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Excessive reactive oxygen species (ROS) can cause oxidative damage and lead to various metabolic disease. Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn) is a new kind of protein-rich functional food, the protein in which has been proved to have good antioxidant capacity. In this study, in order to further explore the antioxidant mechanism of Tartary buckwheat protein, 4 peptides (CR-8, LR-8, GK-10 and SR-12) were isolated and identified from it. H2O2 was used to induce oxidative damage to Caco-2 cells to evaluate antioxidant capacity of these peptides. The results of superoxide dismutase (SOD), total antioxidant capacity (T-AOC) and mitochondrial membrane potential etc. showed that these peptides have superior antioxidant capacity. CR-8 has the best antioxidant capacity. In order to further clarify the antioxidant mechanism of CR-8, metabolomics was used to analyze related metabolites and metabolic pathways. The results showed that after CR-8 intervention, the content of metabolites such as L-acetyl carnitine has increased. This indicated that CR-8 can improve the antioxidant capacity of damaged cells by intervening in multiple metabolic pathways. This also revealed the anti-oxidant mechanism of tartary buckwheat protein. In conclusion, it provided a theoretical basis for further studying the activity of tartary buckwheat portein and utilizing buckwheat resources.


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Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn) protein-derived antioxidant peptides: mechanisms of action and structure-activity relationship in Caco-2 cell models

Show Author's information Yiming ZhouaXuanming SheaZhidong ChenaYun WeiaYing XiaoaXiaoli Zhoua,b( )
School of Perfume and Aroma Technology, Shanghai Institute of Technology, Shanghai 201418, China
University Think Tank of Shanghai Municipality, Institute of Beautiful China and Ecological Civilization, Shanghai 201418, China

Peer review under responsibility of KeAi Communications Co., Ltd.

Abstract

Excessive reactive oxygen species (ROS) can cause oxidative damage and lead to various metabolic disease. Tartary buckwheat (Fagopyrum tataricum (L.) Gaertn) is a new kind of protein-rich functional food, the protein in which has been proved to have good antioxidant capacity. In this study, in order to further explore the antioxidant mechanism of Tartary buckwheat protein, 4 peptides (CR-8, LR-8, GK-10 and SR-12) were isolated and identified from it. H2O2 was used to induce oxidative damage to Caco-2 cells to evaluate antioxidant capacity of these peptides. The results of superoxide dismutase (SOD), total antioxidant capacity (T-AOC) and mitochondrial membrane potential etc. showed that these peptides have superior antioxidant capacity. CR-8 has the best antioxidant capacity. In order to further clarify the antioxidant mechanism of CR-8, metabolomics was used to analyze related metabolites and metabolic pathways. The results showed that after CR-8 intervention, the content of metabolites such as L-acetyl carnitine has increased. This indicated that CR-8 can improve the antioxidant capacity of damaged cells by intervening in multiple metabolic pathways. This also revealed the anti-oxidant mechanism of tartary buckwheat protein. In conclusion, it provided a theoretical basis for further studying the activity of tartary buckwheat portein and utilizing buckwheat resources.

Keywords: Antioxidant protective, Tartary buckwheat peptides, Metabolic mechanim, Caco-2 cells

References(45)

[1]

M. Aurelia, Nanoparticles induce oxidative and endoplasmic reticulum stresses, MRS Bulletin 10 (2020) 99-138. https://doi.org/10.1557/mrs.2020.264.

[2]

C. Nicco, F. Batteux, ROS modulator molecules with therapeutic potential in cancers treatments, Molecules (2017) 23. https://doi.org/10.3390/molecules23010084.

[3]

B.C. Dickinson, C.J. Chang, Chemistry and biology of reactive oxygen species in signaling or stress responses, Nat. Chem. Biol. 7 (2011) 504-511. https://doi.org/10.1038/nchembio.607.

[4]

N. Kensuke, Y. Iwaihara, T. Tsunoda, et al., ROS-induced cleavage of NHLRC2 by caspase-8 leads to apoptotic cell death in the HCT116 human colon cancer cell line, Cell Death Dis. 8 (2017) 3218. https://doi.org/10.1038/s41419-017-0006-7.

