Selection of studies
The search in the databases yielded 1,009 studies, two of which were duplicates and were eliminated, obtaining 1,007 articles. When examining the titles and abstracts, 78 studies were selected and subsequently examined in full text, applying the inclusion and exclusion criteria. Finally, 23 studies were obtained to write this review (Fig. 1).
Characteristics of the selected studies
The peptides selected in this review came from animal sources (Cheng et al. 2020; Abdelhedi et al. 2017; Montoro-García et al. 2017; Neves et al. 2017; Chen et al. 2018a, b; Xue et al. 2018; Lin et al. 2019; Liu et al. 2019; Yu et al. 2020; Kang et al. 2020; Oh et al. 2020), plant sources (Cooper et al. 2007; Wang et al. 2017, 2021; Chia-Cheng et al. 2019; Dang et al. 2019; Shih et al. 2019; Vásquez-Villanueva et al. 2019; Alcaide-Hidalgo et al. 2020; Zhang et al. 2020) and fungi (Manoharan et al. 2017; Amorim et al. 2019) (Table 1).
Table 1
Characteristic of the studies included in the review.
Author
|
Country
|
Food
|
Extraction method
|
Identification method
|
(Kang et al. 2020)
|
Korea
|
Styela clava
|
Enzymatic hydrolysis (Pepsin, Papain)
|
HPLC-QTOF-ESI
|
(Lin et al. 2019)
|
Taiwan
|
Marine Cobia Skin
|
Enzymatic hydrolysis – ultrafiltration - lyophilization.
|
RP-HPLC-UV
|
(Liu et al. 2019)
|
China
|
Pearl Oyster
(Pinctada fucata martensii)
|
Enzymatic hydrolysis with alkaline protease and ultrafiltration.
|
MALDI-TOF-TOF
|
(Chen et al. 2020)
|
China
|
Lizardfish (Synodus macrops) Scale Gelatin
|
Precipitation and alkaline extraction. Chemical synthesis
|
HPLC
|
(Chen et al. 2018a)
|
China
|
Big-eyed lizardfish (Synodus macrops Tanaka)
|
Enzymatic hydrolysis with bromelain, alcalase, chymotrypsin, papain, acid protease, trypsin and neutral protease.
|
Nano-LC-MS/MS
|
(Oh et al. 2020)
|
Korea
|
Olive Flounder (Paralichthys olivaceus) Surimi
|
Acid hydrolysis with hydrochloric acid.
|
(RP-HPLC) - (ESI)
|
(Chen et al. 2018b)
|
China
|
Ruditapes philippinarum fermented with Bacillus natto
|
Ultrafiltration
|
(Nano-RP HPLC-MS / MS).
|
(Montoro-García et al. 2017)
|
Spain
|
Dry cured pork ham.
|
Chemical degradation with ethanol, centrifugation and lyophilization.
|
Nano-LC - Q/ToF,
|
(Abdelhedi et al. 2017)
|
Tunisia
|
Smooth - hound viscera protein
(Mustelus mustelus)
|
Enzymatic hydrolysis with Esperase.
|
LC-MS/MS
|
(Neves et al. 2017)
|
Ireland
|
Salmon gelatin
|
Enzymatic hydrolysis (Alcalase, Flavourzyme).
|
De novo sequencing
|
(Xue et al. 2018)
|
China
|
Casein
|
Enzymatic hydrolysis with pepsin and trypsin.
|
LC-MC - NSI
|
(Yu et al. 2020)
|
China
|
Egg white
|
Chemical synthesis
|
LC-MS
|
(Wang et al. 2021)
|
China
|
Rapeseed meal
|
Enzymatic hydrolysis with Alcalase.
|
Spectrophotometric method with FAPGG as substrate.
|
(Alcaide-Hidalgo et al. 2020)
|
Spain
|
Olive Oil
|
Gel filtration chromatography
|
Nano-LC-MS/MS
|
(Vásquez-Villanueva et al. 2019)
|
Spain
|
Peach Seed
|
Enzymatic hydrolysis with thermolysin.
