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Pesquisa do Estado de Alagoas","doi-asserted-by":"publisher","award":["E:60030.0000001755\/2022"],"award-info":[{"award-number":["E:60030.0000001755\/2022"]}],"id":[{"id":"10.13039\/501100003401","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Passiflora edulis seeds are frequently discarded as agro-industrial residues despite being a source of bioactive compounds such as piceatannol (PIC). Their valorization through ethanolic extraction aligns with circular economy principles and enables the investigation of antioxidant, anti-inflammatory, and antidiabetic potential relevant to metabolic disorders associated with oxidative stress, inflammation, and impaired glucose homeostasis. Therefore, this study compared the biological activities and toxicological profiles of P. edulis seed ethanol extract (PESE) and PIC using in vitro and in vivo assays, including human and nonhuman models, and hyperglycemia induced during embryogenesis. The zebrafish procedures were approved by the Animal Use Ethics Committee (CEUA; protocol No. 13\/2022). LC\u2013MS identified PIC among the main constituents of PESE, which exhibited a high total phenolic content and relevant antioxidant capacity. PIC showed greater antioxidant potency than PESE against DPPH\u2022, HOCl, and O2\u2022\u2013. It also inhibited \u03b1-amylase and \u03b1-glucosidase, with IC50 values of 11.8 and 3.1 \u03bcg\/mL, respectively, outperforming acarbose against \u03b1-glucosidase, and activated glucokinase. In contrast, PESE inhibited PTP1B (IC50 = 29.8 \u03bcg\/mL), an effect not observed with PIC alone. Both samples reduced ROS production in human neutrophils, with PIC displaying high potency in the luminol assay (IC50 = 0.12 \u03bcg\/mL). In zebrafish embryos, PESE was less embryotoxic than PIC, with LC50 values of 39.3 and 6.2 \u03bcg\/mL, respectively. In the hyperglycemic zebrafish model, both samples significantly reduced total free glucose and oxidant activity (p \u2264 0.05) and induced distinct antioxidant gene-expression responses: PESE upregulated nfe2l2a, sod1, sod2, and cat, whereas PIC upregulated nfe2l2a, gpx1a, and cat. These findings demonstrate that PESE and PIC act through multiple complementary mechanisms to counteract hyperglycemia and oxidative stress, highlighting the therapeutic potential of an underutilized byproduct while emphasizing the importance of developmental toxicity assessment for the safe advancement of plant-derived agents.<\/jats:p>","DOI":"10.1021\/acsomega.6c03845","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T21:01:36Z","timestamp":1789419696000},"page":"56963-56978","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of\n                    <i>Passiflora edulis<\/i>\n                    Seed\nExtract and Piceatannol in Attenuating Hyperglycemia and Oxidative\nStress Using Human and Nonhuman Antidiabetic Enzymes, Human Neutrophil\nOxidative Burst, and Embryonic Zebrafish Hyperglycemia Model"],"prefix":"10.1021","volume":"11","author":[{"given":"Elaine L. S. S.","family":"Mendonc\u0327a","sequence":"first","affiliation":[{"name":"Federal University of Alagoas , , , ,","place":["Maceio\u0301, Alagoas, Brazil, 57072-900"]},{"name":"University of Campinas (UNICAMP) , , , ,","place":["Campinas, Sa\u0303o Paulo, Brazil, 13083-861"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Ramalho","sequence":"additional","affiliation":[{"name":"University of Porto , , ,","place":["Porto, Portugal, 4050-313"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boniek G.","family":"Vaz","sequence":"additional","affiliation":[{"name":"Federal University of Goia\u0301s , , , ,","place":["Goia\u0302nia, GO, Brazil, 74690-900"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alane C. M.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Federal University of Alagoas , , , ,","place":["Maceio\u0301, Alagoas, Brazil, 57072-900"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2878-5589","authenticated-orcid":true,"given":"Jadriane A.","family":"Xavier","sequence":"additional","affiliation":[{"name":"Federal University of Alagoas , , , ,","place":["Maceio\u0301, Alagoas, Brazil, 57072-900"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa","family":"Freitas","sequence":"additional","affiliation":[{"name":"University of Porto , , ,","place":["Porto, Portugal, 4050-313"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6424-0976","authenticated-orcid":true,"given":"Eduarda","family":"Fernandes","sequence":"additional","affiliation":[{"name":"University of Porto , , ,","place":["Porto, Portugal, 4050-313"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9860-3667","authenticated-orcid":true,"given":"Mari\u0301lia O. F.","family":"Goulart","sequence":"additional","affiliation":[{"name":"Federal University of Alagoas , , , ,","place":["Maceio\u0301, Alagoas, Brazil, 57072-900"]},{"name":"University of Campinas (UNICAMP) , , , ,","place":["Campinas, Sa\u0303o Paulo, Brazil, 13083-861"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"issue":"1","key":"2026092911114935500_cit1","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.cmet.2019.05.008","article-title":"Ultra-Processed Diets Cause Excess Calorie Intake and\nWeight Gain: An Inpatient Randomized Controlled Trial of Ad Libitum\nFood Intake","volume":"30","author":"Hall","year":"2019","journal-title":"Cell Metab."