Roles of Dietary Bioactive Peptides in Redox Balance and Metabolic Disorders

Qiao, Qinqin; Chen, Liang; Li, Xiang; Lu, Xiangyang; Xu, Qingbiao

doi:https://doi.org/10.1155/2021/5582245

Oxidative Medicine and Cellular Longevity

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Molecular Mechanisms of Dietary Bioactive Compounds in Redox Balance and Metabolic Disorders

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Review Article | Open Access

Volume 2021 | Article ID 5582245 | https://doi.org/10.1155/2021/5582245

Roles of Dietary Bioactive Peptides in Redox Balance and Metabolic Disorders

Qinqin Qiao,¹Liang Chen,²Xiang Li,³Xiangyang Lu,²and Qingbiao Xu³

Academic Editor: Wuquan Deng

Received21 Jan 2021

Revised30 Apr 2021

Accepted21 May 2021

Published15 Jun 2021

Abstract

Bioactive peptides (BPs) are fragments of 2–15 amino acid residues with biological properties. Dietary BPs derived from milk, egg, fish, soybean, corn, rice, quinoa, wheat, oat, potato, common bean, spirulina, and mussel are reported to possess beneficial effects on redox balance and metabolic disorders (obesity, diabetes, hypertension, and inflammatory bowel diseases (IBD)). Peptide length, sequence, and composition significantly affected the bioactive properties of dietary BPs. Numerous studies have demonstrated that various dietary protein-derived BPs exhibited biological activities through the modulation of various molecular mechanisms and signaling pathways, including Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2/antioxidant response element in oxidative stress; peroxisome proliferator-activated-γ, CCAAT/enhancer-binding protein-α, and sterol regulatory element binding protein 1 in obesity; insulin receptor substrate-1/phosphatidylinositol 3-kinase/protein kinase B and AMP-activated protein kinase in diabetes; angiotensin-converting enzyme inhibition in hypertension; and mitogen-activated protein kinase and nuclear factor-kappa B in IBD. This review focuses on the action of molecular mechanisms of dietary BPs and provides novel insights in the maintenance of redox balance and metabolic diseases of human.

1. Introduction

Dietary food proteins contain short sequences of amino acids (AAs) that possess various biological activities. The short chains of AAs with biological properties are known as bioactive peptides (BPs). BPs usually contain 2–15 AA residues. The BP sequences present in the food proteins are generally hidden in the inner core of the parent proteins [1]. However, bioactive peptides can be released from food proteins with the help of several techniques including proteolysis, microbial fermentation, and gastrointestinal (GI) digestion [2–4]. Among these methods, in vitro enzymatic hydrolysis using commercial proteolytic enzymes is the widely employed method in recent times. The proteases cleave the specific sites on the dietary proteins and release the short chains of BPs [5]. Enzymatic hydrolysis of dietary proteins enhances the nutritional value, bioactivity, and functionality and reduces the allergenicity [6]. Several commercial proteases, namely, thermolysin, bromelain, trypsin, alcalase, papain, pepsin, neutrase, pancreatin, corolase, protamex, and pronase, have been employed to generate biologically active peptides from various dietary proteins. Among the above-mentioned proteases, alcalase, trypsin, pepsin, and pancreatin are the most widely used proteases for the preparation of peptides, with various health benefitting properties, from numerous food sources [7–10]. These enzymes are routinely used due to their broad specificity to produce smaller peptides with various bioactivities and easily availability.

Dietary BPs have been shown to positively affect the various systems of the human body including the immune, cardiovascular, GI, and nervous systems [11]. The BPs must cross the GI barrier and reach the target tissue or organ in order to exhibit health benefits. Dietary peptides exert bioactivities through the modulation (either enhance or decrease) of various molecular mechanisms and pathways. Bioactive properties of dietary peptides are affected by the peptide sequence, length, hydrophobicity, and composition [12–14]. Dietary peptides are easily absorbable across the intestinal border via peptide transport 1 (PepT1) and possess excellent functional properties (solubility, foaming, and emulsification properties) [15–18]. Additionally, dietary BPs are generally safer than synthetic drugs. Hence, BPs obtained from dietary sources could be used as health foods/nutraceuticals in the management/prevention of various diseases. Numerous BPs derived from whey, casein, milk, soybean, shark, bonita, pacific whiting, porcine, and bovine have been on the market in various countries for human use as functional foods/health foods/nutraceuticals [19].

Redox homeostasis (balance) is an important cellular process that plays a vital role in the maintenance of a normal physiological steady state [20]. Disturbance of balance between oxidants and antioxidants results in the oxidative stress. Recently, many BPs prepared from various food sources such as walnut, egg, fish, quinoa, soybean, millets, corn, wheat, rice, potato, milk, and spirulina have shown to possess beneficial effects in the maintenance of redox homeostasis and prevention/management of metabolic diseases [21–26]. However, reviews describing the role of dietary BPs in the modulation of molecular mechanisms of redox balance and metabolic diseases are scanty in the literature. Hence, the current review focuses on the recent literature related to the effects of dietary BPs on various molecular mechanisms and signaling pathways involved in the redox homeostasis and metabolic diseases (obesity, diabetes, hypertension, and inflammation), as shown in Figure 1.

Figure 1

Effects of dietary bioactive peptides on molecular mechanisms involved in redox balance and metabolic disorders. ACE: angiotensin-converting enzyme; Akt: protein kinase B; AMPK: AMP-activated protein kinase; ARE: antioxidant response element; C/EBP: CCAAT-enhancer-binding proteins; IRS-1: insulin receptor substrate; PPAR: peroxisome proliferator-activated receptor; Keap1: Kelch-like ECH-associated protein 1; MAPK: mitogen-activated protein kinase; NF-κB: nuclear factor-κB; Nrf2: nuclear factor erythroid 2-related factor 2; PI3K: phosphatidylinositol 3-kinase; SREBP1: sterol regulatory element-binding protein 1.

2. Roles of Dietary Bioactive Peptides in Maintaining Redox Balance

Redox reaction is a chemical reaction that involves the transfer of electrons from the reducing agent to the oxidizing agent [27]. Redox homeostasis (balance) plays a significant role in the maintenance of ordinary physiological functions of the human body. Redox balance is considerably affected by reactive oxygen species (ROS) that are generated during aerobic cellular metabolism [28]. Reactive oxygen species are unstable and highly reactive in the redox reactions due to the presence of unpaired electrons in the outer shells. Under normal physiological conditions, redox balance is maintained through careful regulation of ROS generation and elimination from the body [29]. However, excess production of ROS during oxidative stress conditions could alter the intracellular redox balance and promote the development of numerous diseases such as cancer, diabetes, atherosclerosis, cardiovascular, and neurodegenerative diseases. The body’s natural antioxidant defense system, namely, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT), plays a vital role in the maintenance of balance between ROS formation and elimination [30].

Several studies have demonstrated that a number of peptides identified from various dietary sources have shown the ability to suppress oxidative stress and maintain the redox balance through multiple molecular mechanisms such as scavenging free radicals; chelating transition metals; enhancing the production of endogenous antioxidant enzymes SOD, CAT, and GPx; and stimulating the nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant defense mechanism [12, 15, 17, 26, 31–34]. The antioxidant mechanisms showed by the dietary peptides mainly depend on the peptide sequence, length, composition, and hydrophobicity [12, 34, 35]. The food-derived antioxidant peptides usually contain 3–15 AA residues [12, 32]. Table 1 shows the AA sequences and molecular mechanisms of antioxidant peptides produced from various dietary proteins.

The Kelch-like ECH-associated protein 1- (Keap1-) Nrf2-antioxidant response element (ARE) is the main antioxidant signaling pathway that prevents oxidative stress and helps maintain the optimum redox steady state in the body [36]. The Nrf2 is a vital leucine zipper transcription factor, which controls the expression of several antioxidant proteins in response to ROS stress. Keap1 is a suppressor protein for Nrf2, and under a normal ROS steady state, Keap1 binds with Nrf2 and helps proteasome to degrade the Keap1-Nrf2 complex. However, Nrf2 separates from Keap1 during oxidative stress and migrates to the nucleus where it attaches to ARE and thereby promotes the expression of several antioxidant enzymes/proteins [32, 37, 38]. Endogenous antioxidant enzymes such as SOD, GPx, and CAT scavenge different kinds of ROS and thereby protect the cells from oxidative stress-induced damage. SOD catalyses the transformation of superoxide anion to O₂ and H₂O₂. CAT converts H₂O₂ to H₂O and O₂. GPx helps in the reduction of H₂O₂ to H₂O and O₂ [39]. Hence, it is important to stimulate the Nrf2 antioxidant signaling pathway to suppress/prevent the oxidative stress in the body.

Recently, numerous novel antioxidant peptides that stimulate the Keap1-Nrf2-ARE antioxidant signaling pathway and antioxidant enzymes have been isolated from different dietary sources such as casein [40], milk protein concentrate [41], corn gluten [31], soybean [42], walnut [43], potato, Moringa oleifera seeds [25], watermelon seeds [39], Crassostrea rivularis [44], krill [38], turtle [45], Mytilus coruscus [46], Channa argus [3], and silver carp muscle [12]. Snakehead (Channa argus) soup was hydrolyzed using pepsin and pancreatin and identified four antioxidant peptides, IVLPDEGK, PGMLGGSPPGLLGGSPP, SDGSNIHFPN, and SVSIRADGGEGEVTVFT [3]. The authors performed molecular docking studies for the peptides and indicated that peptides could bind to the active site of Keap1 and thereby activate the cellular antioxidant Keap1-Nrf2 signaling pathway. A peptide RDPEER isolated from alcalase hydrolysate of watermelon seed reduced the oxidative stress by reducing ROS and increasing the antioxidant enzymes, SOD, CAT, and GSH-Px, in HepG2 cells [39]. Four casein-derived peptides, ARHPHPHLSFM, AVPYPQR, NPYVPR, and KVLPVPEK, were shown to decrease the oxidative stress in Caco-2 cells by enhancing antioxidant enzymes, namely, SOD1, Trx1, GR, TrxR1, and NQO1, through the activation of the Keap1-Nrf2 signaling mechanism. It was found that the peptides bound to the Nrf2 and prevented the binding between Keap1 and Nrf2 and thereby stimulated the increased expression of antioxidant enzymes [32]. In a study, a peptide, AMVDAIAR, isolated from pepsin hydrolysate of krill enhanced antioxidant enzymes SOD, CAT, and GPx and thereby suppressed the oxidative stress in H₂O₂-induced hepatocytes through increasing the expression of Nrf2 [38]. Peptide EDYGA derived from soft-shelled turtle enhanced the Nrf2 level through the binding of the glutamate residue of the peptide to Arg 415 of the Kelch receptor pocket [45]. Dipeptide IF identified from potato exhibited antioxidant effects by increasing the antioxidant enzymes GPx 4, SOD1, HO-1, SOD2, and peroxiredoxin 2 in the kidney tissues of the spontaneously hypertensive rats (SHRs) [33]. The authors concluded that the dipeptide showed antioxidative activity through preventing Nrf2 degradation by protein kinase B (Akt) activation and GSK-3β phosphorylation.

