{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T08:40:35Z","timestamp":1768293635468,"version":"3.49.0"},"reference-count":79,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T00:00:00Z","timestamp":1729728000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT\/MEC)","award":["UIDB\/04033\/2020"],"award-info":[{"award-number":["UIDB\/04033\/2020"]}]},{"name":"Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT\/MEC)","award":["UIDB\/00616\/2020"],"award-info":[{"award-number":["UIDB\/00616\/2020"]}]},{"name":"Portuguese Science and Technology Foundation, Ministry of Science and Education (FCT\/MEC)","award":["LA\/P\/0126\/2020"],"award-info":[{"award-number":["LA\/P\/0126\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>The increasing incidence of colorectal cancer and inflammatory diseases poses a major health concern, with oxidative stress playing a significant role in the onset of these pathologies. Factors such as excessive consumption of sugar-rich and fatty foods, synthetic food additives, pesticides, alcohol, and tobacco contribute to oxidative stress and disrupt intestinal homeostasis. Functional foods arise as a potential tool to regulate redox balance in the intestinal tract. Herbs (such as Thymus spp.) have long been screened for their antioxidant properties, but their use as antioxidants for medicinal purposes requires validation in biological models. In this study, we addressed the potential antioxidant protection and preventive effects of extracts from two thyme species at the intestinal level, as well as their molecular mechanisms of action. Caco-2 cells were pre-exposed (4 h) to aqueous (AD) and hydroethanolic (HE) extracts of Thymus carnosus and Thymus capitellatus, followed by a recovery period in culture medium (16 h), and then treated with tert-butyl-hydroperoxide (TBHP; 4 h), before analyzing cell viability. The effect of the extracts\u2019 main components was also analysed. Cellular oxidative stress, cell-death markers, and the expression of antioxidant-related proteins were evaluated using flow cytometry on cells pre-exposed to the AD extracts and salvianolic acid A (SAA). Results showed that pre-exposure to AD extracts or SAA reduced TBHP-induced oxidative stress and cell death, mediated by increased levels of nuclear factor erythroid 2-related factor 2 (Nrf2) protein. The protective activity of T. capitellatus AD extract was shown to be dependent on NAD(P)H quinone dehydrogenase 1 (NQO1) protein expression and on increased glutathione (GSH) content. Furthermore, ursolic acid induced cytotoxicity and low cellular antioxidant activity, and thus the presence of this triterpenoid impaired the antioxidant effect of HE extracts. Thus, AD extracts show high potential as prophylactic dietary agents, while HE extracts arise as a source of nutraceuticals with antioxidant potential.<\/jats:p>","DOI":"10.3390\/antiox13111287","type":"journal-article","created":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T05:47:33Z","timestamp":1729748853000},"page":"1287","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Thymus spp. Aqueous Extracts and Their Constituent Salvianolic Acid A Induce Nrf2-Dependent Cellular Antioxidant Protection Against Oxidative Stress in Caco-2 Cells"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1564-3661","authenticated-orcid":false,"given":"Carlos","family":"Martins-Gomes","sequence":"first","affiliation":[{"name":"Centre for Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Cell Biology and Biochemistry Laboratory, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal"},{"name":"Chemistry Research Centre-Vila Real (CQ-VR), Food and Wine Chemistry Laboratory, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5540-318X","authenticated-orcid":false,"given":"Fernando M.","family":"Nunes","sequence":"additional","affiliation":[{"name":"Chemistry Research Centre-Vila Real (CQ-VR), Food and Wine Chemistry Laboratory, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal"},{"name":"Department of Chemistry, School of Life Sciences and Environment, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7524-9914","authenticated-orcid":false,"given":"Am\u00e9lia M.","family":"Silva","sequence":"additional","affiliation":[{"name":"Centre for Research and Technology of Agro-Environmental and Biological Sciences (CITAB), Cell Biology and Biochemistry Laboratory, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal"},{"name":"Department of Biology and Environment, School of Life Sciences and Environment, University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), 5000-801 Vila Real, Portugal"},{"name":"Institute for Innovation, Capacity Building and Sustainability of Agri-Food Production (Inov4gro), University of Tr\u00e1s-os-Montes and Alto Douro (UTAD), Quinta de Prados, 5000-801 Vila Real, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1177\/0884533612454885","article-title":"Diet and Nutrient Factors in Colorectal Cancer Risk","volume":"27","author":"Vargas","year":"2012","journal-title":"Nutr. Clin. Pract."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.maturitas.2014.12.017","article-title":"Diet and colorectal cancer","volume":"80","author":"Baena","year":"2015","journal-title":"Maturitas"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/ajg.2011.44","article-title":"Dietary Intake and Risk of Developing Inflammatory Bowel Disease: A Systematic Review of the Literature","volume":"106","author":"Hou","year":"2011","journal-title":"Am. J. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e15795","DOI":"10.1097\/MD.0000000000015795","article-title":"Beverage intake and risk of Crohn disease: A meta-analysis of 16 epidemiological studies","volume":"98","author":"Yang","year":"2019","journal-title":"Medicine"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e9070","DOI":"10.1097\/MD.0000000000009070","article-title":"Beverage consumption and risk of ulcerative colitis: Systematic review and meta-analysis of epidemiological studies","volume":"96","author":"Nie","year":"2017","journal-title":"Medicine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e196","DOI":"10.1038\/ctg.2016.54","article-title":"Human Intestinal Barrier Function in Health and Disease","volume":"7","author":"Wells","year":"2016","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Farr\u00e9, R., Fiorani, M., Abdu Rahiman, S., and Matteoli, G. (2020). Intestinal Permeability, Inflammation and the Role of Nutrients. Nutrients, 12.","DOI":"10.3390\/nu12041185"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Martins-Gomes, C., Nunes, F.M., and Silva, A.M. (2024). Natural Products as Dietary Agents for the Prevention and Mitigation of Oxidative Damage and Inflammation in the Intestinal Barrier. Antioxidants, 13.","DOI":"10.3390\/antiox13010065"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Wan, M.L.Y., Turner, P.C., Co, V.A., Wang, M.F., Amiri, K.M.A., and El-Nezami, H. (2019). Schisandrin A protects intestinal epithelial cells from deoxynivalenol-induced cytotoxicity, oxidative damage and inflammation. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-55821-4"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Su, D., Lu, J., Nie, C., Guo, Z., Li, C., Yu, Q., Xie, J., and Chen, Y. (2023). Combined Effects of Acrylamide and Ochratoxin A on the Intestinal Barrier in Caco-2 Cells. Foods, 12.","DOI":"10.3390\/foods12061318"},{"key":"ref_11","first-page":"312","article-title":"Acrylamide exposure aggravates the development of ulcerative colitis in mice through activation of NF-\u03baB, inflammatory cytokines, iNOS, and oxidative stress","volume":"24","author":"Amirshahrokhi","year":"2021","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"113696","DOI":"10.1016\/j.fct.2023.113696","article-title":"Acrylamide in food: Occurrence, metabolism, molecular toxicity mechanism and detoxification by phytochemicals","volume":"175","author":"Yan","year":"2023","journal-title":"Food Chem. Toxicol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.toxlet.2022.01.019","article-title":"Food additive sodium bisulfite induces intracellular imbalance of biothiols levels in NCM460 colonic cells to trigger intestinal inflammation in mice","volume":"359","author":"Wu","year":"2022","journal-title":"Toxicol. Lett."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Shil, A., Olusanya, O., Ghufoor, Z., Forson, B., Marks, J., and Chichger, H. (2020). Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium through Activation of the Sweet Taste Receptor, T1R3. Nutrients, 12.","DOI":"10.3390\/nu12061862"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1136\/gutjnl-2014-307142","article-title":"A polyphenol-rich cranberry extract protects from diet-induced obesity, insulin resistance and intestinal inflammation in association with increased Akkermansia spp. population in the gut microbiota of mice","volume":"64","author":"Fernando","year":"2015","journal-title":"Gut"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2882","DOI":"10.1007\/s11356-015-5519-y","article-title":"Diazinon, an organophosphate pesticide, induces oxidative stress and genotoxicity in cells deriving from large intestine","volume":"23","author":"Boussabbeh","year":"2016","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.toxrep.2014.07.008","article-title":"In vitro impact of five pesticides alone or in combination on human intestinal cell line Caco-2","volume":"1","author":"Ilboudo","year":"2014","journal-title":"Toxicol. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1007\/s00204-013-1032-6","article-title":"Chronic ingestion of cadmium and lead alters the bioavailability of essential and heavy metals, gene expression pathways and genotoxicity in mouse intestine","volume":"87","author":"Breton","year":"2013","journal-title":"Arch. Toxicol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1016\/j.jnutbio.2014.05.007","article-title":"DJ-1 plays an important role in caffeic acid-mediated protection of the gastrointestinal mucosa against ketoprofen-induced oxidative damage","volume":"25","author":"Cheng","year":"2014","journal-title":"J. Nutr. Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.semcdb.2012.03.014","article-title":"Intestinal redox biology and oxidative stress","volume":"23","author":"Circu","year":"2012","journal-title":"Semin. Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Bardel\u010d\u00edkov\u00e1, A., \u0160oltys, J., and Moj\u017ei\u0161, J. (2023). Oxidative Stress, Inflammation and Colorectal Cancer: An Overview. Antioxidants, 12.","DOI":"10.3390\/antiox12040901"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"M\u00e1rmol, I., S\u00e1nchez-de-Diego, C., Pradilla Dieste, A., Cerrada, E., and Rodriguez Yoldi, M.J. (2017). Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18010197"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"982","DOI":"10.7150\/ijbs.12096","article-title":"Significance of antioxidant potential of plants and its relevance to therapeutic applications","volume":"11","author":"Kasote","year":"2015","journal-title":"Int. J. Biol. Sci."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Nwachukwu, I.D., Sarteshnizi, R.A., Udenigwe, C.C., and Aluko, R.E. (2021). A Concise Review of Current In Vitro Chemical and Cell-Based Antioxidant Assay Methods. Molecules, 26.","DOI":"10.3390\/molecules26164865"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1016\/j.freeradbiomed.2004.01.001","article-title":"Flavonoids: Antioxidants or signalling molecules?","volume":"36","author":"Williams","year":"2004","journal-title":"Free Radic. Biol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"127362","DOI":"10.1016\/j.foodchem.2020.127362","article-title":"Polyphenol composition and biological activity of Thymus citriodorus and Thymus vulgaris: Comparison with endemic Iberian Thymus species","volume":"331","author":"Taghouti","year":"2020","journal-title":"Food Chem."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Martins-Gomes, C., Steck, J., Keller, J., Bunzel, M., Santos, J.A., Nunes, F.M., and Silva, A.M. (2023). Phytochemical Composition and Antioxidant, Anti-Acetylcholinesterase, and Anti-\u03b1-Glucosidase Activity of Thymus carnosus Extracts: A Three-Year Study on the Impact of Annual Variation and Geographic Location. Antioxidants, 12.","DOI":"10.3390\/antiox12030668"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Martins-Gomes, C., Steck, J., Keller, J., Bunzel, M., Nunes, F.M., and Silva, A.M. (2022). Molecular Characterization of Thymus capitellatus Extracts and Their Antioxidant, Neuroprotective and Anti-Proliferative Activities. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232315187"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Martins-Gomes, C., Nunes, F.M., and Silva, A.M. (2024). Linking Variability in Phytochemical Composition with Safety Profile of Thymus carnosus Boiss. Extracts: Effect of Major Compounds and Evaluation of Markers of Oxidative Stress and Cell Death. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25105343"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Silva, A.M., Martins-Gomes, C., Souto, E.B., Sch\u00e4fer, J., Santos, J.A., Bunzel, M., and Nunes, F.M. (2020). Thymus zygis subsp. zygis an Endemic Portuguese Plant: Phytochemical Profiling, Antioxidant, Anti-Proliferative and Anti-Inflammatory Activities. Antioxidants, 9.","DOI":"10.3390\/antiox9060482"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"100437","DOI":"10.1016\/j.fochx.2022.100437","article-title":"Elderberry (Sambucus nigra L.) extracts promote anti-inflammatory and cellular antioxidant activity","volume":"15","author":"Ferreira","year":"2022","journal-title":"Food Chem. X"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Silva, A.M., Martins-Gomes, C., Ferreira, S.S., Souto, E.B., and Andreani, T. (2022). Molecular Physicochemical Properties of Selected Pesticides as Predictive Factors for Oxidative Stress and Apoptosis-Dependent Cell Death in Caco-2 and HepG2 Cells. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23158107"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.jff.2019.01.010","article-title":"Thymus carnosus extracts induce anti-proliferative activity in Caco-2 cells through mechanisms that involve cell cycle arrest and apoptosis","volume":"54","author":"Souto","year":"2019","journal-title":"J. Funct. Foods"},{"key":"ref_34","unstructured":"CST (2024, September 17). Cell Signaling Technology, Inc.\u2014Flow Cytometry, Methanol Permeabilization Protocol. Available online: https:\/\/www.cellsignal.com\/learn-and-support\/protocols\/protocol-flow-methanol-permeabilization."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"8896","DOI":"10.1021\/jf0715166","article-title":"Cellular Antioxidant Activity (CAA) Assay for Assessing Antioxidants, Foods, and Dietary Supplements","volume":"55","author":"Wolfe","year":"2007","journal-title":"J. Agric. Food Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.aca.2012.11.051","article-title":"Evaluating the antioxidant capacity of natural products: A review on chemical and cellular-based assays","volume":"763","author":"Denicola","year":"2013","journal-title":"Anal. Chim. Acta"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"6621","DOI":"10.1021\/jf9035832","article-title":"Cellular Antioxidant Activity of Common Vegetables","volume":"58","author":"Song","year":"2010","journal-title":"J. Agric. Food Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"8418","DOI":"10.1021\/jf801381y","article-title":"Cellular Antioxidant Activity of Common Fruits","volume":"56","author":"Wolfe","year":"2008","journal-title":"J. Agric. Food Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.lwt.2015.09.008","article-title":"Antioxidant activity of papaya seed extracts against H2O2 induced oxidative stress in HepG2 cells","volume":"66","author":"Salla","year":"2016","journal-title":"LWT\u2014Food Sci. Technol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1093\/jpp\/rgac069","article-title":"Ginkgo biloba extracts (GBE) protect human RPE cells from t-BHP-induced oxidative stress and necrosis by activating the Nrf2-mediated antioxidant defence","volume":"75","author":"Li","year":"2022","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.foodchem.2017.10.035","article-title":"Modification of the cellular antioxidant activity (CAA) assay to study phenolic antioxidants in a Caco-2 cell line","volume":"244","author":"Kellett","year":"2018","journal-title":"Food Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1007\/s12079-014-0248-4","article-title":"New considerations on hormetic response against oxidative stress","volume":"8","year":"2014","journal-title":"J. Cell Commun. Signal."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/bs.acc.2018.07.004","article-title":"Chapter Five\u2014Glutathione as a Marker for Human Disease","volume":"Volume 87","author":"Makowski","year":"2018","journal-title":"Advances in Clinical Chemistry"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/S1353-8020(02)00018-4","article-title":"Glutathione depletion and oxidative stress","volume":"8","author":"Mytilineou","year":"2002","journal-title":"Park. Relat. Disord."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3008","DOI":"10.1016\/j.fct.2010.07.041","article-title":"Protective effect of simple phenols from extravirgin olive oil against lipid peroxidation in intestinal Caco-2 cells","volume":"48","author":"Deiana","year":"2010","journal-title":"Food Chem. Toxicol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3450","DOI":"10.1002\/fsn3.3335","article-title":"Antioxidant, anti-inflammatory, and anticancer function of Engleromyces goetzei Henn aqueous extract on human intestinal Caco-2 cells treated with t-BHP","volume":"11","author":"Ni","year":"2023","journal-title":"Food Sci. Nutr."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.cbi.2007.01.020","article-title":"Water and methanolic extracts of Salvia officinalis protect HepG2 cells from t-BHP induced oxidative damage","volume":"167","author":"Lima","year":"2007","journal-title":"Chem. Biol. Interact."