Ancient Latin-American food crops: An overview of their nutraceutical and antiobesity peptides

Abstract

Most of the plants used for human consumption comprise various peptides with health benefits, such as antihypertensive, antioxidant, anti-inflammatory, anticancer, and immunomodulatory capacity. The intake of plant-based bioactive peptides is important in the prevention of some chronic diseases. Also, peptides show positive effects on lipid metabolism and mineral absorption and act as analgesic, antithrombotic, antiatherosclerotic, and opioid agents; it is pertinent to mention that peptides quite often exhibit multiple bioactivities. Bioactive peptides are released by the hydrolysis of digestive enzymes, that is, pepsin, chymotrypsin, trypsin, or by in vitro producers using specific enzymes, pH, and temperature. These peptides comprise hydrophobic amino acids, positive charge and are resistant to digestive hydrolysis by peptidases and proteases. Small peptides with a dipeptide of proline–proline at their C terminal are more resistant to gastrointestinal enzymes; otherwise, large peptides are active outside the intestinal epithelium. This review is focused on three selected ancient crops from Latin America, amaranth, chia, and quinoa, because of their outstanding nutritional and agronomic characteristics that provide a broad of functional compounds with high antioxidant, anti-inflammatory, immunomodulatory, antidiabetic, antihypertensive, anticancer, and antiobesity capacity.

Keywords

Antioxidant food proteins nutraceuticals obesity bioactive peptides functional plant crops

INTRODUCTION

In the last decades, the relationship concerning diet and health is clearer than before; interestingly, this relationship has been known since Hippocrates’ times. Peptides, encrypted in the proteins’ primary structure, are released when proteins are hydrolyzed; they show functional characteristics, such as the treatment and prevention of some cardiovascular and chronic degenerative diseases. Peptides are signals that affect almost all life forms and inhibit interactions of protein-to-protein that are essential for bioprocesses and are great promises in innovative biotherapies (Apostolopoulos et al., 2021).

Peptides are unique compounds that offer extraordinary structural and functional diversity in relation to other bioactive compounds. Current findings in different scientific areas and bionanotechnological developments have supported the research on peptides, like those of half-life as well as bioavailability, and the search for the maximum potential to achieve biological applications to combat diverse pathogens (Muttenthaler et al., 2021).

Nowadays, peptides have gained increasing attention due to their biological applications; recently, novel advances in diverse scientific fields and biotechnological developments have been helped to identify their full potential (Bojarska, 2022). Otherwise, fermentation has been evaluated as an effective tool to produce bioactive peptides. Lactobacillus plantarum was used to generate peptides in flaxseed milk in order to achieve the largest amount of functional properties, such as antimicrobial, proteolytic, and antioxidant activities, and ACE inhibition (Sharma et al., 2021).

There is a great interest to interpret peptides with d-enantiomeric amino acids, conversion of amino acid sequences in SMILES code, batch processing, novel quantitative parameters to characterize bioactive fragments in protein sequences as well as search proteinases to release peptides. Nowadays, 764 proteins, 4726 bioactive peptides, 136 allergenic proteins, 582 sensory peptides as well as amino acids have been identified (Minkiewicz et al., 2019). The increase in aging population and public health concerns, besides technological developments in peptide synthesis and extraction, intensify the worldwide market growth in bioactive peptides. In 2022, this global market was around 4960.47 million USD and it is projected to reach 10,710.79 million USD in 2030, with an expected compound annual growth rate of 10.10% for the next 2023 to 2030 (Data Bridge Market Research, 2023). Based on the increased global market requirements for new medical compounds and strategies, it is evident the necessity of developing new technological procedures for producing the different bioactive peptides which are reported in this review.

It is worth to mention that short peptides are versatile molecules, structurally and functionally. They are naturally capable to prevent a wide diversity of pandemic pathogens, regardless of mutation, and have a great impact on the treatment of untreatable and rare health disorders (Apostolopoulos et al., 2021).

