Full Text:   <2228>

Summary:  <1787>

CLC number: 

On-line Access: 2022-04-22

Received: 2020-09-02

Revision Accepted: 2021-02-21

Crosschecked: 2022-04-22

Cited: 0

Clicked: 3636

Citations:  Bibtex RefMan EndNote GB/T7714


Xiaochang WANG


-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2021 Vol.22 No.7 P.575-589


Inhibitory mechanism of angiotensin-converting enzyme inhibitory peptides from black tea

Author(s):  Yating LU, Yu WANG, Danyi HUANG, Zhuang BIAN, Peng LU, Dongmei FAN, Xiaochang WANG

Affiliation(s):  Tea Research Institute, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, China; more

Corresponding email(s):   xcwang@zju.edu.cn

Key Words:  Black tea, Angiotensin-1-converting enzyme (ACE) inhibitory peptide, Kinetic study, Molecular docking, Molecular dynamic (MD) simulation

Yating LU, Yu WANG, Danyi HUANG, Zhuang BIAN, Peng LU, Dongmei FAN, Xiaochang WANG. Inhibitory mechanism of angiotensin-converting enzyme inhibitory peptides from black tea[J]. Journal of Zhejiang University Science B, 2021, 22(7): 575-589.

@article{title="Inhibitory mechanism of angiotensin-converting enzyme inhibitory peptides from black tea",
author="Yating LU, Yu WANG, Danyi HUANG, Zhuang BIAN, Peng LU, Dongmei FAN, Xiaochang WANG",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Inhibitory mechanism of angiotensin-converting enzyme inhibitory peptides from black tea
%A Yating LU
%A Danyi HUANG
%A Zhuang BIAN
%A Peng LU
%A Dongmei FAN
%A Xiaochang WANG
%J Journal of Zhejiang University SCIENCE B
%V 22
%N 7
%P 575-589
%@ 1673-1581
%D 2021
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2000520

T1 - Inhibitory mechanism of angiotensin-converting enzyme inhibitory peptides from black tea
A1 - Yating LU
A1 - Yu WANG
A1 - Danyi HUANG
A1 - Zhuang BIAN
A1 - Peng LU
A1 - Dongmei FAN
A1 - Xiaochang WANG
J0 - Journal of Zhejiang University Science B
VL - 22
IS - 7
SP - 575
EP - 589
%@ 1673-1581
Y1 - 2021
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2000520

The aim of this work is to discover the inhibitory mechanism of tea peptides and to analyse the affinities between the peptides and the angiotensin-converting enzyme (ACE) as well as the stability of the complexes using in vitro and in silico methods. Four peptide sequences identified from tea, namely peptides I, II, III, and IV, were used to examine ACE inhibition and kinetics. The half maximal inhibitory concentration (IC50) values of the four peptides were (210.03±18.29), (178.91±5.18), (196.31±2.87), and (121.11±3.38) μmol/L, respectively. The results of Lineweaver-Burk plots showed that peptides I, II, and IV inhibited ACE activity in an uncompetitive manner, which requires the presence of substrate. Peptide III inhibited ACE in a non-competitive manner, for which the presence of substrate is not necessary. The docking simulations showed that the four peptides did not bind to the active sites of ACE, indicating that the four peptides are allosteric inhibitors. The binding free energies calculated from molecular dynamic (MD) simulation were -72.47, -42.20, -52.10, and -67.14 kcal/mol (1 kcal=4.186 kJ), respectively. The lower IC50 value of peptide IV may be attributed to its stability when docking with ACE and changes in the flexibility and unfolding of ACE. These four bioactive peptides with ACE inhibitory ability can be incorporated into novel functional ingredients of black tea.


方法:用体外酶抑制实验获取茶叶多肽(红茶中分离)对ACE的半抑制浓度(IC50);用酶动力学实验探究红茶多肽对ACE的抑制类型;通过分子对接技术预测茶叶多肽在ACE蛋白中的结合位置;通过100 ns的分子动力学模拟实验评价各多肽对ACE蛋白自由度和展开度的影响以及多肽-蛋白结合物的稳定性。


Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]AsoodehA, YazdiMM, ChamaniJ, 2012. Purification and characterisation of angiotensin I converting enzyme inhibitory peptides from lysozyme hydrolysates. Food Chem, 131(1):291-295.

