. 2023 Jun 29;12(13):2527. doi: 10.3390/foods12132527

Table 2.

Biological activities of pea and its components, and their potential mechanisms of action.

Sample Types	Experimental Models	Major Results	References
Antioxidant effect
Seed flour extracted with 95% ethanol	In vitro (DPPH)	➢ The IC₅₀ values for DPPH free radical scavenging activity were varied in different microwave drying, ranging from 0.1 to 0.9 mg/mL ➢ Microwave drying at 100 W had the highest DPPH free radical scavenging activity among all drying conditions	[74]
Seed flour extracted with 80% ethanol	In vitro (ABTS; DPPH; reducing power) In vitro (cell model, OA-induced HepG2 cells)	➢ The DPPH free radical scavenging efficiency, ABTS free radical scavenging efficiency, and reducing power of pea extracts were 56.58%, 27.25%, and 0.222 at a concentration of 1.0 mg/mL, respectively ➢ ↑ SOD, GSH-Px; ↓ MDA, ROS	[65]
Seed flour extracted with 80% methanol	In vitro (ABTS; DPPH)	➢ A positive correlation was observed between the TPC and ABTS free radical scavenging activity (r = 0.59) ➢ While an inverse trend was observed for DPPH free radical scavenging activity (r = −0.31)	[82]
Seed flour extracted with mixed solution (acetone/water/acetic acid, 70:29.5:0.5, v/v/v)	In vitro (ABTS; FRAP)	➢ The ABTS free radical scavenging capacity of 75 pea varieties ranged from 3.04 to 22.27 μM TE/g ➢ The FRAP of 75 pea varieties ranged from 1.24 to 18.87 mM Fe²⁺/g DW ➢ Dark pea seeds (e.g., brown, purple, dark and brown with strap or dotted) contained more TPC, TFC, ABTS, and FRAP than light-colored seeds (e.g., cream, green).	[68]
Seed coat extracted with mixed solution (methanol/water/acetic acid mixture, 80:19:1, v/v/v)	In vitro (DPPH; FRC; FCC)	➢ The DPPH free radical scavenging activity ranged from 0.72 to 2.55 mM TE/g, exhibiting a good correlation with TPC values (r = 0.971) ➢ The FRC absorbance values at 700 nm ranged from 0.019 to 0.312 ➢ The FCC ranged from 29.6 to 75.8%	[125]
Seed coat extracted with mixed solution (acetone/water/acetic acid mixture, 80:19:1, v/v/v)	In vitro (DPPH; FRC; FCC)	➢ The DPPH free radical scavenging activity ranged from 0.54 to 8.04 mM TE/g ➢ The FRC ranged from 0.021 to 0.346 ➢ The FCC ranged from 8.1% to 33.7%	[126]
Seed coat extracted with water, methanol, and ethyl acetate	In vitro (ABTS; DPPH; FRAP)	➢ The IC₅₀ values of ABTS free radical scavenging activity of ethyl acetate extract (9.61 μM TEAC/g) was higher than that of the methanol extract (1.9 μM TEAC/g) ➢ The IC₅₀ values of DPPH free radical scavenging activity were 350 μg/mL and 650 μg/mL for ethyl acetate and methanol extract, respectively ➢ The FRAP of methanol, water, and ethyl acetate extracts, at a concentration of 2 mg/mL, were 1.32, 0.36, and 1.84, respectively	[127]
Red and yellow pea hull in vitro digestion products	In vitro (DPPH; ABTS; H₂O₂; FRAP)	➢ Strong correlations existed in red hulls between their antioxidant activities (DPPH; ABTS; H₂O₂; FRAP) and TPC/TFC (r > 0.92)	[69]
Pea sprout extracted with 80% methanol	In vitro (DPPH; ORAC; CUPRAC)	➢ The 7th day of germination showed the strongest DPPH free radical scavenging activity (512.64 mg TE/100 g DW), ORAC value (6083.54 mg TE/100 g DW), and CUPRAC inhibition (44.05%) among all tested samples	[70]