Amaranth, chia, and quinoa are some of the rediscovered food crops from Latin America with outstanding agronomical and unique nutritional properties. The nutraceutical potential of these crops has been of great interest mainly due to their bioactive compounds. This review is focused on the antioxidant, anti-inflammatory, immunomodulatory, antidiabetic, antihypertensive, anticancer, and antiobesity capacity of peptides from amaranth, chia, and quinoa. In view of the potentialities of these bioactive peptides, it is becoming evident the necessity of demonstrating the benefits through special clinical studies in human beings.

BIOACTIVE PROPERTIES OF PLANT PEPTIDES

Bioactive substances are molecules found in foods that regulate metabolic processes. Specific amino acid sequences in food proteins have various benefits on health, showing effects as part of the entire protein or being effective when they are released by enzymatic proteolysis (Minkiewicz et al., 2015). Enzymatic hydrolysis is a traditional and simple method, easy to inactivate, but when it is optimized it gives good yields of high-quality bioactive peptides (Maestri et al., 2019). Small peptides are being more studied because their small size protects them from enzymatic gastrointestinal hydrolysis, thus they reach intact the bloodstream and target organs (Ahmed et al., 2022). Thus, the selection of an adequate enzyme is essential for the best hydrolytic procedure. Otherwise, in silico methods are effective to identify potential bioactive compounds and determine the enzymatic release of bioactive peptides from food proteins (Lacroix and Li-Chan, 2012) and predict families of bioactive peptides from known protein sequences (Lafarga and Hayes, 2017).

Bioactive peptides are absorbed in the intestine and enter intact into the circulatory system, thus performing reactions which are an ideal characteristic to develop functional food products and nutritional supplements (Fan et al., 2022a, 2022b). Additionally, peptide mixtures are usually not more efficient than pure peptides as result of the loss of potential synergistic effects with other type of peptides (Akbarian et al., 2022).

Obesity is still a worldwide pandemic that is linked to millions of deaths every year, such as cardiovascular disease and diabetes. The excess of body fat in obese people harms the body's organs and tissues and is related to inflammation affecting numerous metabolic pathways. Plant peptides have demonstrated a potential anti-inflammatory and immunomodulatory capacity. Scientific literature reveals that bioactive peptides promote the decrease of pro-inflammatory cytokines and adipokines, as well as macrophage polarization to M2 phenotype (de Medeiros et al., 2022).

Novel peptides of plant origin are being constantly identified as well as advances in technologies for their extraction, purification, and characterization. Although the diverse functions rely on the amino acids’ structure and composition, their industrial application as bioactive peptides is still under study. Data on crop proteomics reveal that as much as 6000 proteins could comprise bioactive peptides (Bouglé and Bouhallab, 2017). Hence, additional clinical experiments are necessary to confirm their health benefits (Yuan et al., 2022).

As a result of the above mentioned items, our review is focused on the nutraceutical and therapeutical potential of peptides from three of the recently recovered outstanding Latin American seeds, amaranth, chia, and quinoa (Figure 1). The importance of these crops on human health, besides their interesting agronomic performance, also relies on their remarkable nutritional value and thus nowadays they have started to be frequently included in the daily diet at a worldwide level.

Figure 1.

(a) Amaranth plant and seeds, (b) chia plant and flowers, and (c) quinoa plants and seeds, respectively.

LATIN AMERICAN REGIONAL CROPS WITH BIOACTIVE PEPTIDES

Amaranth

Amaranth (Amaranthus hypochondriacus L.) is an ancient food crop used since pre-Columbian times, around 6000–8000 years ago. It is considered a pseudocereal with outstanding chemical composition from a nutraceutical perspective, as well as technofunctional properties, that is, production of emulsions and edible films to release substances with bioactive potential. Additionally, the importance of amaranth also relies on its gluten-free composition which is an excellent option for celiac patients. Metabolic processes involved in the germination of amaranth seed produce different bioactive peptides (Orona-Tamayo and Paredes-López, 2024). Amaranth peptides exhibit antihypertensive, anticancer, antioxidant, immunomodulatory, hypolipidemic, antimicrobial, antidiabetic, and antithrombotic properties (Figure 2) (Orona-Tamayo et al., 2019).

Figure 2.

Main health benefits of amaranth, chia, and quinoa peptides.