3. Role of Dietary Bioactive Peptides in Obesity

Obesity is a public health issue worldwide and characterized by excessive body fat accumulation due to the difference between energy intake and energy spending, which enhances the risk of metabolic disorders, namely, type 2 diabetes mellitus (T2DM), hypertension, and cardiovascular disorders [47, 48]. It is estimated that globally, 18% men and 21% women will suffer from obesity by 2025 [49]. Adipocytes are fat cells and the main function of adipocytes is the storage of energy as fat. Preadipocytes differentiate into mature adipocytes through a process known as adipogenesis. Hypertrophy and hyperplasia of adipocytes are two mechanisms that contribute to the obesity and obesity-related metabolic disorders [50, 51].

Several recent studies demonstrated that various dietary peptides from soybean, quinoa, common bean, camel whey, spirulina, blue mussel, skate, tuna, Alaska pollock, sardinella, hazelnut, and kefir exhibited antiobesity effects through modulation of multiple molecular mechanisms including the reduction of adipogenesis through downregulation of the expression of peroxisome proliferator-activated receptor- (PPAR-) γ, CCAAT/enhancer binding protein alpha (C/EBP-α), sterol regulatory element binding protein- (SREBP-) 1, and HMGCR, enhancing lipolysis, reducing body weight (BW) and food intake, inhibiting lipase activity, decreasing the accumulation of triglycerides, and blocking lipogenesis by reducing the fatty acid synthase [2, 10, 52, 53]. Various molecular mechanisms of antiobesity peptides are shown in Table 2.

During maturation of preadipocytes into adipocytes, several transcriptional factors are involved. PPAR and C/EBP are two transcription factors that stimulate adipocyte differentiation [50]. Lipid and carbohydrate metabolism is regulated by the PPARs. SREBP1 is a lipogenic transcription factor upon activation by PPAR-γ which promotes the adipogenesis and lipogenesis. SREBP1 stimulates lipoprotein lipase and fatty acid synthase and thereby enhances the lipid accumulation in the adipocytes [50]. Therefore, inhibition of the PPARs, C/EBP, and SREBP1 transcriptional factors involved the adipogenesis and lipogenesis using dietary-derived BPs is an efficient approach in the prevention or treatment of obesity and related diseases. It has been revealed that numerous dietary peptides from soy bean, quinoa, hazelnut, canola, tuna, ark shell, and blue mussel showed antiobesity activities by inhibiting the expression of PPAR-γ, C/EBP, and SREBP1 transcriptional factors [10, 51, 54].

It was found that the antiobesity effects of dietary BPs are related to the peptide sequence, length, composition, and protein source [13]. Peptides with < 1 kDa from blue mussel by pepsin hydrolysis exhibited antiobesity effects by enhancing lipolysis and downregulating adipogenic transcription factors, such as PPAR-γ, C/EBP-α, and SREBP1 [10]. An antiobesity pentapeptide RLLPH was isolated from alcalase hydrolysate of hazelnut (Corylus heterophylla Fisch) and found that the pentapeptide could decrease adipogenesis through reducing the expression of PPAR-γ, C/EBP-α, SREBP-1c, adipocyte protein (aP2), FAS, acetyl-CoA carboxylase 1 (ACC1), and HMGCR in 3T3-L1 adipocytes [13]. Additionally, the authors indicated that the hydrophobic AAs, proline, and leucine, of the peptide, might have contributed to the antiobesity effects of the peptides. Peptides with more hydrophobic AAs can easily penetrate the cell membrane and increase lipid solubility. In a study, from ark shell (Scapharca subcrenata) protein inhibited intracellular lipid buildup and enhanced the lipolysis [51]. The authors were also demonstrated that ark shell peptides inhibited adipogenesis by decreasing the expressions of PPAR-γ, C/EBP-α, SREBP-1c, lipoprotein lipase, and FAS in mouse mesenchymal stem cells. Moreover, the expression of PPAR-γ, C/EBP-α, and aP2 was decreased by tuna skin collagen-derived peptides in obese mice, which resulted in the decrease of adipocyte size [55].

In addition to the downregulation of vital transcriptional factors (PPAR-γ, C/EBP-α, and SREBP-1c) of adipogenesis, several in vivo studies demonstrated that the antiobesity activity of dietary peptides is due to the decrease of BW and food consumption. Oral administration of peptides (10 mg/mL), produced from smooth hound (Mustelus mustelus) muscle by alkaline crude enzyme from M. mustelus intestines, for 21 days reduced the BW and food intake in rats [5]. The authors suggested that BW reduction was probably due to the regulation of appetite. The antiobesity effect of Alaska pollack-derived peptides was investigated, and it was found that peptide administration (100 or 300 mg/kg BW) to rats for 3 days decreased the weight of white adipose tissue and reduced the food intake [56]. The authors suggested that the decrease in food intake and white adipose tissue weight of rats after peptide treatment was due to downregulation/suppression of gene expressions of neuropeptide-Y and agouti-related peptide in hypothalamus, which may reduce the appetite. In a study, it was found that antiobesity effects of sardinella- (Sardinella aurita-) derived peptides were mediated by reducing the BW gain, food intake, and the relative epididymal adipose tissue weight in Wistar rats after 10 weeks of peptide treatment [2]. It was demonstrated that Spirulina platensis-derived peptides exhibited antiobesity effects by reducing BW (39.8%) and lowering serum glucose (23.8%) through altering the gene expressions of Acadm, Retn, Fabp4, Ppard, and Slc27a1 in the brain and liver of mice fed with peptides (2 g/kg BW) for 4 weeks [57]. Recently, it was reported that walleye pollock skin collagen-derived peptides considerably reduced the BW gain in obese mice after 8 weeks of peptide treatment [58]. The authors also pointed that peptides inhibited the growth of adipocytes and the accumulation of adipose tissue in obese mice. Furthermore, in a placebo-controlled, randomized clinical investigation, salmon fish-derived peptide supplementation (16 g/d) for 42 days notably decreased (5.6%) the BMI in obese humans [59].

Pancreatic lipase is an important enzyme that aids in the hydrolysis of dietary fat in the small intestine. Therefore, inhibition of pancreatic lipase is an efficient approach in the management and treatment of being overweight and obesity [2, 24]. Apart from inhibition of adipogenesis and lipogenesis, some dietary peptides exhibited pancreatic lipase inhibitory activity. Peptides produced from camel milk by using alcalase-, bromelin-, and papain-inhibited porcine pancreatic lipase [24]. It was also found that sardinella peptide administration to rats for 10 weeks decreased the pancreatic lipase activity [2].

4. The Role of Dietary Bioactive Peptides in Diabetes Mellitus

Diabetes mellitus (DM) is a complex metabolic disorder with increased blood sugar levels and T2DM accounts for 90% of diabetes patients. T2DM results from insulin resistance (cells less responsive to the insulin actions) and/or insufficient insulin production from pancreatic beta cells. Obesity () has been reported to greatly increase the risk of developing T2DM [60]. Uncontrolled T2DM can cause severe complications such as high blood pressure, stroke, heart attack, atherosclerosis, retinopathy, nephropathy, neuropathy, and dementia.

Recently, several peptides derived from a variety of dietary protein sources including egg white, whey, casein, egg yolk, rice bran, quinoa, soybean, wheat, corn, black bean, oat globulin, walnut, potato, common bean, millets, spirulina, bovine, porcine, Atlantic cod, Atlantic salmon, halibut skin, Styela clava, boarfish, tilapia skin, largemouth bass, zebra blenny, blue whiting, and sea cucumber have shown antidiabetic effects by altering several molecular mechanisms of diabetes such as inhibition of enzymes including α-amylase, dipeptidyl peptidase- (DPP-) IV, and α-glucosidase; reduction of FBG and HbA1C; enhancement of HOMA-IR; stimulation of secretion of glucagon-like polypeptide-1 (GLP-1) and insulin levels; upregulation of phosphatidylinositol 3-kinase (PI3K), p-GSK-3β, p-Akt, and glucose transporter (GLUT)2/4 signaling pathways; blocking of glucose transporters GLUT2 and SGLT1; decreasing of the activation of p38 and c-Jun N-terminal kinase (JNK)1/2; enhancement of the stimulation of insulin receptor substrate-1 (IRS-1) tyrosine residue and Akt; and decreasing of gluconeogenesis through activation of IRS-1/PI3K/Akt and AMP-activated protein kinase (AMPK) [6, 21, 61–64]. The isolated peptide sequences and molecular mechanisms of dietary antidiabetic peptides are shown in Table 3.

α-Amylase is an important enzyme in the carbohydrate digestion that breaks down α-1,4 glycosidic linkages of starch and produces oligosaccharides. α-Glucosidase is present in the brush borders of the small intestine and hydrolyzes the disaccharides and starch to glucose by acting upon α(1 → 4) glycosidic bonds. Therefore, inhibition of α-amylase and α-glucosidase prevents carbohydrate digestion and thus diminishes the postprandial increase of blood glucose. Several chemical α-glucosidase and α-amylase inhibitors (acarbose, voglibose, and miglitol) have been in use for the management and treatment of T2DM [65]. However, side effects associated with these inhibitors limited their use [63]. Recently, many peptides isolated from several food sources including egg white, corn, oat, egg yolk, spirulina, quinoa, soybean, Phaseolus vulgaris, and zebra blenny have exhibited α-amylase and α-glucosidase inhibitory activities [61, 62, 66, 67]. Egg white albumin was hydrolyzed using alcalase, and a pentapeptide KLPGF was isolated with α-glucosidase (50% inhibitory concentration (IC₅₀) 59.5 μmol/L) and α-amylase (IC₅₀ 120 μM) inhibitory activities [66]. Three peptides, GVPMPNK, LRSELAAWSR, and RNPFVFAPTLLTVAAR, were extracted from spirulina platensis, and it was found that peptide LRSELAAWSR strongly inhibited α-amylase with IC₅₀ of 313.6 μg/mL and α-glucosidase with IC₅₀ of 134.2 μg/mL [68]. A α-glucosidase inhibitory peptide, LAPSLPGKPKPD, was identified from egg yolk hydrolysate produced by proteinase from Asian pumpkin with an IC₅₀ value of 1065.6 μmol/L [67]. Three peptides, LLPLPVL, SWLRL, and WLRL, produced from soy protein showed α-glucosidase inhibitory activity with IC₅₀ 162.2–237.4 μmol/L [63]. A study reported isolation of α-glucosidase inhibitory peptide, QHPHGLGALCAAPPST, from quinoa with an IC₅₀ of 1.0–1.45 mg/mL [62]. Recently, corn germ protein was hydrolyzed by using alcalase, trypsin, and flavourzyme and it was found that the peptide fraction (2–10 kDa) showed strong α-amylase inhibition (71.3%) and α-glucosidase inhibition (37.1%) activities [61].