Pea hull extracted with 95% ethanol	In vitro (DPPH; reducing power; FRAP)	➢ The DPPH free radical scavenging activity ranged from 76.55% to 91.03% ➢ The reducing power ranged from 0.5 to 0.63 ➢ The FRAP values ranged from 0.25 to 0.34 mmol/L	[128]
Peptides derived from pea protein hydrolysate	In vitro (DPPH; OH)	➢ The second fraction (F1-2) purified from hydrolysates (<1 kDa) had the highest DPPH radical scavenging rate of 37.94% and OH free radical scavenging rate of 28.43% among all samples	[129]
Whole seed flour	In vivo (HFD-induced Sprague–Dawley (SD) male rats)	➢ ↑ GSH-Px, SOD, and T-AOC ➢ ↑ Nrf2, NQO1, CAT, HO-1 ➢ ↓ MDA	[65]
Seed coat extracted with water	In vivo (DOX-induced albino male rats)	➢ ↑ SOD, GPX, CAT; ↑ GSH ➢ ↓ MDA, NO	[72]
Green pea hull extracted with 80% methanol	In vivo (D-galactose-induced SD female rats)	➢ ↑ T-AOC, SOD, GSH-Px; ↑ GSH ➢ ↓ MDA	[130]
Yellow pea hull extracted with 80% methanol	In vivo (D-galactose-induced SD female rats)	➢ ↑ T-AOC, SOD, GSH-Px; ↑ GSH ➢ ↓ MDA	[73]
Anti-inflammatory effect
Green pea hull in vitro digestion products	In vitro (LPS-induced Caco-2/Raw264.7 cells coculture)	➢ ↓ NO, IL-6, TNF-α ➢ ↓ COX-2, iNOS	[131]
Peptides derived from pea protein hydrolysate	In vitro (LPS/IFN-γ-induced RAW 264.7 cells)	➢ ↓ NO, IL-6, TNF-α	[132]
Whole seed flour	In vivo (DSS-induced colitis in HFD-fed C57BL/6J female mice)	➢ ↓ IL-6, IL-17, IFN-γ ➢ ↓ iNOS, COX-2, MCP-1 ➢ ↑ MUC-2, goblet cell differentiation markers (e.g., Tff3, Klf4, Spdef1)	[133]
Green pea hull extracted with 80% ethanol	In vivo (DSS-induced colitis in C57BL/6 male mice)	➢ ↓ NO, IL-6, TNF-α ➢ ↓ COX-2, iNOS ➢ ↓ Keap1; ↑ Nrf2 ➢ ↑ SCFAs (e.g., acetic acid, propionic acid, and n-butyric acid) ➢ ↑ Lactobacillaceae, Lachnospiraceae, Firmicutes; ↓ Bacteroidetes	[77]
Two pea seed albumin extracts (PSE/AF-PSE)	In vivo (DSS-induced colitis in C57BL/6J male mice)	➢ PSE: ↓ IFN-γ, IL-6, IL-12, TNF-α; ↓ iNOS, COX-2, MMP-2, MMP-9, MMP-14, ICAM-1; ↑ MUC-3, ZO-1, occluding; ↓ TLR-2, -4, -6, -9 ➢ AF-PSE: ↓ IL-6, IL-12; ↓ COX-2, MMP-9 and -14, ICAM-1; ↓ TLR-4, -6, -9	[134]
Regulation of metabolic syndrome
*Anti-hypertensive activity*
Peptides derived from pea protein hydrolysate	In vitro (ACE inhibition assay)	➢ The peptide fraction (B) had the highest ACE inhibitory activity (IC₅₀ = 0.073 mg/mL) among all tested samples	[135]
Peptides derived from pea protein hydrolysate	In vitro (A7r5 cells)	➢ A peptide with the sequence of AKSLSDRFSY was identified as a novel ACE2 upregulating peptide	[136]
Tripeptide (Leu-Arg-Trp)	In vitro (A7r5 cells)	➢ ↑ ACE2 and MasR to upregulate the ACE2-Ang-(1-7)-MasR axis	[137]
Peptides derived from pea protein hydrolysate	In vitro (ACE and renin inhibition assays) In vivo (male SHRs)	➢ The peptide fraction 7 had the highest dual inhibitory effects of renin and ACE with 52.16% and 95.17% inhibition rates, respectively ➢ The renin and ACE inhibitory activities of synthesized peptides were ranged from 17.4 to 49.9% and 5.72 to 87.54%, respectively, and three of them (LTFPG, IFENLQN, and FEGTVFENG) showed strong ACE and renin inhibitory activities ➢ LTFPG acted the fastest in reducing SBP of SHR with a maximum of −37 mmHg after 2 h of oral administration	[28]
