{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T16:19:15Z","timestamp":1788884355199,"version":"build-2803163510"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T00:00:00Z","timestamp":1598572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"DOI":"10.3389\/fphar.2020.01325","type":"journal-article","created":{"date-parts":[[2020,9,7]],"date-time":"2020-09-07T12:23:29Z","timestamp":1599481409000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":61,"title":["The Antidepressant-Like Effects of Hesperidin in Streptozotocin\u2010Induced Diabetic Rats by Activating Nrf2\/ARE\/Glyoxalase 1 Pathway"],"prefix":"10.3389","volume":"11","author":[{"given":"Xia","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiyan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajing","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaowu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxing","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,8,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3187","DOI":"10.1039\/c7fo00212b","article-title":"Profiles of free and bound phenolics extracted from Citrus fruits and their roles in biological systems: content, and antioxidant, anti-diabetic and anti-hypertensive properties","volume":"8","author":"Alu\u2019datt","year":"2017","journal-title":"Food Funct."},{"key":"B2","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1016\/s0006-8993(97)00651-3","article-title":"Role of ventral hippocampus in acquisition, consolidation and retrieval of rat\u2019s passive avoidance response memory trace","volume":"768","author":"Ambrogi Lorenzini","year":"1997","journal-title":"Brain Res."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1415","DOI":"10.1016\/j.nut.2014.03.024","article-title":"Protective effect of hesperidin in a model of Parkinson\u2019s disease induced by 6-hydroxydopamine in aged mice","volume":"30","author":"Antunes","year":"2014","journal-title":"Nutrition"},{"key":"B4","doi-asserted-by":"publisher","first-page":"18338","DOI":"10.1523\/Jneurosci.1249-11.2011","article-title":"Role of the Glyoxalase System in Astrocyte-Mediated Neuroprotection","volume":"31","author":"Belanger","year":"2011","journal-title":"J. Neurosci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1374","DOI":"10.1074\/jbc.M110.144097","article-title":"Overexpression of glyoxalase-I reduces hyperglycemia-induced levels of advanced glycation end products and oxidative stress in diabetic rats","volume":"286","author":"Brouwers","year":"2011","journal-title":"J. Biol. Chem."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2170","DOI":"10.2337\/diabetes.49.12.2170","article-title":"Defective intracellular antioxidant enzyme production in type 1 diabetic patients with nephropathy","volume":"49","author":"Ceriello","year":"2000","journal-title":"Diabetes"},{"key":"B7","doi-asserted-by":"publisher","first-page":"3330","DOI":"10.1021\/jf904549s","article-title":"Hesperidin Upregulates Heme Oxygenase-1 To Attenuate Hydrogen Peroxide-Induced Cell Damage in Hepatic L02 Cells","volume":"58","author":"Chen","year":"2010","journal-title":"J. Agric. Food Chem."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1007\/s12272-001-2130-1","article-title":"Neuroprotective Effects of Chronic Hesperetin Administration in Mice","volume":"31","author":"Choi","year":"2008","journal-title":"Arch. Pharmacal. Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.brainresbull.2014.03.004","article-title":"Hesperidin exerts antidepressant-like effects in acute and chronic treatments in mice: Possible role of L-arginine-NO-cGMP pathway and BDNF levels","volume":"104","author":"Donato","year":"2014","journal-title":"Brain Res. Bull."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1472","DOI":"10.1111\/j.2042-7158.2012.01512.x","article-title":"Hesperidin-mediated expression of Nrf2 and upregulation of antioxidant status in senescent rat heart","volume":"64","author":"Elavarasan","year":"2012","journal-title":"J. Pharm. Pharmacol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1139\/cjpp-2014-0281","article-title":"Anti-depressant effect of hesperidin in diabetic rats","volume":"92","author":"El-Marasy","year":"2014","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1002\/ddr.21439","article-title":"Neuroprotection of rhGLP-1 in diabetic rats with cerebral ischemia\/reperfusion injury via regulation of oxidative stress, EAAT2, and apoptosis","volume":"79","author":"Fang","year":"2018","journal-title":"Drug Dev. Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2387","DOI":"10.2147\/NDT.S114560","article-title":"Nine traditional Chinese herbal formulas for the treatment of depression: an ethnopharmacology, phytochemistry, and pharmacology review","volume":"12","author":"Feng","year":"2016","journal-title":"Neuropsych. Dis. Treat"},{"key":"B14","doi-asserted-by":"publisher","first-page":"S56","DOI":"10.1016\/S0165-0327(12)70009-5","article-title":"Co-occurrence of diabetes and depression: conceptual considerations for an emerging global health challenge","author":"Fisher","year":"2012","journal-title":"J. Affect. Disord."},{"key":"B15","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.ejphar.2019.03.035","article-title":"The antidepressant effects of hesperidin on chronic unpredictable mild stress-induced mice","volume":"853","author":"Fu","year":"2019","journal-title":"Eur. J. Pharmacol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/S0091-3057(00)00221-5","article-title":"Ethopharmacology of the antidepressant effect of clonazepam in diabetic rats","volume":"66","author":"Gomez","year":"2000","journal-title":"Pharmacol. Biochem. Behav."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1016\/s0022-3999(02)00417-8","article-title":"Prevalence of anxiety in adults with diabetes - A systematic review","volume":"53","author":"Grigsby","year":"2002","journal-title":"J. Psychosom. Res."},{"key":"B18","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1111\/j.1464-5491.2005.01414.x","article-title":"Affective and anxiety disorders in a German sample of diabetic patients: prevalence, comorbidity and risk factors","volume":"22","author":"Hermanns","year":"2005","journal-title":"Diabetic Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1002\/mnfr.201100682","article-title":"Cytoprotective effects of hesperetin and hesperidin against amyloid ss-induced impairment of glucose transport through downregulation of neuronal autophagy","volume":"56","author":"Huang","year":"2012","journal-title":"Mol. Nutr. Food Res."},{"key":"B20","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.expneurol.2011.12.015","article-title":"Protection from diabetes-induced peripheral sensory neuropathy - A role for elevated glyoxalase I","volume":"234","author":"Jack","year":"2012","journal-title":"Exp. Neurol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1002\/ar.22641","article-title":"Quantitative Analysis of Histological Staining and Fluorescence Using ImageJ","volume":"296","author":"Jensen","year":"2013","journal-title":"Anat. Rec."},{"key":"B22","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.ejphar.2007.08.001","article-title":"Curcumin attenuates diabetic encephalopathy in rats: Behavioral and biochemical evidences","volume":"576","author":"Kuhad","year":"2007","journal-title":"Eur. J. Pharmacol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.3109\/13880209.2012.694106","article-title":"Protective effects of hesperidin derivatives and their stereoisomers against advanced glycation end-products formation","volume":"50","author":"Li","year":"2012","journal-title":"Pharm. Biol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.etap.2010.06.007","article-title":"Effects of beta-cypermethrin on male rat reproductive system","volume":"30","author":"Liu","year":"2010","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.pbb.2011.12.003","article-title":"Ginsenoside Re attenuates diabetes-associated cognitive deficits in rats","volume":"101","author":"Liu","year":"2012","journal-title":"Pharmacol. Biochem. Behav."},{"key":"B26","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1007\/s00213-013-3061-5","article-title":"Suppression of methylglyoxal hyperactivity by mangiferin can prevent diabetes-associated cognitive decline in rats","volume":"228","author":"Liu","year":"2013","journal-title":"Psychopharmacol. (Berl.)"