Another strategy for the management and treatment of T2DM is to inhibit the DPP-IV that degrades and inactivates incretin hormones, namely, glucose-dependent insulinotropic peptide (GIP) and GLP-1. Therefore, inhibition of DPP-IV by dietary-derived BPs can enhance the half-life of GLP-1 and thereby increase the release of glucose-dependent insulin from pancreatic cells [61]. For inhibition of DPP-IV activity, several synthetic drugs such as saxagliptin, linagliptin, sitagliptin, and vildagliptin are presently used. However, side effects (diarrhea, nausea, stomach pain, headache, and sore throat) associated with these drugs have forced researches to search for DPP-IV inhibitors from natural dietary sources without any side effects [69]. Many recent studies have reported that dietary protein-derived peptides are an excellent source of DPP-IV inhibitors. Peptides obtained from millet, corn, quinoa, egg yolk, oat, whey, casein, Spirulina platensis, porcine, Atlantic salmon, sea cucumber, largemouth bass, blue whiting, and Capros aper inhibited the DPP-IV activity [67, 70–72]. It has been found that dietary peptides inhibit DPP-IV through attaching the peptides to the active sites of DPP-IV via hydrogen bonds and hydrophobic interactions and thereby prevent the enzyme action [14, 21]. Two peptides NDWHTGPLS and TYPHQQPPILT derived from papain hydrolysates of millet proteins inhibited DPP-IV activity (75%) [21]. It was demonstrated that both the peptides inhibited DPP-IV activity by occupying the active sites of DPP-IV via hydrogen and pi bonds. In a recent study, Atlantic salmon skin was hydrolyzed by using trypsin and isolated a new DPP-IV inhibitory peptide, LDKVFR, with IC₅₀ of 128.7 μM [14]. Additionally, it was found that 6 H bonds and 8 hydrophobic interactions played a significant role in the inhibition of DPP-IV by LDKVFR. A peptide, LDQWLCEKL, obtained from trypsin hydrolysate of α-lactalbumin-rich whey proteins inhibited DPP-IV (IC₅₀ 131 μM) through a noncompetitive mode of inhibition.

The PI3K/Akt signaling pathway regulates the glucose uptake. When cells are resistant to insulin, glucose uptake is impaired in the liver and skeletal muscles. Insulin activates IRS after binding to IRS and the activated IRS phosphorylates IRS-1. Phosphorylation of IRS-1 results in the activation of PI3K. The activated PI3K phosphorylates Akt, and the activated Akt helps in the migration of intracellular GLUT2/4 to the plasma membrane and therefore increases the glucose absorption into cells. But insulin resistance weakens the PI3K/Akt signaling pathway [73, 74]. Hence, stimulation of the PI3K/Akt molecular pathway is an efficient approach in the management of insulin resistance. In a study, the authors hydrolyzed walnut protein using alcalase and isolated an antidiabetic peptide LPLLR with a molecular weight of 610.4 Da. The authors reported that the identified peptide improved hepatic insulin resistance (IR) through enhancing glycogen synthesis and glucose uptake and reducing gluconeogenesis via activating the IRS-1/PI3K/Akt and AMPK signaling pathways in hepatic HepG2 cells [75]. Two hundred forty-two peptides, with a molecular weight ranging from 203 to 1907 Da, were isolated from the hydrolysate of sea cucumber and found that the peptides showed antidiabetic effects by upregulation of PI3K, p-Akt, p-GSK-3β, and GLUT2/4 signaling pathways, while decreasing p-IRS1 expression in diabetic rats [73].

In addition to the peptides described above, the antidiabetic activities of dietary peptides have also been investigated in human subjects. In a randomized and crossover clinical trial, whey peptide (<5000 Da) (1400 or 2800 mg/kg BW) administration to 21 prediabetic human subjects decreased under the curve (iAUC) of glucose as well as showed a minor insulinotropic effect and reduced HbA1c [76]. A double-blind crossover clinical trial conducted using peptides (<2000 Da) derived from Atlantic cod showed that a single dose of 20 mg/kg BW considerably decreased the postprandial insulin in 41 healthy individuals [77]. Moreover, peptides derived from Styela clava have also been shown to decrease the hemoglobin A1c and plasma insulin levels after 4 weeks of administration in patients with T2DM [78].

5. The Role of Dietary Bioactive Peptides in Hypertension

Hypertension is an important risk factor that can increase the chance of developing heart attack or stroke. Clinically, systolic blood pressure (SBP) 140 mmHg or above and/or DBP 90 mmHg or above are considered as hypertension [79]. It is estimated that over a billion people (1 in 5 women and 1 in 4 men) are suffering from hypertension.

Food-derived peptides play a significant role in the prevention of hypertension. Recently, numerous antihypertensive peptides are isolated from different food sources such as milk [80], casein [81, 82], egg white ovotransferrin [22], rice bran [1], wheat [83], soybean [84], potato [85], turmeric and ginger [9], quinoa [62], black cumin [86], coix [87], pistachio [88], hazelnut [89], mung bean [90], lentil [91], seahorse [92], egg white from ostrich [93], chum salmon [94], skate [95], cuttlefish [96], Sipuncula [97], bighead carp [98], shrimp (Pandalus borealis) [79], and beef [99]. The isolated dietary protein-derived peptides have been demonstrated to exhibit antihypertensive activities through influencing various molecular mechanisms including inhibition of angiotensin-converting enzyme (ACE), reduction of SBP, decrease of angiotensin II levels and AT1R expression, enhancing vasodilation, improving central blood pressure and arterial stiffness, and inhibition of vasoconstriction via PPAR-γ expression [9, 79, 84, 90]. Table 4 shows the molecular mechanisms of antihypertensive peptides isolated from various dietary sources.

Human blood pressure is regulated by ACE (EC 3.4.15.1). ACE cleaves the dipeptide, HL, from angiotensin I and converts the inactive angiotensin I into angiotensin II and thereby enhances the blood pressure. Angiotensin II is a powerful vasoconstrictor, and ACE inactivates the bradykinin, which is a potent vasodilator. Therefore, inhibition of ACE is an important molecular target in the prevention and management of hypertension. Currently, several peptide drugs, namely, captopril, lisinopril, and enalapril, are used as ACE inhibitors for the management of high blood pressure [80, 97, 100]. Due to the side effects (cough, fatigue, dizziness, headaches, and loss of taste) associated with these synthetic drugs, there is an increasing interest to search for safe ACE inhibitors from natural food sources. Various food sources are an excellent source of ACE inhibitory peptides. Most dietary ACE inhibitory peptides contained 3–15 AA residues. Recently, several peptides have been isolated with ACE inhibitory activity from numerous dietary sources such as milk [80], casein [82], egg white [93], soybean [84], rice bran [1], wheat [83], pistachio [88], potato and rapeseed [85], turmeric and ginger [9], quinoa [62], black cumin [86], hazelnut [89], lentil [91], seahorse [92], chum salmon [94], skate [95], cuttlefish [96], Sipuncula [97], bighead carp [98], and beef [99].

It has been demonstrated that hydrogen bonds play a vital role in the binding of BPs to the ACE catalytic pocket and thereby facilitate ACE inhibition. Three ACE inhibitory peptides, LLSGTQNQPSFLSGF, NSLTLPILRYL, and TLEPNSVFLPVLLH, were isolated from lentil seeds with IC₅₀ of 44–120 μM, and it was found that the peptides inhibited ACE through interactions by hydrogen bonds with three residues of the ACE catalytic site [91]. A tripeptide YSK with ACE inhibition was identified from trypsin hydrolysate of rice bran, and ACE inhibition of YSK was due to the formation of hydrogen bonds with the binding site of ACE [1]. The molecular interactions between dipeptide, YV, obtained from ostrich egg white and ACE were studied and it demonstrated that YV inhibited ACE (IC₅₀ 63.97 μg/mL) by binding to S1 and S2 pocket sites of ACE through hydrogen bonds [93]. A pentapeptide, ACKEP, purified from pistachio kernel hydrolysates was shown to inhibit ACE (IC₅₀ 126 μM) by binding with seven AAs of the ACE catalytic site (His383, His387, Glu384, Arg522, Asp358, Ala356, and Asn70) and two atoms of ACKEP [88]. In a study, three ACE inhibitory peptides, AVKVL, YLVR, and TLVGR, were identified from alcalase hydrolysate of hazelnut. The authors found that all the three peptides exhibited ACE inhibition (IC₅₀ 5.42–249.3 μM) via a noncompetitive inhibition through the formation of cation–pi interactions [89]. In another study, four ACE inhibitory peptides, EDEVSFSP, SRPFNL, RSPFNL, and ENPFNL, were purified from fermented soybean with IC₅₀ of 0.131–0.811 mg/mL [84]. It was suggested that the N-terminal sequence and the location of AAs in the peptides play an essential role in ACE inhibition. Recently, a peptide, VTPVGVPK, produced by α-chymotrypsin hydrolysis from black cumin seed was shown to inhibit ACE (IC₅₀ 1.8 μM) through a noncompetitive inhibition [86]. A peptide, QHPHGLGALCAAPPST, identified from chymotrypsin hydrolysate of quinoa inhibited ACE by binding to the number of active hotspots of the ACE enzyme [62]. Moreover, two peptides, SAGGYIW and APATPSFW, were isolated from wheat gluten with ACE inhibition of IC₅₀ 0.002–0.036 mg/mL [83]. The authors concluded that two peptides with proline and negatively charged residues inhibited ACE through the modulation of ionic and hydrophobic connections of the ACE active site.

In addition to ACE inhibition, several in vivo studies (animal and human) have reported the blood pressure-lowering effects of numerous peptides isolated from various food sources. Peptides, SLVSPSAAAAAAPGGS and KKRSKKKSFG, generated from potato and rapeseed were found to reduce (154.7 mmHg) the mean arterial blood pressure of treated rats compared to the control (177 mmHg) group [85]. Two antihypertensive peptides, IQW and LKP, were identified from thermolysin and pepsin hydrolysates prepared from egg white ovotransferrin and demonstrated that tripeptide (IQW and LKP) administration reduced the mean blood pressure by 19 and 30 mmHg, respectively, compared to control SHRs [22]. Administration of a peptide, VELYP, produced from Sepia officinalis muscle, to SHR exhibited antihypertensive effects by decreasing SBP [96]. In a study, a beef myofibrillar protein-derived peptide LIVGIIRCV at 400 and 800 mg/kg BW decreased SBP by 28 and 35 mmHg in SHRs, respectively [99]. A randomized and double-blind human trial conducted on level 1 hypertensive patients demonstrated that eight-week supplementation of casein-derived tripeptides, VPP and IPP, ameliorated central blood pressure and arterial stiffness [81]. In a recent randomized, double-blind clinical trial, the administration of shrimp-derived peptides (1200 mg/d) for eight weeks reduced the BP in mild- or moderate-hypertension patients [79]. Additionally, the authors suggested that the reduction of BP was probably due to the decrease of angiotensin II levels in hypertension patients.

6. The Role of Dietary Bioactive Peptides in Inflammatory Bowel Diseases (IBD)

Inflammation is a complex and natural response of the body in an attempt to resolve harmful stimuli such as pathogens, tissue injuries, infections, or toxins. However, uncontrolled and chronic inflammation has been reported to be linked with several diseases such as T2DM, metabolic syndrome, IBD, cardiovascular disease, cancer, asthma, arthritis, and chronic obstructive lung disease [101]. IBD symptoms such as diarrhea, abdominal pain, fever, vomiting, BW loss, and rectal bleeding affect the quality of life of patients [102]. Crohn’s disease (DC) and ulcerative colitis (UC) are two major forms of IBD [103]. UC is the inflammation of colon. Chronic inflammation in the intestine produces excessive and uncontrolled proinflammatory cytokines including tumor necrosis factor-alpha (TNF-α), interleukin- (IL-) 1β, IL-6, IL-8, IL-12, interferon-gamma (IFN-γ), and IL-17 [102, 103].