|
RP-HPLC-MS/MS
|
(Dang et al. 2019)
|
China
|
Broccoli
|
Enzymatic hydrolysis
(chymotrypsin and thermolysin)
|
HPLC Q-TOF.
|
(Shih et al. 2019)
|
Taiwan
|
Cassia obtusifolia seeds
|
Enzymatic hydrolysis with four types
of proteases, trypsin, α-chymotrypsin, pepsin and thermolysin.
|
LC-MS/MS - Novo sequencing.
|
(Li et al. 2019)
|
Taiwan
|
corn silk
|
Centrifugation.
|
LC-MS/MS
|
(Wang et al. 2017)
|
China
|
Rice bran
|
Hidrolisis enzimática con tripsina
|
TOF-Q II - ESI
|
(Zhang et al. 2019)
|
China
|
Glutelin of
vinegar-soaked black soybean
|
Enzymatic hydrolysis with pepsin, trypsin, α-chymotrypsin and alcalase
|
LC-MS/MS).
|
(Sonklin et al. 2020)
|
Canada
|
Mung bean protein
|
Enzymatic hydrolysis with bromelain.
|
MS/MS - ESI
|
(Manoharan et al. 2017)
|
Malaysia
|
Pleurotus pulmonarius.
|
SDS-PAGE.
|
MALDI-TOF/TOF.
|
(Amorim et al. 2019)
|
Portugal
|
Spent brewer yeast
|
Enzymatic autolysis and hydrolysis, membrane filtration fractionation, ultrafiltration, hydrolysis with Cynara cardunculus proteases and nanofiltration.
|
MALDI-TOF/TOF.
|
HPLC: high performance liquid chromatography; QTOF: Quadrupole time-of-flight; ESI: Electrospray ionization; MALDI: matrix-assisted laser desorption/ionization; TOF: Time of flight mass spectrometer; LC: Liquid chromatography |
Bioactive peptides identified
Bioactive peptides of animal origin
In total, 12 articles were found that studied peptides of animal origin, among which nine came from marine animals (Abdelhedi et al. 2017; Neves et al. 2017; Chen et al. 2018a, b; Lin et al. 2019; Liu et al. 2019; Kang et al. 2020; Oh et al. 2020); one of milk, one of egg, and one of pork (Montoro-García et al. 2017; Yu et al. 2020) (Table 2).
Table 2
Bioactive peptides with hypertensive activity of animal origin.
Food
|
Peptide sequence
|
IC50
|
Main result
|
Styela clava
(Kang et al. 2020)
|
LWHTH
|
16,42 − 0,45 µM.
|
LWHTH strongly inhibited ACE in a concentration-dependent manner. Blood pressure in hypertensive rats decreased and was maintained until 9 h with a clear difference compared to captopril at 9 h. (p < .01).
|
Marine Cobia Skin (Lin et al. 2019)
|
TAA
|
118,5 µM
|
TAA and TL were the most potent ACE inhibitory peptides at in vitro level and had evident antihypertensive activity in vivo when oral doses were administered to hypertensive rats; four hours later, the blood pressure of the experimental group had fallen below controls.
|
ATT
|
9,40 µM
|
ITT
|
0,50 µM
|
TL
|
26.8 µM.
|
Pearl Oyster
(Pinctada fucata martensii) (Liu et al. 2019)
|
HLHT
|
458,06 ± 3,24 µM.
|
Peptides HLHT and GWA exhibited high ACE inhibitory activity and competitive and noncompetitive inhibition pathways.
|
GWA
|
109,25 ± 1,45 µM.
|
Lizardfish (Synodus macrops) Scale Gelatin
(Chen et al. 2020)
|
LSGYGP
|
2,577 µM
|
LSGYGP exerted a feasible antihypertensive effect in vitro without cytotoxic concentration; it acts as a mixed non-competitive inhibitor, unlike captopril which is competitive. In vivo tests showed a significant decrease in blood pressure after 6 hours, and good digestive stability was maintained for 4 hours.
