Roles of Dietary Bioactive Peptides in Redox Balance and Metabolic Disorders

Table 4

Molecular mechanisms of action of antihypertensive peptides isolated from various food sources.

Dietary protein source	Enzyme used to produce peptides	Peptide sequence or molecular weight	Object	IC50/EC50 values	Activity/mechanisms of action	Reference
Pea protein	Thermolysin	<3 kDa	SHR and clinical trial	—	Peptides (100 and 200 mg/kg BW) reduced SBP	[140]
Casein	—	VPP and IPP	Clinical trial	—	VPP and IPP improved central blood pressure and arterial stiffness	[81]
Pistachio kernel	Pepsin and trypsin	ACKEP	ACE inhibition assay	ACE IC50 126 μM	ACKEP inhibited ACE by binding with ACE active site	[88]
Chum salmon (Oncorhynchus keta) skin	Trypsin	GLPLNLP	ACE inhibition assay and SHRs	ACE IC50 18.7 μM	GLP exhibited ACE inhibition and antihypertensive effect by decreasing SBP	[94]
Skate (Okamejei kenojei) skin	Alcalase and protease	LGPLGHQ and MVGSAPGVL	ACE inhibition assay and SHRs	ACE IC50 3.09–4.22 μM	Peptides inhibited ACE and decreased SBP and inhibited vasoconstriction via PPAR-γ expression, activation, and phosphorylation of eNOS in lungs	[95]
Egg white ovotransferrin	Thermolysin and pepsin	IQW and LKP	SHRs	—	Peptides reduced mean blood pressure	[22]
Cuttlefish (Sepia officinalis) muscle	Crude enzymes from B. mojavensis and cuttle fish hepatopancreas	VELYP, AFVGYVLP, and EKSYELP	ACE inhibition assay and SHRs	ACE IC50 5.22 μM	VELYP showed strong ACE inhibition through a noncompetitive inhibition and had antihypertensive effects by decreasing SBP	[96]
Potato and rapeseed	Alcalase and potato autolysis	SLVSPSAAAAAAPGGS and KKRSKKKSFG	Goldblatt rat with hypertension and ACE inhibition	ACE IC50 324 μg/mL and 156 μg/mL	Peptides inhibited ACE and exhibited antihypertensive effects by reducing SBP	[85]
Rice bran protein	Trypsin	YSK	ACE inhibition assay	ACE IC50 76 mM	YSK showed ACE inhibition through the formation of hydrogen bonds with active pockets of human ACE	[1]
Sipuncula (Phascolosoma esculenta)	Pepsin and trypsin	RYDF, YASGR and GNGSGYVSR	ACE inhibition assay and SHRs	ACE IC50 235 μM, 185 μM, and 29 μM	Three peptides inhibited ACE noncompetitively. GNGSGYVSR (5 mg/kg BW) showed antihypertensive effect by decreasing SBP	[97]
Lentil seeds (Lens culinaris var.)	Savinase	LLSGTQNQPSFLSGF, NSLTLPILRYL, and TLEPNSVFLPVLLH	ACE inhibition assay	ACE IC50 44–120 μM	Inhibited ACE through interaction by hydrogen bonds with three ACE residues of the catalytic site	[91]
Bighead carp muscle	Pepsin	YNLKERYAAW and YNRLPEL	ACE inhibition assay	ACE IC50 1.35–3.42 μM	Peptides inhibited ACE activity	[98]
Bovine casein	Pepsin and trypsin	YQKFPQYLQY	ACE inhibition assay and SHRs	ACE IC50 11.1 μM	Peptide inhibited ACE via competitive inhibition and exhibited antihypertension by decreasing SBP	[82]
Hazelnut (Corylus heterophylla Fisch.)	Alcalase	AVKVL, YLVR, and TLVGR	ACE inhibition assay and SHRs	ACE IC50 15.42–249.3 μM	Peptides inhibited ACE activity via a noncompetitive mode via the formation of cation–pi interactions and YLVR reduced SBP	[89]
Egg white from ostrich	Alkaline hydrolysis	YV	ACE inhibition assay	ACE IC50 63.97 μg/mL	YV showed ACE inhibition by binding to S1 and S2 ACE pocket sites via hydrogen bonds	[93]
Soybean	Pediococcus pentosaceus SDL1409	EDEVSFSP, SRPFNL, RSPFNL, and ENPFNL	ACE inhibition assay	ACE IC50 0.131–0.811 mg/mL	Peptides inhibited ACE via essential N-terminal sequence and amino acid position	[84]
Shrimp (Pandalus borealis) protein	—	—	Randomized, double-blind, placebo-controlled, 8-week clinical study	—	Peptides (1200 mg/d) reduced the blood pressure due to a reduction of angiotensin II levels	[79]
Beef (Bos taurus coreanae) myofibrillar proteins	Alkaline-AK and papain	LIVGIIRCV	ACE inhibition assay and SHRs	—	Peptides (400 and 800 mg/kg BW) inhibited ACE by 74.29% and decreased SBP	[99]
Milk	Fermented using L. delbrueckii QS306	LPYPY	ACE inhibition assay	ACE IC50 12.87 μg/mL	LPYPY inhibited ACE with IC50 12.87 μg/mL	[80]
Mung bean protein	Bromelain	LPRL, YADLVE, LRLESF, HLNVVHEN, and PGSGCAGTDL	ACE inhibition assay and SHRs	ACE IC50 5.39–1912 μM	Peptides showed ACE inhibition and reduced SBP	[90]
Seahorse (Hippocampus abdominalis)	Protamex	APTL, CNVPLSP, and PWTPL	ACE inhibition assay and SHRs	ACE IC50 0.044 μM	Peptides exhibited antihypertension by lowering blood pressure via vasodilation and ACE inhibition	[92]
Black cumin seed	α-Chymotrypsin	VTPVGVPK	ACE inhibition assay	ACE IC50 value 1.8 μM	VTPVGVPK inhibited ACE via a noncompetitive inhibition	[86]
Quinoa protein	Chymotrypsin	QHPHGLGALCAAPPST	ACE inhibition assay	—	Peptide displayed ACE inhibition by binding to ACE active hotspots	[62]
White turmeric, turmeric, and ginger proteins	Pepsin and trypsin	VTYM, RGPFH, AEPPR, GSGLVP, KM, SPV, CACGGV, DVDP, CGVGAA, HVVV, and RSC	ACE inhibition assay	ACE IC50 16.4–36.5 μM	Peptides showed ACE inhibition	[9]
Coix prolamin	Pepsin	VDMF	ACE inhibition assay	ACE IC50 382.28 μM	VDMF reduced ACE and AT1R expression in AngII-injury HUVECs	[87]
Wheat gluten	Alcalase and PaproA	SAGGYIW and APATPSFW	ACE inhibition assay	ACE IC50 0.002–0.036 mg/mL	Peptides and negatively charged amino acids inhibited ACE via modulating ionic and hydrophobic interactions on ACE catalytic sites	[83]

ACE: angiotensin-converting enzyme; BW: body weight; IC₅₀: 50% inhibitory concentration; SBP: systolic blood pressure; SHR: spontaneously hypertensive rat; PPAR-γ: peroxisome proliferator-activated receptor γ.