The mechanism of anti-inflammation by food protein-derived BPs is that they can inhibit the phosphorylation of signaling pathways including nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK), Janus kinase-signal transducer and activator of transcription (JAK-STAT), and peptide transporter PepT1 as shown in Figure 2 [26, 104, 105]. The NF-κB pathway contains IKKs, IκBs, and p65/p50, while the MAPK pathway contains p38, JNK, and extracellular signal-regulated kinases (ERK). BPs can inhibit the NF-κB receptor, resulting in the inhibition of the activation of inhibitory κB kinases (IKKα/β/γ), which can lead to phosphorylation of cytoplasmic transcription factor (IκBα/β/γ) and IκBα degradation. BPs can inhibit the MAPK receptor and inhibit MAP3K phosphorylation, which can mediate the phosphorylation of the downstream MAP2K and MAPK. The inhibition of phosphorylation of MAPK and JAK2-STATs by BPs can alleviate the release of cytokines. The BP inhibition of translocations of the above transcription factors in nucleus (ATF-2, AP-1, and c-Jun) can cause the gene change, reducing the productions of proinflammatory cytokines, such as IL-1β, IL-6, IL-8, TNF-α, and IFN-γ, resulting in the inflammation suppression (Figure 2). In addition, the PepT1 can transport small BPs to the bloodstream; therefore, the role of PepT1 is vital to the bioactivity of BPs and needs further investigation [15, 26].

Peptides isolated from a variety of dietary protein sources (e.g., soy bean, common bean, corn, egg white, whey, casein, salmon, and crucian carp) have shown to inhibit intestinal inflammation through multiple molecular mechanisms. These include downregulation of the expression of IL-8, IL-1β, IL-6, TNF-α, IFN-γ, IL-12, and IL-17; upregulation of IL-10; and inhibition of activation of the NF-κB and MAPK pathways via suppression of phosphorylation of p65, ERK1/2, p38, JNK1/2, and Syk signaling molecules [102, 103, 106, 107]. The isolated peptides and their molecular mechanisms of anti-intestinal inflammatory effects are presented in Table 5.

Dietary anti-intestinal inflammatory peptides are short chains of AAs that generally contain 2–10 AAs. The common AAs of these peptides are alanine, valine, leucine, serine, methionine, tyrosine, and phenylalanine [102, 103, 108]. Pepsin and pancreatin are the two most commonly employed proteolytic enzymes to produce anti-inflammatory peptides from various food proteins [103, 109, 110]. The TNF-α-treated Caco-2 cell is a widely used human intestinal cell model for the investigation of the anti-inflammatory property of dietary peptides. TNF-α activates the both NF-κB and MAPK signaling pathways in Caco-2 cells and thereby produces large quantities of proinflammatory mediators [110]. Excess and uncontrolled production of proinflammatory cytokines plays a vital role in the progression of intestinal inflammation [103].

Numerous recent studies reported that dietary BPs could inhibit the intestinal inflammation through the reduction of proinflammatory mediators. Four peptides, DEDTQAMPFR, MLGATSL, SLSFASR, and MSYSAGF, isolated from egg white exerted anti-inflammatory activities in colitis mouse by inhibiting the production of TNF-α and IL-6 as well as reducing the mRNA-expressions TNF-α, IL-6, IL-17, IL-1β, IFN-γ, and MCP-1 [111]. Tripeptide VPY from soybean inhibited IL-8 secretion in Caco-2 cells [108]. The peptide was also found to decrease the mRNA expressions of inflammatory mediators TNF-α, IL-6, IL-1β, IFN-γ, and IL-17 in the peptide-treated mice colon. Dipeptides (CR, FL, HC, lLL, and MK) produced from egg white ovotransferrin, by using pepsin and trypsin hydrolysis, decreased the gene expression of TNF-α, IL-8, IL-6, IL-1β, and IL-12, while enhancing IL-10 expression, in Caco-2 cells [103]. Crucian carp-derived 178 peptides (<1500 Da) at 50, 100, and 150 μg/mL considerably reduced the secretion of TNF-α, IL-6, and IL-1β in IEC-6 small intestine cells as well as in dextran sodium sulfate-induced ulcerative colitis mice [106].

Several recent reports demonstrated the role of NF-κB in the pathogenesis of IBD [106]. Activation of NF-κB has been shown to be involved in the IBD patients [112]. The NF-κB and MAPK pathways are two vital proinflammatory signaling pathways that majorly regulate cellular inflammatory responses by secreting various cytokines after activation by various inflammatory stimuli [113]. Transcription factor NF-κB regulates the inflammatory responses by stimulating the production of various proinflammatory cytokines and chemokines. Phosphorylation of IκB by inflammatory stimuli (LPS and TNF-α) releases the NF-κB that migrates to the nucleus and activates expression of the numerous genes connected with inflammation [110, 112]. The MAPK family contains three components such as p38 MAPK, ERK1/2, and JNK/SAPK. Phosphorylation of MAPK components stimulates the other kinases and migrates to the nucleus where they induce the transcription of several inflammatory genes and thereby enhance the secretion of proinflammatory mediators [110].

Peptides derived from egg, milk, fish, and beans exhibited the anti-intestinal inflammatory activity through the inhibition of MAPK and NF-κB molecular pathways [102, 103, 110]. A tetrapeptide, IPAV, isolated from whey proteins exhibited anti-inflammatory activity in Caco-2 cells by inhibiting IL-8 expression and by suppression of phosphorylation of p65, ERK1/2, p38, JNK1/2, and Syk signaling molecules [102]. Bean milk- and yogurt-derived LLV, γ-E-S-(Me)C, and γ-EL inhibited TNF-α-induced IL-8 production and gene expression of inflammatory mediators, TNF-α, IL-1β, IL-8, and IL-6, through the inhibition of phosphorylation of IκB-α of NF-κB and JNK of MAPK signaling pathways in Caco-2 cells [113]. Four peptides DEDTQAMPFR, DEDTQAMPF, MLGATSL, and MSYSAGF isolated from egg considerably suppressed the phosphorylation of JNK, p38, and IκB of NF-κB and MAPK signaling pathways and thereby reduced the gene expression of IL-8, IL-1β, IL-6, TNF-α, and IL-12 in TNF-α-stimulated Caco-2 cells [110]. These results indicated that dietary BPs had the potential to treat inflammation or IBD via NF-κB or MAPK or other signaling pathways.

7. Conclusions and Further Perspectives

Numerous dietary peptides showed beneficial effects on redox balance and metabolic disorders (obesity, T2D, hypertension, and inflammation). Dietary peptides modulated several molecular mechanisms (e.g., Keap1-Nrf2-ARE signaling pathway in oxidative stress, PPAR-γ, C/EBP-α, SREBP1 pathway in obesity, IRS-1/PI3K/Akt and AMPK signaling pathways in T2D, ACE inhibition in hypertension, and MAPK in IBD) and thereby exerted positive effects in redox balance and metabolic disorders. Most of the studies are conducted using cell and animal models. Although substantial evidence from cell and animal investigations is available for the BPs as described in this review, scientific evidence from clinical studies is still meager. Hence, more clinical investigations are needed to get in-depth knowledge about the BP’s efficacy, absorption, distribution, metabolism, excretion, toxicity, and effect on gut microbiome in the human body in the future. In the future, the benefits and risks of long-term and large-quantity consumption of BPs on human health need to be addressed. The interaction of BPs with other drugs in the human body has to be investigated comprehensively. Additionally, newer technologies are needed to produce BPs cost effectively from dietary sources. The BPs should be produced with consumer-acceptable taste, quality, and stability. Although there are several challenges for future growth, the dietary BPs could be used as health foods in the management/prevention of metabolic disorders (obesity, T2DM, hypertension, and inflammation) and oxidative stress-related diseases (e.g., cancer and IBD). We hope that the BP’s industry will have a bright future in the coming years as people are increasingly aware of health benefits of dietary BPs.

Data Availability

No data were used to support this review article.

Conflicts of Interest

The authors declare no conflict of interest.

Authors’ Contributions

Qinqin Qiao, Liang Chen, Xiang Li, Xiangyang Lu, and Qingbiao Xu wrote the manuscript. Xiang Li, Xiangyang Lu, and Qingbiao Xu revised the manuscript. All authors reviewed and approved the final manuscript. Qinqin Qiao, Liang Chen, and Xiang Li contributed equally to this work.

Acknowledgments

This work was supported by grants from the Open Project Program of Key Laboratory of Feed Biotechnology, the Fundamental Research Funds for the Central Universities (2662019QD021), the State Key Laboratory of Animal Nutrition (2004DA125184F1906), the National Natural Science Foundation of China (C31802087), and the Key Laboratory of Molecular Animal Nutrition of Zhejiang University.