[2]BougatefA, Nedjar-ArroumeN, Ravallec-PléR, et al., 2008. Angiotensin I-converting enzyme (ACE) inhibitory activities of sardinelle (Sardinella aurita) by-products protein hydrolysates obtained by treatment with microbial and visceral fish serine proteases. Food Chem, 111(2):350-356.

[3]CaseDA, CheathamTE III, DardenT, et al., 2005. The amber biomolecular simulation programs. J Computat Chem, 26(16):1668-1688.

[4]ChamataY, WatsonKA, JauregiP, 2020. Whey-derived peptides interactions with ACE by molecular docking as a potential predictive tool of natural ACE inhibitors. Int J Mol Sci, 21(3):864.

[5]CheungBMY, LiC, 2012. Diabetes and hypertension: is there a common metabolic pathway? Curr Atheroscler Rep, 14(2):160-166.

[6]CollierSR, LandramMJ, 2012. Treatment of prehypertension: lifestyle and/or medication. Vasc Health Risk Manag, 8:613-619.

[7]DangYL, ZhouTY, HaoL, et al., 2019. In vitro and in vivo studies on the angiotensin-converting enzyme inhibitory activity peptides isolated from broccoli protein hydrolysate. J Agric Food Chem, 67(24):6757-6764.

[8]Daskaya-DikmenC, YucetepeA, Karbancioglu-GulerF, et al., 2017. Angiotensin-I-converting enzyme (ACE)-inhibitory peptides from plants. Nutrients, 9(4):316.

[9]DingL, ZhangY, JiangYQ, et al., 2014. Transport of egg white ACE-inhibitory peptide, Gln-Ile-Gly-Leu-Phe, in human intestinal Caco-2 cell monolayers with cytoprotective effect. J Agric Food Chem, 62(14):3177-3182.

[10]DingL, WangLY, ZhangT, et al., 2018. Hydrolysis and transepithelial transport of two corn gluten derived bioactive peptides in human Caco-2 cell monolayers. Food Res Int, 106:475-480.

[11]EscuderoE, MoraL, FraserPD, et al., 2013. Purification and identification of antihypertensive peptides in Spanish dry-cured ham. J Proteomics, 78:499-507.

[12]EttehadD, EmdinCA, KiranA, et al., 2016. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet, 387(10022):957-967.

[13]FanHB, WangJP, LiaoW, et al., 2019. Identification and characterization of gastrointestinal-resistant angiotensin-converting enzyme inhibitory peptides from egg white proteins. J Agric Food Chem, 67(25):7147-7156.

[14]FerreiraSH, 1965. A bradykinin-potentiating factor (BPF) present in the venom of Bothrops jararaca. Br J Pharmacol Chemother, 24(1):163-169.

[15]ForghaniB, ZareiM, EbrahimpourA, et al., 2016. Purification and characterization of angiotensin converting enzyme-inhibitory peptides derived from Stichopus horrens: stability study against the ACE and inhibition kinetics. J Funct Foods, 20:276-290.

[16]García-MoraP, Martín-MartínezM, Angeles BonacheM, et al., 2017. Identification, functional gastrointestinal stability and molecular docking studies of lentil peptides with dual antioxidant and angiotensin I converting enzyme inhibitory activities. Food Chem, 221:464-472.

[17]GronebergDA, DöringF, EynottPR, et al., 2001. Intestinal peptide transport: ex vivo uptake studies and localization of peptide carrier PEPT1. Am J Physiol-Gastrointestin Liver Physiol, 281(3):G697-G704.

[18]GuanSS, HanWW, ZhangH, et al., 2016. Insight into the interactive residues between two domains of human somatic Angiotensin-converting enzyme and Angiotensin II by MM-PBSA calculation and steered molecular dynamics simulation. J Biomol Struct Dyn, 34(1):15-28.

[19]GuY, MajumderK, WuJP, 2011. QSAR-aided in silico approach in evaluation of food proteins as precursors of ACE inhibitory peptides. Food Res Int, 44(8):2465-2474.

[20]GunalanS, SomarathinamK, BhattacharyaJ, et al., 2020. Understanding the dual mechanism of bioactive peptides targeting the enzymes involved in renin angiotensin system (RAS): an in-silico approach. J Biomol Struct Dyn, 38(7):5044-5061.