Antioxidant capacity

In a beverage of germinated amaranth fermented with Lactiplantibacillus plantarum, Hernández-García et al. (2022) observed higher antioxidant capacity (DPPH, ABTS, and FRAP). The peptidomic approach demonstrated 30 peptides with scavenging capacity in the 1–3 kDa fraction. Additionally, gastrointestinal digestion (in vitro) of germinated amaranth produced antioxidant and anti-inflammatory peptides. They were released following incubation for 90 min using pancreatin and were fractioned: F1, F2, and F3 (>10, 3–10, and <3 kDa), respectively. F2 showed high antioxidant potential, and F1 and F2 showed significant anti-inflammatory capacity induced through lipopolysaccharide stimulation of RAW 264.7 macrophages. Eleven peptides were identified with biological benefits to treat noncommunicable diseases (Sandoval-Sicairos et al., 2021).

Taniya et al. (2020) observed that heat denaturation in amaranth protein hydrolysates improved the digestibility, and thus the release of peptides and essential amino acids with antioxidant and free radical scavenging capacity. Otherwise, in Wistar rats fed either A. mantegazzianus protein isolate or flour in high-cholesterol and -fat diets, their intestine in amaranth flour diet showed higher antioxidant activity. The protein diet decreased blood levels of cholesterol and total lipids, in a dose–response relationship; although this trend was observed only when consuming high doses of the flour diet (García Fillería et al., 2021).

Amaranthus caudatus, kiwicha, subjected to gastrointestinal digestion (in vitro) released peptides with different function. Five of 13 peptides identified showed high potential as functional ingredients to prevent and control chronic degenerative disorders related to oxidative stress (Vilcacundo et al., 2017). During simulated digestion, A. caudatus protein concentrate had more susceptibility to intestinal digestion than gastric hydrolysis of pepsin. They exhibited antioxidant capacity (in vivo) in larvae of zebrafish. Lipid oxidation was reduced in the intestinal and gastric digests (96% and 73%, respectively), whereas the quenching of ROS was 48% in intestinal and 53% in gastric digests (Vilcacundo et al., 2018).

Anti-inflammatory and immunomodulatory effect

A lunasin-like peptide from A. hypochondriacus exhibited anticancer potential in NIH/3T3 cells. This peptide decreased the formation of anisokaryosis in the carcinogenic cells (Mazorra-Carrillo et al., 2022). Also, amaranth peptides demonstrated anti-inflammatory capacity at cellular level. Otherwise, peptides obtained by gastrointestinal digestion (in vitro) of germinated amaranth showed high anti-inflammatory capacity in lipopolysaccharide-induced RAW 264.7 macrophages. It is worth mentioning that 11 peptides were identified with biological potential to treat non-communicable diseases (Sandoval-Sicairos et al., 2021).

Antidiabetic potential

Conventional pharmacological therapies for type 2 diabetes (T2D) are effective but possess underlying side effects. Some specific peptides and amaranth hydrolysates show high potential to inhibit dipeptidyl peptidase-IV, α-glucosidase, and α-amylase activity. Amaranth protein hydrolyzed with bromelain exhibited higher anti-α-glucosidase and -DPP-IV capacity than using pronase or chymotrypsin. FPFPPTLGY and FPFPR peptides showed binding capacity for hotspots of α-glucosidase and DPP-IV, respectively (Kamal et al., 2021) (Table 1). Thus, amaranth peptides should be a healthier alternative than the available antidiabetic drugs for practical applications.

Table 1.

Bioactivity of amaranth peptides.

Peptide sequence	Bioactivity	Reference
IQAEGGLT, DKDYPK	DPP-IV and α-amylase inhibition	Sandoval-Sicairos et al. (2021)
GEHGSDGNV	α-glucosidase inhibition	Sandoval-Sicairos et al. (2021)
FPFPR, FPFPPTLGY	DPP-IV and α-amylase inhibition	Kamal et al. (2021)
FPFPPTLGY, FGAPR	Pancreatic lipase inhibitor	Ajayi et al. (2021)
FPFVPAPT	Cholesterol esterase inhibitor	Ajayi et al. (2021)
GGV, IVG, VGVL	HMG-CoA reductase inhibitor	Ajayi et al. (2021)
VIKP	ACE inhibitor	Soares et al. (2015)
NIDMLRL, LVRW, VRWS, VR, CIHNIVY	ACE inhibitor	Nardo et al. (2020), Vecchi and Añón (2009)

DPP-IV: dipeptidyl peptidase IV; HMG-CoA: 3 hydroxy-3-methylglutaryl-coenzyme A; ACE: angiotensin-converting enzyme.