References

X. Wang, H. Chen, X. Fu, S. Li, and J. Wei, “A novel antioxidant and ACE inhibitory peptide from rice bran protein: biochemical characterization and molecular docking study,” LWT, vol. 75, pp. 93–99, 2017.
View at: Publisher Site | Google Scholar
I. Jemil, O. Abdelhedi, R. Nasri et al., “Hypolipidemic, antiobesity and cardioprotective effects of sardinelle meat flour and its hydrolysates in high-fat and fructose diet fed Wistar rats,” Life Sciences, vol. 176, pp. 54–66, 2017.
View at: Publisher Site | Google Scholar
J. Zhang, M. Li, G. Zhang et al., “Identification of novel antioxidant peptides from snakehead (Channa argus) soup generated during gastrointestinal digestion and insights into the anti- oxidation mechanisms,” Food Chemistry, vol. 337, p. 127921, 2021.
View at: Publisher Site | Google Scholar
Y. Zhang, S. Chen, X. Zong et al., “Peptides derived from fermented soybean meal suppresses intestinal inflammation and enhances epithelial barrier function in piglets,” Food and Agricultural Immunology, vol. 31, no. 1, pp. 120–135, 2020.
View at: Publisher Site | Google Scholar
A. Bougatef, R. Ravallec, N. Nedjar-Arroume, A. Barkia, D. Guillochon, and M. Nasri, “Evidence of in vivo satietogen effect and control of food intake of smooth hound (Mustelus mustelus) muscle protein hydrolysate in rats,” Journal of Functional Foods, vol. 2, no. 1, pp. 10–16, 2010.
View at: Publisher Site | Google Scholar
S. Marthandam Asokan, T. Wang, W.-T. Su, and W.-T. Lin, “Antidiabetic effects of a short peptide of potato protein hydrolysate in STZ-induced diabetic mice,” Nutrients, vol. 11, no. 4, p. 779, 2019.
View at: Publisher Site | Google Scholar
P.-X. Gong, B.-K. Wang, Y.-C. Wu, Q.-Y. Li, B.-W. Qin, and H.-J. Li, “Release of antidiabetic peptides from Stichopus japonicas by simulated gastrointestinal digestion,” Food Chemistry, vol. 315, article 126273, 2020.
View at: Publisher Site | Google Scholar
X. Fan, Y. Cui, R. Zhang, and X. Zhang, “Purification and identification of anti-obesity peptides derived from Spirulina platensis,” Journal of Functional Foods, vol. 47, pp. 350–360, 2018.
View at: Publisher Site | Google Scholar
K. Sompinit, S. Lersiripong, O. Reamtong, W. Pattarayingsakul, N. Patikarnmonthon, and W. Panbangred, “In vitro study on novel bioactive peptides with antioxidant and antihypertensive properties from edible rhizomes,” LWT, vol. 134, article 110227, 2020.
View at: Publisher Site | Google Scholar
Y. Oh, C.-B. Ahn, and J.-Y. Je, “Low molecular weight blue mussel hydrolysates inhibit adipogenesis in mouse mesenchymal stem cells through upregulating HO-1/Nrf2 pathway,” Food Research International, vol. 136, article 109603, 2020.
View at: Publisher Site | Google Scholar
M. Hajfathalian, S. Ghelichi, P. J. García-Moreno, A.-D. Moltke Sørensen, and C. Jacobsen, “Peptides: production, bioactivity, functionality, and applications,” Critical Reviews in Food Science and Nutrition, vol. 58, no. 18, pp. 3097–3129, 2018.
View at: Publisher Site | Google Scholar
K. Wang, L. Han, H. Hong, J. Pan, H. Liu, and Y. Luo, “Purification and identification of novel antioxidant peptides from silver carp muscle hydrolysate after simulated gastrointestinal digestion and transepithelial transport,” Food Chemistry, vol. 342, article 128275, 2021.
View at: Publisher Site | Google Scholar
J. Wang, M. Zhou, T. Wu, L. Fang, C. Liu, and W. Min, “Novel anti-obesity peptide (RLLPH) derived from hazelnut (Corylus heterophylla Fisch) protein hydrolysates inhibits adipogenesis in 3T3-L1 adipocytes by regulating adipogenic transcription factors and adenosine monophosphate-activated protein kinase (AMPK) activation,” Journal of Bioscience and Bioengineering, vol. 129, no. 3, pp. 259–268, 2020.
View at: Publisher Site | Google Scholar
R. Jin, X. Teng, J. Shang, D. Wang, and N. Liu, “Identification of novel DPP-IV inhibitory peptides from Atlantic salmon (Salmo salar) skin,” Food Research International, vol. 133, article 109161, 2020.
View at: Publisher Site | Google Scholar
Q. Xu, H. Hong, J. Wu, and X. Yan, “Bioavailability of bioactive peptides derived from food proteins across the intestinal epithelial membrane: a review,” Trends in Food Science and Technology, vol. 86, pp. 399–411, 2019.
View at: Publisher Site | Google Scholar
Q. Xu, H. Fan, W. Yu, H. Hong, and J. Wu, “Transport study of egg-derived antihypertensive peptides (LKP and IQW) using Caco-2 and HT29 coculture monolayers,” Journal of Agricultural and Food Chemistry, vol. 65, no. 34, pp. 7406–7414, 2017.
View at: Publisher Site | Google Scholar
Q. Xu, X. Yan, Y. Zhang, and J. Wu, “Current understanding of transport and bioavailability of bioactive peptides derived from dairy proteins: a review,” International Journal of Food Science and Technology, vol. 54, no. 6, pp. 1930–1941, 2019.
View at: Publisher Site | Google Scholar
Q. Lin, Q. Xu, J. Bai, W. Wu, H. Hong, and J. Wu, “Transport of soybean protein-derived antihypertensive peptide LSW across Caco-2 monolayers,” Journal of Functional Foods, vol. 39, pp. 96–102, 2017.
View at: Publisher Site | Google Scholar
M. Chalamaiah, S. Keskin Ulug, H. Hong, and J. Wu, “Regulatory requirements of bioactive peptides (protein hydrolysates) from food proteins,” Journal of Functional Foods, vol. 58, pp. 123–129, 2019.
View at: Publisher Site | Google Scholar
F. Ursini, M. Maiorino, and H. J. Forman, “Redox homeostasis: the Golden mean of healthy living,” Redox Biology, vol. 8, pp. 205–215, 2016.
View at: Publisher Site | Google Scholar
H. Gu, J. Gao, Q. Shen et al., “Dipeptidyl peptidase-IV inhibitory activity of millet protein peptides and the related mechanisms revealed by molecular docking,” LWT, vol. 138, article 110587, 2021.
View at: Publisher Site | Google Scholar
K. Majumder, S. Chakrabarti, J. S. Morton et al., “Egg-derived ACE-inhibitory peptides IQW and LKP reduce blood pressure in spontaneously hypertensive rats,” Journal of Functional Foods, vol. 13, pp. 50–60, 2015.
View at: Publisher Site | Google Scholar
M. Son and J. Wu, “Egg white hydrolysate and peptide reverse insulin resistance associated with tumor necrosis factor-α (TNF-α) stimulated mitogen-activated protein kinase (MAPK) pathway in skeletal muscle cells,” European Journal of Nutrition, vol. 58, no. 5, pp. 1961–1969, 2019.
View at: Publisher Site | Google Scholar
P. Mudgil, H. Kamal, G. C. Yuen, and S. Maqsood, “Characterization and identification of novel antidiabetic and anti-obesity peptides from camel milk protein hydrolysates,” Food Chemistry, vol. 259, pp. 46–54, 2018.
View at: Publisher Site | Google Scholar
L. Liang, S. Cai, M. Gao et al., “Purification of antioxidant peptides of Moringa oleifera seeds and their protective effects on H₂O₂ oxidative damaged Chang liver cells,” Journal of Functional Foods, vol. 64, article 103698, 2020.
View at: Publisher Site | Google Scholar
W. Zhu, L. Ren, L. Zhang, Q. Qiao, M. Z. Farooq, and Q. Xu, “The potential of food protein-derived bioactive peptides against chronic intestinal inflammation,” Mediators of Inflammation, vol. 2020, Article ID 6817156, 15 pages, 2020.
View at: Publisher Site | Google Scholar
E. H. Sarsour, M. G. Kumar, L. Chaudhuri, A. L. Kalen, and P. C. Goswami, “Redox control of the cell cycle in health and disease,” Antioxidants & Redox Signaling, vol. 11, no. 12, pp. 2985–3011, 2009.
View at: Publisher Site | Google Scholar
A. Ayer, C. W. Gourlay, and I. W. Dawes, “Cellular redox homeostasis, reactive oxygen species and replicative ageing in Saccharomyces cerevisiae,” FEMS Yeast Research, vol. 14, no. 1, pp. 60–72, 2014.
View at: Publisher Site | Google Scholar
R. Basria, S. M. N. Mydin, and S. I. Okekpa, “Reactive Oxygen Species, Cellular Redox Homeostasis and Cancer,” in Homeostasis - An Integrated Vision, IntechOpen, 2019.
View at: Google Scholar
B. Marengo, M. Nitti, A. L. Furfaro et al., “Redox homeostasis and cellular antioxidant systems: crucial players in cancer growth and therapy,” Oxidative Medicine and Cellular Longevity, vol. 2016, Article ID 6235641, 16 pages, 2016.
View at: Publisher Site | Google Scholar
X. Jiang, Z. Cui, L. Wang, H. Xu, and Y. Zhang, “Production of bioactive peptides from corn gluten meal by solid-state fermentation with Bacillus subtilis MTCC5480 and evaluation of its antioxidant capacity in vivo,” LWT, vol. 131, p. 109767, 2020.
View at: Publisher Site | Google Scholar
F. Tonolo, A. Folda, L. Cesaro et al., “Milk-derived bioactive peptides exhibit antioxidant activity through the Keap1-Nrf2 signaling pathway,” Journal of Functional Foods, vol. 64, article 103696, 2020.
View at: Publisher Site | Google Scholar
B. C.-K. Tsai, D. J.-Y. Hsieh, W.-T. Lin et al., “Functional potato bioactive peptide intensifies Nrf2-dependent antioxidant defense against renal damage in hypertensive rats,” Food Research International, vol. 129, article 108862, 2020.
View at: Publisher Site | Google Scholar
X. Lu, L. Zhang, Q. Sun, G. Song, and J. Huang, “Extraction, identification and structure-activity relationship of antioxidant peptides from sesame (Sesamum indicum L.) protein hydrolysate,” Food Research International, vol. 116, pp. 707–716, 2019.
View at: Publisher Site | Google Scholar
M. Chalamaiah, B. Dinesh kumar, R. Hemalatha, and T. Jyothirmayi, “Fish protein hydrolysates: proximate composition, amino acid composition, antioxidant activities and applications: a review,” Food Chemistry, vol. 135, no. 4, pp. 3020–3038, 2012.
View at: Publisher Site | Google Scholar
W. Rungratanawanich, M. Memo, and D. Uberti, “Redox homeostasis and natural dietary compounds: focusing on antioxidants of rice (Oryza sativa L.),” Nutrients, vol. 10, no. 11, p. 1605, 2018.
View at: Publisher Site | Google Scholar
L. Zheng, H. Yu, H. Wei et al., “Antioxidative peptides of hydrolysate prepared from fish skin gelatin using ginger protease activate antioxidant response element-mediated gene transcription in IPEC-J2 cells,” Journal of Functional Foods, vol. 51, pp. 104–112, 2018.
View at: Publisher Site | Google Scholar
I. P. S. Fernando, S. Y. Park, E. J. Han et al., “Isolation of an antioxidant peptide from krill protein hydrolysates as a novel agent with potential hepatoprotective effects,” Journal of Functional Foods, vol. 67, article 103889, 2020.
