thr-Scr-Gln-Lcu-Lcu-Ser-Asp-Gin, Th r-A rg-Thr-Gl y-A sp- Pro- Phe -Phe, Asn-Phe-His-Pro-Gin Phe-Arg-Asp-Glu-His-Lys- Lys and Lys-His-Asp- Arg-Gly-Asp-Glu- Phe

Antioxidant activity with DPPH and ABTS radical scavenging activity and in FRAP-Fe3* reducing assay.

Li ct al. 2007J. Zhang ct al.20l0Yanctal.20l5

Chickpea protein


Asp-His-Gly and Val-Gly-Asp-Ile

Scavenging effect of DPPH radicals was seen.

Ghribi et al. 2015

Wheat germ

Bacillus licheniformis


This sequence found as contributor to the ACE inhibition.

Matsui, Li, and Osajima 1999

Hemp seed protein (Cannabis sativa L.) hydrolysate



Trp-Val-Tyr-Tyr and Pro- Scr-Lcu-Pro-Ala

DPPH radical scavenging assay and metal chelation activity for measurement of antioxidant activity.

Girgih et al 20I4


Alkaline protease


Measurement of antioxidant activity by ferric thiocyanate assay.

Chen, Muramoto, and Yamauchi 1995

Egg (egg white)

Protease Pepsin-



Asp-His-Thr-Lys-Glu. Met-Pro-Asp- Ala-His-Leu, Phe-Phe-Gly-Phe-Asn Al a-G lu-Gl u- Arg-Tyr- Pro, Asp-Glu-Asp-Thr-Gln-Ala-Met-Pro

Antioxidant activity has been measured by DPPH. ORAC radical scavenging assays.

Davalos et al. 2004J.B. Liu et al. 2015 Nimalaratne. Bandara. and Wu 2015

Wheat germ protein




Antioxidant activity conducted by ABTS assay.

Karami ct al. 2019


Peptide Source

Hydrolysis Method

Amino Acid Sequence



Com gluten meal

Alkaline protease and Flavourzyme

Lcu-Pro-Phc, Leu-Leu-Pro-Phc, Phe-Leu-Pro-Phe and Asp-Pro-Pro-His

Antioxidant activities by ABTS, and hydroxyl radicals scavenging assay.

Zhuang, Tang, and Yuan 2013





DPPH. ABTS, Fe2* chelating activity and reducing power assay have been conducted to evaluate the antioxidant activity.

Agrawal, Joshi, and Gupta 2017

Sweet potato



OH radical scavenging.

Zhang, Mu. and Sun 2014

Palmaria palmata protein

Corolase PP



Showed high antioxidant activity at ORAC and FRAP radicals.

Hamedy, O'Keeffe, and FitzGerald 2017

Grass carp (Ctenopharyngodon idella) skin


Pro-Tyr-Scr-Phc-Lys, Gly-Phc-Gly- Pro-Glu-Leu and Val-Gly-Gly-Arg-Pro

Antioxidant activities by DPPH, OH radical, ABTS radical scavenging and inhibit lipid peroxidation.

Cai etal.2015

Sea squirt (Halocynlhia roretzi) protein


Leu-Glu-Trp, Tyr-Tyr-Pro-Tyr-Gln- Leu and Met-Thr-Thr-Leu

Measured antioxidant activity by DPPH and ORAC radicals.

Kimetal. 2018

Bluefin leatherjacket skin (Navodon

septentrionalis) and heads

Trypsin, Flavourzyme, neutrase. papain, alcalase, and pepsin, and protein hydrolysate (BSH) Papain

Gly-Ser-Gly-Gly-Leu. Gly-Pro-GlyGly-Phe-Ile and Phe-Ile-Gly-Pro

Trp-Glu-Gly-ProLys. Gly-Pro-Pro and Gly-Val-Pro-Leu-Thr

Antioxidant activity by DPPH, HO, 0,' radical scavenging assays.

DPPH. hydroxyl. ABTS. superoxide radicals scavenging and inhibit the peroxidation of linoleic acid to measure the antioxidant activity.

