Natural phenolic compounds are secondary metabolites found in a wide range of plants including food crops. As many of them are known to be antioxidants and can prevent several chronic and degenerative diseases in humans, they are a part of a healthy diet. However, these antioxidants can act as prooxidants under high phenolic concentration, high pH, or in the presence of transition metal ions such as Cu 2+ or Fe 3+ , producing reactive oxygen species (ROS) including hydroxyl radicals resulting in oxidative stress and cell toxicity. While this can lead to pathogenesis including the development of various types of cancers, elevated levels of ROS are beneficial to kill malignant cells and food borne pathogens to improve food safety. Thus, the dual nature of phenolic compounds allows them to act as antioxidants and prooxidants. Similarly, depending on the level of prooxidant activity, ROS can induce either pathogenesis or serve as a potential agent to kill malignant cells and foodborne pathogens.
Prior, R.L. and Cao, G. (2000) Antioxidant Phytochemicals in Fruits and Vegetables: Diet and Health Implications. HortScience, 35, 588-592. https://doi.org/10.21273/HORTSCI.35.4.588
Vieira do Carmo, M.J., Granato, D. and Azevedo, L. (2012) Antioxidant/Pro-Oxidant and Antiproliferative Activities of Phenolic-Rich Foods and Extracts: A Cell-Based Point of View. Advances in Food and Nutrition Research, 98, 253-280. https://doi.org/10.1016/bs.afnr.2021.02.010
Jideani, A.I.O., Silungwe, H., Takalani, T., Omolola, A., Udeh, H.O. and Anyasi, T. (2021) Antioxidant-Rich Natural Fruit and Vegetable Products and Human Health. International Journal of Food Properties, 24, 41-67. https://doi.org/10.1080/10942912.2020.1866597
Foyer, C.H. and Noctor, G. (2005) Oxidant and Antioxidant Signalling in Plants: A Reevaluation of the Concept of Oxidative Stress in a Physiological Context. Plant Cell and Environment, 28, 1056-1071. https://doi.org/10.1111/j.1365-3040.2005.01327.x
Halliwell, B. (2006) Reactive Species and Antioxidants. Redox Biology Is a Fundamental Theme of Aerobic Life. Plant Physiology, 141, 312-322. https://doi.org/10.1104/pp.106.077073
Valko, M., Leibfritz, D., Moncol, J., Cronin, M.T., Mazur, M. and Telser, J. (2007) Free Radicals and Antioxidants in Normal Physiological Functions and Human Disease. The International Journal of Biochemistry and Cell Biology, 39, 44-84. https://doi.org/10.1016/j.biocel.2006.07.001
Yordi, E.G., Perez, E.M., Matos, M.J. and Villares, E.U. (2012) Antioxidant and Prooxidant Effects of Polyphenolic Compounds and Structure-Activity Relationship Evidence. In: Bouayed, J. and Bohn, T., Eds., Nutrition, Well-Being and Health, Intech, Shanghai, 23-48.
Leon-Gonzales, A.J., Auger, C. and Schini-Kerth, V.B. (2015) Pro-Oxidant Activity of Polyphenols and Its Implication on Cancer Chemoprevention and Chemotherapy. Biochemical Pharmacology, 98, 371-380. https://doi.org/10.1016/j.bcp.2015.07.017
Rajashekar, C.B., Carey, E.E., Zhao, X. and Oh, M. (2009) Health-Promoting Phytochemicals in Fruits and Vegetables: Impact of Abiotic Stresses and Production Practices. Functional Plant Science and Biotechnology, 3, 30-38.
Zhang, Y., Gan, R., Li, S., Zhou, Y., Li, A., Xu, D. and Li, H. (2015) Antioxidant Phytochemicals for the Prevention and Treatment of Chronic Diseases. Molecules, 20, 21138-21156. https://doi.org/10.3390/molecules201219753
GAO (2002) Fruits and Vegetables: Enhanced Federal Efforts to Increase Consumption Could Yield Health Benefits for Americans. GAO-02-657.