[5]

D. Trachootham, J. Alexandre, H. Peng, Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nat. Rev. Drug Discov. 8 (2009) 579-591. https://doi.org/10.1038/nrd2803.

[6]

C.T. Madreiter-Sokolowski, C. Thomas, M. Ristow, Interrelation between ROS and Ca2+ in aging and age-related diseases, Redox Biol. 36 (2020) 101678. https://doi.org/10.1016/j.redox.2020.101678.

[7]

E. Rendra, V. Riabov, D.M. Mossel, et al., Reactive oxygen species (ROS) in macrophage activation and function in diabetes, Immunobiology 224 (2019) 242-253. https://doi.org/10.1016/j.imbio.2018.11.010.

[8]

C. Cheignon, M. Tomas, D. Bonnefont-Rousselot, et al., Oxidative stress and the amyloid beta peptide in Alzheimer's disease, Redox Biol. 14 (2018) 450-464. https://doi.org/10.1016/j.redox.2017.10.014.

[9]

I.S. Harris, G.M. DeNicola, The complex interplay between antioxidants and ROS in cancer, Trends Cell Biol. 30 (2020) 440-451. https://doi.org/10.1016/j.tcb.2020.03.002.

[10]

V. Lobo, A. Patil, A. Phatak, et al., Free radicals, antioxidants and functional foods: impact on human health, Pharmacogn. Rev. 4 (2010) 118-126. https://doi.org/10.4103/0973-7847.70902.

[11]

C. Stushnoff, D. Holm, M.D. Thompson, et al., Antioxidant properties of cultivars and selections from the colorado potato breeding program, Am. J. Pot. Res. 85 (2008) 267-276. https://doi.org/10.1007/s12230-008-9032-4.

[12]

X. Guo, H. Yao, Fractionation and characterization of Tartary buckwheat flour proteins, Food Chem. 98 (2006) 90-94. https://doi.org/10.1016/j.foodchem.2005.05.055.

[13]

Y. Zhou, Y. Jiang, R. Shi, et al., Structural and antioxidant analysis of Tartary buckwheat (Fagopyrum tartaricum Gaertn.) 13S globulin, J. Sci. Food Agric. 100 (2020) 1220-1229. https://doi.org/10.1002/jsfa.10133.

[14]

E.H. Baugh, S. Lyskov, B.D. Weitzner, et al., Real-time PyMOL visualization for Rosetta and PyRosetta, PLoS ONE 6 (2011) e21931. https://doi.org/10.1371/journal.pone.0021931.

[15]

D. Seeliger, B.L. Groot, Ligand docking and binding site analysis with PyMOL and Autodock/Vina, J. Comput. Aided Mol. Des. 24 (2010) 417-422. https://doi.org/10.1007/s10822-010-9352-6.

[16]

M.A. Lill, M.L. Danielson, Computer-aided drug design platform using PyMOL, J. Comput. Aided Mol. Des. 25 (2011) 13-19. https://doi.org/10.1007/s10822-010-9395-8.

[17]

C.H. Johnson, J. Ivanisevic, G. Siuzdak, Metabolomics: beyond biomarkers and towards mechanisms, Nat. Rev. Mol. Cell Biol. 17 (2016) 451-459. https://doi.org/10.1038/nrm.2016.25.

[18]

L. Li, M. Wang, S. Chen, et al., A urinary metabonomics analysis of long-term effect of acetochlor exposure on rats by ultra-performance liquid chromatography/mass spectrometry, Pestic. Biochem. Physiol. 128 (2016) 82-88. https://doi.org/10.1016/j.pestbp.2015.09.013.

[19]

R. Ramautar, G.J. de Jong, Recent developments in liquid-phase separation techniques for metabolomics, Bioanalysis 6 (2014) 1011-1026. https://doi.org/10.4155/bio.14.51.

[20]

D. Bedoya-Ramirez, A. Cilla, J. Contreras-Calderon, et al., Evaluation of the antioxidant capacity, furan compounds and cytoprotective/cytotoxic effects upon Caco-2 cells of commercial Colombian coffee, Food Chem. 219 (2017) 364-372. https://doi.org/10.1016/j.foodchem.2016.09.159.

[21]

M.G. Ormerod, X.M. Sun, D. Brown, et al., Quantification of apoptosis and necrosis by flow cytometry, Acta Oncol. 32 (1993) 417-424. https://doi.org/10.3109/02841869309093620.

[22]

X. Li, A.C. Chung, S. Li, et al., LC-MS-based metabolomics revealed SLC25A22 as an essential regulator of aspartate-derived amino acids and polyamines in KRAS-mutant colorectal cancer, Oncotarget 8 (2017) 101333. https://doi.org/10.18632/oncotarget.21093.

[23]

C. Ma, Y. Li, H. Wu, et al., Metabolomics analysis of the potential anticancer mechanism of annonaceous acetogenins on a multidrug resistant mammary adenocarcinoma cell, Anal. Biochem. 553 (2018) 1-6. https://doi.org/10.1016/j.ab.2018.04.022.

[24]

A. Tsopmo, A. Romanowski, L. Banda, et al., Novel anti-oxidative peptides from enzymatic digestion of human milk, Food Chem. 126 (2011) 1138-1143. https://doi.org/10.1016/j.foodchem.2010.11.146.

[25]

J.Y. Je, Z.J. Qian, H.G. Byun, et al., Purification and characterization of an antioxidant peptide obtained from tuna backbone protein by enzymatic hydrolysis, Process Biochem. 42 (2007) 840-846. https://doi.org/10.1016/j.procbio.2007.02.006.

[26]

S. Cho, H.H. Szeto, E. Kim, et al., A novel cell-permeable antioxidant peptide, SS31, attenuates ischemic brain injury by down-regulating CD36, J. Biol. Chem. 282 (2007) 4634-4642. https://doi.org/10.1074/jbc.M609388200.

[27]

B. Wang, L. Li, C.F. Chi, et al., Purification and characterisation of a novel antioxidant peptide derived from blue mussel (Mytilus edulis) protein hydrolysate, Food Chem. 138 (2013) 1713-1719. https://doi.org/10.1016/j.foodchem.2012.12.002.

[28]

S. Bekeschus, C.S. Schütz, F. Nießner, et al., Elevated H2AX phosphorylation observed with kINPen plasma treatment is not caused by ROS-Mediated DNA damage but is the consequence of apoptosis, Oxid. Med. Cell Longev. (2019) 1-15. https://doi.org/10.1155/2019/8535163.

[29]

A. Cilla, A. Attanzio, R. Barberá, et al., Anti-proliferative effect of main dietary phytosterols and β-cryptoxanthin alone or combined in human colon cancer Caco-2 cells through cytosolic Ca2+–and oxidative stress-induced apoptosis, J. Funct. Foods 12 (2015) 282-293. https://doi.org/10.1016/j.jff.2014.12.001.

[30]

L.L. Yang, W.J. Sui, Y.Q. Li, et al., Substance P inhibits hyperosmotic stress-induced apoptosis in corneal epithelial cells through the mechanism of Akt activation and reactive oxygen species scavenging via the neurokinin-1, PLoS ONE 11 (2016) e0149865. https://doi.org/10.1371/journal.pone.0149865.

[31]

J. Yang, X. Zhao, M. Tang, et al., The role of ROS and subsequent DNA-damage response in PUMA-induced apoptosis of ovarian cancer cells, Oncotarget 4 (2017) 23492-23506. https://doi.org/10.18632/oncotarget.15626.

[32]

C. Zhou, L. Na, R. Shan, et al., Dietary vitamin C intake reduces the risk of type 2 diabetes in Chinese adults: HOMA-IR and T-AOC as potential mediators, PLoS ONE 11 (2016) e0163571. https://doi.org/10.1371/journal.pone.0163571.

[33]

Y. Jiang, J. Sun, Z. Yin, et al., Evaluation of antioxidant peptides generated from Jiuzao (residue after Baijiu distillation) protein hydrolysates and their effect of enhancing healthy value of Chinese Baijiu, J. Sci. Food Agric. 100 (2020) 59-73. https://doi.org/10.1002/jsfa.9994.

[34]

P.D. Ray, B.W. Huang, Y. Tsuji, Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling, Cell Signal 24 (2012) 981-990. https://doi.org/10.1016/j.cellsig.2012.01.008.

[35]

M. Ri, Endoplasmic-reticulum stress pathway-associated mechanisms of action of proteasome inhibitors in multiple myeloma, Int. J. Hematol. 104 (2016) 273-280. https://doi.org/10.1007/s12185-016-2016-0.

[36]

Z. Akbarbaglu, S.M. Jafari, K. Sarabandi, et al., Influence of spray drying encapsulation on the retention of antioxidant properties and microstructure of flaxseed protein hydrolysates, Colloids Surf. B Biointerfaces 178 (2019) 421-429. https://doi.org/10.1016/j.colsurfb.2019.03.038.

[37]

Y. Chen, H. Zhang, R. Liu, et al., Antioxidant and anti-inflammatory polyphenols and peptides of common bean (Phaseolus vulga L.) milk and yogurt in Caco-2 and HT-29 cell models, J. Funct. Foods 53 (2019) 125-135. https://doi.org/10.1016/j.jff.2018.12.013.

[38]

H. Zheng, J. Wu, H. Huang, et al., Metabolomics analysis of the protective effect of rubusoside on palmitic acid-induced lipotoxicity in INS-1 cells using UPLC-Q/TOF MS, Mol. Omics. 15 (2019) 222-232. https://doi.org/10.1039/c9mo00029a.

[39]

N.E. Sunny, E.J. Parks, J.D. Browning, et al., Excessive hepatic mitochondrial TCA cycle and gluconeogenesis in humans with nonalcoholic fatty liver disease, Cell Metab. 14 (2011) 804-810. https://doi.org/10.1016/j.cmet.2011.11.004.

[40]

J. Pascoe, D. Hollern, R. Stamateris, et al., Free fatty acids block glucose-induced beta-cell proliferation in mice by inducing cell cycle inhibitors p16 and p18, Diabetes 61 (2012) 632-641. https://doi.org/10.2337/db11-0991.

[41]

J.A. Combs, G.M. DeNicola, The non-essential amino acid cysteine becomes essential for tumor proliferation and survival, Cancers (Basel) 11 (2019) 678. https://doi.org/10.3390/cancers11050678.

[42]

F.P. Kuhajda, Fatty-acid synthase and human cancer new perspectives on its role in tumor biology, Nutrition 16 (2000) 202-208. https://doi.org/10.1016/S0899-9007(99)00266-X.

[43]

M. Cheng, Y. Li, H. Wu, et al., Metabolomics analysis of the potential anticancer mechanism of annonaceous acetogenins on a multidrug resistant mammary adenocarcinoma cell, Anal. Biochem. 553 (2018) 1-6. https://doi.org/10.1016/j.ab.2018.04.022.

[44]

L. Shin, S. Wang, J.S. Lee, et al., Lysophosphatidylcholine inhibits membrane-associated SNARE complex disassembly, J. Cell Mol. Med. 16 (2012) 1701-1708. https://doi.org/10.1111/j.1582-4934.2011.01433.x.

[45]

I. Sevastou, E. Kaffe, M.A. Mouratis, et al., Lysoglycerophospholipids in chronic inflammatory disorders: the PLA(2)/LPC and ATX/LPA axes, Biochim. Biophys. Acta 1831 (2013) 42-60. https://doi.org/10.1016/j.bbalip.2012.07.019.

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Publication history

Received: 13 March 2021
Revised: 28 April 2021
Accepted: 19 June 2021
Published: 18 July 2022
Issue date: November 2022

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© 2022 Beijing Academy of Food Sciences.

Acknowledgements

Acknowledgements

The authors thank Shanghai Natural Science Foundation (20ZR1455800), the National Science Foundation of China (31871805), China Agriculture Research System (CARS-08-D2) and Shanghai Municipal Education Commission (Plateau Discipline Construction Program).

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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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