Algae as a source of peptides inhibitors of the angiotensin-converting enzyme: a systematic review

AMORIM, ANDREZA P. DE; SILVA, GABRIELLY H. DA; BRANDÃO, ROMERO M. P.; PORTO, ANA LÚCIA F.; BEZERRA, RAQUEL P.

doi:10.1590/0001-3765202220201636

ANDREZA P. DE AMORIM

Universidade Federal Rural de Pernambuco/UFRPE, Laboratório de Tecnologia de Bioativos (LABTECBIO), Departamento de Morfologia e Fisiologia Animal, Av. Dom Manoel de Medeiros, s/n, 52171-900 Recife, PE, Brazil

https://orcid.org/0000-0001-7371-6278

GABRIELLY H. DA SILVA

Universidade Federal Rural de Pernambuco/UFRPE, Laboratório de Tecnologia de Bioativos (LABTECBIO), Departamento de Morfologia e Fisiologia Animal, Av. Dom Manoel de Medeiros, s/n, 52171-900 Recife, PE, Brazil

https://orcid.org/0000-0003-4564-3686

ROMERO M. P. BRANDÃO

Universidade de Pernambuco (UPE), Instituto de Ciências Biológicas, Campus Recife, Av. Governador Agamenon Magalhães, s/n, Santo Amaro 50100-010, Recife, PE, Brazil

https://orcid.org/0000-0001-7045-2975

ANA LÚCIA F. PORTO

Universidade Federal Rural de Pernambuco/UFRPE, Laboratório de Tecnologia de Bioativos (LABTECBIO), Departamento de Morfologia e Fisiologia Animal, Av. Dom Manoel de Medeiros, s/n, 52171-900 Recife, PE, Brazil

https://orcid.org/0000-0001-5561-5158

RAQUEL P. BEZERRA

Universidade Federal Rural de Pernambuco/UFRPE, Laboratório de Tecnologia de Bioativos (LABTECBIO), Departamento de Morfologia e Fisiologia Animal, Av. Dom Manoel de Medeiros, s/n, 52171-900 Recife, PE, Brazil

https://orcid.org/0000-0002-1801-2945

Correspondence to: Raquel Pedrosa Bezerra E-mail: raquel.pbezerra@ufrpe.br

AUTHOR CONTRIBUTIONS

(I) Conception and design: AP de Amorim, RP Bezerra; (II) Provision of study materials: Literary data; (III) Collection and assembly of data: AP de Amorim, GH da Silva; (IV) Data analysis and interpretation: All authors; (V) Manuscript writing: All authors; (VI) Final approval of manuscript: All authors.