Peptides derived from pea protein hydrolysate	In vitro (ACE and renin inhibition assays) In vivo (male SHRs)	➢ The IC₅₀ values of inhibition on renin and ACE were 0.57 and 0.10 mg/mL, respectively ➢ The maximum decrease in SBP was −36 mmHg after 2 or 4 h, becoming −18 mmHg after 24 h ➢ The maximum decrease in SBP after 3 weeks was −22 or −26 mmHg with partial substitution of casein 0.5% or 1% (w/w) in the SHR diet, respectively	[138]
*Hypolipidemic activity*
Pea pod autoclaved extract (AE)	In vitro (pancreatic lipase inhibition and cholesterol adsorption capacity assay) In vivo (high-sucrose-induced SD male rats)	➢ AE at 13.3 mg/mL significantly inhibited the pancreatic lipase activity by more than 40% compared to 0 mg/mL ➢ 2000 mg of AE adsorbed approximately 33% of cholesterol ➢ ↑ Total lipid, TG and TC in feces ➢ ↓ Serum TC, TG ➢ ↑ Bifidobacterial; ↓ Clostridia	[139]
Pea seed flour	In vivo (HFD-induced male SD rats)	➢ ↓ Serum TC, LDL-C; ↑ HDL-C	[65]
Pea protein isolate	In vivo (HFD-induced male SD rats)	➢ ↓ Plasma TC, TG ➢ ↑ LDL receptor ➢ ↓ SREBP-1c and the target genes (FAS, SCD1, SCD2)	[140]
*Anti-obesity activity*
Pea protein hydrolysate	In vitro (3T3-L1 preadipocytes subline)	➢ ↑ Lipid accumulation; ↑ glucose uptake ➢ ↑ GLUT4, adiponectin, aP2, PPARγ; ↓ Pref-1 ➢ ↑ PPARγ ligand activity	[141]
Pea flour and dietary fiber	In vivo (HFHSD-induced obese SD male rats)	➢ ↓ Weight gain, final percent body fat, fasting blood glucose; ↑ oral glucose tolerance ➢ ↓ Firmicutes/Bacteroidetes ratio ➢ ↓ Clostridium leptum	[55]
Pea fiber	Clinical trial (12-week single center, double-blind placebo-controlled trial with 53 adults with overweight or obesity)	➢ Fecal SCFAs (↑ acetate; ↓ isovalerate) ➢ Fecal BAs (↓ cholic acid, chenodeoxycholic acid, deoxycholic acid) ➢ ↑ Lachnospira; ↓ Actinomyces, Holdermania, Oscillospira ➢ The change in body weight of participants showed a negative correlation with their change in Lachnospira (r = −0.463) abundance	[51]
*Anti-diabetic effect*
Pea protein hydrolysate	In vitro (α-amylase and α-glucosidase inhibition assays)	➢ The highest inhibitory activity against α-amylase among all samples was 30.52% at the concentration of 225 μg/mL ➢ The highest inhibitory activity against α-glucosidase among all samples was 53.35% at the concentration of 20 mg/mL	[142]
Purified pea glycoproteins (PGP1, PGP2, and PGP3)	In vitro (α-amylase and α-glucosidase inhibition assays)	➢ The inhibition of α-amylase with PGP1 was only about 2.73% at a concentration of 2 mg/mL, while the inhibition rates of PGP2 and PGP3 were 8.71% and 22.34%, respectively ➢ The inhibition of α-glucosidase was most potent with the product of gastric digestion, which showed an increase of about 45.87% compared to undigested PGP2 at the same concentration	[143]
Purified pea glycoprotein (PGP2)	In vivo (STZ-induced diabetic ICR male mice)	➢ ↓ Weight loss, food intake, fasting blood glucose; ↑ oral glucose tolerance, insulin secretion ➢ ↓ Serum TC, TG, LDL-C; ↑ HDL-C; ↓ glycated serum protein ➢ ↓ Insulin resistance index; ↑ β-cell function index, insulin sensitivity index ➢ ↑ IRS-1, IRS-2, GLUT1	[144]
Pea oligopeptide	In vivo (HFD and STZ-induced diabetic Kunming male mice)	➢ ↓ Weight loss, fasting blood glucose; ↑ oral glucose tolerance ➢ ↑ Serum insulin level; ↓ serum TC, TG, FAA; ↑ HDL-C ➢ ↓ Liver fat deposition ➢ ↑ The muscle and liver glycogen ➢ Protect the liver and kidney structures	[145]
