AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
Powered by AMiner. Clicking this button will take you away from SciOpen.
Home Food Science of Animal Products Article
PDF (8.8 MB)
Cite
EndNote(RIS) BibTeX
Collect
Submit Manuscript AI Chat Paper
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Research Article | Open Access

Potential key targets and mechanism of the Mizuhopecten yessoensis derived ACE inhibitory peptide Asn-Cys-Trp (NCW) via network pharmacology and molecular docking

Wenjun Xue1,2, Wenzhu Zhao1, Sijia Wu3, Zhipeng Yu1( )
School of Food Science and Engineering, Hainan University, Haikou 570228, China
Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400030, China
Laboratory of Nutrition and Functional Food, Jilin University, Changchun 130062, China
Show Author Information

Abstract

Mizuhopecten yessoensis-derived angiotensin converting enzyme (ACE) inhibitory peptide Asn-Cys-Trp (NCW) has been found that had a significantly in vivo antihypertensive effect. However, the special mechanism of peptide NCW for lowing blood pressure has not been fully elucidated. This study aimed to screen the key targets and elucidate the antihypertensive mechanism of based on the network pharmacology and molecular docking. A total of 70 potential antihypertensive targets of peptide NCW were identified, which were mainly enriched in Regulation of blood pressure, Positive regulation of smooth muscle cell proliferation, and other biological processes; Plasma membrane, Extracellular exosome, and other cellular components; Endopeptidase activity, Zinc ion binding, and other molecular functions. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that lipid and atherosclerosis pathway, relaxin signaling pathway, and mitogen-activated protein kinase (MAPK) signaling pathway were the key pathways for peptide NCW to regulate the potential antihypertensive targets. Eleven potential key antihypertensive targets were screened via topology analysis of protein and protein interaction network, i.e., albumin (ALB), matrix metallopeptidase 9 (MMP9), MMP2, insulin like growth factor 1, AKT serine/threonine kinase 1 (IGF1), ACE, nitric oxide synthase 3 (NOS3), peroxisome proliferator activated receptor gamma (PPARG), epidermal growth factor receptor (EGFR), catalase (CAT), and renin (REN). In addition, molecular docking results showed that the peptide NCW had high affinities with these potential key antihypertensive targets, and hydrogen bonds were the key interaction forces between the peptide NCW and targets. This study provided a theoretical basis for the multi-target and multi-pathway prevention and improvement of hypertension with peptide NCW.

Keywords

ACE inhibitory peptideantihypertensive mechanismmolecular dockingnetwork pharmacologytarget

Electronic Supplementary Material

Download File(s)
FSAP-2023-0042_ESM.pdf (10.9 MB)

References

[1]

J. Kitt, R. Fox, K. L. Tucker, et al., New approaches in hypertension management: a review of current and developing technologies and their potential impact on hypertension Care, Curr. Hypertens. Rep. 21 (2019) 44. https://doi.org/10.1007/s11906-019-0949-4.
Crossref Google Scholar
[2]

M. Zhou, W. Zhao, W. Xue, et al., Potential antihypertensive mechanism of egg white-derived peptide QIGLF revealed by proteomic analysis, Int. J. Biol. Macromol. 218 (2022) 439–446. https://doi.org/10.1016/j.ijbiomac.2022.07.149.
Crossref Google Scholar
[3]

J. Wu, W. Liao, C. C. Udenigwe, Revisiting the mechanisms of ACE inhibitory peptides from food proteins, Trends Food Sci. Technol. 69 (2017) 214–219. https://doi.org/10.1016/j.jpgs.2017.07.011.
Crossref Google Scholar
[4]

X. Feng, D. Liao, L. Sun, et al., Exploration of interaction between angiotensin I-converting enzyme (ACE) and the inhibitory peptide from Wakame (Undaria pinnatifida), Int. J. Biol. Macromol. 204 (2022) 193–203. https://doi.org/10.1016/j.ijbiomac.2022.01.114.
Crossref Google Scholar
[5]

X. Lan, L. Sun, Y. Muhammad, et al., Studies on the interaction between angiotensin-converting enzyme (ACE) and ACE Inhibitory peptide from Saurida elongata, J. Agric. Food Chem. 66 (2018) 13414–13422. https://doi.org/10.1021/acs.jafc.8b04303.
Crossref Google Scholar
[6]