Chi. Wang, Hu et al. 2015

Chi, Wang, Wang et al. 2015

Peptide Source

Hydrolysis Method

Amino Acid Sequence



Oyster (Saccostrea cucullata)


Leu-Ala-Asn-Ala-Lys, Pro-Scr-Lcu-Val-Gly-Arg-Pro-Pr o-Val-Gly-Lys-Lcu-Thr-Lcu and Val-Lys-Val-Leu-Leu-Glu-His-Pro- Val-Leu

DPPH radicals scavenging assay and human colon carcinoma (HT-29) cell lines inhibition.

Umayaparvathi et al. 2014

Oyster (Crassoslrea la lien whan ensis)

Subtil isin

Pro-Val-Met-Gly-Ala and Glu-His-Gly-Val

High antioxidant activity with DPPH radical scavenging assay.

Q. Wang et al. 2014

Palm Kernel Cake Proteins




Antioxidant activity measurement by metal chelating ability and DPPH radical scavenging.

Zarei et al. 2014

Royal jelly protein

Protease N

Ala-Leu, Phc-Arg, Phc-Lys, Ilc-Arg, Lys-Lcu, Lys-Phc, Lys-Tyr, Туг-Asp, Arg-Tyr, Tyr-Tyr, Lys-Asn-Tyr-Pro, Leu-Asp-Arg

High antioxidant activity at peroxidation of linoleic acid

Guo, Kouzuma, and Yonckura 2009

Blood clam (Tegillarca granosa) muscle

Trinitrobenzene sulfonic acid



Inhibit lipid peroxidation, DPPH, HO, 02, and ABTS radical scavenging activity have been observed to prove the antioxidant activity.

Chi, Hu, Wang, Lee et al. 2015

Croceine croaker (Pseudosciaena croce a) muscle

Pepsin and Alcalase

Tyr-Leu-Met-Ser-Arg. Val-Leu-Tyr- Glu-Glu and Met-lle-Leu- Met-Arg

DPPH. superoxide. ABTS and hydroxyl radical scavenging. Lipid peroxidation activities have also been observed.

Chi. Hu. Wang, Ren et al. 2015

Peptide Source

Hydrolysis Method

Amino Acid Sequence



Spotless smoothhound

(Mustehisgriseus) muscle


Gly-Ala-Ala, GlyPhc-Val-Gly, Gly-Ilc-Ilc-Scr-His-Arg, Glu-Lcu- Leu-Ile and Lys-Phe-Pro-Glu

Hydroxyl, ABTS, superoxide radical scavenging activities have been detected to prove antioxidant activity.

Wang ct al 20I4

Marine Sepia brevimana mantle Sphyma lewini muscle


a-chymotrypsin, and pepsin


Antioxidant activities have measured by DPPH radicals scavenging and lipid peroxidation.

Sudhakar and Nazeer 2015

Sphyrna lewini muscle


Trp-Asp-Arg and Pro-Tyr-Phe-Asn-Lys

ABTS. DPPH radicals scavenging assays and peroxyl free radical scavenging in P-carotene linoleic acid assay was made to measure the antioxidant capacity.

Wang et al. 2012

Tilapia (Oreochromis niloticus) gelatin

Properase E.


Found to have scavenging of hydroxyl radicals to prove the antioxidant activity.

Sun, Zhang, and Zhuang 20l3Zhuang and Sun 2011



High levels of glutamylcysteine

They found high glutathione-promoting activity

Bounous and Gold 1991

Otolitlies ruber muscle protein hydrolysate


Lys-Thr-Phe-Cys-Gly-Arg- His

Hydroxyl and DPPH radical scavenging activities. Inhibition of the lipid peroxidation and DNA damage. Also improved the endogenous cellular antioxidant enzymes (catalase (CAT), superoxide dismutase (SOD) and glutathione-S-transferase (GST)) in study with Wistar rats.