View at: Publisher Site | Google Scholar
C. Wen, J. Zhang, Y. Feng, Y. Duan, H. Ma, and H. Zhang, “Purification and identification of novel antioxidant peptides from watermelon seed protein hydrolysates and their cytoprotective effects on H₂O₂-induced oxidative stress,” Food Chemistry, vol. 327, article 127059, 2020.
View at: Publisher Site | Google Scholar
K. Sowmya, M. I. Bhat, R. Bajaj, S. Kapila, and R. Kapila, “Antioxidative and anti-inflammatory potential with trans-epithelial transport of a buffalo casein-derived hexapeptide (YFYPQL),” Food Bioscience, vol. 28, pp. 151–163, 2019.
View at: Publisher Site | Google Scholar
S. Awad, M. I. El-Sayed, A. Wahba, A. El Attar, M. I. Yousef, and M. Zedan, “Antioxidant activity of milk protein hydrolysate in alloxan-induced diabetic rats,” Journal of Dairy Science, vol. 99, no. 11, pp. 8499–8510, 2016.
View at: Publisher Site | Google Scholar
Q. Zhang, X. Tong, X. Sui et al., “Antioxidant activity and protective effects of alcalase-hydrolyzed soybean hydrolysate in human intestinal epithelial Caco-2 cells,” Food Research International, vol. 111, pp. 256–264, 2018.
View at: Publisher Site | Google Scholar
D. Ren, C. Liu, W. Liu et al., “Antifatigue, antioxidant and immunoregulatory effects of peptides hydrolyzed from Manchurian walnut (Juglans mandshurica Maxim.) on mice,” Grain & Oil Science and Technology, vol. 1, no. 1, pp. 44–52, 2018.
View at: Publisher Site | Google Scholar
Z. Zhang, G. Su, F. Zhou, L. Lin, X. Liu, and M. Zhao, “Alcalase-hydrolyzed oyster (Crassostrea rivularis) meat enhances antioxidant and aphrodisiac activities in normal male mice,” Food Research International, vol. 120, pp. 178–187, 2019.
View at: Publisher Site | Google Scholar
N. Wang, W. Wang, F. A. Sadiq, S. Wang, L. Caiqin, and J. Jianchang, “Involvement of Nrf2 and Keap1 in the activation of antioxidant responsive element (ARE) by chemopreventive agent peptides from soft-shelled turtle,” Process Biochemistry, vol. 92, pp. 174–181, 2020.
View at: Publisher Site | Google Scholar
Z. Zhang, S. Jiang, Y. Zeng, K. He, Y. Luo, and F. Yu, “Antioxidant peptides from Mytilus Coruscus on H₂O₂-induced human umbilical vein endothelial cell stress,” Food Bioscience, vol. 38, p. 100762, 2020.
View at: Publisher Site | Google Scholar
M. Blüher, “Obesity: global epidemiology and pathogenesis,” Nature Reviews Endocrinology, vol. 15, no. 5, pp. 288–298, 2019.
View at: Publisher Site | Google Scholar
R. Ruiz, R. Olías, A. Clemente, and L. A. Rubio, “A pea (Pisum sativum L.) seed vicilins hydrolysate exhibits PPARγ ligand activity and modulates adipocyte differentiation in a 3T3-L1 cell culture model,” Foods, vol. 9, no. 6, p. 793, 2020.
View at: Publisher Site | Google Scholar
I. Kyrou, H. S. Randeva, C. Tsigos, G. Kaltsas, and M. O. Weickert, Clinical problems caused by obesity, Endotext, 2000.
M. Desai, M. Beall, and M. G. Ross, “Developmental origins of obesity: programmed adipogenesis,” Current Diabetes Reports, vol. 13, no. 1, pp. 27–33, 2013.
View at: Publisher Site | Google Scholar
J.-H. Hyung, C.-B. Ahn, and J.-Y. Je, “Ark shell protein hydrolysates inhibit adipogenesis in mouse mesenchymal stem cells through the down-regulation of transcriptional factors,” RSC Advances, vol. 7, no. 11, pp. 6223–6228, 2017.
View at: Publisher Site | Google Scholar
M.-J. Tsou, F.-J. Kao, H.-C. Lu, H.-C. Kao, and W.-D. Chiang, “Purification and identification of lipolysis-stimulating peptides derived from enzymatic hydrolysis of soy protein,” Food Chemistry, vol. 138, no. 2–3, pp. 1454–1460, 2013.
View at: Publisher Site | Google Scholar
M. E. Oseguera Toledo, E. Gonzalez de Mejia, M. Sivaguru, and S. L. Amaya-Llano, “Common bean (Phaseolus vulgaris L.) protein-derived peptides increased insulin secretion, inhibited lipid accumulation, increased glucose uptake and reduced the phosphatase and tensin homologue activation in vitro,” Journal of Functional Foods, vol. 27, pp. 160–177, 2016.
View at: Publisher Site | Google Scholar
A. M. Alashi, C. L. Blanchard, R. J. Mailer et al., “Effects of canola proteins and hydrolysates on adipogenic differentiation of C3H10T/2 mesenchymal stem cells,” Food Chemistry, vol. 185, pp. 226–232, 2015.
View at: Publisher Site | Google Scholar
E. J. Lee, J. Hur, S. A. Ham et al., “Fish collagen peptide inhibits the adipogenic differentiation of preadipocytes and ameliorates obesity in high fat diet-fed mice,” International Journal of Biological Macromolecules, vol. 104, Part A, pp. 281–286, 2017.
View at: Publisher Site | Google Scholar
T. Mizushige, M. Komiya, M. Onda, K. Uchida, K. Hayamizu, and Y. Kabuyama, “Fish protein hydrolysate exhibits anti-obesity activity and reduces hypothalamic neuropeptide Y and agouti-related protein mRNA expressions in rats,” Biomedical Research, vol. 38, no. 6, pp. 351–357, 2017.
View at: Publisher Site | Google Scholar
B. Zhao, Y. Cui, X. Fan et al., “Anti-obesity effects of Spirulina platensis protein hydrolysate by modulating brain-liver axis in high-fat diet fed mice,” PLoS One, vol. 14, no. 6, article e0218543, 2019.
View at: Publisher Site | Google Scholar
S. Wang, Z. Lv, W. Zhao, L. Wang, and N. He, “Collagen peptide from walleye pollock skin attenuated obesity and modulated gut microbiota in high-fat diet-fed mice,” Journal of Functional Foods, vol. 74, article 104194, 2020.
View at: Publisher Site | Google Scholar
B. Framroze, S. Vekariya, and D. Swaroop, “A placebo-controlled, randomized study on the impact of dietary salmon protein hydrolysate supplementation on body mass index in overweight human subjects,” Journal of Obesity and Weight Loss Therapy, vol. 6, no. 1, p. 296, 2016.
View at: Publisher Site | Google Scholar
T. M. Schnurr, H. Jakupović, G. D. Carrasquilla et al., “Obesity, unfavourable lifestyle and genetic risk of type 2 diabetes: a case-cohort study,” Diabetologia, vol. 63, no. 7, pp. 1324–1332, 2020.
View at: Publisher Site | Google Scholar
A. Karimi, M. H. Azizi, and H. Ahmadi Gavlighi, “Fractionation of hydrolysate from corn germ protein by ultrafiltration: in vitro antidiabetic and antioxidant activity,” Food Science & Nutrition, vol. 8, no. 5, pp. 2395–2405, 2020.
View at: Publisher Site | Google Scholar
P. Mudgil, B. P. Kilari, H. Kamal et al., “Multifunctional bioactive peptides derived from quinoa protein hydrolysates: inhibition of α-glucosidase, dipeptidyl peptidase-IV and angiotensin I converting enzymes,” Journal of Cereal Science, vol. 96, article 103130, 2020.
View at: Publisher Site | Google Scholar
R. Wang, H. Zhao, X. Pan, C. Orfila, W. Lu, and Y. Ma, “Preparation of bioactive peptides with antidiabetic, antihypertensive, and antioxidant activities and identification of α-glucosidase inhibitory peptides from soy protein,” Food Science & Nutrition, vol. 7, no. 5, pp. 1848–1856, 2019.
View at: Publisher Site | Google Scholar
N. Ktari, R. Ben Slama-Ben Salem, I. Bkhairia et al., “Functional properties and biological activities of peptides from zebra blenny protein hydrolysates fractionated using ultrafiltration,” Food Bioscience, vol. 34, article 100539, 2020.
View at: Publisher Site | Google Scholar
K. Aoki, H. Sato, and Y. Terauchi, “Usefulness of antidiabetic alpha-glucosidase inhibitors: a review on the timing of administration and effects on gut hormones,” Endocrine Journal, vol. 66, no. 5, pp. 395–401, 2019.
View at: Publisher Site | Google Scholar
Z. Yu, Y. Yin, W. Zhao, J. Liu, and F. Chen, “Anti-diabetic activity peptides from albumin against α-glucosidase and α-amylase,” Food Chemistry, vol. 135, no. 3, pp. 2078–2085, 2012.
View at: Publisher Site | Google Scholar
A. Zambrowicz, E. Eckert, M. Pokora et al., “Antioxidant and antidiabetic activities of peptides isolated from a hydrolysate of an egg-yolk protein by-product prepared with a proteinase from Asian pumpkin (Cucurbita ficifolia),” RSC Advances, vol. 5, no. 14, pp. 10460–10467, 2015.
View at: Publisher Site | Google Scholar
S. Hu, X. Fan, P. Qi, and X. Zhang, “Identification of anti-diabetes peptides from Spirulina platensis,” Journal of Functional Foods, vol. 56, pp. 333–341, 2019.
View at: Publisher Site | Google Scholar
P. A. Harnedy-Rothwell, C. M. McLaughlin, M. B. O'Keeffe et al., “Identification and characterisation of peptides from a boarfish (Capros aper) protein hydrolysate displaying in vitro dipeptidyl peptidase-IV (DPP-IV) inhibitory and insulinotropic activity,” Food Research International, vol. 131, article 108989, 2020.
View at: Publisher Site | Google Scholar
A. B. Nongonierma and R. J. FitzGerald, “Inhibition of dipeptidyl peptidase IV (DPP-IV) by proline containing casein- derived peptides,” Journal of Functional Foods, vol. 5, no. 4, pp. 1909–1917, 2013.
View at: Publisher Site | Google Scholar
P. A. Harnedy, V. Parthsarathy, C. M. McLaughlin et al., “Blue whiting (Micromesistius poutassou) muscle protein hydrolysate with in vitro and in vivo antidiabetic properties,” Journal of Functional Foods, vol. 40, pp. 137–145, 2018.
View at: Publisher Site | Google Scholar
V. Parthsarathy, C. M. McLaughlin, P. A. Harnedy et al., “Boarfish (Capros aper) protein hydrolysate has potent insulinotropic and GLP-1 secretory activityin vitroand acute glucose lowering effects in mice,” International Journal of Food Science and Technology, vol. 54, no. 1, pp. 271–281, 2019.
View at: Publisher Site | Google Scholar
T. Wang, L. Zheng, T. Zhao et al., “Anti-diabetic effects of sea cucumber (Holothuria nobilis) hydrolysates in streptozotocin and high-fat-diet induced diabetic rats via activating the PI3K/Akt pathway,” Journal of Functional Foods, vol. 75, article 104224, 2020.
View at: Publisher Site | Google Scholar
Q. Yuan, B. Zhan, M. Du, R. Chang, T. Li, and X. Mao, “Dietary milk fat globule membrane regulates JNK and PI3K/Akt pathway and ameliorates type 2 diabetes in mice induced by a high-fat diet and streptozotocin,” Journal of Functional Foods, vol. 60, article 103435, 2019.
View at: Publisher Site | Google Scholar