Antihypertensive effect

Hypertension is one of the most common leading causes of cardiovascular disease. This serious medical condition can be controlled by practicing regular exercise with a balanced diet, low salt intake, and quitting smoking (WHO, 2024). In vivo assays of amaranth hydrolysates and peptides confirm their potential against hypertension. A. hypochondriacus hydrolysates obtained with alcalase showed antihypertensive properties compared to VIKP, tetrapeptides with ACE capacity (Vecchi and Añón, 2009). Otherwise, 4–8 amino acid peptides, such as NIDMLRL, CIHNIVY, VR, VRWS, and LVRW exhibited ACE inhibitory capacity (Nardo et al., 2020).

After simulated gastrointestinal digestion, peptides released from an amaranth beverage showed inhibition of ACE, and the purified fractions demonstrated high ACE inhibitory capacity with an IC₅₀ of 60 μg/mL. Six out of the 26 identified peptide sequences exhibited antihypertensive capacity, particularly IERGEGIMGV (Suárez et al., 2024).

Anticancer activity

Protein hydrolysates from A. mantegazzianus, A. caudatus, and A. cruentus demonstrated anticancer capacity against various cancer cell lines (Mazorra-Carrillo et al., 2022). A. caudatus hydrolysates (100 μg/mL) showed more capacity to inhibit breast cancer in MDA-MB-231 cells, than curcumin (Taniya et al., 2020). In vitro assays showed that digested samples inhibited breast cancer cell growth (GI₅₀ 48.3 ± 0.2 μg/mL). Loss of membrane integrity, fragmentation of DNA, translocation of phosphatidylserine, and caspase-3 activity were also observed. Additionally, they reduced cell migration in an induced wound within the cell monolayer.

Antiobesity capacity

Diets based on amaranth protein reduce food intake, as well as body weight, by reducing plasma ghrelin and increasing postprandial cholecystokinin and leptin in rats (Mithila and Khanum, 2015). In addition, amaranth protein decreased plasma insulin levels in mice fed a normal diet; however, those with a high-fat diet showed a reduction in triglycerides. Downregulation of TNF-α and Res suggests anti-inflammatory potential (Escobedo-Moratilla et al., 2017).

Amaranth protein hydrolysates produced with bromelain (AB4) showed higher pancreatic lipase (PL) inhibiting potential than amaranth proteins. AB4 exhibited a significant capacity to inhibit cholesterol esterase (Cease) and PL. Among the 17 peptides that were identified in AB4, three (FPFPPTLGY, FPFVPAPT, and FGAPR) demonstrated PL inhibitory capacity and FPFVPAPT inhibited Cease (Ajayi et al., 2021). In this sense, GGV, VGVL, and IVG peptides inhibited HMG-CoA reductase, thus suggesting hypocholesterolemic effect, which could help to treat overweight and obesity (Soares et al., 2015).

Chia

Seeds from chia (S. hispanica L.) have one of the most high-quality vegetative proteins, they also are rich in omega-3 polyunsaturated fatty acids and soluble fiber, have good gelling capacity, and outstanding amounts of peptides with health benefits. They act as antioxidants, DPP-IV and ACE inhibitors, and hypoglycemic and anti-inflammatory drugs. The daily intake of these compounds, by direct or indirect consumption, provides with a great number of nutraceutical benefits for specific health conditions (Rabail et al., 2021). As indicated by the in silico approach of antibiofilm, antimicrobial, and antioxidant capacity of chia peptides confirmed their potential as novel substances for the food industry since they are not toxic and can easily dissolve in water. KLLKKYL peptide exhibited the most elevated antimicrobial and antibiofilm activity (Table 2). Moreover, according to BIOPEP-UWM database, it showed a greater frequency of occurrence of antioxidant fragments in relation to KKLLKI, YACLKVK, and KLKKNL (León-Madrazo and Segura-Campos, 2022).

Table 2.

Bioactivity of chia peptides.