},{"issue":"393","key":"2026092911114935500_cit2","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1016\/S0140-6736(18)32822-8","article-title":"The Global Syndemic of Obesity, Undernutrition,\nand Climate Change: The Lancet Commission report","volume":"393","author":"Swinburn","year":"2019","journal-title":"Lancet"},{"issue":"1","key":"2026092911114935500_cit3","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-023-01965-7","article-title":"The role of oxidative\nstress in diabetes mellitus-induced vascular\nendothelial dysfunction","volume":"22","author":"An","year":"2023","journal-title":"Cardiovasc. 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Food Chem."},{"issue":"10","key":"2026092911114935500_cit12","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.3390\/nu9101142","article-title":"The Effect of Piceatannol from Passion\nFruit (Passiflora edulis) Seeds on\nMetabolic Health in Humans","volume":"9","author":"Kitada","year":"2017","journal-title":"Nutrients"},{"key":"2026092911114935500_cit13","doi-asserted-by":"publisher","first-page":"2525","DOI":"10.3390\/foods12132525","article-title":"Bioproducts from Passiflora cincinnata\nSeeds: The Brazilian Caatinga Passion Fruit","volume":"12","author":"Reis","year":"2023","journal-title":"Foods"},{"issue":"2","key":"2026092911114935500_cit14","doi-asserted-by":"publisher","first-page":"232","DOI":"10.3390\/ph17020232","article-title":"E-Stilbenes:\nGeneral Chemical and Biological Aspects, Potential Pharmacological\nActivity Based on the Nrf2 Pathway","volume":"17","author":"Mendonc\u0327a","year":"2024","journal-title":"Pharmaceuticals"},{"issue":"13","key":"2026092911114935500_cit15","doi-asserted-by":"publisher","first-page":"4064","DOI":"10.3390\/molecules27134064","article-title":"Antidiabetic, Antiglycation, and\nAntioxidant Activities of Ethanolic Seed Extract of Passiflora edulis and Piceatannol In Vitro","volume":"27","author":"dos Santos","year":"2022","journal-title":"Molecules"},{"issue":"(7)","key":"2026092911114935500_cit16","doi-asserted-by":"publisher","first-page":"701","DOI":"10.21577\/0103-5053.20220003","article-title":"Anti-Zika Virus Effects,\nPlacenta Protection and Chemical Composition of Passiflora edulis Seeds Ethanolic Extract","volume":"33","author":"Xavier","year":"2022","journal-title":"J. Braz. Chem. Soc."},{"issue":"16","key":"2026092911114935500_cit17","doi-asserted-by":"publisher","first-page":"3438","DOI":"10.1080\/10408398.2015.1129309","article-title":"\u03b1-Glucosidase and \u03b1-amylase\ninhibitors\nfrom seed oil: A review of liposoluble substance to treat diabetes","volume":"2","author":"Beidokhti","year":"2017","journal-title":"Crit. Rev. Food Sci. Nutr."},{"issue":"13","key":"2026092911114935500_cit18","doi-asserted-by":"publisher","first-page":"7027","DOI":"10.3390\/ijms23137027","article-title":"Human Protein Tyrosine Phosphatase 1B (PTP1B): From Structure to\nClinical Inhibitor Perspectives","volume":"23","author":"Liu","year":"2022","journal-title":"Int. J. Mol.\nSci."},{"key":"2026092911114935500_cit19","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1016\/j.ijbiomac.2021.04.061","article-title":"Pyrazoles as novel protein tyrosine\nphosphatase 1B (PTP1B) inhibitors: An in vitro and in silico study","volume":"181","author":"Rocha","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"2026092911114935500_cit20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.117746","article-title":"Corn stigma ameliorates\nhyperglycemia in zebrafish and GK rats of type 2 diabetes","volume":"325","author":"Liang","year":"2024","journal-title":"J. Ethnopharmacol."},{"issue":"4","key":"2026092911114935500_cit21","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1016\/j.freeradbiomed.2005.09.017","article-title":"Inhibition\nof human neutrophil oxidative burst by pyrazolone derivatives","volume":"40","author":"Costa","year":"2006","journal-title":"Free Radical Biol. Med."},{"issue":"1","key":"2026092911114935500_cit22","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.aca.2009.06.063","article-title":"Optical probes\nfor detection and\nquantification of neutrophils\u2019 oxidative burst. A review","volume":"649","author":"Freitas","year":"2009","journal-title":"Anal. Chim. Acta"},{"issue":"9","key":"2026092911114935500_cit23","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-41009-3","article-title":"High glucose levels\naffect retinal patterning during\nzebrafish embryogenesis","volume":"9","author":"Singh","year":"2019","journal-title":"Sci. Rep."