J. Wang, T. Wu, L. Fang et al., “Anti-diabetic effect by walnut (Juglans mandshurica Maxim.)-derived peptide LPLLR through inhibiting α-glucosidase and α-amylase, and alleviating insulin resistance of hepatic HepG2 cells,” Journal of Functional Foods, vol. 69, article 103944, 2020.
View at: Publisher Site | Google Scholar
T. Sartorius, A. Weidner, T. Dharsono, A. Boulier, M. Wilhelm, and C. Schön, “Postprandial Effects of a Proprietary Milk Protein Hydrolysate Containing Bioactive Peptides in Prediabetic Subjects,” Nutrients, vol. 11, no. 7, p. 1700, 2019.
View at: Google Scholar
H. F. Dale, C. Jensen, T. Hausken et al., “Effect of a cod protein hydrolysate on postprandial glucose metabolism in healthy subjects: a double-blind cross-over trial,” Journal of Nutritional Science, vol. 7, article e33, 2018.
View at: Publisher Site | Google Scholar
S.-C. Ko, W.-K. Jung, S.-H. Lee, D. H. Lee, and Y.-J. Jeon, “Antihypertensive effect of an enzymatic hydrolysate fromStyela clavaflesh tissue in type 2 diabetic patients with hypertension,” Nutrition Research and Practice, vol. 11, no. 5, pp. 396–401, 2017.
View at: Publisher Site | Google Scholar
K. Musa-Veloso, L. Paulionis, T. Pelipyagina, and M. Evans, “A randomized, double-blind, placebo-controlled, multicentre trial of the effects of a shrimp protein hydrolysate on blood pressure,” International Journal of Hypertension, vol. 2019, Article ID 2345042, 13 pages, 2019.
View at: Publisher Site | Google Scholar
N. Wu, W. Xu, K. Liu, Y. Xia, and Shuangquan, “Angiotensin-converting enzyme inhibitory peptides from Lactobacillus delbrueckii QS306 fermented milk,” Journal of Dairy Science, vol. 102, no. 7, pp. 5913–5921, 2019.
View at: Publisher Site | Google Scholar
T. Nakamura, J. Mizutani, K. Ohki et al., “Casein hydrolysate containing Val-Pro-Pro and Ile-Pro-Pro improves central blood pressure and arterial stiffness in hypertensive subjects: a randomized, double-blind, placebo-controlled trial,” Atherosclerosis, vol. 219, no. 1, pp. 298–303, 2011.
View at: Publisher Site | Google Scholar
L. Xue, X. Wang, Z. Hu et al., “Identification and characterization of an angiotensin-converting enzyme inhibitory peptide derived from bovine casein,” Peptides, vol. 99, pp. 161–168, 2018.
View at: Publisher Site | Google Scholar
P. Zhang, C. Chang, H. Liu, B. Li, Q. Yan, and Z. Jiang, “Identification of novel angiotensin I-converting enzyme (ACE) inhibitory peptides from wheat gluten hydrolysate by the protease of Pseudomonas aeruginosa,” Journal of Functional Foods, vol. 65, article 103751, 2020.
View at: Publisher Site | Google Scholar
E. B.-M. Daliri, B. H. Lee, M. H. Park, J.-H. Kim, and D.-H. Oh, “Novel angiotensin I-converting enzyme inhibitory peptides from soybean protein isolates fermented by Pediococcus pentosaceus SDL1409,” LWT, vol. 93, pp. 88–93, 2018.
View at: Publisher Site | Google Scholar
S. Mäkinen, T. Streng, L. B. Larsen, A. Laine, and A. Pihlanto, “Angiotensin I-converting enzyme inhibitory and antihypertensive properties of potato and rapeseed protein-derived peptides,” Journal of Functional Foods, vol. 25, pp. 160–173, 2016.
View at: Publisher Site | Google Scholar
C. C. Y. Sutopo, A. Sutrisno, L.-F. Wang, and J.-L. Hsu, “Identification of a potent angiotensin-I converting enzyme inhibitory peptide from black cumin seed hydrolysate using orthogonal bioassay-guided fractionations coupled with in silico screening,” Process Biochemistry, vol. 95, pp. 204–213, 2020.
View at: Publisher Site | Google Scholar
P. Chen, L. Li, X. Huo et al., “New angiotensin-converting enzyme inhibitory peptide from Coix prolamin and its influence on the gene expression of renin-angiotensin system in vein endothelial cells,” Journal of Cereal Science, vol. 96, article 103099, 2020.
View at: Publisher Site | Google Scholar
P. Li, J. Jia, M. Fang et al., “In vitro and in vivo ACE inhibitory of pistachio hydrolysates and in silico mechanism of identified peptide binding with ACE,” Process Biochemistry, vol. 49, no. 5, pp. 898–904, 2014.
View at: Publisher Site | Google Scholar
C. Liu, L. Fang, W. Min, J. Liu, and H. Li, “Exploration of the molecular interactions between angiotensin-I-converting enzyme (ACE) and the inhibitory peptides derived from hazelnut (Corylus heterophylla Fisch.),” Food Chemistry, vol. 245, pp. 471–480, 2018.
View at: Publisher Site | Google Scholar
C. Sonklin, M. A. Alashi, N. Laohakunjit, O. Kerdchoechuen, and R. E. Aluko, “Identification of antihypertensive peptides from mung bean protein hydrolysate and their effects in spontaneously hypertensive rats,” Journal of Functional Foods, vol. 64, article 103635, 2020.
View at: Publisher Site | Google Scholar
P. García-Mora, M. Martín-Martínez, M. Angeles Bonache et al., “Identification, functional gastrointestinal stability and molecular docking studies of lentil peptides with dual antioxidant and angiotensin I converting enzyme inhibitory activities,” Food Chemistry, vol. 221, pp. 464–472, 2017.
View at: Publisher Site | Google Scholar
J.-G. Je, H. S. Kim, H. G. Lee et al., “Low-molecular weight peptides isolated from seahorse (Hippocampus abdominalis) improve vasodilation via inhibition of angiotensin-converting enzyme in vivo and in vitro,” Process Biochemistry, vol. 95, pp. 30–35, 2020.
View at: Publisher Site | Google Scholar
S. Khueychai, N. Jangpromma, K. Choowongkomon et al., “A novel ACE inhibitory peptide derived from alkaline hydrolysis of ostrich (Struthio camelus) egg white ovalbumin,” Process Biochemistry, vol. 73, pp. 235–245, 2018.
View at: Publisher Site | Google Scholar
J. K. Lee, J. K. Jeon, and H. G. Byun, “Antihypertensive effect of novel angiotensin I converting enzyme inhibitory peptide from chum salmon (Oncorhynchus keta) skin in spontaneously hypertensive rats,” Journal of Functional Foods, vol. 7, pp. 381–389, 2014.
View at: Publisher Site | Google Scholar
D.-H. Ngo, K. H. Kang, B. M. Ryu et al., “Angiotensin-I converting enzyme inhibitory peptides from antihypertensive skate (Okamejei kenojei) skin gelatin hydrolysate in spontaneously hypertensive rats,” Food Chemistry, vol. 174, pp. 37–43, 2015.
View at: Publisher Site | Google Scholar
R. Balti, A. Bougatef, A. Sila, D. Guillochon, P. Dhulster, and N. Nedjar-Arroume, “Nine novel angiotensin I-converting enzyme (ACE) inhibitory peptides from cuttlefish (Sepia officinalis) muscle protein hydrolysates and antihypertensive effect of the potent active peptide in spontaneously hypertensive rats,” Food Chemistry, vol. 170, pp. 519–525, 2015.
View at: Publisher Site | Google Scholar
M. Guo, X. Chen, Y. Wu et al., “Angiotensin I-converting enzyme inhibitory peptides from Sipuncula (Phascolosoma esculenta): Purification, identification, molecular docking and antihypertensive effects on spontaneously hypertensive rats,” Process Biochemistry, vol. 63, pp. 84–95, 2017.
View at: Publisher Site | Google Scholar
C. Zhang, Y. Zhang, Z. Wang, S. Chen, and Y. Luo, “Production and identification of antioxidant and angiotensin-converting enzyme inhibition and dipeptidyl peptidase IV inhibitory peptides from bighead carp (Hypophthalmichthys nobilis) muscle hydrolysate,” Journal of Functional Foods, vol. 35, pp. 224–235, 2017.
View at: Publisher Site | Google Scholar
S. Y. Lee and S. J. Hur, “Purification of novel angiotensin converting enzyme inhibitory peptides from beef myofibrillar proteins and analysis of their effect in spontaneously hypertensive rat model,” Biomedicine & Pharmacotherapy, vol. 116, p. 109046, 2019.
View at: Publisher Site | Google Scholar
I. Jemil, L. Mora, R. Nasri et al., “A peptidomic approach for the identification of antioxidant and ACE-inhibitory peptides in sardinelle protein hydrolysates fermented by Bacillus subtilis A26 and Bacillus amyloliquefaciens An6,” Food Research International, vol. 89, Part 1, pp. 347–358, 2016.
View at: Publisher Site | Google Scholar
D. Furman, J. Campisi, E. Verdin et al., “Chronic inflammation in the etiology of disease across the life span,” Nature Medicine, vol. 25, no. 12, pp. 1822–1832, 2019.
View at: Publisher Site | Google Scholar
M. Oyama, T. van Hung, K. Yoda, F. He, and T. Suzuki, “A novel whey tetrapeptide IPAV reduces interleukin-8 production induced by TNF-α in human intestinal Caco-2 cells,” Journal of Functional Foods, vol. 35, pp. 376–383, 2017.
View at: Publisher Site | Google Scholar
X. Wang, Y. Zhao, Y. Yao et al., “Anti-inflammatory activity of di-peptides derived from ovotransferrin by simulated peptide-cut in TNF-α-induced Caco-2 cells,” Journal of Functional Foods, vol. 37, pp. 424–432, 2017.
View at: Publisher Site | Google Scholar
S. Chakrabarti, F. Jahandideh, and J. Wu, “Food-derived bioactive peptides on inflammation and oxidative stress,” BioMed Research International, vol. 2014, Article ID 608979, 11 pages, 2014.
View at: Publisher Site | Google Scholar
S. Li, L. Liu, G. He, and J. Wu, “Molecular targets and mechanisms of bioactive peptides against metabolic syndromes,” Food & Function, vol. 9, no. 1, pp. 42–52, 2018.
View at: Publisher Site | Google Scholar
C. Dai, L. Dai, F. J. Yu et al., “Chemical and biological characteristics of hydrolysate of crucian carp swim bladder: focus on preventing ulcerative colitis,” Journal of Functional Foods, vol. 75, article 104256, 2020.
View at: Publisher Site | Google Scholar
A. Mukhopadhya, N. Noronha, B. Bahar et al., “Anti-inflammatory effects of a casein hydrolysate and its peptide-enriched fractions on TNFα-challenged Caco-2 cells and LPS-challenged porcine colonic explants,” Food Science & Nutrition, vol. 2, no. 6, pp. 712–723, 2014.
View at: Publisher Site | Google Scholar
J. Kovacs-Nolan, H. Zhang, M. Ibuki et al., “The PepT1-transportable soy tripeptide VPY reduces intestinal inflammation,” Biochimica et Biophysica Acta (BBA) - General Subjects, vol. 1820, no. 11, pp. 1753–1763, 2012.
View at: Publisher Site | Google Scholar
Q. Liang, X. Ren, M. Chalamaiah, and H. Ma, “Simulated gastrointestinal digests of corn protein hydrolysate alleviate inflammation in caco-2 cells and a mouse model of colitis,” Journal of Food Science and Technology, vol. 57, no. 6, pp. 2079–2088, 2020.
View at: Publisher Site | Google Scholar