[21]HanifK, BidHK, KonwarR, 2010. Reinventing the ACE inhibitors: some old and new implications of ACE inhibition. Hypertens Res, 33(1):11-21.

[22]HarrisonC, AcharyaKR, 2014. ACE for all—a molecular perspective. J Cell Commun Signal, 8(3):195-210.

[23]HomeyerN, GohlkeH, 2012. Free energy calculations by the molecular mechanics poisson-boltzmann surface area method. Mol Inform, 31(2):114-122.

[24]KumarR, ChaudharyK, ChauhanJS, et al., 2015. An in silico platform for predicting, screening and designing of antihypertensive peptides. Sci Rep, 5: 12512.

[25]LacroixIME, MengGT, CheungIWY, et al., 2016. Do whey protein-derived peptides have dual dipeptidyl-peptidase IV and angiotensin I-converting enzyme inhibitory activities? J Funct Foods, 21:87-96.

[26]LafargaT, HayesM, 2017. Bioactive protein hydrolysates in the functional food ingredient industry: overcoming current challenges. Food Rev Int, 33(3):217-246.

[27]LaskowskiRA, SwindellsMB, 2011. LigPlot+: multiple ligand-protein interaction diagrams for drug discovery. J Chem Inf Model, 51(10):2778-2786.

[28]LiDX, WangRR, HuangJB, et al., 2019. Effects and mechanisms of tea regulating blood pressure: evidences and promises. Nutrients, 11(5):1115.

[29]LiY, SadiqFA, LiuTJ, et al., 2015. Purification and identification of novel peptides with inhibitory effect against angiotensin I-converting enzyme and optimization of process conditions in milk fermented with the yeast Kluyveromyces marxianus. J Funct Foods, 16:278-288.

[30]LiuC, FangL, MinW, et al., 2018. Exploration of the molecular interactions between angiotensin-I-converting enzyme (ACE) and the inhibitory peptides derived from hazelnut (Corylus heterophylla Fisch.). Food Chem, 245:471-480.

[31]LuYT, LuP, WangY, et al., 2019. A novel dipeptidyl peptidase IV inhibitory tea peptide improves pancreatic β-cell function and reduces α-cell proliferation in streptozotocin-induced diabetic mice. Int J Mol Sci, 20(2):322.

[32]MajumderK, ChakrabartiS, MortonJS, et al., 2015. Egg-derived ACE-inhibitory peptides IQW and LKP reduce blood pressure in spontaneously hypertensive rats. J Funct Foods, 13:50-60.

[33]MartinM, DeussenA, 2019. Effects of natural peptides from food proteins on angiotensin converting enzyme activity and hypertension. Crit Rev Food Sci Nutr, 59(8):1264-1283.

[34]MillsKT, BundyJD, KellyTN, et al., 2016. Global disparities of hypertension prevalence and control: a systematic analysis of population-based studies from 90 countries. Circulation, 134(6):441-450.

[35]Miner-WilliamsWM, StevensBR, MoughanPJ, 2014. Are intact peptides absorbed from the healthy gut in the adult human? Nutr Res Rev, 27(2):308-329.

[36]MinkiewiczP, DziubaJ, IwaniakA, et al., 2008. Biopep database and other programs for processing bioactive peptide sequences. J AOAC Int, 91(4):965-980.

[37]NingXY, ZhangYL, YuanTT, et al., 2018. Enhanced thermostability of glucose oxidase through computer-aided molecular design. Int J Mol Sci, 19(2):425.

[38]PatilP, MandalS, TomarSK, et al., 2015. Food protein-derived bioactive peptides in management of type 2 diabetes. Eur J Nutr, 54(6):863-880.

[39]PuchalskaP, Marina AlegreML, García LópezMC, 2015. Isolation and characterization of peptides with antihypertensive activity in foodstuffs. Crit Rev Food Sci Nutr, 55(4):521-551.

[40]RegazzoD, MolléD, GabaiG, et al., 2010. The (193‒209) 17-residues peptide of bovineβ‍-casein is transported through Caco-2 monolayer. Mol Nutr Food Res, 54(10):1428-1435.

[41]SaitoY, WanezakiK, KawatoA, et al., 1994. Structure and activity of angiotensin I converting enzyme inhibitory peptides from sake and sake lees. Biosci Biotechnol Biochem, 58(10):1767-1771.