Q. Wu, C. Zhong, G. Zeng, et al., Identification and characterization of a novel tetrapeptide from enzymatic hydrolysates of Baijiu byproduct, Food Sci. Hum. Wellness 11 (2022) 1641–1649. https://doi.org/10.1016/j.fshw.2022.06.023.
Crossref Google Scholar
[7]

Y. Su, Q. Bai, H. Tao, et al., Prospects for the application of traditional Chinese medicine network pharmacology in food science research, J. Sci. Food Agric. 103 (2023) 5183–5200. https://doi.org/10.1002/jsfa.12541.
Crossref Google Scholar
[8]

F. Liang, Y. Shi, W. Cao, et al., The inhibition mechanisms of pancreatic lipase by apigenin and its anti-obesity mechanisms revealed by using network pharmacology, Food Biosci. 45 (2022) 101515. https://doi.org/10.1016/j.fbio.2021.101515.
Crossref Google Scholar
[9]

R. Shi, D. Chen, M. Ji, et al., Network pharmacology-based screening of the active ingredients and mechanisms of Cymbaria daurica against diabetes mellitus, Food Sci. Hum. Wellness 12 (2023) 2001–2013. https://doi.org/10.1016/j.fshw.2023.03.022.
Crossref Google Scholar
[10]

M. Zhou, G. Ren, B. Zhang, et al., Screening and identification of a novel antidiabetic peptide from collagen hydrolysates of Chinese giant salamander skin: network pharmacology, inhibition kinetics and protection of IR-HepG2 cells, Food Funct. 13 (2022) 3329–3342. https://doi.org/10.1039/d1fo03527d.
Crossref Google Scholar
[11]
L. Zhao, M. Zhang, F. Pan, et al., In silico analysis of novel dipeptidyl peptidase-IV inhibitory peptides released from Macadamia integrifolia antimicrobial protein 2 (MiAMP2) and the possible pathways involved in diabetes protection, Curr. Res. Food Sci. 4 (2021) 603−611. https://doi.org/10.1016/j.crfs.2021.08.008.
Crossref
[12]

H. Ge, B. Zhang, T. Li, et al., Potential targets and the action mechanism of food-derived dipeptides on colitis: network pharmacology and bioinformatics analysis, Food Funct. 12 (2021) 5989–6000. https://doi.org/10.1039/d1fo00469g.
Crossref Google Scholar
[13]

W. Liao, H. Fan, S. T. Davidge, et al., Egg white-derived antihypertensive peptide IRW (Ile-Arg-Trp) reduces blood pressure in spontaneously hypertensive rats via the ACE2/Ang (1-7)/Mas receptor axis, Mol. Nutr. Food Res. 63 (2019) e1900063. https://doi.org/10.1002/mnfr.201900063.
Crossref Google Scholar
[14]

Z. Yu, Y. Yin, W. Zhao, et al., Antihypertensive effect of angiotensin-converting enzyme inhibitory peptide RVPSL on spontaneously hypertensive rats by regulating gene expression of the renin-angiotensin system, J. Agric. Food Chem. 62 (2014) 912–917. https://doi.org/10.1021/jf405189y.
Crossref Google Scholar
[15]

Y. Cao, J. Huang, M. Sun, et al., Network pharmacology and molecular docking combined to investigate the mechanism of duck-derived active peptides in preventing hypertension, Int. J. Food Sci. Technol. 43 (2022) 16244. https://doi.org/10.1111/ijfs.16244.
Crossref Google Scholar
[16]

S. Wu, W. Zhao, Z. Yu, et al., Antihypertensive effect and underlying mechanism of tripeptide NCW on spontaneously hypertensive rats using metabolomics analysis, Food Funct. 13 (2022) 1808–1821. https://doi.org/10.1039/d1fo03924e.
Crossref Google Scholar
[17]

X. Wang, Y. Shen, S. Wang, et al., PharmMapper 2017 update: a web server for potential drug target identification with a comprehensive target pharmacophore database, Nucleic Acids Res. 45 (2017) W356–W360. https://doi.org/10.1093/nar/gkx374.
Crossref Google Scholar
[18]

A. Daina, O. Michielin, V. Zoete, Swiss Target Prediction: updated data and new features for efficient prediction of protein targets of small molecules, Nucleic Acids Res. 47 (2019) W357–W364. https://doi.org/10.1093/nar/gkz382.
Crossref Google Scholar
[19]