Pea dietary fiber	In vivo (STZ-induced diabetic Balb/c male mice)	➢ ↓ Blood glucose, weight loss; ↑ oral glucose tolerance ➢ ↓ TC, TG ➢ The pancreatic islet morphology was improved	[50]
Pea protein	Clinical trial (a randomised controlled trial with a high-carbohydrate beverage intake in healthy individuals)	➢ ↓ Glucose incremental area under the curve (iAUC180)	[146]
Antimicrobial effect
11S pea globulin (11SGP)	In vitro Bacteria: Bacillus cereus, Listeria monocytogenes, Streptococcus pyogenes, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa; Fungi: Alternaria alternate, Aspergillus flavus, Fusarium oxysporum, and Monascus purpureus	➢ The minimum inhibitory concentrations of 11SGP against bacteria ranged from 120 to 190 μg/mL ➢ The minimum inhibitory concentrations of 11SGP against fungi ranged from 55 to 80 μg/mL	[147]
Pea lectin	In vitro Bacteria: Staphylococcus aureus, Streptococcus mutants, Pseudomonas aeruginosa, and Klebsiella pneumonia Fungi: Candida albicans	➢ The minimum inhibitory concentrations of pea lectin (90% fractions) against bacteria ranged from 62.5 to 125 μg/mL ➢ The minimum inhibitory concentration of pea lectin (90% fractions) against C. albicans was 250 μg/mL	[148]
Pea peel extracted with water, methanol, and ethyl acetate	In vitro Bacteria: Staphylococcus aureus, Salmonella enterica, Escherichia coli, and Pseudomonas aeruginosa Fungi: Aspergillus niger and Candida albicans	➢ The ethyl acetate extract of pea peel exhibited the strongest antimicrobial activity among all tested samples ➢ The minimum inhibitory concentrations of ethyl acetate extract against bacteria ranged from 350 to 850 μg/mL ➢ The minimum inhibitory concentrations of ethyl acetate extract against fungi ranged from 450 to 550 μg/mL	[127]
Pea pod polysaccharide	In vitro Bacteria: Bacillus thuringiensis, B. subtilis, Actinomycete sp., Enterococcus faecalis, Listeria monocytogenes, Micrococcus luteus, Klebsiella pneumonia, Pseudomonas aeruginosa, and Salmonella Typhimirium	➢ The largest zones of inhibition were detected against B. subtilis, B. thuringiensis and M. luteus with inhibition zones of 16, 15, and 15 mm at the concentration of 50 mg/mL, respectively ➢ The greatest inhibition was detected against P. aeruginosa with an inhibition zone of 15 mm at the concentration of 50 mg/mL	[149]
Anti-renal fibrosis effect
Peptides derived from pea protein hydrolysate	In vitro (glucose-induced MES13 SV40 cells)	➢ ↓ TGF-β1, SMAD2, SMAD3, SMAD4; ↑ SMAD7	[150]
Peptides derived from pea protein hydrolysate	In vitro (glucose-induced MES13 SV40 cells)	➢ ↑ Cell proliferation; ↓ FN, TGF-β1	[151]
Anti-cancer effect
Pea seed coat extracted with water	In vitro (cell lines, human colon denocarcinoma LS174, breast carcinoma MDA-MB-453, lung carcinoma A594, and myelogenous leukemia K562)	➢ MDA-MB-453, IC₅₀ values ranged from 0.89% up to above 10.0% ➢ LS174, IC₅₀ values ranged from 1.84% up to above 10.0% ➢ A549, IC₅₀ values ranged from 1.17% up to above 10.0% ➢ K562, IC₅₀ values ranged from 0.41% up to above 10.0%	[126]
Pea lectin	In vitro (cell line, Ehrlich ascites carcinoma (EAC) cells) In vivo (Ehrlich ascites carcinoma cells in adult Swiss albino mice)	➢ Pea lectin showed 11.7–84% inhibitory effect against EAC cells at the concentration range of 8–120 μg/mL as determined by MTT assay ➢ Pea lectin showed 63% and 44% growth inhibition against EAC cells in vivo when administered 2.8 mg/kg/day and 1.4 mg/kg/day ➢ Pea lectin can arrest the cell cycle at G2/M phase ➢ ↑ Bax gene expression; ↓ Bcl-2 and Bcl-X gene expression	[152]
