Table 1.

Health benefits of soybean-derived peptides.

Soybean sources	Bioactive peptide sequence	Targeted model	Biological function	Outcomes	Reference
Soybean glycinin	IAVPGEVA IAVPTGVA LPYP	HepG2 cells	Anti-hypocholesterolemic	Inhibit 3-hydroxymethylglutaryl coenzyme A (HMGCoA) reductase and stimulate the LDL receptor pathway which in turn reduces the cholesterol	(19)
Mature and young soybean proteins hydrolysates	FPFPRPPHQ, FMYL, MMLM, SFFFPFELPRE	Pancreatic lipase (PL) and cholesterol esterase (C-Ease) enzymes	Anti-lipidemic	Compared to flavorzyme and alcalase, bromelain showed higher levels of protein degradation, and its hydrolysis resulted in enhanced PL and C-Ease inhibition effectiveness. FPFPRPPHQ, FMYL, MMLM, and SFFFPFELPRE were effective inhibitors of the C-Ease enzyme. FPFPRPPHQ and SFFFPFELPRE had inhibitory potencies against both PL and C-Ease	(42)
Soybean	VHVV	Rats	Anti-hypertensive	Reduced p-PI3K, p-AKT, anti-apoptosis proteins (Bcl2 and Bcl-XL), SIRT1, and FOXO3 in rats. Activated cell survival, AMPKα1, Sirt1, PGC1α, and FoX3α proteins	(43, 44)
Soy protein hydrolysates	ILL LLL VHVV	HepG2 cells	Anti-obesity	Hydrolysates of soybean may reduce serum levels of triglycerides by decreasing fatty acid synthase (13.6) than control (17.0)	(6)
Soybean meal fermented by Bacillus subtilis E20	KHPHGRSYKTKLRILA LRFRAPAPVLRRIAKR HTSKALLDMLKRLGK	Shrimp	Anti-bacterial	Effective against microbes Vibrio alginolyticus and V. parahaemolyticus	(45, 46)
Soybean	PGTAVFK	In vitro	Anti-bacterial	At a concentration of 31 M, PGTAVFK also exhibits antibacterial action against E. coli and S. aureus	(47, 48)
Cheese peptidome	KFVPKQPNMIL	Glycoprotein receptor-binding domain (RBD) and main protease (3CLPro)	Anti-viral activity	Cheese peptidome could be used against the SARS-CoV-2 virus with binding energy values ranging from −8.45 to −26.8 kcal/mol and −15.22 to −22.85 kcal/mol to inhibit viruses' effect	(49)
Soy cheese fermented by Lactobacillus delbrueckii WS4	KFVPKQPNMIL	Human red blood cells	Anti-viral	Soy cheese is made with Lb. delbrueckii WS4 could be potential meal for SARS-CoV-2 and related viruses' prophylaxis	(49, 50)
Glycinin	IAVPTGVA LPYP	Caco-2 cells in the intestine of humans and HK-2 cells in the kidney	ACE enzyme inhibition	The activity of the ACE enzyme of renal and intestinal get decreased enzyme activity with desired IC50 values of 14.7 ± 0.28 and 5.0 ± 0.28 μM for Caco-2 cells, and 6.0 ± 0.35 and 6.8 ± 0.20 μM for HK-2 cells	(51, 52)
Soybean	PGTAVFK IKAFKEATKVVVVLWTA	In vitro	Anti-bacterial	Inhibitory concentration of 37.2 M, the peptide with long chain (IKAFKEATKVVVVLWTA) is more efficient in opposing Listeria monocytogenes and Pseudomonas aeruginosa	(53, 54)
Soybean protein concentrate	FPLLVLLGTVFLASVCVSLKVREDE NNPFYFR FFEITPEKN- PQLRDLDIFLSSVDINEGALLLPHFNSK	In vitro	Antioxidant and inhibitory assay	High molecular mass peptides demonstrated maximum antioxidant activity than low molecular mass peptides, however in case of inhibitory activities, low molecular peptides resulted better effects for α -glucosidase inhibition (IC50 = 0.94) and lipases (IC50 = 4.06) than high molecular peptides inhibition of α-glucosidase (IC50 = 3.4) and of pancreatic lipase (IC50 = 2.02)	(55)
Germinated soybean protein digest	VVNPDNNEN QEPQESQQ SDESTESETEQA	Human colon cancer cells, mouse macrophages RAW 264.7	Anticancer and anti-inflammatory effects	Fractions, 5–10 kDa peptides revealed maximum showed potency with IC50 = 11.70 mg/mL as compared to >10 kDa, which showed IC50 = 13.21 mg/mL values against cancer while 45% inhibition observed against inflammation	(56–58)
Soybean	SKWQHQQDSC RKQKQGVNLT PCEKHIMEKI QGRGDDDDDDD DD	Mice	Hypocholesterolemic	After 4 weeks of receiving lunasin with 0.125–0.5 μmol/kg·day dose mice had remarkably low PCSK9 and high amounts of LDLR levels in hepatic tissue, moreover, it decreased total-cholesterol (T-CHO), LDL-C in blood and up-regulated LDLR in HepG2 cells	(59)
β-conglycinin	YVVNPDNDEN	Mouse liver	Anti-obesity	Weight of adipose tissue reduced by increasing postprandial circulating FGF21	(60)
Soybean protein	EKPQQQSSRRGS	Mice	Immunomodulatory effect	Enhanced phagocytosis, retard excessive inflammatory response, and induced macrophages M1 polarization in the spleen of mice	(61)
Soy protein isolate (bromelain and thermolysin)	-	Human oral squamous carcinoma cell line, HSC-3	Anti-proliferative activity	After 72 h, both isolates showed inhibition against cancer cells which were 35.45–76.39%	(62)
Hydrolysates of soy protein Flavorzyme (F-SPIH)	VHVV	Hypertensive rats	Neuroprotective effect	A peptide that is bioactive VHVV had stimulated CREB-induced downstream proteins that might decrease the long-term memory loss mediated by hypertension and maintain the survival of neurons	(63, 64)
Black soy	–	In vivo	Blood pressure	Systolic blood pressure reduced clearly in peptide supplemented group (−9.69 ± 12.37 mm Hg) as compared to control (−2.91 ± 13.29 mm Hg)	(65)
Soy β-Conglycinin	YVVNPDNDEN YVVNPDNNEN	HepG2 Cells	Hypocholesterolemic	At 350 μM 1st peptide upregulates the mature SREBP2 protein level (134.0 ± 10.5%), enhanced the LDLR protein (152.0 ± 20.0%), and HMGCoA reductase protein (171 ± 29.9%), as compared to 2nd peptide where mature SREBP2 protein regulation was 158.0 ± 9.2%, the increase in LDL and HMGCoA reductase was 164.0 ± 17.9%, and 170 ± 50.0%, respectively	(66)
Glycinin	IAVPTGVA	Human intestinal Caco-2 cells and serum	Anti-diabetic	Stopped DPP-IV action in situ, with IC50 values 223.2 μM	(67, 68)
Glycinin and β-conglycinin,	–	Human intestinal Caco-2 cells	Hypocholesterolemic Anti-Diabetic	Peptides enhanced protein levels (51.5–63.0%, 55.2–85.8%) than control (0.5–1.0 mg/mL) moreover DPP-IV activity decreased (16.3–31.4% and 15.3–11.0%) than control (1.0 and 2.5 mg/mL)	(69)
Soybean protein isolate	FDPAL	Caenorhabditis elegans	Anti- oxidative	Caused a remarkably increase in resistance to oxidative stress, upregulated the specific expression of genes in Caenorhabditis elegans	(70)
Soybean glycinin	VAWWMY	Rats	Anti- hypocholesterolemic	Serum (0.03), liver (0.03), and intestine (0.2) detected low values of cholesterol	(71)
Soybean	QRPR	RAW 264.7	Anti-inflammation	Soybean peptide reduced the cytokines levels such as TNF-α and IL-6 that are responsible for inflammation	(72)
Bacillus. licheniformis KN1G mediated soybean	KFVPKQPNMIL	Human ACE2 cell receptor	Anti-viral	Preventative measures against SARS-CoV-2 infection	(16)
Soybean fermented by Bacillus subtilis (KN2B and KN2M).	ALPEEVIQHTFNLKSQ	In silico	Anti-viral	Effective against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).	(16)
Soybean induced peptide	QRPR	RAW264.7 cell model	Anti-inflammation	Autophagy was activated by QRPR in the inflammatory cell; however, autophagy was inhibited by reducing QRPR inhibitory effect	(73, 74)
R95, N98-4445A, S03-543CR	–	Human blood, breast, and prostate	Anti-proliferative activity	Showed up to 68.0% inhibition of cancer lines	(75)
Glycinin, β-conglycinin and lectin from soy milk	HSYNLRQSQVSELKYEGNWGPLV NPESQQGSPRV	In vitro	Anti-oxidative and anti-hypertensive effects	Peptides (10 kDa) resulted maximum antioxidant and DDPH values as 1,831 ± 20.29 TEAC μm and 50.74 ± 0.27%, respectively while ace inhibition was 75.97 ± 1.5%.	(76)
Soybean	VHVV	Rats	Antihypertensive	Antioxidant defense induced, stabilized mitochondrial homeostasis, decreased renal damage, induced free radicals in rats	(77)
Alcalase and neutrase	QNGEQE RGASADGPR YGGGGE	Macrophage RAW264.7 cells	Immunoregulatory effect	The cell viabilities decreased from 97.61 to 115.01% to 86.65%	(78)
Soybean protein	DGWFR ALSWLR DGWFRL PNGPVWR	Mice model	Sleep effects	Mice provided with 0.65 g kg−1 soybean-derived peptides showed 59.21% sleep duration on 3rd day of observation and increased melatonin levels (95.31%) while with 2.60 g kg−1 peptides doubled the serotonin in the brain and increased the awaking situation	(79)
Alcalase low molecular weight fraction (SPH-I, MW < 3 kDa)	VVFVDRL VIYVVDLR IYVVDLR IYVFVR	Human intestinal Caco-2 cells	Anti-oxidative effect	Desirable results showed in the case of ORAC (143 ± 2.1–171 ± 4.8 μM TE/μM), FRAP (54.7 ± 1.2–79.0 ± 0.6 mM Fe2+/μM), radical-scavenging activity (3.42 ± 0.2–4.24 ± 0.4 mMTE/μM) and DPPH (16.5 ± 0.5–20.3 ± 1.0 μM (TE)/μM). SPH-IC (85.9%) and SPH-ID (96.2%) restrained maximum H2O2-induced ROS generation	(80)
Lunasin, lectin	SKWQHQQDSCRKQKQGVNLTPCEK HIMEKIQGRGDDDDDDDDD	Cancer cells of the human breast	Anti-cancer effect	MDA-MB-231 cells were inhibited with these bioactive peptides (glycitein, Genistein, β-sitosterol, and genistin) while 142.67 ± 5.88 μM, 93.75 ± 5.15 μM, 196.28 ± 4.45 μM and 127.82 ± 4.70 μM and values were detected	(81)