Chobot, V. and Hadacek, F. (2009) Milieu-Dependent Pro- and Antioxidant Activity of Juglone May Explain Linear and Nonlinear Effects on Seedling Development. Journal of Chemical Ecology, 35, 383-390. https://doi.org/10.1007/s10886-009-9609-5
Kondakci, Y., Ozyurek, M., Guclu, K. and Apak, R. (2013) Novel Pro-Oxidant Activity Assay for Polyphenols, Vitamin C and E Using Modified CUPRAC Method. Talanta, 115, 583-589. https://doi.org/10.1016/j.talanta.2013.06.006
Podmore, I.D., Griffiths, H.R., Herbert, K.E., Mistry, N., Mistry, P. and Lunec, J. (1998) Vitamin C Exhibits Pro-Oxidant Properties. Nature, 392, 559. https://doi.org/10.1038/33308
Fukuhara, K. and Miyata, N. (1998) Resveratrol as a New Type of DNA-Cleaving Agent. Bioorganic Medicinal Chemistry Letters, 8, 3187-3192. https://doi.org/10.1016/S0960-894X(98)00585-X
Yamashita, N., Murata, M., Inoue, S., BurKitt, M.J., Miline, L. and Kawanishi, S. (1998) Tocopherol Induces Oxidative Damage to DNA in the Presence of Copper(II) Ions. Chemical Research Toxicology, 11, 855-862. https://doi.org/10.1021/tx970129v
Eghbaliferiz, S. and Iranshahi, M. (2016) Prooxidant Activity of Polyphenols, Flavonoids, Anthocyanins and Carotenoids: Updated Review of Mechanisms and Catalyzing Metals. Phytotherapy Research, 30, 1379-1391. https://doi.org/10.1002/ptr.5643
Farhan, M. and Rizvi, A. (2022) Understanding the Prooxidant Action of Plant Phenols in the Cellular Microenvironment of Malignant Cells: Role of Copper and Therapeutic Implications. Frontiers in Pharmacology, 13, 1-11. https://doi.org/10.3389/fphar.2022.929853
Zhang, L., Dai, F., Zhou, B., Yang, L. and Liu, Z. (2008) Prooxidant Activity of Hydroxycinnamic Acids on DNA Damage in Presence of Cu(II) Ions: Mechanisms and Structure-Activity Relationship. Food and Chemical Toxicology, 46, 149-156. https://doi.org/10.1016/j.fct.2007.07.010
Hagerman, A.E., Riedi, K.M., Jones, G.A., Sovik, K.N., Ritchard, N.T., Hartzfeld, P.W. and Riechel, T.L. (1998) High Molecular Weight Polyphenolics Tannins as Biological Antioxidants. Journal of Agricultural Food Chemistry, 46, 1887-1892. https://doi.org/10.1021/jf970975b
Blokhina, O., Virolainen, E. and Fagerstedt, K.V. (2003) Antioxidants, Oxidative Damage and Oxygen Deprivation Stress: A Review. Annals of Botany, 91, 179-194. https://doi.org/10.1093/aob/mcf118
Zhou, L. and Elias, R.J. (2013) Antioxidant and Pro-Oxidant Activity of (-)epigallocatechin-3-gallate in Food Emulsions: Influence of pH and Phenolic Concentration. Food Chemistry, 138, 1503-1509. https://doi.org/10.1016/j.foodchem.2012.09.132
Simic, A., Manojlovic, D., Segan, D. and Todorovic, M. (2007) Electrochemical Behavior and Antioxidant and Prooxidant Activity of Natural Phenolics. Molecules, 12, 2327-2340. https://doi.org/10.3390/12102327
Sugihara, N., Arakawa, T., Ohnishi, M. and Furuno, K. (1999) Anti- and Pro-Oxidative Effects of Flavonoids on Metal-Induced Lipid Hydroperoxide-Dependent Lipid Peroxidation in Cultured Hepatocytes Loaded with Alpha-Linolenic Acid. Free Radical Biology and Medicine, 27, 1313-1323. https://doi.org/10.1016/S0891-5849(99)00167-7