Immunomodulatory effect
Peptides derived from pea protein hydrolysate	In vivo (BALB/c female mice)	➢ ↑ Phagocytic activity ➢ ↑ IgA+, IL-4+, IL-10+, IFN-γ+ cells ➢ ↑ IL-6 via ↑ TLR2 and TLR4	[132]
Anti-osteoporosis effect
Pea tripeptide (Leu-Arg-Trp)	In vitro (MC3T3-E1 cell)	➢ ↑ Cell proliferation, osteoblastic differentiation, matrix mineralization, ➢ ↑ Runx2, ALP, COL1A2, phosphorylation Akt ➢ ↓ Osteoclastogenesis	[153]
Anti-fatigue effect
Peptides derived from pea protein hydrolysate	In vivo (Kunming mice)	➢ ↑ Swimming times ➢ ↑ Muscle glycogen, hepatic glycogen, insulin level, lactate dehydrogenase activity ➢ ↓ Blood urea nitrogen, blood lactic acid ➢ ↑ SOD, GSH-Px; ↓ MDA ➢ ↑ Phagocytic activity, sIgA secretion; ↓ IL-6, TNF-α	[154]

ABTS, 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid); ACE, angiotensin I-converting enzyme; AF-PSE, albumin fraction from pea seed extract; ALP, alkaline phosphatase; ALT, alanine amino transferase; Ang II, angiotensin II; aP2, adipocyte fatty acid-binding protein; AST, aspartate amino transferase; BAs, bile acids; Bcl, B-cell lymphoma; CAT, catalase; COL1A2, alpha-2 type I collagen; COX-2, cyclooxygenase-2; CUPRAC, cupric reducing antioxidant capacity; DOX, doxorubicin hydrochloride; DPPH, 2,2-Diphenyl-1-picrylhydrazyl; DSS, dextrane sodium sulphate; EAC, Ehrlich ascites carcinoma; FAA, free amino acid; FAS, fatty acid synthase; FCC, ferrous ion-chelating capacity; FN, fibronectin; FRAP, ferric reducing antioxidant power; FRC, ferric ion-reducing capacity; GLUT, glucose transporter; GSH, glutathione; GSH-Px, glutathione peroxidase; HDL, high-density lipoprotein; HDL-C, high-density lipoprotein cholesterol; HFD, high-fat diet; HFHSD, high-fat/high-sucrose diet; H₂O₂, hydrogen peroxide; HO-1, heme oxygenase 1; ICAM, intercellular adhesion molecule; IFN-γ, interferon-gamma; IgA+, immunoglobulin class A+; IgG, immunoglobulin class G; IL, interleukin; iNOS, inducible nitric oxide synthase; IRS, insulin receptor substrate; Keap1, Kelch-like ECH-associated protein 1; Klf4, Kruppel-like factor 4; LDL, low-density lipoprotein; LDL-C, low-density lipoprotein cholesterol; LPS, lipopolysaccharide; MCP, monocyte chelator protein; MDA, malondialdehyde; MMP, metalloproteinase; NO, nitric oxide; NQO1, NAD(P)H quinone dehydrogenase 1; Nrf2, transcription factor NF-E2-related factor 2; OA, oleic acid; OH, hydroxyl; ORAC, oxygen radical absorbance capacity; PPARγ, peroxisome proliferator-activated receptor γ; Pref, preadipocyte factor; PSE, pea seed extract; ROS, reactive oxygen species; Runx2, runt-related transcription factor; SBP, systolic blood pressure; SCD, stearoyl-CoA desaturase; SCFAs, short-chain fatty acids; SHR, spontaneously hypertensive rat; SOD, superoxide dismutase; Spdef1, SAM pointed domain ETS factor 1; SREBP, sterol regulatory element-binding protein; STZ, streptozotocin; T-AOC, total antioxidant capacity; TC, total cholesterol; TFC, total flavonoid content; Tff3, trefoil factor 3; TG, triglyceride; TGF-β1, transforming growth factor beta; TLR, toll-like receptors; TNF-α, tumor necrosis factor α; TPC, total phenolic content.