[42]SatohE, TohyamaN, NishimuraM, 2005. Comparison of the antioxidant activity of roasted tea with green, oolong, and black teas. Int J Food Sci Nutr, 56(8):551-559.

[43]ShalabySM, ZakoraM, OtteJ, 2006. Performance of two commonly used angiotensin-converting enzyme inhibition assays using FA-PGG and HHL as substrates. J Dairy Res, 73(2):178-186.

[44]SharmaA, SinglaD, RashidM, et al., 2014. Designing of peptides with desired half-life in intestine-like environment. BMC Bioinformatics, 15:282.

[45]ShenYM, MaupetitJ, DerreumauxP, et al., 2014. Improved PEP-FOLD approach for peptide and miniprotein structure prediction. J Chem Theory Comput, 10(10):4745-4758.

[46]ShimizuM, 1999. Modulation of intestinal functions by food substances. Nahrung, 43(3):154-158.

[47]SornwatanaT, BangphoomiK, RoytrakulS, et al., 2015. Chebulin: Terminalia chebula Retz. fruit-derived peptide with angiotensin-I-converting enzyme inhibitory activity. Biotechnol Appl Biochem, 62(6):746-753.

[48]SunLP, WuBY, YanMY, et al., 2019. Antihypertensive effect in vivo of QAGLSPVR and its transepithelial transport through the Caco-2 cell monolayer. Mar Drugs, 17(5):288.

[49]TanzadehpanahH, AsoodehA, SaberiMR, et al., 2013. Identification of a novel angiotensin-I converting enzyme inhibitory peptide from ostrich egg white and studying its interactions with the enzyme. Innovat Food Sci Emerg Technol, 18:212-219.

[50]TaoC, YuDH, CorneliusV, et al., 2017. Potential health impact and cost-effectiveness of drug therapy for prehypertension. Int J Cardiol, 240:403-408.

[51]TaoML, SunHJ, LiuL, et al., 2017. Graphitized porous carbon for rapid screening of angiotensin-converting enzyme inhibitory peptide GAMVVH from silkworm pupa protein and molecular insight into inhibition mechanism. J Agric Food Chem, 65(39):8626-8633.

[52]TrottO, OlsonAJ, 2010. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem, 31(2):455-461.

[53]WangQ, WangY, ChenGJ, 2016. Influence of secondary-structure folding on the mutually exclusive folding process of GL5/I27 protein: evidence from molecular dynamics simulations. Int J Mol Sci, 17(11):1962.

[54]WangYF, YangZW, WeiXL, 2010. Sugar compositions, α‍-glucosidase inhibitory and amylase inhibitory activities of polysaccharides from leaves and flowers of Camellia sinensis obtained by different extraction methods. Int J Biol Macromol, 47(4):534-539.

[55]WuQY, JiaJQ, YanH, et al., 2015. A novel angiotensin-I converting enzyme (ACE) inhibitory peptide from gastrointestinal protease hydrolysate of silkworm pupa (Bombyx mori) protein: biochemical characterization and molecular docking study. Peptides, 68:17-24.

[56]YuDY, WangC, SongYF, et al., 2019. Discovery of novel angiotensin-converting enzyme inhibitory peptides from Todarodes pacificus and their inhibitory mechanism: in silico and in vitro studies. Int J Mol Sci, 20(17):4159.

[57]ZhangZF, LiQ, LiangJ, et al., 2010. Epigallocatechin-3-O-gallate (EGCG) protects the insulin sensitivity in rat L6 muscle cells exposed to dexamethasone condition. Phytomedicine, 17(1):14-18.

[58]ZhaoTR, LiuBT, YuanL, et al., 2019. ACE inhibitory activity in vitro and antihypertensive effect in vivo of LSGYGP and its transepithelial transport by Caco-2 cell monolayer. J Funct Foods, 61:103488.

[59]ZhengYJ, WangX, ZhuangYL, et al., 2019. Isolation of novel ACE-inhibitory and antioxidant peptides from quinoa bran albumin assisted with an in silico approach: characterization, in vivo antihypertension, and molecular docking. Molecules, 24(24):4562.

[60]ZhengYJ, WangX, ZhuangYL, et al., 2020. Isolation of novel ACE-inhibitory peptide from naked oat globulin hydrolysates in silico approach: molecular docking, in vivo antihypertension and effects on renin and intracellular endothelin-1. J Food Sci, 85(4):1328-1337.

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE