{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T20:29:59Z","timestamp":1773952199324,"version":"3.50.1"},"reference-count":39,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2013,7,25]],"date-time":"2013-07-25T00:00:00Z","timestamp":1374710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Polyphenols are able to trap free radicals, which contributes to their known antioxidant capacity. In plant extracts, these secondary metabolites may act in concert, in a way that their combined activities will be superior to their individual effects (synergistic interaction). Several polyphenols have demonstrated clear antioxidant properties in vitro, and many of their biological actions have been attributed to their intrinsic reducing capabilities. As so, the intake of these compounds at certain concentrations in the diet and\/or supplementation may potentiate the activity of reduced form glutathione  (GSH), thus better fighting oxidative stress. The aim of this work was to predict a structure-antioxidant activity relationship using different classes of flavonoids and to assess, for the first time, possible synergisms and antagonisms with GSH. For these purposes a screening microassay involving the scavenging of DPPH\u2022 was applied.  In general, among the tested compounds, those lacking the catechol group in B ring showed antagonistic behaviour with GSH. Myricetin displayed additive effect, while quercetin, fisetin, luteolin, luteolin-7-O-glucoside, taxifolin and (+)-catechin demonstrated synergistic actions. Furthermore, adducts formed at C2\u2032 and C5\u2032 of the B ring seem to be more important for the antioxidant capacity than adducts formed at C6 and C8 of the A ring.<\/jats:p>","DOI":"10.3390\/molecules18088858","type":"journal-article","created":{"date-parts":[[2013,7,25]],"date-time":"2013-07-25T13:54:18Z","timestamp":1374760458000},"page":"8858-8872","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":64,"title":["Glutathione and the Antioxidant Potential of Binary Mixtures with Flavonoids: Synergisms and Antagonisms"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8500-7364","authenticated-orcid":false,"given":"Renato","family":"Pereira","sequence":"first","affiliation":[{"name":"REQUIMTE\/Laborat\u00f3rio de Farmacognosia, Departamento de Qu\u00edmica, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, n\u00ba 228, 4050-313 Porto, Portugal"}]},{"given":"Carla","family":"Sousa","sequence":"additional","affiliation":[{"name":"REQUIMTE\/Laborat\u00f3rio de Farmacognosia, Departamento de Qu\u00edmica, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, n\u00ba 228, 4050-313 Porto, Portugal"}]},{"given":"Andreia","family":"Costa","sequence":"additional","affiliation":[{"name":"REQUIMTE\/Laborat\u00f3rio de Farmacognosia, Departamento de Qu\u00edmica, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, n\u00ba 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9764-3920","authenticated-orcid":false,"given":"Paula","family":"Andrade","sequence":"additional","affiliation":[{"name":"REQUIMTE\/Laborat\u00f3rio de Farmacognosia, Departamento de Qu\u00edmica, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, n\u00ba 228, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0740-4396","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Valent\u00e3o","sequence":"additional","affiliation":[{"name":"REQUIMTE\/Laborat\u00f3rio de Farmacognosia, Departamento de Qu\u00edmica, Faculdade de Farm\u00e1cia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, n\u00ba 228, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2013,7,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/abbi.1995.1261","article-title":"Protein sulfhydryls and their role in the antioxidant function of protein S-thiolation","volume":"319","author":"Thomas","year":"1995","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/S0006-2952(02)01175-9","article-title":"Glutathionylation of proteins by glutathione disulfide S-oxide","volume":"64","author":"Huang","year":"2002","journal-title":"Biochem. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"445","DOI":"10.3109\/10409239509083491","article-title":"The glutathione S-transferase supergene family: Regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance","volume":"30","author":"Hayes","year":"1995","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1080\/10715760000300291","article-title":"Regulation of \u03b3-glutamylcysteine synthetase subunit gene expression: Insights into transcriptional control of antioxidant defenses","volume":"32","author":"Wild","year":"2000","journal-title":"Free Radic. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"375","DOI":"10.3109\/10715769509145649","article-title":"The relative antioxidant activities of plant-derived polyphenolic flavonoids","volume":"22","author":"Miller","year":"1995","journal-title":"Free Radic. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/0891-5849(95)02227-9","article-title":"Structure-antioxidant activity relationships of flavonoids and phenolic acids","volume":"20","author":"Miller","year":"1996","journal-title":"Free Radic. Biol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"5293","DOI":"10.1021\/jf104991z","article-title":"Role of the cultivar in choosing Clementine fruits with a high level of health-promoting compounds","volume":"59","author":"Milella","year":"2011","journal-title":"J. Agric. Food Chem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.freeradbiomed.2004.01.002","article-title":"Absorption and metabolism of flavonoids","volume":"36","author":"Walle","year":"2004","journal-title":"Free Radic. Biol. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1007\/s11164-010-0220-8","article-title":"Antioxidant activities of phenols in different solvents using DPPH assay","volume":"36","author":"Gaikwad","year":"2010","journal-title":"Res. Chem. Intermed."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1166S","DOI":"10.1093\/ajcn\/59.5.1166S","article-title":"Cancer preventive properties of varieties of Brassica oleracea\u2014A review","volume":"59","author":"Beecher","year":"1994","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_11","first-page":"159","article-title":"Brassica vegetables and cancer prevention\u2014Epidemiology and mechanisms","volume":"2","author":"Verhoeven","year":"1999","journal-title":"Adv. Nutr. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/S0308-8146(97)00126-X","article-title":"Antioxidative activity of phenolic compounds on the metal-ion breakdown of lipid peroxidation system","volume":"61","author":"Millic","year":"1998","journal-title":"Food Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1007\/s12161-008-9067-7","article-title":"Review of methods to determine antioxidant capacities","volume":"2","author":"Karadag","year":"2009","journal-title":"Food Anal. Methods"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/j.ejmech.2010.12.016","article-title":"Synthesis and antioxidant activity of long chain alkyl hydroxycinnamates","volume":"46","author":"Menezes","year":"2011","journal-title":"Eur. J. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/S0924-2244(01)00027-9","article-title":"Some methodological problems in the determination of antioxidant activity using chromogen radicals: A practical case","volume":"11","author":"Arnao","year":"2000","journal-title":"Trends Food Sci. Technol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.talanta.2004.03.021","article-title":"The antioxidant activity of wines determined by the ABTS\u2022+ method: Influence of sample dilution and time","volume":"64","author":"Troncoso","year":"2004","journal-title":"Talanta"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Grotewold, E. (2007). The Science of Flavonoids, Springer Press.","DOI":"10.1007\/978-0-387-28822-2"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/S0006-291X(03)01438-4","article-title":"Oxidized quercetin reacts with thiols rather than with ascorbate: Implication for quercetin supplementation","volume":"308","author":"Boots","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1211\/002235702559","article-title":"Anti- and pro-oxidant activity of rutin and quercetin derivatives","volume":"55","author":"Kessler","year":"2003","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s11130-004-0049-7","article-title":"Flavonoids in food and their health benefits","volume":"59","author":"Yao","year":"2004","journal-title":"Plant Foods Hum. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1002\/lipi.19530550708","article-title":"Beziehung zwischen chemischer konstitution und antioxygener wirkung bei flavonolen","volume":"55","author":"Heimann","year":"1953","journal-title":"Fette Seifen Anstr-Mittel."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/0076-6879(90)86128-I","article-title":"Flavonoids as antioxidants: Determination of radical scavenging efficiencies","volume":"186","author":"Bors","year":"1990","journal-title":"Methods Enzymol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0891-5849(91)90181-2","article-title":"In vitro scavenger activity of some flavonoids and melanins against O2\u2022\u2212","volume":"11","author":"Sichel","year":"1991","journal-title":"Free Radic. Biol. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.ejmech.2008.03.001","article-title":"QSAR study of antioxidant activity of wine polyphenols","volume":"44","author":"Rastija","year":"2009","journal-title":"Eur. J. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Harborne, J.B., Mabry, T.J., and Mabry, H. (1975). The Flavonoids, Chapman and Hall.","DOI":"10.1007\/978-1-4899-2909-9"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2774","DOI":"10.1021\/jf001413m","article-title":"Antioxidant and antiradical activities of flavonoids","volume":"49","author":"Burda","year":"2001","journal-title":"J. Agric. Food Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/0885-4505(88)90060-6","article-title":"Effects of flavonoids on nonenzymatic lipid peroxidation: Structure-activity relationship","volume":"39","author":"Ratty","year":"1988","journal-title":"Biochem. Med. Metab. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0891-5849(96)00277-8","article-title":"Hydrogen bond formation as basis for radical scavenging activity: A structure-activity study of C-methylated dihydrochalcones from Myrica gale and structurally related acetophenones","volume":"2","author":"Matthiesen","year":"1997","journal-title":"Free Radic. Biol. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"6305","DOI":"10.1021\/jf050511a","article-title":"Antioxidant activity of Glossogyne tenuifolia","volume":"53","author":"Wu","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0065-2571(84)90007-4","article-title":"Quantitative analysis of dose-effect relationships: The combined effects of multiple drugs or enzyme inhibitors","volume":"22","author":"Chou","year":"1984","journal-title":"Adv. Enzyme Regul."},{"key":"ref_31","first-page":"66","article-title":"Effect of More than One Inhibitor","volume":"Volume 1","author":"Webb","year":"1963","journal-title":"Enzyme and Metabolic Inhibitors"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1021\/tx010132l","article-title":"The regioselectivity of glutathione adduct formation with flavonoid quinone\/quinone methides is pH-dependent","volume":"15","author":"Awad","year":"2002","journal-title":"Chem. Res. Toxicol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2345","DOI":"10.1016\/0006-2952(86)90461-2","article-title":"Inhibition of mitochondrial respiration and production of toxic oxygen radicals by flavonoids: A structure-activity study","volume":"35","author":"Hodnick","year":"1986","journal-title":"Biochem. Pharmacol."},{"key":"ref_34","first-page":"200","article-title":"Isolation and characterization of flavonol converting enzymes from Mentha piperita plants and from Mentha arvensis cell suspension cultures","volume":"34C","author":"Barz","year":"1979","journal-title":"Z. Naturforsch."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1039\/a901460h","article-title":"One-electron oxidation of quercetin derivatives in protic and non protic media","volume":"2","author":"Dangles","year":"1999","journal-title":"J. Chem. Soc. Perkin Trans."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.cbi.2005.12.005","article-title":"Consequences of quercetin methylation for its covalent glutathione and DNA adduct formation","volume":"160","author":"Boersma","year":"2006","journal-title":"Chem. Biol. Interact."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1021\/tx000216e","article-title":"Structure-activity study on the quinone\/quinone methide chemistry of flavonoids","volume":"14","author":"Awad","year":"2001","journal-title":"Chem. Res. Toxicol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1021\/tx000235o","article-title":"Catechin metabolism: Glutathione conjugate formation catalyzed by tyrosinase, peroxidase, and cytochrome p450","volume":"14","author":"Moridani","year":"2001","journal-title":"Chem. Res. Toxicol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.foodchem.2005.06.019","article-title":"Antioxidative properties of tronchuda cabbage (Brassica oleracea L. var. costata DC) external leaves against DPPH\u2022, superoxide radical, hydroxyl radical and hypochlorous acid","volume":"98","author":"Sousa","year":"2006","journal-title":"Food Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/18\/8\/8858\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:48:14Z","timestamp":1760219294000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/18\/8\/8858"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,7,25]]},"references-count":39,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2013,8]]}},"alternative-id":["molecules18088858"],"URL":"https:\/\/doi.org\/10.3390\/molecules18088858","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,7,25]]}}}