|
Big-eyed lizardfish (Synodus macrops Tanaka)
(Chen et al. 2018a)
|
AGPPGSDGQPGAK.
|
420 ± 20 µM.
|
AGPPGSDGQPGAK exhibited high ACE inhibitory activity and antihypertensive effect in hypertensive rats at a dose of 2 g kg− 1. The decrease in SBP caused by gelatin peptide was greater than that caused by 2 mg/kg captopril.
|
Olive Flounder (Paralichthys olivaceus)
(Oh et al. 2020)
|
IVDR
|
46900 µM.
|
IVDR, WYK, and VASVI, all three peptides have high ACE inhibitory activity. However, IVDR exhibited the highest ACE binding energy and negative interaction energy in molecular docking analyses.
|
WYK
|
32970 µM.
|
VSAVI
|
32660 µM.
|
Ruditapes philippinarum fermented with Bacillus natto (Chen et al. 2018b)
|
VISDEDGVTH LDSGDGVT
VVVGDGAVGK
FAGDDAPRA.
|
VISDEDGVTH: 8,16 µM.
|
VISDEDGVTH presented high ACE inhibitory activity, acts as a competitive inhibitor against active sites, is stable against gastrointestinal proteases, also in vivo in hypertensive rats, demonstrated an important antihypertensive effect.
|
Dry cured pork ham
(Montoro-García et al. 2017)
|
KAAAAP
AAPLAP
AAATP
KPVAAP,
VPPAK
KPGRP
PAAPPK.
|
12,37 − 25,94 µM.
|
The peptides KAAAAP, AAPLAP, AAATP, KPVAAP, VPPAK, KPGRP, and PAAPPK, demonstrated potent ACE inhibitory activity. A daily intake of 80 g of cured ham did not affect BP or sodium excretion in 24 h.
|
Smooth - hound viscera protein
(Mustelus mustelus)
(Abdelhedi et al. 2017)
|
MYPGIADRM
MEKIWHHT GDDAPRAVFPS GPAGPRGPA IAGPPGSAGPAG PRGPAGPHGPP VVPFEGAV PLPKREE
DSFEGLQQ PTVPKRPSPT EGLQQLR.
|
571,39–164,56 µg mL− 1
|
All peptides were able to inhibit ACE activity to different degrees. In molecular docking studies, the lowest interaction energy scores were recorded for IAGPPGSAGPAG (-21.076), followed by PLPKREE (-21.143) and PTVPKRPSPT (-21.679), indicating that these peptides could efficiently interact with ACE.
|
Salmon gelatin (Neves et al. 2017)
|
PP
|
1912,46 ± 63,15µM.
|
PP was the most potent ACE inhibitory peptide, followed by GGPAGPAV. In addition, Salmon gelatin hydrolysates improved SBP, DBP, and MAP in hypertensive rats and reduced heart rate to an extent equivalent to that of Captopril.
|
GF
|
178,14 ± 24,51 µM.
|
GPVA
|
445,61 ± 6,94 µM.
|
GGPAGPAV
|
673,16 ± 15,03 µM.
|
Casein
(Xue et al. 2018)
|
YQK
|
15,2 mg mL− 1
|
Of 8 peptides identified, only YQK and INNQFLPYPY showed ACE inhibitory activity. YQK in vivo reached a maximal pressure drop in hypertensive rats of 36.8 ± 3.3 mmHg at 4 h in the first dose, and in the second dose, the pressure remained stable for 4 h.
|
INNQFLPYPY
|
211 mg mL− 1
|
Egg white
(Yu et al. 2020)
|
TNGIIR
|
70 µM.
|
At a 50mg kg− 1 dose, the TNGIIR peptide showed excellent in vitro ACE inhibitory activity. In addition, an excellent inhibitory effect on ACE and AT1 receptor mRNA expression was observed in hypertensive rats, and it also significantly decreased the serum concentration of ATII.
|
IC50: Half maximal inhibitory concentration; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; MAP: Mean arterial pressure; AT1: Angiotensin I, ATII: Angiotensin II. |
Foods of animal origin are highly consumed due to their nutritional contribution, represented in the large number of essential amino acids that have (Quesada and Gómez 2019); They are also more easily digested. During this review, it was found that 52% of the selected studies analyzed peptides of animal origin from foods such as fish (Abdelhedi et al. 2017; Neves et al. 2017; Chen et al. 2018a; Lin et al. 2019; Kang et al. 2020; Oh et al. 2020) pork ham (Montoro-García et al. 2017), milk (Xue et al. 2018) and egg white (Yu et al. 2020).
