{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T06:56:47Z","timestamp":1764053807900,"version":"build-2065373602"},"reference-count":68,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,7,30]],"date-time":"2022-07-30T00:00:00Z","timestamp":1659139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Improvement for Higher Education Personnel (Capes) doctorate fellowship","award":["01P-3370-2017","141087-2014\/5","2013-25256-8","010887\/2014-8"],"award-info":[{"award-number":["01P-3370-2017","141087-2014\/5","2013-25256-8","010887\/2014-8"]}]},{"name":"The National Council for Scientific and Technological Development (CNPq) doctorate fellowship","award":["01P-3370-2017","141087-2014\/5","2013-25256-8","010887\/2014-8"],"award-info":[{"award-number":["01P-3370-2017","141087-2014\/5","2013-25256-8","010887\/2014-8"]}]},{"DOI":"10.13039\/501100001807","name":"F.A.P.E.S.P.","doi-asserted-by":"publisher","award":["01P-3370-2017","141087-2014\/5","2013-25256-8","010887\/2014-8"],"award-info":[{"award-number":["01P-3370-2017","141087-2014\/5","2013-25256-8","010887\/2014-8"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CNPq","award":["01P-3370-2017","141087-2014\/5","2013-25256-8","010887\/2014-8"],"award-info":[{"award-number":["01P-3370-2017","141087-2014\/5","2013-25256-8","010887\/2014-8"]}]},{"name":"F.A.E.P.E.X. (Support to Teaching Research and Extension)","award":["01P-3370-2017","141087-2014\/5","2013-25256-8","010887\/2014-8"],"award-info":[{"award-number":["01P-3370-2017","141087-2014\/5","2013-25256-8","010887\/2014-8"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>The antioxidant, anti-inflammatory and antiproliferative properties of Passiflora alata Curtis are due to the presence of polyphenols in its composition. Our previous work showed that non-obese diabetic (NOD) mice undergoing treatment with aqueous leaf extract of P. alata present reduced insulitis in the pancreas, possibly due to its anti-inflammatory properties. However, depending on the concentration and their ability to interact with other molecules, these phenolic compounds may promote oxidation reactions in some cellular components, such as proteins and lipids, thus presenting a pro-oxidant effect. The present work aimed to evaluate the in vitro effects of aqueous leaf extract of P. alata and its polyphenols (vitexin, isoorientin, rutin and catechin) on lymphocyte proliferation and viability, the cell cycle and oxidative stress. Our results showed that T lymphocytes stimulated with concanavalin A mitogen (ConA) and in the presence of IC50 concentrations of P. alata extract and polyphenols undergo cell injury via inhibition of proliferation, with these effects being more pronounced concerning CD4+ T cells (P. alata, 3.54 \u00b1 0.34%; isoorientin, 57.07 \u00b1 6.4%; vitexin, 16.95 \u00b1 1.11%; catechin, 37.9 \u00b1 4.2% and rutin, 40.14 \u00b1 4.5%), compared to the non-treated group (77.17 \u00b1 6.29) (p &lt; 0.0001 for all comparisons). This process includes late apoptosis\/necrosis induction (P. alata, 77.5 \u00b1 0.7%; vitexin, 83 \u00b1 3.3%; isoorientin, 83.8 \u00b1 1.4%; catechin, 83 \u00b1 1.9% and rutin, 74.9 \u00b1 3.2, while the control presented 53.6% \u00b1 3.1 (p &lt; 0.0001 for all comparisons)) and mitochondrial depolarization leading to cell-death induction. Furthermore, an in vitro model of a mixed culture of NOD mice T cells with a mouse pancreatic beta-cell line (MIN6) showed increased intracellular nitric oxide and lipid peroxidation in NOD T cells submitted to P. alata extract (46.41 \u00b1 3.08) compared to the untreated control group (33.57 \u00b1 1.99, p = 0.01315). These results suggest that aqueous leaf extract of P. alata and the polyphenols in these leaves represent a target for translational research showing the plant\u2019s benefits for developing new drugs with immunomodulatory properties against inflammatory diseases such as diabetes mellitus.<\/jats:p>","DOI":"10.3390\/antiox11081503","type":"journal-article","created":{"date-parts":[[2022,7,31]],"date-time":"2022-07-31T21:49:02Z","timestamp":1659304142000},"page":"1503","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Antiproliferative and Pro-Oxidant Effect of Polyphenols in Aqueous Leaf Extract of Passiflora alata Curtis on Activated T Lymphocytes from Non-Obese Diabetic (NOD SHILT\/J) Mice"],"prefix":"10.3390","volume":"11","author":[{"given":"Talita Cristina","family":"Colomeu","sequence":"first","affiliation":[{"name":"Laboratory of Translational Immunology, Department of Internal Medicine, School of Medical Sciences, University of Campinas\u2014Rua Tess\u00e1lia Vieira de Camargo, 126, Cidade Universit\u00e1ria Zeferino Vaz, Campinas 13083-887, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniella","family":"de Figueiredo","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Immunology, Department of Internal