J. Pinero, J. Sauch, F. Sanz, et al., The DisGeNET cytoscape app: exploring and visualizing disease genomics data, Comput. Struct. Biotechnol. J. 19 (2021) 2960–2967. https://doi.org/10.1016/j.csbj.2021.05.015.
Crossref Google Scholar
[20]

A. P. Davis, T. C. Wiegers, J. Wiegers, et al., CTD tetramers: a new online tool that computationally links curated chemicals, genes, phenotypes, and diseases to inform molecular mechanisms for environmental health, Toxicol. Sci. 195 (2023) 155–168. https://doi.org/10.1093/toxsci/kfad069.
Crossref Google Scholar
[21]

Y. Lin, Z. Hu, Bioinformatics analysis of candidate genes involved in ethanol-induced microtia pathogenesis based on a human genome database: GeneCards, Int. J. Pediatr. Otorhinolaryngol. 142 (2021) 110595. https://doi.org/10.1016/j.ijporl.2020.110595.
Crossref Google Scholar
[22]

H. Yang, C. Qin, Y. Li, et al., Therapeutic target database update 2016: enriched resource for bench to clinical drug target and targeted pathway information, Nucleic Acids Res. 44 (2023) D1069–D1074. https://doi.org/10.1093/nar/gkv1230.
Crossref Google Scholar
[23]
B. T. Sherman, M. Hao, J. Qiu, et al., DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update), Nucleic Acids Res. 50 (2022) W216−W221. http://doi.org/10.1093/nar/gkac194.
Crossref
[24]
D. Szklarczyk, A. L. Gable, D. Lyon, et al., STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets, Nucleic Acids Res. 47 (2019) D607−D613. http://doi.org/10.1093/nar/gky1131.
Crossref
[25]

W. Xue, X. Liu, W. Zhao, et al., Identification and molecular mechanism of novel tyrosinase inhibitory peptides from collagen, J. Food Sci. 87 (2022) 2744–2756. https://doi.org/10.1111/1750-3841.16160.
Crossref Google Scholar
[26]

L. Sun, H. Yin, M. Liu, et al., Impaired albumin function: a novel potential indicator for liver function damage?, Ann. Med. 51 (2019) 333–344. https://doi.org/10.1080/07853890.2019.1693056.
Crossref Google Scholar
[27]

G. A. Cabral-Pacheco, I. Garza-Veloz, C. Castruita-de la Rosa, et al., The roles of matrix metalloproteinases and their inhibitors in human diseases, Int. J. Mol. Sci. 21 (2020) 9739. https://doi.org/10.3390/ijms21249739.
Crossref Google Scholar
[28]

M. L. Lindsey, Assigning matrix metalloproteinase roles in ischaemic cardiac remodelling, Nat. Rev. Cardiol. 15 (2018) 471–479. https://doi.org/10.1038/s41569-018-0022-z.
Crossref Google Scholar
[29]

Yasmin, S. Wallace, C. M. McEniery, et al., Matrix metalloproteinase-9 (MMP-9), MMP-2, and serum elastase activity are associated with systolic hypertension and arterial stiffness, Arterioscler Thromb. Vasc. Biol. 25 (2005) 372–378. https://doi.org/10.1161/01.ATV.0000151373.33830.41.
Crossref Google Scholar
[30]
E. Hardy, A. Hardy-Sosa, C. Fernandez-Patron, MMP-2: is too low as bad as too high in the cardiovascular system?, Am. J. Physiol. Heart. Circ. Physiol. 315 (2018) H1332−H1340. http://doi.org/10.1152/ajpheart.00198.2018.
Crossref
[31]

D. Cannata, A. Vijayakumar, Y. Fierz, et al., The GH/IGF-1 axis in growth and development: new insights derived from animal models, Adv. Pediatr. 57 (2010) 331–351. https://doi.org/10.1016/j.yapd.2010.09.003.
Crossref Google Scholar
[32]

J. D. Symons, S. L. McMillin, C. Riehle, et al., Contribution of insulin and Akt1 signaling to endothelial nitric oxide synthase in the regulation of endothelial function and blood pressure, Circ. Res. 104 (2009) 1085–1094. https://doi.org/10.1161/CIRCRESAHA.108.189316.
Crossref Google Scholar
[33]

K. Bian, M. F. Doursout, F. Murad, Vascular system: role of nitric oxide in cardiovascular diseases, J. Clin. Hypertens. 10 (2008) 304–310. https://doi.org/10.1111/j.1751-7176.2008.06632.x.
Crossref Google Scholar
[34]