Most of the animal-derived peptides were obtained from marine sources such as fish, oysters, and clams; interesting fact because these are a good source of protein, and their peptides have shown a wide spectrum of antimicrobial, antiviral, antihypertensive, antidiabetic activities, among others (Cheung et al. 2015), for this reason, they have potential applications in the pharmaceutical and nutritional industry. In the case of the marine invertebrate Styela clava (Kang et al. 2020) (67% protein), the LWHTH peptide was found to regulate blood pressure in hypertensive rats by strongly inhibiting ACE (IC50 = 6.42–0.45 µM). In addition, this peptide was shown to be stable against digestion with gastrointestinal enzymes (pepsin, trypsin, and alpha chymotrypsin) and showed better absorption since it is structurally made up of essential nutrients amino acids, thus favoring its potential use as a natural antihypertensive (Kang et al. 2020).
Other sources such as olive flounder (P. Olivaceus) surimi also showed important physiological actions in the regulation of blood pressure (Oh et al. 2020); in which the IVDR, WYK, and VASVI sequences were identified (IC50: 46.90, 32.97 and 32.66 µM, respectively). This study reinforces that evidenced by Ko et al. (2016), where other peptides with antihypertensive activity from the muscle of P. olivaceus were identified, including MEVFVP (IC50 = 79 µM) and VSQLTR (IC50 = 105 µM) (Ko et al. 2016); a fact that demonstrates the potential of this animal as a rich source of bioactive peptides, which are maintained even in preparations such as surimi.
Regarding fish by-products (skin, scales, visors, and bones), it has been found that in addition to obtaining valuable components such as oil, proteins, collagen, enzymes, and minerals, they also have bioactive compounds with antihypertensive action, as reported by Abdelhedi et al. (2017). In this study, bioactive peptides from fish viscera (IAGPPGSAGPAG, VVPFEGAV, PLPKREE, and PTVPKRPSPT) were identified, which showed in silico inhibitory activity against ACE to different degrees, revealing that they bind to the catalytic site of the enzyme (Abdelhedi et al. 2017). For their part, Chen et al. (2020) found the peptide LSGYGP (IC50 = 2,577 µM) in tilapia skin, which showed a significant decrease in blood pressure in hypertensive rats as well as good digestive stability (Cheng et al. 2020).
On the other hand, sources derived from animals such as milk and eggs have been subject of much research in terms of bioactive peptides. In this sense, Xue et al. (2018) identified a new ACE-inhibiting peptide derived from bovine casein (YQK, IC50 = 11.1 µM) and from the YQKFPQYLQY sequence, which was shown to significantly reduce blood pressure systolic blood pressure of hypertensive rats (Xue et al. 2018). Another source of peptides was egg white, of which Yu et al. (2020) found the TNGIIR hexapeptide (70 µM), whose activity inhibited the expression of ACE and AT1 receptor mRNA in hypertensive rats and also significantly decreased the serum concentration of ATII (Yu et al. 2020).
Regarding cured meats such as ham, Montoro et al. (2017) showed that the peptides KAAAAP, AAPLAP, AAATP, KPVAAP, VPPAK, KPGRP, and PAAPPK (IC50 = 12.37 to 25.94 µM) did not show a decrease in blood pressure of individuals when they were given a daily intake of 80 g of ham (Montoro-García et al. 2017). This shows that their in vivo effect may be observed when they are previously digested.