Medicine, School of Medical Sciences, University of Campinas\u2014Rua Tess\u00e1lia Vieira de Camargo, 126, Cidade Universit\u00e1ria Zeferino Vaz, Campinas 13083-887, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Priscila","family":"de Matos da Silva","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Immunology, Department of Internal Medicine, School of Medical Sciences, University of Campinas\u2014Rua Tess\u00e1lia Vieira de Camargo, 126, Cidade Universit\u00e1ria Zeferino Vaz, Campinas 13083-887, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0771-1027","authenticated-orcid":false,"given":"Lu\u00eds Gustavo Romani","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Immunology, Department of Internal Medicine, School of Medical Sciences, University of Campinas\u2014Rua Tess\u00e1lia Vieira de Camargo, 126, Cidade Universit\u00e1ria Zeferino Vaz, Campinas 13083-887, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1639-2841","authenticated-orcid":false,"given":"Ricardo de Lima","family":"Zollner","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Immunology, Department of Internal Medicine, School of Medical Sciences, University of Campinas\u2014Rua Tess\u00e1lia Vieira de Camargo, 126, Cidade Universit\u00e1ria Zeferino Vaz, Campinas 13083-887, SP, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,30]]},"reference":[{"key":"ref_1","first-page":"48","article-title":"Phenolic Compounds: A Review of Their Possible Role as In Vivo Antioxidants of Wine","volume":"23","author":"Beer","year":"2002","journal-title":"S. Afr. J. Enol. Vitic."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Thitimuta, S., Pithayanukul, P., Nithitanakool, S., Bavovada, R., Leanpolchareanchai, J., and Saparpakorn, P. (2017). Camellia sinensis L. Extract and its potential beneficial effects in antioxidant, anti-inflammatory, anti-hepatotoxic, and anti-tyrosinase activities. Molecules, 22.","DOI":"10.3390\/molecules22030401"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.cofs.2016.02.002","article-title":"Dietary polyphenols, oxidative stress and antioxidant and anti-inflammatory effects","volume":"8","author":"Zhang","year":"2016","journal-title":"Curr. Opin. Food Sci."},{"key":"ref_4","first-page":"673","article-title":"The effects of plant flavonoids on mammalian cells: Implications for inflammation, heart disease, and cancer","volume":"52","author":"Middleton","year":"2000","journal-title":"Pharmacol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.canlet.2006.01.027","article-title":"Green tea polyphenols and its constituent epigallocatechin gallate inhibits proliferation of human breast cancer cells in vitro and in vivo","volume":"245","author":"Thangapazham","year":"2007","journal-title":"Cancer Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1590\/S0102-695X2013005000025","article-title":"The catechin flavonoid reduces proliferation and induces apoptosis of murine lymphoma cells LB02 through modulation of antiapoptotic proteins","volume":"23","author":"Papademetrio","year":"2013","journal-title":"Rev. Bras. Farmacogn."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1093\/carcin\/bgi040","article-title":"Epigallocatechin-3-gallate induces mitochondrial membrane depolarization and caspase-dependent apoptosis in pancreatic cancer cells","volume":"26","author":"Qanungo","year":"2005","journal-title":"Carcinogenesis"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"598313","DOI":"10.1155\/2014\/598313","article-title":"Genetic diversity in passiflora species assessed by morphological and ITS sequence analysis","volume":"2014","author":"Ramaiya","year":"2014","journal-title":"Sci. World J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.intimp.2013.11.005","article-title":"Antioxidant and anti-diabetic potential of Passiflora alata Curtis aqueous leaves extract in type 1 diabetes mellitus (NOD-mice)","volume":"18","author":"Colomeu","year":"2014","journal-title":"Int. Immunopharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.intimp.2016.03.031","article-title":"Aqueous leaf extract of Passiflora alata Curtis promotes antioxidant and anti-inflammatory effects and consequently preservation of NOD mice beta cells (non-obese diabetic)","volume":"35","author":"Figueiredo","year":"2016","journal-title":"Int. Immunopharmacol."