Nazeer, Kumar, and JaiGanesh 2012

potentially assumed as agents that lower the blood pressure (Kannan, Hettiarachchy, and Marshall 2012). Therefore, a great deal of research has been carried out on the peptide production which shows anti hypertensive activity from milk, cheese, meat, fish, and a wide variety of plants and algae. However, no correlation has been reported between in vivo antihypertensive effects and the results of in vitro studies investigating the inhibition of ACE enzymes. In this manner, there is no assurance that the result that is taken from ACE inhibition acquired in vitro will have a similar impact in vivo (Majumder and Wu 2013; Miralles, Amigo, and Recio 2018; Unal, §ener, and Cemek 2018; Girija 2018).

Anticancerogenic Activity

The yellow eld pea seed hydrolysate has been shown to be an important contributor to the peptide antioxidant properties of net charge and hydrophobicity through a progression of investigations including column chromatography divisions of a thermo- lysin digestion. Due to its low toxicity and small size, it has advantages of high tissue penetration, permeability, and cell dissemination. Peptides can also influence at least one specific molecular pathway that is associated with cancer development and the pathways are not commonly genotoxic. The main mechanisms that can be described are via inhibiting the cell migration, antioxidant activity, gene transcription/inhibi- tion of proliferation on cells, inhibition of the formation of blood vessels on tumor cells, induction of apoptosis, cytotoxicity, and induction of disorganization of tubulin structure. Peptides that have a potent cytotoxic activity can be derived from various substances such as eggs, milk, marine organisms, and plants (Su et al. 2014; Cicero, Fogacci, and Colletti 2017; Unal, §ener, and Cemek 2018).

Cholesterol Reducer and Anti-Obesity Activity

Obesity is a fact that shortens the life span and also impairs the quality of life with its side effects (Yardim et al. 2017). There are findings that obesity increases the risk of heart disease, hypertension, and diabetes. When the cholesterol and/or triglyceride levels increase in plasma, development of atherosclerosis can increase. In addition, a decrease in high-density lipoprotein levels can also contribute to atherosclerosis development. Protein hydrolysates containing a specific peptide sequence have been found to exhibit lipid-lowering (hypolipidemic) effects in in vitro, ex vivo, and in vivo studies. Hypolipidemic peptides display their activities by binding bile acids, breaking down cholesterol micelles, and hindering their absorption. It also has the ability to influence the activities of liver and fat cell enzymes and to activate gene expression of lipogenic proteins, receptors and the 3-hydroxy-3-methylglutaryl CoA reductase enzyme. The 3-hydroxy-3-methylgl- utaryl CoA reductase enzyme acts as the main regulatory enzyme in cholesterol biosynthesis. Inhibition of this enzyme is the main target to reduce the cholesterol biosynthesis rate (Mazorra-Manzano, Ramfrez-Suarez, and Yada 2017; White, Garber and Anantharamaiah 2014) and finally, it has role in the lipid metabolism and obesity (Unal, §ener, and Cemek 2018).

Anti-Diabetic Activity

Diabetes is the most common non-communicable disease that occurs, due to the insufficiency of the pancreas in insulin production or the ineffectiveness of secreted insulin. This type of deficiency causes increased blood sugar and damages the body tissue, especially blood vessels and nerves. While the number of patients with diabetes in the world was 108 million in 1980, it increased to 422 million in 2014 (Agarwa and Gupta 2016; Arrutia et al. 2016; Brown et al. 2017; Unal, §ener, and Cemek 2018). Another alluring alternative in pharmacological mediations is the utilization of bioactive peptides capable of inhibiting key enzymes that regulate blood sugar levels (e.g. dipeptitil peptitase IV (DPP-IV) and alpha-glycosidase). DPP-IV (EC is the key compound in intestinal processing and ingestion systems. The movement of this enzyme is associated with the breakdown of incretions such as glucagon-like peptide (GLP-1) and gastric inhibitory peptide (GIP). GLP-1 and GIP peptides are known to assume a significant job in the regulation of glucose homeostasis in the digestive tract in the first minutes of food intake. The existence of bioactive peptides in protein hydrolysates, which can hinder DPP-IV in vitro and lower blood sugar levels in vivo, increased the production of hydrolysates with antidiabetic activity. Milk protein hydrolysates containing bioactive peptide capable of inhibiting DPP-IV were produced using microbial, animal, and vegetable proteases (Mazorra-Manzano et al. 2017; Yan et al. 2019).

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