Table 6.

Cellular antioxidant effects of cereal peptides and hydrolysates.

Protein Source	Enzyme	Peptide Sequence/Hydrolysate	Cellular Model	Cellular Outcome	Reference
Wheat germ	Trypsin, Alcalase	AREGETVVPG	Vascular smooth muscle cells	High glucose-induced cell growth and generation of intracellular ROS was significantly decreased by AOP (5 µM). Suppression of PKCζ, AKT and Erk1/2 phosphorylation, and inhibition of Nox4 protein expression by AOP (5 µM).	[182]
Wheat germ	neutral protease	ADWGGPLPH	Vascular smooth muscle cells	High glucose-induced cell proliferation and intracellular ROS generation was significantly reduced by peptide at 10 µM and 20 µM. Stimulation of AMPK activity, inhibition of PKCζ, AKT and Erk1/2 phosphorylation, and suppression of NOX4 protein expression.	[172]
Wheat gluten protein	Alcalase	Protein hydrolysate	Human peripheral blood mononuclear cells	Hydrolysate (0.5 mg/mL) directly scavenged free radicals, increased GSH levels, reduced NO overproduction, and, thus, enhanced cells’ antioxidant capacity. Also, cell proliferation, Th1 and Th17 pro-inflammatory cytokines IFN-γ and and IL-17 were reduced.	[178]
Foxtail millet	Alcalase	PFLF, IALLIPF	Human keratinocyte HaCaT cells	ROS, MDA production was effectively reduced and GSH levels increased by MPP (300 µg/mL) in H2O2-induced HaCaT cells.	[179]
Sorghum	Pepsin-pancreatin	Kafirin hydrolysate	THP-1 human macrophages	Kafirin (100 μg/mL) reduced LPS-induced intracellular ROS production, inflammatory cytokines (IL-1β, IL-6 and TNF-α) production, and nuclear translocation of p65 and c-JUN.	[176]
Rice bran	-	KHNRGDEF	Human umbilical vein endothelial cells (HUVECs)	H2O2-induced HUVECs oxidant injury was protected by rice bran peptide (0.1 mM) supplementation via TLR4 binding, pathway inhibition, and suppression of NF-κB activation.	[177]
Rice	-	OP60 commercial peptide	HepG2 cells	H2O2- or APAP-induced HepG2 cytotoxicity was reduced by 5 mg/mL OP60 pretreatment via glutathione homeostasis restoration and increased mRNA expression of antioxidant enzymes.	[175]
Corn	Alcalase	Zein hydrolysate/peptides	HepG2 cells	Hydrolysate showed higher ORAC activity than native proteins. Peptides (1155.56–1781.63 ng/mL IC50) induced apoptosis at 24 hr by increasing caspase 3 expression.	[183]
Corn germ meal	Alcalase	MGGN, MNN, MEN	HepG2 cells	Peptides (0.2 mM) significantly reduced ROS generation in H2O2-induced HepG2 cells. MNN showed the highest cellular antioxidant activity.	[125]
Corn gluten meal	Alcalase	corn gluten hydrolysate (CGH1) <1 kDa	HepG2 cells	CGH1-pretreated cells at 2.5 mg/mL upregulated the genes GPX3, GPX5, SOD3, CYGB, SEPP1, and MT3 involved in antioxidant defense. CGH1 suppressed EPHX2 expression, increased cellular EETs, EET-phospholipids formation, and, thus, protected against H2O2-induced HepG2 cell damage.	[180]
Corn gluten meal	Alcalase	GLLLPH	HepG2 cells	Corn peptide fractions (CPF) at 2.50 mg/mL exhibited high cellular antioxidant activities and increased the levels of intracellular antioxidant enzymes (SOD, CAT, GR and GSH) in oxidized HepG2 cells.	[73]

ROS: reactive oxygen species; AOP: antioxidant peptide; NOX: NADPH oxidase; PKCζ: phospho-protein kinase ζ; AMPK: AMP-activated protein kinase; Erk: extracellular signal–related kinase; AKT: Th1: Type 1 T helper; Th17: Type 17 T helper; IFN-γ: interferon-γ; IL17: interleukin 17; GSH: reduced glutathione; GR: glutathione reductase; SOD: superoxide dismutase; CAT: catalase; NO: nitric oxide; MDA: malondialdehyde; MPP: millet prolamins peptides; LPS: lipopolysaccharide; TLR4: Toll-like receptor 4; EET: epoxyeicosatrienoic acid.