Reference	Does the article reports the procedure to obtain bioactive compounds?	Does the article reports the description of the process of carrying out biological activity in vitro?	Does the article reports the molecular weight of peptides?”	Does the article characterizes the ACEi peptides	Does the article describes the inhibition mode of ACEi peptides?	Does the article uses different sequence of methods to identify the peptides	Does the article determines the IC50 of peptide?	Percentage of positive answers (yes) for each study that attained the risk of bias
Pan et al. (2016)PAN S, WANG S, JING L & YAO D. 2016. Purification and characterisation of a novel angiotensin-I converting enzyme (ACE)-inhibitory peptide derived from the enzymatic hydrolysate of Enteromorpha clathrata protein. Food Chem 211: 423-430. doi: 10.1016/j.foodchem.2016.05.087.	Y	Y	Y	Y	Y	Y	Y	100
Wu et al. (2016)WU Q ET AL. 2016. Purification and characterization of two novel angiotensin I-converting enzyme inhibitory peptides derived from R-phycoerythrin of red algae (Bangia fusco-purpurea). Eur Food Res Technol 243: 779-789. https://doi.org/10.1007/s00217-016-2792-z. https://doi.org/.https://doi.org/10.1007...	Y	Y	N	Y	N	Y	Y	71.4
Paiva et al. (2016)PAIVA L, LIMA E, NETO AI & BAPTISTA J. 2016. Isolation and characterization of angiotensin I-converting enzyme (ACE) inhibitory peptides from Ulva rigida C. Agardh protein hydrolysate. J Funct Food 26: 65-76. doi: 10.1016/j.jff.2016.07.006.	Y	Y	N	Y	Y	Y	Y	85.7
Furuta et al. (2016)FURUTA T, MIYABE Y, YASUI H, KINOSHITA Y & KISHIMURA H. 2016. Angiotensin I Converting Enzyme Inhibitory Peptides Derived from Phycobiliproteins of Dulse Palmaria palmata. Mar Drugs 14(2): 32. doi: 10.3390/md14020032.	Y	Y	N	Y	N	Y	Y	71.4
Cao et al. (2017)CAO D, LV X, XU X, YU H, SUN X & XU N. 2017. Purification and identification of a novel ACE inhibitory peptide from marine alga Gracilariopsis lemaneiformis protein hydrolysate. Eur Food Res Technol 243(10): 1829-1837. doi: 10.1007/s00217-017-2886-2.	Y	Y	N	Y	N	Y	Y	71.4
Joel et al. (2018)JOEL CH, SUTOPO CCY, PRAJITNO A, SU JH & HSU JL. 2018. Screening of Angiotensin-I Converting Enzyme Inhibitory Peptides Derived from Caulerpa lentillifera. Molecules 23(11): 3005. doi: 10.3390/molecules23113005. PMID: 30453595; PMCID: PMC6278394.	Y	Y	N	Y	Y	Y	Y	85.7
Garcia-Vaquero et al. (2018)	Y	Y	Y	Y	N	Y	N	71.4
Deng et al. (2018)DENG Z, LIU Y, WANG J, WU S, GENG L, SUI Z & ZHANG Q. 2018. Antihypertensive Effects of Two Novel Angiotensin I-Converting Enzyme (ACE) Inhibitory Peptides from Gracilariopsis lemaneiformis (Rhodophyta) in Spontaneously Hypertensive Rats (SHRs). Mar Drugs 16(9): 299. doi: 10.3390/md16090299.	Y	Y	Y	Y	Y	N	Y	85.7
Sun et al. (2019)SUN S, XU X, SUN X, ZHANG X, CHEN X & XU N. 2019. Preparation and Identification of ACE Inhibitory Peptides from the Marine Macroalga Ulva intestinalis. Mar Drugs 17(3): 179. doi: 10.3390/md17030179.	Y	Y	N	Y	N	Y	Y	71.4
Ko et al. (2012)KO SC ET AL. 2012. A novel angiotensin I-converting enzyme (ACE) inhibitory peptide from a marine Chlorella ellipsoidea and its antihypertensive effect in spontaneously hypertensive rats. Process Biochem 47(12): 2005-2011. doi: 10.1016/j.procbio.2012.07.015.	Y	Y	Y	Y	Y	Y	Y	100
Samarakoon et al. (2013)SAMARAKOON KW, O-NAM K, KO JY, LEE JH, KANG MC, KIM D, LEE JB, LEE JS & JEON YJ. 2013. Purification and identification of novel angiotensin-I converting enzyme (ACE) inhibitory peptides from cultured marine microalgae (Nannochloropsis oculata) protein hydrolysate. J Appl Phycol 25(5): 1595-1606. doi: 10.1007/s10811-013-9994-6.	Y	Y	Y	Y	N	Y	Y	85.4
Wu et al. (2014)WU H ET AL. 2014. Hydrolysis and purification of ACE inhibitory peptides from the marine microalga Isochrysis galbana. J Appl Phycol 27: 351-361 https://doi.org/10.1007/s10811-014-0347-x. https://doi.org/.https://doi.org/10.1007...	N	Y	N	Y	Y	Y	Y	85.4
Lin et al. (2018)LIN YH, CHEN GW, YEH C, SONG H & TSAI JS. 2018. Purification and Identification of Angiotensin I-Converting Enzyme Inhibitory Peptides and the Antihypertensive Effect of Chlorella sorokiniana Protein Hydrolysates. Nutrients 10(10): 1397. doi: 10.3390/nu10101397.	Y	Y	Y	Y	N	Y	Y	71.4
Xie et al. (2018)XIE J, CHEN X, WU J, ZHANG Y, ZHOU Y, ZHANG L, TANG YJ & WEI D. 2018. Antihypertensive Effects, Molecular Docking Study, and Isothermal Titration Calorimetry Assay of Angiotensin I-Converting Enzyme Inhibitory Peptides from Chlorella vulgaris. J Agric Food Chem 66(6): 1359-1368. doi: 10.1021/acs.jafc.7b04294.	Y	Y	Y	Y	Y	N	Y	71.4
Percentage of positive answers (yes) for each quality criteria (%)	100	100	50	100	50	85	92	-

Quality criteria	Percentage (%)
Does the article reports the procedure to obtain bioactive compounds?	100
Does the article reports the description of the process of carrying out biological activity in vitro	100
Does the article reports the molecular weight of peptides?	50
Does the article characterizes the ACEi peptides?	100
Does the article describes the inhibition mode of ACEi peptides?	50
Does the article uses different sequence of methods to identify the peptides?	85
Does the article determines the IC50 of peptide?	92