Peptide sequence	Bioactivity	Reference
HYGGPPGGCR	Interaction with p65-NF-κB	Suárez et al. (2024)
KLLKKYL	Antimicrobial	Suárez et al. (2024)
KKLLKI, YACLKVK, KLKKNL	Antioxidant	Rabail et al. (2021)
NSPGPHDVALDQ, RMVLPEYELLYE	Interaction with FAS and monoacylglycerol lipase and PPAR-γ receptor	Grancieri et al. (2021)
TGPSPTAGPPAPGGGTH, YLGAHPGTAN	PPAR-γ and MAGL inhibition	Grancieri et al. (2021)
(PAP)-1, PAP-2, PAP-3, PAP-4, PAP-5	Anticancer	Quintal Bojórquez et al. (2024)
RGQVIYVL	ACE-inhibitory	Zheng et al. (2019)

NF-κB: nuclear factor kappa B; FAS: fatty acid synthase; PPAR-γ: peroxisome proliferator-activated receptor; MAGL, monoacylglycerol lipase; ACE, angiotensin-converting enzyme; PAP: potentially anticancer peptide.

Antioxidant capacity

Chia seeds have proteins of high quality which comprise nutraceutical peptides with health benefits. Twenty chia proteins of the total amount have been classified, which are involved in basal metabolism (Gómez-Favela et al., 2017). Chia seeds coproducts, resulting from the oil production, were subjected to papain digestion and released <15 kDa peptides; they showed significant radical scavenging capacity against DPPH and ABTS radicals in relation to nondigested samples (Cotabarren et al., 2019).

Ozón et al. (2023) supplemented wheat bread with ≥10 mg S. hispanica expeller hydrolysate/g. Protein hydrolysates obtained by alcalase reached 54.3% hydrolysis degree and 55.8% antioxidant capacity after incubation at 25 °C for 6 h. They exhibit considerable technofunctional and chemical properties for the bakery industry.

Anti-inflammatory and immunomodulatory effect

Chia protein fractions released albumin, globulin, prolamin, as well as glutelin peptides that are related to COX-2 (cyclooxygenase-2), NF-κB p65, LOX-1 (oxidized low-density lipoprotein) receptor, and TLR4 (toll-like receptor 4). They also exhibited anti-inflammatory capacity, while the peptides fraction of 1–3 kDa exhibited high potential when reducing nitric oxide, ROS, prostaglandins, TNF-α, MCP-1, (IL)-6, and -10 concentration (65.1%, 19.7%, 34.6%, 24.1%, 18.9%, and 39.6%, respectively) (Suárez et al., 2024).

Cárdenas et al. (2018) observed that S. hispanica protein concentrate (100–1000 μg/mL) at pH 3 showed important anti-inflammatory potential (56.32%), which was dose dependent. Otherwise, the intake of chia (150 g/kg) demonstrated immunostimulant capacity and improved the concentration of antibodies (IgE) in rats (Sierra et al., 2015).

Antidiabetic potential

The primary goal to prevent and treat diabetes is the control of postprandial hyperglycemia. The reduction of blood glucose levels by inhibiting the activity of α-amylase and α-glucosidase to moderate carbohydrate absorption is a key strategy to control T2D (Dowarah and Singh, 2020).

Chia protein isolate delivered several peptides when subjected to different types of hydrolysis. DPP-IV has an important role in the control of blood glucose levels. The molecular docking approach in chia seed determined the fragments of the peptides with capacity to inhibit DPP-IV and α-glucosidase: PW\PF\PPG\PM\SW\IW\SF\PP\PPL\PG\PY\VW\PL and PP/PW, respectively (Valenzuela Zamudio et al., 2022).

Antihypertensive effect

Peptides from chia globulin and albumin exhibited significant antiradical capacity against DPPH, ABTS, and ACE. The intake of bioactive peptides from S. hispanica demonstrates ACE inhibitory potential which is directly related to their hydrolysis process (Orona-Tamayo et al., 2019). Chia peptides (3 kDa) reduced the rate of HMG-CoA reductase at 80.7%, which was inhibited with pravastatin (81.5%). These peptides have inhibitory HMG-CoA reductase activity and thus suppress the mevalonate pathway and reduce hypercholesterolemia (Coelho et al., 2018).

