Roles of Dietary Bioactive Peptides in Redox Balance and Metabolic Disorders

Table 1

Molecular mechanisms of action of dietary peptides in redox balance.

Dietary protein source	Enzyme used to produce peptides	Peptide sequence or molecular weight	Object	IC50/EC50 values	Activity/mechanisms of action	Reference
Ziziphus jujuba fruits	Papain and trypsin	VGQHTR and GWLK	DPPH, ABTS, and metal chelating assays	—	Peptides scavenged ABTS and DPPH and showed strong metal chelating activity	[114]
Corn gluten	Alcalase	<1 kDa and GLLLPH	H2O2-induced HepG2	—	Peptides reduced ROS and increased SOD, CAT activities, and GSH levels and GR activity	[115]
Milk protein concentrate	Trypsin	—	Healthy and diabetic rats	—	Peptides enhanced the activities of CAT, SOD and reduced glutathione, glutathione-S-transferase, and GPx	[41]
Palmaria palmata macroalgal protein	Corolase PP	SDITRPGGNM	ORAC and FRAP assays	—	Peptide showed strong oxygen radical absorbance capacity and ferric-reducing antioxidant power activity	[116]
Rice bran	Trypsin	YSK	DPPH and reducing power assays	DPPH IC50 0.15 mg/mL	Peptide exhibited high DPPH free radical scavenging activity and reducing power	[1]
Nile tilapia skin gelatin	Ginger protease	GPA	H2O2-induced IPEC-J2 cell	—	GPA activated the expression of antioxidant response element-driven antioxidant enzyme genes HO-1, NAD(P)H quinone oxidoreductase-1, and glutamyl cysteine ligase modulator and suppressed ROS production	[37]
Manchurian walnut (Juglans mandshurica Maxim.)	Alkaline protease	<3 kDa	Mice	—	Peptides increased the antioxidant capacity by enhancing SOD, GSH-Px, and CAT activities and reducing the MDA content	[43]
Soybean	Alcalase	<3 kDa	H2O2-incuded oxidative stress in Caco-2 cell and DPPH assay	DPPH IC50 2.56 mg/mL	Peptides displayed DPPH radical scavenging activity and decreased intracellular ROS and stimulated the antioxidant enzymes CAT, GP, and GR	[42]
Oyster (Crassostrea rivularis) meat	Alcalase	<3 kDa	Normal male mice	—	Peptides showed antioxidant capacity by increasing the activities of GSH-Px, SOD, and CAT and reducing MDA levels	[44]
Buffalo casein	—	YFYPQL	H2O2 induced Caco-2 cell and ABTS and ORAC assays	—	YFYPQL showed antioxidant and inhibited ROS generation and decreased cellular oxidative products, MDA, and protein carbonyls and increased CAT, SOD, and GPx by stimulating Nrf2 stress signaling and scavenged ABTS and ORAC free radicals	[40]
Wheat germ protein	Alcalase, pepsin, and proteinase K	TVGGAPAGRIVME, VGGIDEVIAK, GNPIPREPGQVPAY, SGGSYAD ELVSTAK, and MDATALHYENQK	ABTS assay	—	Peptides exhibited strong ABTS radical scavenging activity	[117]
Carp (Cyprinus carpio) skin gelatin	Protamex	—	Healthy adult Wistar rats	—	Peptides showed antioxidant activity by increasing the glutathione reductase activity	[118]
Sesame (-icum L.) seed protein	Alcalase and trypsin	RDRHQKIG, TDRHQKLR, MNDRVNQGE, RENIDKPSRA, SYPTECRMR, GGVPRSGEQEQQ, and AGEQGFEYVTFR	DPPH and ABTS assays	DPPH IC50 0.105 and ABTS IC50 0.004 mg/mL	SYPTECRMR exhibited the highest DPPH and ABTS free radical scavenging antioxidant activity	[34]
Finger millet	Trypsin	STTVGLGISMRSASVR and TSSSLNMAVRGGLTR	DPPH assay	DPPH 75–80%	Peptides exhibited DPPH and ABTS radical scavenging activities by interaction of serine and threonine residues of peptides with free radicals	[119]
Potato	—	Dipeptide IF	SHR rats	—	Peptides increased the antioxidant enzymes HO-1, GPx, SOD, and peroxiredoxin 2 through the Akt pathway to regulate Nrf2 activity and prevented Nrf2 degradation by Akt activation and GSK-3β phosphorylation	[33]
Mytilus Coruscus mussel	Trypsin	<1 kDa	H2O2-induced HUVEC and OH, O2, and ferric-reducing assays	—	Peptides reduced the accumulation of ROS and MDA production and increased the levels of the SOD, CAT, and GSH-Px cellular antioxidant capacities through regulating the Nrf2-driven antioxidant defense mechanisms. Peptides showed strong OH, O2 radical scavenging activities and ferric-reducing power	[46]