N. Kubis, C. Richer, V. Domergue, et al., Role of microvascular rarefaction in the increased arterial pressure in mice lacking for the endothelial nitric oxide synthase gene (eNOS–/–), J. Hypertens. 20 (2002) 1581–1587. https://doi.org/10.1097/00004872-200208000-00021.
Crossref Google Scholar
[35]

A. Z. Fernandez, Peroxisome proliferator-activated receptors in the modulation of the immune/inflammatory response in atherosclerosis, PPAR Res. 2008 (2008) 285842. https://doi.org/10.1155/2008/285842.
Crossref Google Scholar
[36]

A. C. Li, W. Palinski, Peroxisome proliferator-activated receptors: how their effects on macrophages can lead to the development of a new drug therapy against atherosclerosis, Annu. Rev. Pharmacol. Toxicol. 46 (2006) 1–39. https://doi.org/10.1146/annurev.pharmtox.46.120604.141247.
Crossref Google Scholar
[37]

J. M. Gerry, G. Pascual, Narrowing in on cardiovascular disease: the atheroprotective role of peroxisome proliferator-activated receptor gamma, Trends Cardiovasc. Med. 18 (2008) 39–44. https://doi.org/10.1016/j.tcm.2007.12.001.
Crossref Google Scholar
[38]

L. A. Grisanti, S. Guo, D. G. Tilley, Cardiac GPCR-mediated EGFR transactivation: impact and therapeutic implications, J. Cardiovasc. Pharmacol. 70 (2017) 3–9. https://doi.org/10.1097/FJC.0000000000000462.
Crossref Google Scholar
[39]

N. Makki, K. W. Thiel, F. J. Miller, The epidermal growth factor receptor and its ligands in cardiovascular disease, Int. J. Mol. Sci. 14 (2013) 20597–20613. https://doi.org/10.3390/ijms141020597.
Crossref Google Scholar
[40]

S. J. Forrester, T. Kawai, S. O'Brien, et al., Epidermal growth factor receptor transactivation: mechanisms, pathophysiology, and potential therapies in the cardiovascular system, Annu. Rev. Pharmacol. Toxicol. 56 (2016) 627–653. https://doi.org/10.1146/annurev-pharmtox-070115-095427.
Crossref Google Scholar
[41]

Y. C. Tan, M. A. Sattar, A. F. Ahmeda, et al., Apocynin and catalase prevent hypertension and kidney injury in cyclosporine A-induced nephrotoxicity in rats, PLoS ONE 15 (2020) e0231472. https://doi.org/10.1371/journal.pone.0231472.
Crossref Google Scholar
[42]

R. E. Aluko, Food protein-derived renin-inhibitory peptides: in vitro and in vivo properties, J. Food Biochem. 43 (2019) e12648. https://doi.org/10.1111/jfbc.12648.
Crossref Google Scholar
[43]

R. Kan, Z. Yu, W. Zhao, Identificaretion and molecular action mechanism of novel TAS2R14 blocking peptides from egg white proteins, LWT-Food Sci. Technol. 180 (2023) 114716. https://doi.org/10.1016/j.lwt.2023.114716.
Crossref Google Scholar
[44]

Z. Yu, Y. Wang, D. Shuian, et al., Identification and molecular mechanism of novel immunomodulatory peptides from gelatin hydrolysates: molecular docking, dynamic simulation, and cell experiments, J. Agric. Food Chem. 71 (2023) 2924–2934. https://doi.org/10.1021/acs.jafc.2c06982.
Crossref Google Scholar
Food Science of Animal Products
Volume 1 Issue 4,
December 2023
Article number: 9240041
DOI: 10.26599/FSAP.2023.9240041
Cite this article:
Xue W, Zhao W, Wu S, et al. Potential key targets and mechanism of the Mizuhopecten yessoensis derived ACE inhibitory peptide Asn-Cys-Trp (NCW) via network pharmacology and molecular docking. Food Science of Animal Products, 2023, 1(4): 9240041. https://doi.org/10.26599/FSAP.2023.9240041

1162

Views

281

Downloads

0

Crossref

Altmetrics
Received: 14 November 2023
Revised: 15 December 2023
Accepted: 25 December 2023
Published: 05 February 2024
© Beijing Academy of Food Sciences 2023.

Food Science of Animal Products published by Tsinghua University Press. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Return