},{"key":"ref_11","first-page":"398","article-title":"Passiflora alata curtis: A brazilian medicinal plant","volume":"10","author":"Noriega","year":"2011","journal-title":"Bolet\u00edn Latinoam. Y Caribe Plantas Med. Y Arom\u00e1ticas"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1093\/carcin\/bgq039","article-title":"Pro-oxidative activities and dose\u2013response relationship of (\u2212)-epigallocatechin-3-gallate in the inhibition of lung cancer cell growth: A comparative study in vivo and in vitro","volume":"31","author":"Li","year":"2010","journal-title":"Carcinogenesis"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1002\/jbt.10058","article-title":"Diabetes, oxidative stress, and antioxidants: A review","volume":"17","author":"Maritim","year":"2003","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.abb.2010.06.013","article-title":"The antioxidant and pro-oxidant activities of green tea polyphenols: A role in cancer prevention","volume":"501","author":"Lambert","year":"2010","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1177\/15353702-0322807-09","article-title":"Hydrogen peroxide inhibits insulin signaling in vascular smooth muscle cells","volume":"228","author":"Gardner","year":"2003","journal-title":"Exp. Biol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"361","DOI":"10.4161\/oxim.3.6.14415","article-title":"Signaling of Reactive Oxygen and Nitrogen Species in Diabetes Mellitus","volume":"3","year":"2010","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1021\/ar960010y","article-title":"In Vivo Aspects of Nitric Oxide (NO) Chemistry:\u2009 Does Peroxynitrite (-O.O.N.O.) Play a Major Role in Cytotoxicity?","volume":"30","author":"Fukuto","year":"1997","journal-title":"Acc. Chem. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1006\/clin.1995.1081","article-title":"Role of nitric oxide in autoimmunity","volume":"76","author":"Vladutiu","year":"1995","journal-title":"Clin. Immunol. Immunopathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1016\/S1567-5769(01)00087-X","article-title":"Inducible nitric oxide synthase-derived nitric oxide in gene regulation, cell death and cell survival","volume":"1","author":"Fehsel","year":"2001","journal-title":"Int. Immunopharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1006\/cimm.1993.1197","article-title":"Rat splenocytes inhibit antigen-specific lymphocyte proliferation through a reactive nitrogen intermediate (R.N.I.)-dependent mechanism and exhibit increased R.N.I. production in response to ifn-\u03b3","volume":"150","author":"Stein","year":"1993","journal-title":"Cell. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.4049\/jimmunol.145.7.2220","article-title":"Alloantigen-induced activation of rat splenocytes is regulated by the oxidative metabolism of L-arginine","volume":"145","author":"Hoffman","year":"1990","journal-title":"J. Immunol."},{"key":"ref_22","first-page":"469","article-title":"Nitric oxide and superoxide in inflammation and immune regulation","volume":"54","author":"Guzik","year":"2003","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1007\/s00125-013-3125-4","article-title":"Islet infiltration, cytokine expression and beta cell death in the NOD mouse, BB rat, Komeda rat, LEW.1AR1-iddm rat and humans with type 1 diabetes","volume":"57","author":"Arndt","year":"2014","journal-title":"Diabetologia"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1038\/nrendo.2014.2","article-title":"Immune modulation in humans: Implications for type 1 diabetes mellitus","volume":"10","author":"Roep","year":"2014","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.bbalip.2014.08.010","article-title":"Marine omega-3 fatty acids and inflammatory processes: Effects, mechanisms and clinical relevance","volume":"1851","author":"Calder","year":"2015","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/S0923-2494(97)87242-2","article-title":"The role of CD4 and CD8 T cells in type I diabetes in the NOD mouse","volume":"148","author":"Wong","year":"1997","journal-title":"Res. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1146\/annurev.immunol.23.021704.115643","article-title":"The NOD mouse: A model of immune dysregulation","volume":"23","author":"Anderson","year":"2005","journal-title":"Annu. Rev. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/ar554","article-title":"Immunotherapy of type 1 diabetes: Lessons for other autoimmune diseases","volume":"4","author":"Bach","year":"2002","journal-title":"Arthritis Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/S0065-2776(08)60490-3","article-title":"The murine autoimmune diabetes model: NOD and related strains","volume":"51","author":"Kikutani","year":"1992","journal-title":"Adv. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"155832","DOI":"10.1016\/j.cyto.2022.155832","article-title":"Aqueous extract of Passiflora alata leaves modulates in vitro the indoleamine 2,3-dioxygenase (I.D.O.) and CD86 expression in bone marrow-derived professional antigen-presenting cells polarizing NOD mice T cells to a Treg profile","volume":"152","author":"Schumacher","year":"2022","journal-title":"Cytokine"},{"key":"ref_31","unstructured":"(2022, July 15). Diabetes Onset in NOD\/ShiLtJ. Available online: https:\/\/www.jax.org\/jax-mice-and-services\/strain-data-sheet-pages\/diabetes-chart-001976."},{"key":"ref_32","unstructured":"Henry, C., Chen, Y.U., Stout, R., and Swain, S.L. (1980). Cell separation: Nylon wool. Selected Methods in Cellular Immunology, W H Freeman & Co."