When comparing the inhibitory activities of peptides of animal origin against ACE (Table 2), it was found that the best in decreasing order were: LSGYGP (tilapia skin gelatin), ITT (marine cobia skin), VISDEDGVTH (Ruditapes philippinarum), ATT (Cobia Marina skin) and LWHTH (Styela clava).
Bioactive peptides of plant origin
A total of 9 articles identified bioactive peptides of plant origin, derived from cereals (Wang et al. 2017, 2021; Chia-Cheng et al. 2019; Shih et al. 2019), legumes (Ciau-Solís et al. 2018; Zhang et al. 2020), fruits (Alcaide-Hidalgo et al. 2020), vegetables (Vásquez-Villanueva et al. 2019), and oils (Dang et al. 2019) (Table 3).
Table 3
Bioactive peptides with hypertensive activity of plant origin.
Food
|
Peptide sequence
|
IC50
|
Main result
|
Rapeseed meal
(Wang et al. 2021)
|
CI
|
0,01 − 0,8 mg mL− 1
|
Rapeseed peptides showed antihypertensive activity in hypertensive rats at 25 g kg− 1 doses, reducing blood pressure after 4-6h. What was highly significant (p < 0.01) in SBP, by 21.4 mmHg after 6h of administration, while the Captopril group decreased (p < 0.01) by 19.6 mmHg after 4h of oral administration.
|
CL
|
VAP
|
Olive oil (Alcaide-Hidalgo et al. 2020)
|
RDGGYCC
|
0,84 ± 0,02 µM.
|
Peptides RDGGYCC and CCGNAVPQ produced maximal SBP reductions of 10 and 12% (19 and 23 mmHg), respectively, similar to the reduction produced by Captopril. The antihypertensive effect of the CCGNAVPQ peptide was maintained for 4–8 h and was even significant at 24 h when the Captopril group had returned to baseline levels.
|
LEEFCC
|
--
|
HCGCNTH
|
--
|
CCGNAVPQ
|
39,56 ± 2,09 µM
|
Peach seeds (Vásquez-Villanueva et al. 2019)
|
IMAPH
|
--
|
IFSPR and IYSPH had a greater inhibitory effect on ACE. Oral administration of the peptide IYSPH at a dose of 1.5 mg kg− 1 produced a 16% reduction in SBP (about 30 mmHg) after 3–6 h of treatment, compared with captopril at 10 mg kg− 1, showed its maximum hypotensive effect 3 hours after administration. Furthermore, there were no statistical differences between the hypotensive effects of captopril and peptides at 6 h after administration (p > 0.05).
|
ILMH
|
--
|
IYTPH
|
--
|
IFSPR
|
31 ± 2 µg mL− 1
|
IYSPH
|
24 ± 3 µg mL− 1
|
VAIP
|
142 ± 22 µg mL− 1
|
ALPDEV
|
--
|
PILNDE
|
--
|
Broccoli
(Dang et al. 2019)
|
IPPAYTK
|
--
|
LVLPGE and LAK exhibit high ACE inhibitory activity; they were found after digestion. LVLPGE peptide at a dose of 10 mg/kg showed a stronger hypotensive effect than Captopril at a dose of 5 mg/kg in hypertensive rats.
|
LVLPGE
|
13,5 µM
|
LAK
|
48,0 µM.
|
TFQGPPHGIQVER
|
--
|
Cassia obtusifolia Seeds
(Shih et al. 2019)
|
FHAPWK
|
FHAPWK: 6,83 ± 0,90 µM.
|
FHAPWK was identified as a true competitive inhibitor of ACE; it interacts with several key residues of the enzyme's active site and demonstrated an antihypertensive effect in hypertensive rats.
|
LYIPH
|
LYLPH
|
IYIPH
|
IYLPH
|
Corn silk
(Li et al. 2019)
|
GLIYPPFSNIR
EPFIRPPR MNVPPGPFMAR
SKFDNLYGCR AMPTFFLIK
|
SKFDNLYGCR: 44,11 ± 1,04 µM.
|
SKFDNLYGCR was the most active ACE-inhibiting peptide, lowering SBP by 30 mmHg, while captopril lowered it by 60 mmHg at 2 h; moreover, the decrease by this peptide was persistent for about 6 h.