Mackerel (Scomber japonicus) muscle	Protamex	ALSTWTLQLGSTSFSASPM	DPPH assay	DPPH 36.34%	Peptide showed strong DPPH radical scavenging activity with 36% inhibition	[120]
Soft-shelled turtle	Neutrase, papain, proteinase, pepsin, and trypsin	EDYGA	HepG2 cells	—	EDYGA modulated the Nrf2/ARE pathway by enhancing the Nrf2 level via Nrf2 stabilization and decreasing the level of Keap1 and glutamate residues of EDYGA bound to the Arg 415 of Kelch domain receptor pocket	[45]
Foxtail millet (Setaria italica) prolamins	Alcalase	PFLF and IALLIPF	H2O2-induced human keratinocyte HaCaT cells	—	Peptides decreased the production of ROS and MDA and enhanced the GSH level	[121]
Krill	Pepsin	AMVDAIAR	H2O2-stimulated hepatocytes	DPPH IC50 0.87 mM	Peptide reduced oxidative stress by enhancing SOD, CAT, and GPx. Peptide increased Nrf2 and HO-1 expression and activated Nrf2/HO-1 by activating the ERK pathway	[38]
Watermelon seed protein	Alcalase	RDPEER	H2O2-induced oxidative stress in HepG2 cells	—	RDPEER reduced the oxidative stress by increasing CAT, SOD, and GSH-Px, and reducing MDA production and ROS accumulation	[39]
Scallop (Patinopecten yessoensis) shellfish	Pepsin, dispase, and alcalase	<3 kDa	DPPH, HO, and ABTS assays and H2O2-induced PC-12 cells	DPPH EC50 1.30–2.40, ABTS EC50 0.75–1.98, and OH EC50 1.07–1.43 mg/mL	Peptides scavenged the free radicals of DPPH, HO, ABTS, and inhibited ROS accumulation	[122]
Milk casein	—	ARHPHPHLSFM, AVPYPQR, NPYVPR, and KVLPVPEK	Peroxide-induced oxidative stress Caco-2 cells	—	Peptides enhanced the expression of SOD1, Trx1, TrxR1, GR, and NQO1 by activating the Keap1-Nrf2 pathway. Peptides inhibited the interaction between Keap1 and Nrf2, by binding to Nrf2 in the Keap1 pocket and increased antioxidant enzyme expression	[32]
Corn gluten meal	Fermentation mice with Bacillus subtilis MTCC5480 (BS5480)	<10 kDa	Aging rats	—	Peptides increased activities of total SOD, CAT, GPx, and total antioxidant capacity and decreased MDA	[31]
Moringa oleifera seeds	Flavor protease	GY, PFE, YTR, FG, QY, IN, SF, SP,YFE, IY, and LY	H2O2 induced oxidative damage in Chang liver cells and DPPH and ABTS assays	DPPH EC50 0.75–2.28 mg/mL and ABTS EC50 0.32–1.03 mg/mL	Peptides exhibited strong scavenging activities on free radicals DPPH and ABTS^+. SF and QY scavenged ROS by increasing SOD and CAT and reducing MDA	[25]
Ginger	Pepsin and trypsin	VTYM	DPPH and ABTS assays	EC50 of DPPH and ABTS	VTYM showed potent DPPH and ABTS radical scavenging activity	[9]
Snakehead (Channa argus) soup	Pepsin and pancreatin	IVLPDEGK, PGMLGGSPPGLLGGSPP, SDGSNIHFPN, and SVSIRADGGEGEVTVFT	DPPH and Fe^2+ chelating assays and H2O2 induced HepG2 cells	DPPH IC50 1.39 mM and Fe^2+ chelating ability IC50 4.60 mM	Peptides exhibited strong DPPH and Fe^2+ chelating ability and molecular docking indicated that peptides can bind to the active site of Keap1 and thereby activate the cellular antioxidation Keap1-Nrf2 pathway	[3]
Silver carp muscle	Papain and alcalase	<1 kDa and LVPVAVF	H2O2 induced oxidative stress Caco-2 cells and DPPH assay	DPPH EC50 0.65 mg/mL	Peptides showed antioxidant activity by enhancing the activity of SOD, CAT, and GSH-Px and reduced ROS and showed strong DPPH scavenging activity	[12]

ARE: antioxidant response element; ATBS: 2,2-azino-bis (3-ethylbenzothiazoline-6 sulphonic acid) diammonium salt; Akt: protein kinase B; CAT: catalase; DPPH: 2,2-diphenyl-1-picrylhydrazyl; ERK: extracellular signal-regulated kinases; FRAP: ferric reducing antioxidant power; GPx: glutathione peroxidase; GSH: glutathione; GR: glutathione reductase; H₂O₂: hydrogen peroxide; HO-1: heme oxygenase 1; IC₅₀: 50% inhibitory concentration; ROS: reactive oxygen species; SHR: spontaneously hypertensive rats; SOD: superoxide dismutase; MDA: malondialdehyde; NQO1: NAD(P)H quinine dehydrogenase 1; Nrf2: nuclear factor erythroid 2-related factor; HUVEC: human umbilical vein endothelial cells; Keap 1: Kelch-like ECH-associated protein 1; HO: heme oxygenase; Trx1: thioredoxin 1; TrxR1: thioredoxin reductase 1; ORAC: oxygen radical absorbance capacity.