Anticancer activity

Hydrolyzed chia oil (12.5–400 μg/mL) used to treat cancer cells for 48 h produced a considerable reduction (23.88%) of cell viability in Caco2 lines, at 25 μg/mL concentration. Conversely, higher concentrations (200 and 400 μg/mL) were required to increase the viability of tumorigenic cells in breast cancer lines (Ortega et al., 2022).

Peptide sequences from a protein fraction (<1 kDa) of S. hispanica subjected to multiple criteria decision analysis and molecular docking revealed potential anticancer peptides [(PAP)-1, -2, -3, -4, -5] by their binding affinities with molecules related to apoptosis and cancer. The binding interactions of these PAPs were strong (<−100 kcal/mol); otherwise, PAP-3 exhibited a very low free energy to bind to various targets. Therefore, PAP-3 might be considered a functional compound to adjuvate in cancer therapies (Quintal Bojórquez et al., 2024).

Antiobesity capacity

Grancieri et al. (2021) observed that differentiated 3T3-L1 preadipocytes with digested total proteins, or albumin or glutelin at 1 mg/mL, or pure peptides (NSPGPHDVALDQ and RMVLPEYELLYE, 100 µM) from chia seeds reduced adipogenesis, diminished (≥50%) the expression of PPAR-γ, fatty acid synthase, lipoprotein lipase, SREBP1, lipase activity, and triglycerides in a lesser degree.

Chia peptides are implicated in lipogenesis and glucose metabolism. PPAR-γ and SREBP1 modulate Lp1 expression and other types of lipoproteins. Lp1 promotes lipid metabolism and transport, which impact energy balance and lipid transport in the body. Also, PPAR-γ regulates adipogenesis and its expression could be influenced by other elements, that is, SREBP1, that control adipogenesis induced by insulin (Batista et al., 2023).

Quinoa

The interest in the intake of quinoa (Chenopodium quinoa) is rising in the entire world, and it is mainly due to its outstanding amount of gluten-free protein. This seed is a good source of high-quality proteins that include all the essential amino acids (Abbasi et al., 2022). Additionally, it provides bioactive peptides with various properties, such as antidiabetic, antihypertensive, antioxidant, and anti-inflammatory capacity. Bioinformatics analyses (simulation of proteolysis, virtual screening, molecular docking) are alternatives to explore their potential health benefits (Figure 3).

Figure 3.

Processing of bioactive peptides from amaranth, chia, and quinoa seeds.

Nongonierma et al. (2015) found that protein hydrolysates from quinoa obtained after in vitro enzymolysis exhibit important antidiabetic capacity as result of the inhibition of certain types of enzymes. Vilcacundo et al. (2017) evaluated the effect of gastrointestinal digestion (in vitro) of kiwicha proteins in peptide production. Five out of 13 peptides found in kiwicha digests demonstrated high capacity as nutraceuticals to prevent and treat chronic disorders related to aging, diabetes, and hypertension. Synthetic peptides (DKDYPK, IQAEGGLT, and GEHGSDGNV) corresponding to sequences identified in concentrates of digested quinoa protein showed inhibitory activity of α-amylase, DPP-IV, and α-glucosidase, respectively.

Antioxidant capacity

After in silico analysis, ASPKPSSA (743.8 Da) and QFLLAGR (803.5 Da) peptides with antioxidant capacity (Table 3) were produced from quinoa bran albumin hydrolysates. They also demonstrated high·OH and ABTS+ scavenging activity and Fe2 + chelating capacity. It is worth mentioning that their activity was stable after gastrointestinal digestion (Zheng et al., 2019).

Table 3.

Bioactivity of some peptides from quinoa.

Peptide sequence	Bioactivity	Reference
ASPKPSSA, QFLLAGR	Antioxidant	Ortega et al. (2022)
RGQVIYVL	ACE-inhibitor and antioxidant	Abbasi et al. (2022)
IVLVQEG, TLFRPEN, VGFGI, FTLIIN, LENSGDKKY	Antioxidant	Zheng et al. (2019)
LAHMIVAGA, VAHPVF	α-glucosidase and ACE inhibitory	Capraro et al. (2020)
IPI, IPV, VAYPL, IPIN, APFTVV	DPP-IV inhibition	Obaroakpo et al. (2019)

ACE: angiotensin-converting enzyme; DPP-IV: dipeptidyl peptidase IV.