Species	Enzyme	Purification Method	Peptide	IC ₅₀	Inhibition Pattern	Reference
Macroalgae
Enteromorpha clathrata	Alcalase	Ultrafiltration (UF), sephadex G-15 gel and reverse-phase high performance liquid chromatography (RP-HPLC)	PAFG	35.9 μM	Non-competitive	Pan et al. (2016)PAN S, WANG S, JING L & YAO D. 2016. Purification and characterisation of a novel angiotensin-I converting enzyme (ACE)-inhibitory peptide derived from the enzymatic hydrolysate of Enteromorpha clathrata protein. Food Chem 211: 423-430. doi: 10.1016/j.foodchem.2016.05.087.
Bangia. fusco-purpurea	Pepsin and trypsin	Sephadex G-15 column chromatograph, RP-HPLC	ALLAGDPSVLEDR, VVGGTGPVDEWGIGAR	57.2 ± 5.0 and 66.2 ± 4.2 μg/mL	-	Wu et al. (2016)WU Q ET AL. 2016. Purification and characterization of two novel angiotensin I-converting enzyme inhibitory peptides derived from R-phycoerythrin of red algae (Bangia fusco-purpurea). Eur Food Res Technol 243: 779-789. https://doi.org/10.1007/s00217-016-2792-z. https://doi.org/.https://doi.org/10.1007...
Ulva rigida	Pepsin and bromelain	UF, sephadex G-25 size exclusion column, RP-HPLC	IP, AFL	0.020 and 0.023 mg/mL	Non-competitive, Competitive	Paiva et al. (2016)PAIVA L, LIMA E, NETO AI & BAPTISTA J. 2016. Isolation and characterization of angiotensin I-converting enzyme (ACE) inhibitory peptides from Ulva rigida C. Agardh protein hydrolysate. J Funct Food 26: 65-76. doi: 10.1016/j.jff.2016.07.006.
Palmaria palmata	Thermolysin	UF, Sephadex G-25 gel fltration column, RP-HPLC	LRY	0.044 μM	-	Furuta et al. (2016)FURUTA T, MIYABE Y, YASUI H, KINOSHITA Y & KISHIMURA H. 2016. Angiotensin I Converting Enzyme Inhibitory Peptides Derived from Phycobiliproteins of Dulse Palmaria palmata. Mar Drugs 14(2): 32. doi: 10.3390/md14020032.
Gracilariopsis lemaneiformis	Trypsin	Sephadex G-15 gel fltration column, Hydrophobic interaction chromatography (HIC)	QVEY	474.36 μM	-	Cao et al. (2017)CAO D, LV X, XU X, YU H, SUN X & XU N. 2017. Purification and identification of a novel ACE inhibitory peptide from marine alga Gracilariopsis lemaneiformis protein hydrolysate. Eur Food Res Technol 243(10): 1829-1837. doi: 10.1007/s00217-017-2886-2.
Caulerpa lentillifera	Thermolysin	UF, RP-HPLC	FDGIP, AIDPVRA	58.89 ± 0.68 and 65.76 ± 0.92μM	Competitive, Competitive	Joel et al. (2018)JOEL CH, SUTOPO CCY, PRAJITNO A, SU JH & HSU JL. 2018. Screening of Angiotensin-I Converting Enzyme Inhibitory Peptides Derived from Caulerpa lentillifera. Molecules 23(11): 3005. doi: 10.3390/molecules23113005. PMID: 30453595; PMCID: PMC6278394.
Ulva luctua	Papain	UF, HPLC	48 differents peptides	-	-	Garcia-Vaquero et al. (2019)
Gracilariopsis lemaneiformis	Trypsin	UF	FQINMCILR, TGAPCR	9.64 ± 0.36 and 23.94 ± 0.82 μM	Non-competitive, Non-competitive	Deng et al. (2018)DENG Z, LIU Y, WANG J, WU S, GENG L, SUI Z & ZHANG Q. 2018. Antihypertensive Effects of Two Novel Angiotensin I-Converting Enzyme (ACE) Inhibitory Peptides from Gracilariopsis lemaneiformis (Rhodophyta) in Spontaneously Hypertensive Rats (SHRs). Mar Drugs 16(9): 299. doi: 10.3390/md16090299.
Ulva intestinalis	Trypsin	UF, Sephadex G-25 gel fltration column, Sephadex G-15 gel, RP-HPLC	FGMPLDR, MELVLR	219.35 and 236.85 μM	-	Sun et al. (2019)SUN S, XU X, SUN X, ZHANG X, CHEN X & XU N. 2019. Preparation and Identification of ACE Inhibitory Peptides from the Marine Macroalga Ulva intestinalis. Mar Drugs 17(3): 179. doi: 10.3390/md17030179.
Microalgae
Chlorella ellipsoidea	Alcalase	UF, Sephadex G-25 gel fltration column, RP-HPLC	VGGY	128.4 μM	Competitive	Ko et al. (2012)KO SC ET AL. 2012. A novel angiotensin I-converting enzyme (ACE) inhibitory peptide from a marine Chlorella ellipsoidea and its antihypertensive effect in spontaneously hypertensive rats. Process Biochem 47(12): 2005-2011. doi: 10.1016/j.procbio.2012.07.015.
Nannochloropsis oculata	Pepsin	UF, Sephadex G-25 gel fltration column, RP-HPLC	GMNNLTP, LEQ	123 and 173 μM	-	Samarakoon et al. (2013)SAMARAKOON KW, O-NAM K, KO JY, LEE JH, KANG MC, KIM D, LEE JB, LEE JS & JEON YJ. 2013. Purification and identification of novel angiotensin-I converting enzyme (ACE) inhibitory peptides from cultured marine microalgae (Nannochloropsis oculata) protein hydrolysate. J Appl Phycol 25(5): 1595-1606. doi: 10.1007/s10811-013-9994-6.
Isochrysis galbana	Trypsin	Sephadex G-25 column, HIC	YMGLDLK	36.1 μM	Non-competitive	Wu et al. (2014)WU H ET AL. 2014. Hydrolysis and purification of ACE inhibitory peptides from the marine microalga Isochrysis galbana. J Appl Phycol 27: 351-361 https://doi.org/10.1007/s10811-014-0347-x. https://doi.org/.https://doi.org/10.1007...
Chlorella sorokiniana	Protease N	Sephadex G-15 gel fltration column, HPLC	WV, VW, IW, LW	307.61, 0.58, 0.50, and 1.11 μM,	-	Lin et al. (2018)LIN YH, CHEN GW, YEH C, SONG H & TSAI JS. 2018. Purification and Identification of Angiotensin I-Converting Enzyme Inhibitory Peptides and the Antihypertensive Effect of Chlorella sorokiniana Protein Hydrolysates. Nutrients 10(10): 1397. doi: 10.3390/nu10101397.
Chlorella vulgaris	Pepsin, trypsin and chymotrypsin (in silico)	-	TTW, VHW	0.61 ± 0.12 and 0.91 ± 0.31 μM	Non-competitive, Non-competitive	Xie et al. (2018)XIE J, CHEN X, WU J, ZHANG Y, ZHOU Y, ZHANG L, TANG YJ & WEI D. 2018. Antihypertensive Effects, Molecular Docking Study, and Isothermal Titration Calorimetry Assay of Angiotensin I-Converting Enzyme Inhibitory Peptides from Chlorella vulgaris. J Agric Food Chem 66(6): 1359-1368. doi: 10.1021/acs.jafc.7b04294.