Sakihama. Y., Cohen, M.F., Grace, S.C. and Yamasaki, H. (2002) Plant Phenolic Antioxidant and Prooxidant Activities: Phenolic-Induced Oxidative Damage Mediated by Metals in Plants. Toxicology, 177, 67-68. https://doi.org/10.1016/S0300-483X(02)00196-8
Salcedo, C., Lopez de Mishima, A. and Nazareno, A. (2010) Walnuts and Almonds as Model Systems of Foods Constituted by Oxidizable, Pro-Oxidant and Antioxidant Factors. Food Research International, 43, 1187-1197. https://doi.org/10.1016/j.foodres.2010.02.016
Kalinowska, M., Gryko, K., Wroblewska, A.M., Jablonska-Trypuk, A. and Karpowics, D. (2020) Phenolic Content, Chemical Composition and Anti-/Pro-Oxidant Activity of Gold Milenium and Papierowka Apple Peels Extracts. Scientific Reports, 10, 14951. https://doi.org/10.1038/s41598-020-71351-w
Weisburg, J.H., Schuck, A.G., Silverman, M.S., Otis-Levy, C.G., Solodokin, L.J., Zuckerbraun, H.L. and Babich, H. (2010) Pomegranate Extract, a Prooxidant with Antiproliferative and Proapoptotic Activities Preferentially towards Carcinoma Cells. Anti-Cancer Agents in Medicinal Chemistry, 10, 634-644. https://doi.org/10.2174/187152010794474000
Cotoras, M., Vivano, H., Melo, R., Aguirre, M., Silva, E. and Mendoza, L. (2014) In Vitro and in Vivo Evaluation of the Antioxidant and Prooxidant Activity of Phenolic Compounds Obtained from Grape (Vitis vinifera) Pomace. Molecules, 19, 21154-21167. https://doi.org/10.3390/molecules191221154
Fukumoto, L.R. and Mazza, G. (2000) Assessing Antioxidant and Prooxidant Activities of Phenolic Compounds. Journal of Agricultural Food Chemistry, 48, 3597-3604. https://doi.org/10.1021/jf000220w
Barbehenn, R., Cheek, S., Gasperut, A., Lister, E. and Maben, R. (2005) Phenolic Compounds in Red Oak and Sugar Maple Leaves Have Prooxidant Activities in the Midgut Fluids of Malacosoma disstria and Orgyia leucostigma Caterpillars. Journal of Chemical Ecology, 31, 969-988. https://doi.org/10.1007/s10886-005-4242-4
Moran, J.F., Klucas, R.V., Grayer, R.J., Abian, J. and Becana, M. (1997) Complexes of Iron with Phenolic Compounds from Soybean Nodules and Other Legume Tissues; Prooxidant and Antioxidant Properties. Free Radical Biology and Medicine, 22, 861-870. https://doi.org/10.1016/S0891-5849(96)00426-1
Feugang, J.M., Ye, F., Zhang, D.Y., Yu, Y., Zhong, M., Zhang, S. and Zou, C. (2010) Cactus Pear Extracts Induce Reactive Oxygen Species Production and Apoptosis in Ovarian Cancer Cells. Nutrition and Cancer, 62, 692-699. https://doi.org/10.1080/01635581003605508
Bayliak, M.M., Burdyliuk, N.I. and Lushchak, V.I. (2016) Effects of pH on Antioxidant and Prooxidant Properties of Common Medicinal Herbs. Open Life Sciences, 11, 298-307. https://doi.org/10.1515/biol-2016-0040
Jukic, H., Habes, S., Aldzic, S. and Kosalec, I.D.K. (2015) Antioxidant and Prooxidant Activities of Phenolic Compounds of the Extracts of Echinacea purpurea (L.). Bulletin of the Chemists and Technologists of Bosnia and Herzegovina, 44, 43-52.