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.foodchem.2012.01.037","article-title":"Protective effect of extracts of Perilla frutescens treated with sucrose on tert-butyl hydroperoxide-induced oxidative hepatotoxicity in vitro and in vivo","volume":"133","author":"Yang","year":"2012","journal-title":"Food Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.fct.2012.12.042","article-title":"The hepatoprotection of caffeic acid and rosmarinic acid, major compounds of Perilla frutescens, against t-BHP-induced oxidative liver damage","volume":"55","author":"Yang","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"41576","DOI":"10.1039\/C5RA02710A","article-title":"Pennyroyal and gastrointestinal cells: Multi-target protection of phenolic compounds against t-BHP-induced toxicity","volume":"5","author":"Ferreres","year":"2015","journal-title":"RSC Adv."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3665","DOI":"10.1039\/C8FO00568K","article-title":"Thymus lanceolatus ethanolic extract protects human cells from t-BHP induced oxidative damage","volume":"9","author":"Caprioli","year":"2018","journal-title":"Food Funct."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4191","DOI":"10.1016\/j.fct.2012.08.015","article-title":"In vitro protective effects of Thymus quinquecostatus Celak extracts on t-BHP-induced cell damage through antioxidant activity","volume":"50","author":"Kim","year":"2012","journal-title":"Food Chem. Toxicol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1111\/joa.13599","article-title":"Hoechst 33342 as a marker for imaging neurites of Dorsal Root Ganglion in vitro","volume":"240","author":"Merolli","year":"2022","journal-title":"J. Anat."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"12246","DOI":"10.1007\/s11356-016-6450-6","article-title":"Tetrabromobisphenol A (TBBPA)-stimulated reactive oxygen species (ROS) production in cell-free model using the 2\u2032,7\u2032-dichlorodihydrofluorescein diacetate (H2DCFDA) assay\u2014Limitations of method","volume":"23","author":"Szychowski","year":"2016","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.redox.2016.12.036","article-title":"Tert-butyl hydroperoxide (t-BHP) induced apoptosis and necroptosis in endothelial cells: Roles of NOX4 and mitochondrion","volume":"11","author":"Zhao","year":"2017","journal-title":"Redox Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.jim.2015.04.025","article-title":"Quantification of apoptosis and necroptosis at the single cell level by a combination of Imaging Flow Cytometry with classical Annexin V\/propidium iodide staining","volume":"423","author":"Pietkiewicz","year":"2015","journal-title":"J. Immunol. Methods"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.foodchem.2019.03.127","article-title":"Determination of polycyclic aromatic hydrocarbon content in heat-treated meat retailed in Egypt: Health risk assessment, benzo[a]pyrene induced mutagenicity and oxidative stress in human colon (CaCo-2) cells and protection using rosmarinic and ascorbic acids","volume":"290","author":"Darwish","year":"2019","journal-title":"Food Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"112098","DOI":"10.1016\/j.fct.2021.112098","article-title":"Regulatory effects of flavonoids luteolin on BDE-209-induced intestinal epithelial barrier damage in Caco-2 cell monolayer model","volume":"150","author":"Yuan","year":"2021","journal-title":"Food Chem. Toxicol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"110430","DOI":"10.1016\/j.foodres.2021.110430","article-title":"Intracellular quercetin accumulation and its impact on mitochondrial dysfunction in intestinal Caco-2 cells","volume":"145","author":"Vissenaekens","year":"2021","journal-title":"Food Res. Int."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1016\/j.toxrep.2021.06.015","article-title":"Selective in vitro cytotoxicity effect of Drimia calcarata bulb extracts against p53 mutant HT-29 and p53 wild-type Caco-2 colorectal cancer cells through STAT5B regulation","volume":"8","author":"Laka","year":"2021","journal-title":"Toxicol. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Ngo, V., and Duennwald, M.L. (2022). Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease. Antioxidants, 11.","DOI":"10.3390\/antiox11122345"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1016\/j.jnutbio.2015.08.001","article-title":"The complexity of the Nrf2 pathway: Beyond the antioxidant response","volume":"26","author":"Huang","year":"2015","journal-title":"J. Nutr. Biochem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.phrs.2018.06.013","article-title":"Canonical and non-canonical mechanisms of Nrf2 activation","volume":"134","author":"Maldonado","year":"2018","journal-title":"Pharmacol. Res."