Species	Peptide	SBP maximum reduction (mmHg)	Reference
Chlorella ellipsoidea	VEGY	- 22.8 mmHg after 4 h	Ko et al. (2012)KO SC ET AL. 2012. A novel angiotensin I-converting enzyme (ACE) inhibitory peptide from a marine Chlorella ellipsoidea and its antihypertensive effect in spontaneously hypertensive rats. Process Biochem 47(12): 2005-2011. doi: 10.1016/j.procbio.2012.07.015.
Chlorella vulgaris	TTWT VHW	- 35 mmHg after 2 h - 50 mmHg after 2 h	Xie et al. (2018)XIE J, CHEN X, WU J, ZHANG Y, ZHOU Y, ZHANG L, TANG YJ & WEI D. 2018. Antihypertensive Effects, Molecular Docking Study, and Isothermal Titration Calorimetry Assay of Angiotensin I-Converting Enzyme Inhibitory Peptides from Chlorella vulgaris. J Agric Food Chem 66(6): 1359-1368. doi: 10.1021/acs.jafc.7b04294.
Chlorella sorokiniana	-	-11.1 mmHg after 6 h -21 mmHg after 6 h	Lin et al. (2018)LIN YH, CHEN GW, YEH C, SONG H & TSAI JS. 2018. Purification and Identification of Angiotensin I-Converting Enzyme Inhibitory Peptides and the Antihypertensive Effect of Chlorella sorokiniana Protein Hydrolysates. Nutrients 10(10): 1397. doi: 10.3390/nu10101397.
Gracilariopsis lemaneiformis	TTWT VHW	- 34 mmHg after 2 h - 27 mmHg after 2 h	Deng et al (2018)

[1] Correspondence to: Raquel Pedrosa Bezerra E-mail: raquel.pbezerra@ufrpe.br

Brasil

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Algae as a source of peptides inhibitors of the angiotensin-converting enzyme: a systematic review

Abstract