Quinoa proteins released chemopreventive peptides by in vitro digestion, and after sequential incubation (pepsin and pancreatin) peptide fractions (<5 kDa) exhibited potent radical scavenging activity (Vilcacundo et al., 2018). Quinoa peptides obtained after 0.5 and 4 h (≤10 and ≥3 kDa, respectively) using alcalase and trypsin, respectively, showed elevated antioxidant capacity (Abbasi et al., 2022).

Five quinoa peptides (5–9 amino acid residues) showed high antioxidant potential. IVLVQEG and TLFRPEN peptides are encrypted into a quinoa globulin B; VGFGI and FTLIIN peptides were produced from a salt-sensitive protein, otherwise LENSGDKKY was found in a maturase K protein (Rizzello et al., 2017).

Anti-inflammatory and immunomodulatory effect

Ravisankar et al. (2015) observed that quinoa peptides regulate the NF-κB pathway by downregulating NF-κB and upregulating PPAR-γ on lipopolysaccharide-induced human umbilical vein endothelial cells, which is associated with apoptosis, cellular differentiation, as well as anti-inflammatory reactions.

Lunasin (43 amino acids) is a quinoa peptide with the ability to inhibit NO production, interleukin-6 and TNF-α (Ren et al., 2017). Chenopodin (a quinoa seed 11S globulin) reduced NF-κB activation and interleukin-8 expression, thus protecting Caco-2 cells from inflammation. Additionally, intact albumin from quinoa seed shows better anti-inflammatory capacity as compared to fractions from globulin (Capraro et al., 2020).

Antidiabetic potential

After hydrolysis by trypsin, quinoa protein released peptides (≥3 kDa) with high α-glucosidase inhibitory activity (Abbasi et al., 2022). A protein hydrolysate from a yogurt beverage made with sprouted quinoa showed antidiabetic potential by the α-glucosidase inhibition, which resulted from the germination time and inoculants strains. Based on in silico analysis, hydrolysates of quinoa protein are proposed as inhibitors of DPP-IV (Obaroakpo et al., 2019).

White quinoa hydrolysates, germinated during 2 h and digested with pepsin and trypsin, showed a higher capacity to inhibit DPP-IV than those using papain, alcalase, neutrase, and flavoenzyme. The QPH1 (1 kDa) quinoa fraction demonstrated good in vitro and in situ inhibitory potential against DPP-IV (IC₅₀ 3.40 and 2.20 mg/mL, respectively) on caco-2 cells. Twenty quinoa peptides showed in vitro potential to inhibit DPP-IV (IC₅₀ values 500 μM). IPV, IPI, IPIN, and VAYPL peptides exhibited the highest capacity (IC₅₀ 26.15, 5.25, 56.58, and 42.93 μM, respectively) (You et al., 2022).

Antihypertensive effect

After in silico analysis of quinoa bran albumin, some peptides were identified, such as RGQVIYVL (946.6 Da) with ACE inhibitory potential and antioxidant capacity, as well as ASPKPSSA (743.8 Da) and QFLLAGR (803.5 Da) with antioxidant activity. RGQVIYVL exhibited significant ACE inhibitory potential (IC₅₀: 38.16 µM), demonstrating considerable antihypertensive effect in hypertensive rats (Zheng et al., 2019).

Protein hydrolysates from germination-based quinoa yogurt showed a dose- and strain-dependent capacity to inhibit ACE (127 mg/mL); QLCZ peptide exhibited the strongest inhibition, IC₅₀= 0.03 mg/mL. LAHMIVAGA and VAHPVF peptide sequences also had significant ACE inhibitory activity (Capraro et al., 2020). In digested quinoa protein isolates subjected to NWFPLPR, NIFRPF, and FHPFPR peptides were identified, showing outstanding capacity against ACE (Guo et al., 2020).