Babich, H., Ackerman, N.J., Burekhovich, F., Zukerbraun, H. and Schuck, A.G. (2009) Gingko Biloba Leaf Extract Induces Oxidative Stress in Carcinoma HSC-2 Cells. Toxicology in Vitro, 23, 992-999. https://doi.org/10.1016/j.tiv.2009.06.023
Akagawa, M., Shigemitsu, T. and Suyama, K. (2003) Production of Hydrogen Peroxide by Polyphenols and Polyphenol-Rich Beverages under Quasi-Physiological Conditions. Bioscience, Biotechnology, and Biochemistry, 67, 2632-2640. https://doi.org/10.1271/bbb.67.2632
Yen, G., Chen, H. and Peng, H. (1997) Antioxidant and Pro-Oxidant Effects of Various Tea Extracts. Journal of Agricultural and Food Chemistry, 45, 30-34. https://doi.org/10.1021/jf9603994
Lambert, J.D. and Elias, R.J. (2010) The Antioxidant and Pro-Oxidant Activities of Green Tea Polyphenols: A Role in Cancer Prevention. Archives of Biochemistry and Biophysics, 501, 65-72. https://doi.org/10.1016/j.abb.2010.06.013
Liu, X., Li, J., Wang, Y., Li, T., Zhao, J. and Zhang C. (2013) Green Tea Polyphenols Function as Prooxidants to Inhibit Pseudomonas aeruginosa and Induce Expression of Oxidative Stress-Related Genes. Folia Microbiologica, 58, 211-217. https://doi.org/10.1007/s12223-012-0198-2
Chai, P.C. Long, L.H. and Halliwell, B. (2003) Contribution of Hydrogen Peroxide to the Cytotoxicity of Green Tea and Red Wines. Biochemical and Biophysical Research Communications, 304, 650-654. https://doi.org/10.1016/S0006-291X(03)00655-7
Taleb, H., Maddocks, S.E., Morris, R.K. and Kanekanian, A.D. (2016) The Antibacterial Activity of Date Syrup Polyphenols against S. aureus and E. coli. Frontiers in Microbiology, 7, 198. https://doi.org/10.3389/fmicb.2016.00198
Brudzynski, K., Abubaker, K. and Miotto, D. (2012) Unraveling a Mechanism of Honey Antibacterial Action: Polyphenol/H2O2-Induced Oxidative Effect on Bacterial Cell Growth and on DNA Degradation. Food Chemistry, 133, 329-336. https://doi.org/10.1016/j.foodchem.2012.01.035
Cianciosi, D., Forbes-Hernandez, T.Y., Afrin, S., Gasparrini, M., Reboredo-Rodriguez, P., Manna, P.P., Zhang, J., Lamas, L.B., Flores, S.M., Toyos, P.A., Quiles, J.L., Giampieri, F. and Battino, M. (2018) Phenolic Compounds in Honey and Their Associated Health Benefits: A Review. Molecules, 23, 2322. https://doi.org/10.3390/molecules23092322
Fan, G.J., Jin, X.L., Qian, Y.P., Wang, Q., Yang, R.T., Dai, F., Tang, J.J., Shang, Y.J., Cheng, L.X. and Zhou, B. (2009) Hydroxycinnamic Acids as DNA-Cleaving Agents in the Presence of Cu(II) Ions: Mechanisms, Structure-Activity Relationship, and Biological Implications. Chemistry, 15, 12889-12899. https://doi.org/10.1002/chem.200901627