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Villavicencio Tejo, F., and Quintanilla, R.A. (2021). Contribution of the Nrf2 Pathway on Oxidative Damage and Mitochondrial Failure in Parkinson and Alzheimer\u2019s Disease. Antioxidants, 10.","DOI":"10.3390\/antiox10071069"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.cotox.2017.10.005","article-title":"NQO1 in protection against oxidative stress","volume":"7","author":"Ross","year":"2018","journal-title":"Curr. Opin. Toxicol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Ross, D., and Siegel, D. (2017). Functions of NQO1 in Cellular Protection and CoQ10 Metabolism and its Potential Role as a Redox Sensitive Molecular Switch. Front. Physiol., 8.","DOI":"10.3389\/fphys.2017.00595"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Adesso, S., Russo, R., Quaroni, A., Autore, G., and Marzocco, S. (2018). Astragalus membranaceus Extract Attenuates Inflammation and Oxidative Stress in Intestinal Epithelial Cells via NF-\u03baB Activation and Nrf2 Response. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030800"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Jeon, Y.-D., Lee, J.-H., Lee, Y.-M., and Kim, D.-K. (2020). Puerarin inhibits inflammation and oxidative stress in dextran sulfate sodium-induced colitis mice model. Biomed. Pharmacother., 124.","DOI":"10.1016\/j.biopha.2020.109847"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2320","DOI":"10.1159\/000493833","article-title":"Salvianolic Acid A Protects Against Oxidative Stress and Apoptosis Induced by Intestinal Ischemia-Reperfusion Injury Through Activation of Nrf2\/HO-1 Pathways","volume":"49","author":"Zu","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.freeradbiomed.2014.01.025","article-title":"Salvianolic acid A protects RPE cells against oxidative stress through activation of Nrf2\/HO-1 signaling","volume":"69","author":"Zhang","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1089\/rej.2018.2107","article-title":"Rosmarinic Acid Ameliorates H2O2-Induced Oxidative Stress in L02 Cells Through MAPK and Nrf2 Pathways","volume":"22","author":"Ding","year":"2018","journal-title":"Rejuvenation Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1016\/j.freeradbiomed.2007.02.017","article-title":"Action of Nrf2 and Keap1 in ARE-mediated NQO1 expression by quercetin","volume":"42","author":"Tanigawa","year":"2007","journal-title":"Free Radic. Biol. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1671","DOI":"10.1167\/iovs.07-1099","article-title":"Essential roles of the PI3 kinase\/Akt pathway in regulating Nrf2-dependent antioxidant functions in the RPE","volume":"49","author":"Wang","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Xu, W., Zheng, H., Fu, Y., Gu, Y., Zou, H., Yuan, Y., Gu, J., Liu, Z., and Bian, J. (2022). Role of PI3K\/Akt-Mediated Nrf2\/HO-1 Signaling Pathway in Resveratrol Alleviation of Zearalenone-Induced Oxidative Stress and Apoptosis in TM4 Cells. Toxins, 14.","DOI":"10.3390\/toxins14110733"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Tanase, C.P., Ogrezeanu, I., and Badiu, C. (2012). 6\u2014Signal Transduction. Molecular Pathology of Pituitary Adenomas, Elsevier.","DOI":"10.1016\/B978-0-12-415830-6.00015-9"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Martins-Gomes, C., Nunes, F.M., and Silva, A.M. (2023). Modulation of Cell Death Pathways for Cellular Protection and Anti-Tumoral Activity: The Role of Thymus spp. Extracts and Their Bioactive Molecules. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24021691"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.tox.2008.06.010","article-title":"Rosmarinic acid protects human dopaminergic neuronal cells against hydrogen peroxide-induced apoptosis","volume":"250","author":"Lee","year":"2008","journal-title":"Toxicology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"153673","DOI":"10.1016\/j.phymed.2021.153673","article-title":"Thymus quinquecostatus Celak. ameliorates cerebral ischemia-reperfusion injury via dual antioxidant actions: Activating Keap1\/Nrf2\/HO-1 signaling pathway and directly scavenging ROS","volume":"91","author":"Fan","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1111\/jcmm.12968","article-title":"Thymus vulgaris alleviates UVB irradiation induced skin damage via inhibition of MAPK\/AP-1 and activation of Nrf2-ARE antioxidant system","volume":"21","author":"Sun","year":"2017","journal-title":"J. Cell. Mol. Med."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/13\/11\/1287\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:19:27Z","timestamp":1760113167000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/13\/11\/1287"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,24]]},"references-count":79,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["antiox13111287"],"URL":"https:\/\/doi.org\/10.3390\/antiox13111287","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,24]]}}}