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1210\/endo-127-1-126","article-title":"Establishment of a Pancreatic \u03b2 Cell Line That Retains Glucose-Inducible Insulin Secretion: Special Reference to Expression of Glucose Transporters Isoforms","volume":"127","author":"Miyazaki","year":"1990","journal-title":"Endocrinology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1507\/endocrj.K08E-172","article-title":"MIN6 Is Not a Pure Beta Cell Line but a Mixed Cell Line with Other Pancreatic Endocrine Hormones","volume":"56","author":"Nakashima","year":"2009","journal-title":"Endocr. J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e430","DOI":"10.1038\/cddis.2012.171","article-title":"JC-1: Alternative excitation wavelengths facilitate mitochondrial membrane potential cytometry","volume":"3","author":"Perelman","year":"2012","journal-title":"Cell Death Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1210\/edrv-15-4-516","article-title":"Insulin-Dependent Diabetes Mellitus as an Autoimmune Disease","volume":"15","author":"Bach","year":"1994","journal-title":"Endocr. Rev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/9442","article-title":"The NOD mouse model of type 1 diabetes: As good as it gets?","volume":"5","author":"Atkinson","year":"1999","journal-title":"Nat. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.jaut.2013.12.003","article-title":"CD8 T-cell reactivity to islet antigens is unique to type 1 while CD4 T-cell reactivity exists in both type 1 and type 2 diabetes","volume":"50","author":"Sarikonda","year":"2014","journal-title":"J. Autoimmun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.intimp.2014.06.033","article-title":"Role of the immune system in type 1 diabetes mellitus pathogenesis","volume":"22","author":"Szablewski","year":"2014","journal-title":"Int. Immunopharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1159\/000375305","article-title":"How effective are antioxidant supplements in obesity and diabetes?","volume":"24","author":"Abdali","year":"2015","journal-title":"Med. Princ. Pract."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"13","DOI":"10.17533\/udea.penh.17897","article-title":"Antioxidant and antiproliferative activity of ethanolic and aqueous extracts from leaves and fruits juice Passiflora edulis","volume":"15","author":"Osma","year":"2013","journal-title":"Perspect. EN Nutr. Hum."},{"key":"ref_42","first-page":"1008","article-title":"Comparison, synthesis and evaluation of anticancer drug-loaded polymeric nanoparticles on breast cancer cell lines","volume":"44","author":"Eatemadi","year":"2016","journal-title":"Artif. Cells Nanomed. Biotechnol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Matula, K., Collie-Duguid, E., Murray, G., Parikh, K., Grabsch, H., Tan, P., Lalwani, S., Garau, R., Ong, Y., and Bain, G. (2015). Regulation of cellular sphingosine-1-phosphate by sphingosine kinase 1 and sphingosine-1-phopshate lyase determines chemotherapy resistance in gastroesophageal cancer. BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1718-7"},{"key":"ref_44","first-page":"1","article-title":"Comparison of Antioxidant and Ant proliferative Effect among Four Passiflora spp.","volume":"4","author":"Colomeu","year":"2017","journal-title":"J. Agric. Life Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.fitote.2006.09.030","article-title":"Passiflora alata and Passiflora edulis spray-dried aqueous extracts inhibit inflammation in mouse model of pleurisy","volume":"78","author":"Vargas","year":"2007","journal-title":"Fitoterapia"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1177\/1559325817691158","article-title":"Catechin treatment ameliorates diabetes and its complications in streptozotocin-induced diabetic rats","volume":"15","author":"Samarghandian","year":"2017","journal-title":"Dose-Response"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.foodchem.2007.06.016","article-title":"Inhibitory effect of mung bean extract and its constituents vitexin and isovitexin on the formation of advanced glycation endproducts","volume":"106","author":"Peng","year":"2008","journal-title":"Food Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1515\/znc-2004-11-1204","article-title":"Evaluation of in vivo biological activity profile of isoorientin","volume":"59","author":"Asian","year":"2004","journal-title":"Zeitschrift Naturforsch. Sect. C J. Biosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1016\/j.biopha.2016.11.001","article-title":"Rutin inhibits proliferation, attenuates superoxide production and decreases adhesion and migration of human cancerous cells","volume":"84","author":"Sghaier","year":"2016","journal-title":"Biomed. Pharmacother."