Vatansever, F., de Melo, W.C.M.A., Avci, P., Vecchio, D., Sadasivam, M., Gupta, A., Chandran, R., Karimi, M., Parizotto, N.A., Yin, R., Tegos, G. and Hamblin, M.R. (2013) Antimicrobial Strategies Centered around Reactive Oxygen Species-Bactericidal Antibiotics, Photodynamic Therapy, and Beyond. Federation of European Microbiological Societies, 37, 955-989. https://doi.org/10.1111/1574-6976.12026
Mochizuki, M., Yamazaki, S., Kano, K. and Ikeda, T. (2002) Kinetic Analysis and Mechanistic Aspects of Autooxidation of Catechins. Biochimica et Biophysica Acta, 1569, 35-44. https://doi.org/10.1016/S0304-4165(01)00230-6
El-Agamey, A., Lowe, G.M., McGarvey, D.J., Mortensen, A., Phillip, D.M., Truscott, T.G. and Young, A.J. (2004) Carotenoid Radical Chemistry and Antioxidant/Pro-Oxidant Properties. Archives of Biochemistry and Biophysics, 430, 37-48. https://doi.org/10.1016/j.abb.2004.03.007
Perillo, B., Donato, M.D.F., Pezone, A., Zazzo, E.D., Giovannelli, P., Galasso, G., Castoria, G. and Migliaccio, A. (2020) ROS in Cancer Therapy: The Bright Side of the Moon. Experimental and Molecular Medicine, 52, 192-203. https://doi.org/10.1038/s12276-020-0384-2
Joubert, E., Winterton, P., Britz, T.J. and Gelderblom, W.C.A. (2005) Antioxidant and Pro-Oxidants Activities of Aqueous Extracts and Polyphenolic Fractions of Rooibos (Aspalathus linearis). Journal of Agricultural and Food Chemistry, 53, 10260-10267. https://doi.org/10.1021/jf051355a
Grzesik, M., Bartosz, G., Stefaniuk, I., Pichla, M., Namiesnik, J. and Sanowska-Bartosz, I. (2019) Dietary Antioxidants as a Source of Hydrogen Peroxide. Food Chemistry, 2778, 692-699. https://doi.org/10.1016/j.foodchem.2018.11.109
Bjelakovic, G., Nikolova, D., Gluud, L.L., Simonetti, R.G. and Gluud, C. (2007) Mortality in Randomized Trials of Antioxidant Supplements for Primary and Secondary Prevention: Systematic Review and Meta-Analysis. Journal of the American Medical Association, 297, 842-857. https://doi.org/10.1001/jama.297.8.842
Labieniec, M., Gabryelak, T. and Falcioni, G. (2003) Antioxidant and Prooxidant Effects of Tannins in Digestive Cells of the Freshwater Mussel Unio tumidus. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 539, 19-28. https://doi.org/10.1016/S1383-5718(03)00115-3
Cosme, P., Rodriguez, A.B., Espino, J. and Garrido, M. (2020) Plant Phenolics: Bioavailability as a Key Determinant of Their Potential Health-Promoting Applications. Antioxidants, 9, 1263. https://doi.org/10.3390/antiox9121263
Wang, F. Jiao, P., Qi, M., Frezza, M., Dou, Q.P. and Yan, B. (2010) Turning Tumor-Promoting Copper into an Anti-Cancer Weapon via High-Throughput Chemistry. Current Medicinal Chemistry, 17, 2685-2698. https://doi.org/10.2174/092986710791859315
Szatrowski, T.P. and Nathan, C.F. (1991) Production of Large Amounts of Hydrogen Peroxide by Human Tumor Cells. Cancer Research, 51, 794-798.
Kawanishi, S., Hiraku, Y., Pinlaor, S. and Ma, N. (2006) Oxidative and Nitrative DNA Damage in Animals and Patients with Inflammatory Diseases in Relation to Inflammation-Related Carcinogenesis. Biological Chemistry, 387, 365-372. https://doi.org/10.1515/BC.2006.049
Lopez-Lazaro, M. (2007) Dual Role of Hydrogen Peroxide in Cancer: Possible Relevance to Cancer Chemoprevention and Therapy. Cancer Letters, 252, 1-8. https://doi.org/10.1016/j.canlet.2006.10.029
Hadi, S.M., Asad, S.F., Singh, S. and Ahmad, A. (2000) Putative Mechanism for Anticancer and Apoptosis-Inducing Properties of Plant-Derived Polyphenolic Compounds. IUBMB (International Union of Biochemistry and Molecular Biology) Life, 50, 167-171. https://doi.org/10.1080/152165400300001471
Azmi, A.S., Bhat, S.H. and Hadi, S.M. (2005) Resveratrol-Cu(II) Induced DNA Breakage in Human Peripheral Lymphocytes: Implications for Anticancer Properties. Federation of European Biochemical Societies Letters, 579, 3131-3135. https://doi.org/10.1016/j.febslet.2005.04.077
Schumacker, P.T. (2006) Reactive Oxygen Species in Cancer Cells: Live by the Sword, Die by the Sword. Cancer Cell, 10, 175-176. https://doi.org/10.1016/j.ccr.2006.08.015
Wang, J. and Yi, J. (2008) Cancer Cell Killing via ROS: To Increase or Decrease That Is the Question. Cancer Biology and Therapy, 7, 1875-1884. https://doi.org/10.4161/cbt.7.12.7067
Kumar, J.P. and Mandal, B.B. (2019) Silk Sericin Induced Pro-Oxidative Stress Leads to Apoptosis in Human Cancer Cells. Food and Chemical Toxicology, 123, 275-287. https://doi.org/10.1016/j.fct.2018.10.063
Abotaleb, M., Liskova, A., Kubatka, P. and Busselberg, D. (2020) Therapeutic Potential of Plant Phenolic Acids in the Treatment of Cancer. Biomolecules, 10, 221. https://doi.org/10.3390/biom10020221
Sotler, R., Poljdak, B., Dahmane, R., Jukic, T., Jukic, D.P., Rotim, C., Trebse, P. and Starc, A. (2019) Proxidant Activities of Antioxidants and Their Impact on Health. Acta Clinica Croatica, 58, 726-736. https://doi.org/10.20471/acc.2019.58.04.20
Trachootham, D., Alexandre, J. and Huang, P. (2009) Targeting Cancer Cells by ROS-Mediated Mechanisms: A Radical Therapeutic Approach? Nature Reviews, 8, 579-591. https://doi.org/10.1038/nrd2803
Fang, J., Nakamura, H. and Iyer, A.K. (2007) Tumor-Targeted Induction of Oxystress for Cancer Therapy. Journal of Drug Targeting, 15, 475-486. https://doi.org/10.1080/10611860701498286
Summers, C.B. and Felton, G.W. (1994) Prooxidant Effects of Phenolic Acids on the Generalist Herbivore Helicoverpa zea (Lepidoptera: Noctuidae): Potential Mode of Action in Plant-Herbivore Chemistry. Insect Biochemistry and Molecular Biology, 24, 943-953. https://doi.org/10.1016/0965-1748(94)90023-X
Bouarab-Chilbane, L., Forquet, V., Lanteri, P., Clement, Y., Leonard-Akkari, Oulahal, N., Degraeve, P. and Bordes, C. (2019) Antibacterial Properties of Polyphenols: Characterization and QSAR (Quantitative Structure-Activity Relationship) Models. Frontiers in Microbiology, 10, 829. https://doi.org/10.3389/fmicb.2019.00829
Gyawali, R. and Ibrahim, A.A. (2014) Natural Products as Antimicrobial Agents. Food Control, 46, 412-429. https://doi.org/10.1016/j.foodcont.2014.05.047
Bucekova, M., Buriova, M., Pekarik, L., Majtan, V. and Majtan, J. (2018) Phytochemicals-Mediated Production of Hydrogen Peroxide Crucial for High Antibacterial Activity of Honeydew Honey. Scientific Reports, 8, Article No. 9061. https://doi.org/10.1038/s41598-018-27449-3
Foster, H.A., Ditta, I.B., Varghese, S. and Steele, A. (2011) Photocatalytic Disinfection Using Titanium Dioxide: Spectrum and Mechanism of Antimicrobial Activity. Applied Microbiology and Biotechnology, 90, 1847-1868. https://doi.org/10.1007/s00253-011-3213-7