},{"issue":"12","key":"2026092911114935500_cit24","doi-asserted-by":"publisher","first-page":"2058","DOI":"10.3390\/antiox12122058","article-title":"Extracts\nand Scirpusin B from Recycled Seeds and Rinds of Passion Fruits (Passiflora edulis var. Tainung No. 1) Exhibit Improved\nFunctions in Scopolamine-Induced Impaired-Memory ICR Mice","volume":"12","author":"Sie","year":"2023","journal-title":"Antioxidants"},{"issue":"1","key":"2026092911114935500_cit25","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.microc.2008.08.011","article-title":"A reproducible,\nrapid and inexpensive Folin\u2013Ciocalteu micro-method in determining\nphenolics of plant methanol extracts","volume":"91","author":"Cicco","year":"2009","journal-title":"Microchem.\nJ."},{"issue":"55","key":"2026092911114935500_cit26","doi-asserted-by":"publisher","first-page":"1884","DOI":"10.1080\/13880209.2017.1340962","article-title":"anti-glycation, antioxidant and cytotoxic\nactivities of several samples of propolis from the northeastern semi-arid\nregion of Brazil.","volume":"20","author":"Xavier","year":"2017","journal-title":"Pharm. 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Environ. Chem. Eng."},{"key":"2026092911114935500_cit36","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2019.109776","article-title":"Effects of low concentrations of\ntriphenyltin on neurobehavior\nand the thyroid endocrine system in zebrafish","volume":"186","author":"Li","year":"2019","journal-title":"Ecotoxicol. Environ. Saf."},{"issue":"4","key":"2026092911114935500_cit37","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1373\/clinchem.2008.112797","article-title":"The MIQE guidelines:\nminimum information for publication of quantitative real-time PCR\nexperiments","volume":"55","author":"Bustin","year":"2009","journal-title":"Clin. Chem."},{"key":"2026092911114935500_cit38","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/hvaf043","article-title":"MIQE 2.0:\nRevision of\nthe Minimum Information for Publication of Quantitative Real-Time\nPCR Experiments Guidelines","volume":"71","author":"Bustin","year":"2025","journal-title":"Clin. Chem."},{"issue":"11","key":"2026092911114935500_cit39","doi-asserted-by":"publisher","first-page":"2846","DOI":"10.1021\/acs.jnatprod.6b00608","article-title":"13C NMR and LC-MS Profiling\nof Stilbenes from\nElicited Grapevine Hairy Root Cultures","volume":"79","author":"Tisserant","year":"2016","journal-title":"J. Nat.\nProd."},{"issue":"18","key":"2026092911114935500_cit40","doi-asserted-by":"publisher","first-page":"4241","DOI":"10.3390\/molecules25184241","article-title":"Development\nand Optimization of a High Sensitivity LC-MS\/MS Method for the Determination\nof Hesperidin and Naringenin in Rat Plasma: Pharmacokinetic Approach","volume":"25","author":"Araujo-Leo\u0301n","year":"2020","journal-title":"Molecules"},{"issue":"3","key":"2026092911114935500_cit41","doi-asserted-by":"publisher","first-page":"316","DOI":"10.3390\/foods11030316","article-title":"A Rapid LC-MS\/MS\nMethod for Simultaneous Determination of Ten Flavonoid Metabolites\nof Naringin in Rat Urine and Its Application to an Excretion Study","volume":"11","author":"Zeng","year":"2022","journal-title":"Foods"},{"issue":"4","key":"2026092911114935500_cit42","doi-asserted-by":"publisher","first-page":"73","DOI":"10.3390\/ph13040073","article-title":"Identification and Quantification\nof Stilbenes (Piceatannol and Resveratrol) in Passiflora edulis By-Products","volume":"13","author":"Krambeck","year":"2020","journal-title":"Pharmaceuticals"},{"issue":"12","key":"2026092911114935500_cit43","doi-asserted-by":"publisher","first-page":"6248","DOI":"10.3390\/ijms22126248","article-title":"Selective\nExtraction of Piceatannol from Passiflora edulis by-Products: Application of HSPs Strategy and Inhibition of Neurodegenerative\nEnzymes","volume":"22","author":"dos Santos","year":"2021","journal-title":"Int. J. Mol. Sci."},{"issue":"11","key":"2026092911114935500_cit44","doi-asserted-by":"publisher","first-page":"6209","DOI":"10.1021\/jf104959t","article-title":"Identification\nof the strong vasorelaxing substance scirpusin B, a dimer of piceatannol,\nfrom passion fruit (Passiflora edulis) seeds","volume":"59","author":"Sano","year":"2011","journal-title":"J. Agric. Food Chem."},{"issue":"5","key":"2026092911114935500_cit45","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1248\/bpb.b12-00708","article-title":"The protective\neffects of piceatannol from passion fruit (Passiflora edulis) seeds in UVB-irradiated keratinocytes","volume":"36","author":"Maruki-Uchida","year":"2013","journal-title":"Biol. Pharm. 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