|
Rice bran
(Wang et al. 2017)
|
TSL
|
75,95 µM.
|
TSL exhibited potent ACE inhibitory activity. Rice bran hydrolysates were administered to hypertensive rats (50 mg kg− 1) showing a significant decrease in SBP and DBP of 34–40 mmHg at 6 h, while for the positive control captopril (10 mg kg− 1) the SBP decreased 35 mmHg and DBP 30 mmHg at 6 h after administration.
|
Glutelin of
vinegar-soaked black soybean (Zhang et al. 2019)
|
LSF
LAL
FGSF
IIP
ARF.
|
FGSF: 117,11 µM.
|
FGSF exhibited potent in vitro ACE inhibitory activity and hypotensive effect with the maximal drop of 21.95 mmHg for SBP in hypertensive rats.
|
Mung bean
(Sonklin et al. 2020)
|
LPRL
YADLVE
LRLESF
HLNVVHEN PGSGCAGTDL
|
LRLESF: 5,4 µM. LPRL: 1912 µM.
|
LRLESF was the most potent ACE inhibitor, and YADLVE was the strongest renin inhibitor with 97% inhibition. Oral administration to Hypertensive Rats revealed strong blood pressure reductions of up to -36 mmHg compared to -15 mmHg for MPH. Furthermore, YADLVE had the most persistent effect after 24 h.
|
IC50: Half maximal inhibitory concentration; SBP: Systolic blood pressure; DBP: Diastolic blood pressure; MAP: Mean arterial pressure; AT1: Angiotensin I, ATII: Angiotensin II. |
Plant-based proteins also play an important role in meeting dietary protein needs; 39% of the studies examined peptides from foods such as peaches (Vásquez-Villanueva et al. 2019), broccoli (Shih et al. 2019), corn (Chia-Cheng et al. 2019), rice (Wang et al. 2017) and beans (Sonklin et al. 2020), and olive oil (Alcaide-Hidalgo et al. 2020). Plant-derived peptides have potential ACE inhibitory activities and are also a sustainable option for global consumption (Quesada and Gómez 2019).
Vegetables are a good source of protein despite containing a lower amount of essential amino acids, or in addition to being less accessible to digestive enzymes since they are generally stored in granules, and some plants have inhibitors of these enzymes, for these and other reasons have been widely studied for the extraction of bioactive peptides (Willett et al. 2019).
Among other plant-based foods, we find rice, one of the main cereals that serves as a staple food for almost half of the human population, and its by-product, rice bran, is rich in proteins that are efficient for body growth (Han et al. 2015; Shobako and Ohinata 2020). Wang et al. (2017) isolated a peptide from the rice bran protein, TSL, that exhibits potent ACE inhibitory activity (IC50 = 75.95 µM); similar to the study reported by Shobako et al. (2018), which identified two peptides, LRA and YY, derived from this protein and which also demonstrated inhibitory activity of the enzyme (IC50 = 62 µM and 16.5 µM, respectively) (Wang et al. 2017; Shobako et al. 2018).
Peptides from rapeseed meals reported by Wang et al. (2021) (CI, CL, and VAP, IC50 = 0.01 to 0.8 mg mL− 1) showed relatively good ACE inhibitory activity in vitro and in vivo (hypertensive rats) (Wang et al. 2021). Additionally, these authors indicated that when administered concomitantly with captopril, no synergistic effect was observed in the inhibition of the enzyme; however, they found an improvement in nitric oxide levels in hypertensive rats.
Alcaide-Hidalgo et al. (2020) identified olive oil’s bioactive peptides RDGGYCC, LEEFCC, HCGCNTH, and CCGNAVPQ. Of these, RDGGYCC (IC50 = 0.84 ± 0.02 µM) and CCGNAVPQ (IC50 = 39.56 ± 2.09 µM), showed the highest inhibitory activity against ACE; in addition, their hypotensive effect was similar to that produced by captopril under in vivo conditions (Alcaide-Hidalgo et al. 2020).