Glutelin-2 hydrolysates of quinoa bran, digested with papain and flavoenzyme, analyzed by UPLC-ESI–MS/MS, released four peptides. Only AVPKPS peptide showed ACE inhibition (IC₅₀= 123.13 μmol/L) and remained stable under gastrointestinal digestion (Li et al., 2023).

Anticancer activity

Quinoa protein digests demonstrated anticancer activity, through the analysis of Caco-2, HCT-116, and HT-29 human colorectal cancer cell lines. High molecular weight (>5 kDa) peptides showed more capacity to inhibit cell viability than low molecular weight (<5 kDa) peptides. Various 11S globulin peptides and quinoa proteins have bioactive properties and could be used as novel nutraceuticals product to reduce chronic disease associated with oxidative stress (Vilcacundo et al., 2018). Additionally, HYNPYFPGGA, FHPFPR, and NWFPLPR quinoa peptides exerted antiproliferative activity against colon cancer cells (Fan et al., 2022a, 2022b).

Antiobesity capacity

Quinoa peptides are involved in the management of energy, lipid and glucose metabolism, adipogenesis, and gut microbiota, as well as in the inhibition of carbohydrate digestion with incretin signaling (Little et al., 2021).

A 60% high-fat diet (treated with 10 mg 20-hydroxyecdysone/kg bw/day) administered to mice for 13 weeks supported a greater reduction of weight gain and adipose-lean ratio than an HFD. Adiponectin was expressed 7.9-fold higher than HFD in their visceral fat tissue (Kizelsztein et al., 2009). Rivero-Pino et al. (2021) improved the bioactivity of quinoa protein through enzymatic hydrolysis and found that the released APFTVV peptide showed DPP-IV inhibitory potential.

CONCLUSIONS

Bioactive peptides with health-promoting potential have focused the interest in plant food proteins for the development of functional products. These compounds could prevent and control the onset of several health disorders, such as hypertension, different cancers, obesity, and heart disease.

Mesoamerica and the Andean area in South America are outstanding centers of domestication of a great number of food crops. When European conquerors arrived in South America, the native population used to cultivate practically as much plant species as farmers of Europe and Asia. It is worth mentioning that amaranth, chia, and quinoa are nutritious crops cultivated in increasing community areas of Latin America. These seeds were used as traditional ingredient of indigenous dietary habits. Nowadays, they show excellent characteristics for the food industry and for special needs such as gluten-free diets and other possible options (Melgarejo-Cabello et al., 2023).

Even though substantial work on the production, processing, and use of peptides with bioactive capacity, further research is necessary to achieve more scientific data to understand the effects of these selected proteins and peptides; however, it is clear the need to determine their bioactive potential for various specific disease biomarkers. There are several research works and preclinical studies (Quintal Bojórquez and Segura Campos, 2024), but it is evident that clinical studies in humans are really very scarce; therefore, it is extremely important to carry out research investigations over this latter topic. In brief, amaranth, chia, and quinoa bioactive peptides require additional studies about their specific sequences as well as their diverse health benefits.

FUTURE RESEARCH DIRECTIONS

In order to improve human health, it is important to introduce into the daily diet, or as supplement, food crops with essential compounds as well as bioactive peptides.

There is a need for further research on preclinical and clinical studies on humans, in order to establish a better relationship between the benefits of peptides from these Latin American crops on obesity. On the other hand, as it has been stated in this report, chia, amaranth, and quinoa are crops with unique agronomical and nutritional characteristics that may provide a wide range of bioactive peptides.

We have found research studies showing that there is no synergistic effect with the tested peptides. However, it is believed that wider experimentations are needed to clarify the potential of this effect with other different peptides and compounds. The scientific literature shows a lack of research works through out in vivo and clinical studies in relation to the properties of bioactive peptides; there are mostly works on preclinical experimentations, thus, we are suggesting that a clear emphasis should be on the type of studies we are indicating here. Up to our knowledge, there is a lack of relevant investigations on the antiobesity potential of bioactives isolated from each of the three crops; this is another field pending more experimental work.

Footnotes

ACKNOWLEDGEMENTS

The authors would like to acknowledge partial financial support from Consejo Nacional de Humanidades, Ciencia y Tecnología (CONAHCyT-México).

DECLARATION OF CONFLICTING INTERESTS

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

FUNDING

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Octavio Paredes-López

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