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2351","DOI":"10.1128\/MCB.23.7.2351-2361.2003","article-title":"Commitment Point during G0\u2192G1 That Controls Entry into the Cell Cycle","volume":"23","author":"Lea","year":"2003","journal-title":"Mol. Cell. Biol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"7432797","DOI":"10.1155\/2016\/7432797","article-title":"Oxidative Stress and Inflammation: What Polyphenols Can Do for Us?","volume":"2016","author":"Hussain","year":"2016","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"16970","DOI":"10.3390\/ijms140816970","article-title":"Structural properties of polyphenols causing cell cycle arrest at G1 phase in HCT116 human colorectal cancer cell lines","volume":"14","author":"Shin","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_53","first-page":"4599","article-title":"Vitexin induces G2\/M-phase arrest and apoptosis via Akt\/mTOR signaling pathway in human glioblastoma cells","volume":"17","author":"Zhang","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"269165","DOI":"10.1155\/2013\/269165","article-title":"Anti-tumor effect of rutin on human neuroblastoma cell lines through inducing G2\/M cell cycle arrest and promoting apoptosis","volume":"2013","author":"Chen","year":"2013","journal-title":"Sci. World J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1080\/13880209.2017.1310906","article-title":"Bioassay-guided isolation, identification of compounds from Origanum rotundifolium and investigation of their antiproliferative and antioxidant activities","volume":"55","author":"Erenler","year":"2017","journal-title":"Pharm. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"7370536","DOI":"10.1155\/2016\/7370536","article-title":"Kinetics Extraction Modelling and Antiproliferative Activity of Clinacanthus nutans Water Extract","volume":"2016","author":"Fazil","year":"2016","journal-title":"Sci. World J."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/S0005-2728(99)00027-4","article-title":"Nitric oxide and lipid peroxidation","volume":"1411","author":"Hogg","year":"1999","journal-title":"Biochim. Biophys. Acta Bioenerg."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/01926230701320337","article-title":"Apoptosis: A Review of Programmed Cell Death","volume":"35","author":"Elmore","year":"2007","journal-title":"Toxicol. Pathol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.cell.2014.02.049","article-title":"To be or not to be? How selective autophagy and cell death govern cell fate","volume":"157","author":"Green","year":"2014","journal-title":"Cell"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.taap.2012.09.022","article-title":"Isoorientin induces apoptosis through mitochondrial dysfunction and inhibition of PI3K\/Akt signaling pathway in HepG2 cancer cells","volume":"265","author":"Yuan","year":"2012","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.foodchem.2010.12.131","article-title":"Antiproliferative, proapoptotic and morphogenic effects of the flavonoid rutin on human glioblastoma cells","volume":"127","author":"Santos","year":"2011","journal-title":"Food Chem."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"213","DOI":"10.3390\/ijms9030213","article-title":"Modulatory effects of polyphenols on apoptosis induction: Relevance for cancer prevention","volume":"9","author":"Santangelo","year":"2008","journal-title":"Int. J. Mol. Sci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"213","DOI":"10.2174\/156720209789630375","article-title":"Oxidative stress-induced necrotic cell death via mitochondira-dependent burst of reactive oxygen species","volume":"6","author":"Choi","year":"2009","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1016\/j.bcp.2015.07.017","article-title":"Pro-oxidant activity of polyphenols and its implication on cancer chemoprevention and chemotherapy","volume":"98","author":"Auger","year":"2015","journal-title":"Biochem. Pharmacol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1016\/j.bbabio.2012.03.007","article-title":"Cytotoxicity of a mitochondriotropic quercetin derivative: Mechanisms","volume":"1817","author":"Sassi","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1002\/mnfr.201300427","article-title":"The role of the mitochondrial oxidative stress in the cytotoxic effects of the green tea catechin, (-)-epigallocatechin-3-gallate, in oral cells","volume":"58","author":"Tao","year":"2014","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Singh, A.K., Cabral, C., Kumar, R., Ganguly, R., Rana, H.K., Gupta, A., Lauro, M.R., Carbone, C., Reis, F., and Pandey, A.K. (2019). Beneficial Effects of Dietary Polyphenols on Gut Microbiota and Strategies to Improve Delivery Efficiency. Nutrients, 11.","DOI":"10.3390\/nu11092216"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Wang, X., Qi, Y., Zheng, H., Wang, X., Qi, Y., and Zheng, H. (2022). Dietary Polyphenol, Gut Microbiota, and Health Benefits. 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