As for the by-products of food processing, such as peach pits; Vásquez et al. (2019) identified the peptides IFSPR (IC50 = 31 ± 2 µg mL− 1), IYSPH (IC50 = 24 ± 3 µg mL− 1), and VAIP (IC50 = 142 ± 22 µg mL− 1) with antihypertensive activities. IYSPH showed the best ACE inhibitory capacity (IC50 = 24µg mL− 1); it was less susceptible to intestinal peptidases, and its oral administration produced a 16% reduction in its oral administration SBP (around 30 mmHg) in hypertensive rats after 3 to 6 h of treatment (Vásquez-Villanueva et al. 2019). For their part, Shih et al. (2019) identified the peptide FHAPWK (IC50 = 16.83 ± 0.90 µM) from the seeds of Cassia obtusifolia. This peptide proved to be a competitive inhibitor of ACE, whose action managed to reduce at 17 mmHg the SBP of hypertensive rats (Shih et al. 2019). Sonklin et al. (2018) reported five bioactive peptides derived from mung beans, among them, only LRLESF (IC50 = 5.4 µM) exhibited significant inhibitory activity against ACE. However, despite not showing in vitro inhibitory activity against ACE, the YADLVE peptide did show a 97% inhibition of renin; it also reduced the SBP of hypertensive rats between 36 and 15 mmHg, and whose effect was persistent after 24h (Sonklin et al. 2020).
On the other hand, Dang et al. (2019) reported that peptides derived from broccoli, such as LVLPGE (IC50 = 13.5 µM) and LAK: (IC50 = 48.0 µM), which showed inhibitory activity against ACE. However, only LVLPGE exhibited a significant antihypertensive effect against ACE in hypertensive rats (Dang et al. 2019). Li et al. (2019) identified the bioactive peptides GLIYPPFSNIR, EPFIRPPR, MNVPPGPFMAR, SKFDNLYGCR, and AMPTFFLIK from corn silk. However, only SKFDNLYGCR (IC50 = 44.11 ± 1.04 µM) showed potent in vivo activity against ACE (Chia-Cheng et al. 2019). Zhang et al. (2019) reported the bioactive peptides LSF, LAL, FGSF, IIP, and ARF from black soybean glutelin soaked in vinegar. Despite the number of peptides obtained, only FGSF (IC50 = 117.11 µM) showed a significant hypotensive effect in hypertensive rats (Zhang et al. 2020).
When comparing the inhibitory activities of plant-derived peptides against ACE (Table 3), it was found that the best in decreasing order were: RDGGYCC (olive oil), LRLESF (mung bean), FHAPWK (Cassia obtusifolia seeds) and LVLPGE (broccoli).
Fungus-derived bioactive peptides
Two studies identified bioactive peptides derived from fungi (37, 38), as seen in Table 4.
The fungus has been the subject of recent studies, thanks to its beneficial effects on health (Lau et al. 2013). Although the protein content and quality of mushrooms rank below most animal proteins, they rank above most other foods (Lau et al. 2013; Zhang et al. 2017), making them a good starting material for the production of peptides with bioactive activities, including ACE inhibitory activity.
Manoharan et al. (2017) identified the bioactive peptides ALGVR, VTVGLVVR, VVLRNNK, and ATGNLNPR from the fungus Pleurotus Pulmonarius, among this group, only the ALGVR pentapeptide (IC50 = 55 mg mL− 1) was considered a strong competitive ACE inhibitor (Manoharan et al. 2017). Amorim et al. (2019) observed a high percentage (85%) of ACE inhibition in brewer’s yeast extracts, which can be easily absorbed due to their size and hydrophobicity (Amorim et al. 2019). The peptides identified in these extracts were: SPQW, PWW, and RYW, of which SQPW showed the highest inhibitory activity against ACE (IC50 = 12 µM).
Both studies indicated that the peptides with the highest inhibitory activities (ALGVR and SQPW) were resistant to the action of gastrointestinal enzymes, which favors their absorption in the active form, thus potentiating their antihypertensive effect.