M. Zhang, Y. Zhao, Y. Yao et al., “Isolation and identification of peptides from simulated gastrointestinal digestion of preserved egg white and their anti-inflammatory activity in TNF- α-induced Caco-2 cells,” The Journal of Nutritional Biochemistry, vol. 63, pp. 44–53, 2019.
View at: Publisher Site | Google Scholar
M. Zhang, Y. Zhao, N. Wu et al., “The anti-inflammatory activity of peptides from simulated gastrointestinal digestion of preserved egg white in DSS-induced mouse colitis,” Food & Function, vol. 9, no. 12, pp. 6444–6454, 2018.
View at: Publisher Site | Google Scholar
T. Liu, L. Zhang, D. Joo, and S. C. Sun, “NF-κB signaling in inflammation,” Signal Transduction and Targeted Therapy, vol. 2, no. 1, article 17023, 2017.
View at: Publisher Site | Google Scholar
Y. Chen, H. Zhang, L. Mats et al., “Anti-inflammatory effect and cellular uptake mechanism of peptides from common bean (Phaseolus vulga L.) milk and yogurts in Caco-2 mono- and Caco-2/EA.hy926 co-culture models,” Journal of Agricultural and Food Chemistry, vol. 67, no. 30, pp. 8370–8381, 2019.
View at: Publisher Site | Google Scholar
M. Memarpoor-Yazdi, H. Mahaki, and H. Zare-Zardini, “Antioxidant activity of protein hydrolysates and purified peptides from Zizyphus jujuba fruits,” Journal of Functional Foods, vol. 5, no. 1, pp. 62–70, 2013.
View at: Publisher Site | Google Scholar
L. Wang, L. Ding, Z. Yu, T. Zhang, S. Ma, and J. Liu, “Intracellular ROS scavenging and antioxidant enzyme regulating capacities of corn gluten meal-derived antioxidant peptides in HepG2 cells,” Food Research International, vol. 90, pp. 33–41, 2016.
View at: Publisher Site | Google Scholar
P. A. Harnedy, M. B. O'Keeffe, and R. J. FitzGerald, “Fractionation and identification of antioxidant peptides from an enzymatically hydrolysed Palmaria palmata protein isolate,” Food Research International, vol. 100, Part 1, pp. 416–422, 2017.
View at: Publisher Site | Google Scholar
Z. Karami, S. H. Peighambardoust, J. Hesari, B. Akbari-Adergani, and D. Andreu, “Antioxidant, anticancer and ACE-inhibitory activities of bioactive peptides from wheat germ protein hydrolysates,” Food Bioscience, vol. 32, article 100450, 2019.
View at: Publisher Site | Google Scholar
J. Tkaczewska, B. Borczak, E. Piątkowska, J. Kapusta-Duch, M. Morawska, and T. Czech, “Effect of protein hydrolysates from carp (Cyprinus carpio) skin gelatine on oxidative stress biomarkers and other blood parameters in healthy rats,” Journal of Functional Foods, vol. 60, article 103411, 2019.
View at: Publisher Site | Google Scholar
M. Kumar, T. Ahmad, A. Sharma et al., “Let-7 microRNA-mediated regulation of IL-13 and allergic airway inflammation,” The Journal of Allergy and Clinical Immunology, vol. 128, no. 5, pp. 1077–1085.e10, 2011.
View at: Publisher Site | Google Scholar
K. M. I. Bashir, J. H. Sohn, J. S. Kim, and J. S. Choi, “Identification and characterization of novel antioxidant peptides from mackerel (Scomber japonicus) muscle protein hydrolysates,” Food Chemistry, vol. 323, article 126809, 2020.
View at: Publisher Site | Google Scholar
Z. Ji, J. Mao, S. Chen, and J. Mao, “Antioxidant and anti-inflammatory activity of peptides from foxtail millet (Setaria italica) prolamins in HaCaT cells and RAW264.7 murine macrophages,” Food Bioscience, vol. 36, article 100636, 2020.
View at: Publisher Site | Google Scholar
Z. Wang, X. Liu, H. Xie et al., “Antioxidant activity and functional properties of Alcalase-hydrolyzed scallop protein hydrolysate and its role in the inhibition of cytotoxicity in vitro,” Food Chemistry, vol. 344, p. 128566, 2021.
View at: Publisher Site | Google Scholar
M.-J. Tsou, F. J. Kao, C. K. Tseng, and W. D. Chiang, “Enhancing the anti-adipogenic activity of soy protein by limited hydrolysis with flavourzyme and ultrafiltration,” Food Chemistry, vol. 122, no. 1, pp. 243–248, 2010.
View at: Publisher Site | Google Scholar
M.-R. Kim, J. W. Kim, J. B. Park, Y. K. Hong, S. K. Ku, and J. S. Choi, “Anti-obesity effects of yellow catfish protein hydrolysate on mice fed a 45% kcal high-fat diet,” International Journal of Molecular Medicine, vol. 40, no. 3, pp. 784–800, 2017.
View at: Publisher Site | Google Scholar
S. Jafar, H. Kamal, P. Mudgil, H. M. Hassan, and S. Maqsood, “Camel whey protein hydrolysates displayed enhanced cholesteryl esterase and lipase inhibitory, anti-hypertensive and anti-haemolytic properties,” LWT, vol. 98, pp. 212–218, 2018.
View at: Publisher Site | Google Scholar
M. Woo, Y. Song, K. H. Kang, and J. Noh, “Anti-obesity effects of collagen peptide derived from skate (Raja kenojei) skin through regulation of lipid metabolism,” Marine Drugs, vol. 16, no. 9, p. 306, 2018.
View at: Publisher Site | Google Scholar
Y.-T. Tung, H. L. Chen, H. S. Wu, M. H. Ho, K. Y. Chong, and C. M. Chen, “Kefir peptides prevent hyperlipidemia and obesity in high-fat-diet-induced obese rats via lipid metabolism modulation,” Molecular Nutrition & Food Research, vol. 62, no. 3, article 1700505, 2018.
View at: Publisher Site | Google Scholar
Z. Shi, Y. Hao, C. Teng, Y. Yao, and G. Ren, “Functional properties and adipogenesis inhibitory activity of protein hydrolysates from quinoa (Chenopodium quinoa Willd.),” Food Science & Nutrition, vol. 7, no. 6, pp. 2103–2112, 2019.
View at: Publisher Site | Google Scholar
D. Fangmann, C. Geisler, K. Schlicht et al., “Differential effects of protein intake versus intake of a defined oligopeptide on FGF-21 in obese human subjects in vivo,” Clinical Nutrition, vol. 40, no. 2, pp. 600–607, 2020.
View at: Publisher Site | Google Scholar
T. Hatanaka, Y. Inoue, J. Arima et al., “Production of dipeptidyl peptidase IV inhibitory peptides from defatted rice bran,” Food Chemistry, vol. 134, no. 2, pp. 797–802, 2012.
View at: Publisher Site | Google Scholar
T. Lafarga, P. O’Connor, and M. Hayes, “Identification of novel dipeptidyl peptidase-IV and angiotensin-I-converting enzyme inhibitory peptides from meat proteins using in silico analysis,” Peptides, vol. 59, pp. 53–62, 2014.
View at: Publisher Site | Google Scholar
S.-L. Huang, C.-C. Hung, C.-L. Jao, Y.-S. Tung, and K.-C. Hsu, “Porcine skin gelatin hydrolysate as a dipeptidyl peptidase IV inhibitor improves glycemic control in streptozotocin-induced diabetic rats,” Journal of Functional Foods, vol. 11, pp. 235–242, 2014.
View at: Publisher Site | Google Scholar
L. Mojica, E. Gonzalez de Mejia, M. Á. Granados-Silvestre, and M. Menjivar, “Evaluation of the hypoglycemic potential of a black bean hydrolyzed protein isolate and its pure peptides using in silico, in vitro and in vivo approaches,” Journal of Functional Foods, vol. 31, pp. 274–286, 2017.
View at: Publisher Site | Google Scholar
M. Kato, T. Nakanishi, T. Tani, and T. Tsuda, “Low-molecular fraction of wheat protein hydrolysate stimulates glucagon-like peptide-1 secretion in an enteroendocrine L cell line and improves glucose tolerance in rats,” Nutrition Research, vol. 37, pp. 37–45, 2017.
View at: Publisher Site | Google Scholar
F. Wang, Y. Zhang, T. Yu et al., “Oat globulin peptides regulate antidiabetic drug targets and glucose transporters in Caco-2 cells,” Journal of Functional Foods, vol. 42, pp. 12–20, 2018.
View at: Publisher Site | Google Scholar
E. Valencia-Mejía, K. A. Batista, J. J. A. Fernández, and K. F. Fernandes, “Antihyperglycemic and hypoglycemic activity of naturally occurring peptides and protein hydrolysates from easy-to-cook and hard-to-cook beans (Phaseolus vulgaris L.),” Food Research International, vol. 121, pp. 238–246, 2019.
View at: Publisher Site | Google Scholar
K. Wang, X. Yang, W. Lou, and X. Zhang, “Discovery of dipeptidyl peptidase 4 inhibitory peptides from Largemouth bass (Micropterus salmoides) by a comprehensive approach,” Bioorganic Chemistry, vol. 105, article 104432, 2020.
View at: Publisher Site | Google Scholar
C. Jia, N. Hussain, O. Joy Ujiroghene et al., “Generation and characterization of dipeptidyl peptidase-IV inhibitory peptides from trypsin-hydrolyzed α-lactalbumin-rich whey proteins,” Food Chemistry, vol. 318, article 126333, 2020.
View at: Publisher Site | Google Scholar
C. M. McLaughlin, S. J. Sharkey, P. Harnedy-Rothwell et al., “Twice daily oral administration of Palmaria palmata protein hydrolysate reduces food intake in streptozotocin induced diabetic mice, improving glycaemic control and lipid profiles,” Journal of Functional Foods, vol. 73, article 104101, 2020.
View at: Publisher Site | Google Scholar
H. Li, N. Prairie, C. C. Udenigwe et al., “Blood pressure lowering effect of a pea protein hydrolysate in hypertensive rats and humans,” Journal of Agricultural and Food Chemistry, vol. 59, no. 18, pp. 9854–9860, 2011.
View at: Publisher Site | Google Scholar
D. Young, M. Ibuki, T. Nakamori, M. Fan, and Y. Mine, “Soy-derived Di- and tripeptides alleviate colon and ileum inflammation in pigs with dextran sodium sulfate-induced colitis,” The Journal of Nutrition, vol. 142, no. 2, pp. 363–368, 2012.
View at: Publisher Site | Google Scholar
T. Grimstad, B. Bjørndal, D. Cacabelos et al., “A salmon peptide diet alleviates experimental colitis as compared with fish oil,” Journal of Nutritional Science, vol. 2, p. e2, 2013.
View at: Publisher Site | Google Scholar
Y. Shi, P. Rupa, B. Jiang, and Y. Mine, “Hydrolysate from eggshell membrane ameliorates intestinal inflammation in mice,” International Journal of Molecular Sciences, vol. 15, no. 12, pp. 22728–22742, 2014.
View at: Publisher Site | Google Scholar
S. K. Ramadass, S. L. Jabaris, R. K. Perumal, V. I. HairulIslam, A. Gopinath, and B. Madhan, “Type I collagen and its daughter peptides for targeting mucosal healing in ulcerative colitis: a new treatment strategy,” European Journal of Pharmaceutical Sciences, vol. 91, pp. 216–224, 2016.
View at: Publisher Site | Google Scholar
Y. Zhao, Y. Yao, M. Xu, S. Wang, X. Wang, and Y. Tu, “Simulated gastrointestinal digest from preserved egg white exerts anti- inflammatory effects on Caco-2 cells and a mouse model of DSS-induced colitis,” Journal of Functional Foods, vol. 35, pp. 655–665, 2017.
View at: Publisher Site | Google Scholar

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