},{"key":"B27","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/j.ejphar.2013.08.029","article-title":"Up-regulation of glyoxalase 1 by mangiferin prevents diabetic nephropathy progression in streptozotocin-induced diabetic rats","volume":"721","author":"Liu","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.3390\/nu9121312","article-title":"Protective Effects of Hesperidin (Citrus Flavonone) on High Glucose Induced Oxidative Stress and Apoptosis in a Cellular Model for Diabetic Retinopathy","volume":"9","author":"Liu","year":"2017","journal-title":"Nutrients"},{"key":"B29","doi-asserted-by":"publisher","first-page":"4060","DOI":"10.1007\/s12035-016-9978-z","article-title":"Mangiferin Upregulates Glyoxalase 1 Through Activation of Nrf2\/ARE Signaling in Central Neurons Cultured with High Glucose","volume":"54","author":"Liu","year":"2017","journal-title":"Mol. Neurobiol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"e21226","DOI":"10.1371\/journal.pone.0021226","article-title":"Fisetin lowers methylglyoxal dependent protein glycation and limits the complications of diabetes","volume":"6","author":"Maher","year":"2011","journal-title":"PloS One"},{"key":"B31","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1016\/j.jdiacomp.2012.06.001","article-title":"Hesperidin and naringin attenuate hyperglycemia-mediated oxidative stress and proinflammatory cytokine production in high fat fed\/streptozotocin-induced type 2 diabetic rats","volume":"26","author":"Mahmoud","year":"2012","journal-title":"J. Diabetes Its Complications"},{"key":"B32","first-page":"6049","article-title":"Superoxide dismutase","volume":"244","author":"McCord","year":"1969","journal-title":"Enzymic Funct. Erythrocuprein (Hemocuprein) J. Biol. Chem."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1016\/j.neuro.2012.07.007","article-title":"Potential neuroprotective effects of hesperidin on 3-nitropropionic acid-induced neurotoxicity in rats","volume":"33","author":"Menze","year":"2012","journal-title":"Neurotoxicology"},{"key":"B34","doi-asserted-by":"publisher","first-page":"2383","DOI":"10.2337\/dc08-0985","article-title":"Depression and type 2 diabetes over the lifespan: a meta-analysis","volume":"31","author":"Mezuk","year":"2008","journal-title":"Diabetes Care"},{"key":"B35","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.bbr.2010.11.057","article-title":"Lowering barometric pressure aggravates depression-like behavior in rats","volume":"218","author":"Mizoguchi","year":"2011","journal-title":"Behav. Brain Res."},{"key":"B36","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1097\/FBP.0000000000000488","article-title":"A single administration of Neurotropin reduced the elongated immobility time in the forced swimming test of rats exposed to repeated cold stress","volume":"30","author":"Nasu","year":"2019","journal-title":"Behav. Pharmacol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"194","DOI":"10.3390\/biom5010194","article-title":"Advanced glycation end products and oxidative stress in type 2 diabetes mellitus","volume":"5","author":"Nowotny","year":"2015","journal-title":"Biomolecules"},{"key":"B38","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1002\/ptr.5256","article-title":"Antioxidant and Anti-Inflammatory Properties of the Citrus Flavonoids Hesperidin and Hesperetin: An Updated Review of their Molecular Mechanisms and Experimental Models","volume":"29","author":"Parhiz","year":"2015","journal-title":"Phytother. Res."},{"key":"B39","volume-title":"The Rat Brain in Stereotaxic Coordinates","author":"Paxinos","year":"1986"},{"key":"B40","doi-asserted-by":"publisher","first-page":"261","DOI":"10.5966\/sctm.2015-0380","article-title":"Glyoxalase-1 Overexpression Reverses Defective Proangiogenic Function of Diabetic Adipose-Derived Stem Cells in Streptozotocin-Induced Diabetic Mice Model of Critical Limb Ischemia","volume":"6","author":"Peng","year":"2017","journal-title":"Stem Cells Transl. Med."},{"key":"B41","doi-asserted-by":"publisher","first-page":"50","DOI":"10.2337\/db13-1606","article-title":"The Critical Role of Methylglyoxal and Glyoxalase 1 in Diabetic Nephropathy","volume":"63","author":"Rabbani","year":"2014","journal-title":"Diabetes"},{"key":"B42","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1016\/S0006-8993(00)02212-5","article-title":"Oxidative stress and HNE conjugation of GLUT3 are increased in the hippocampus of diabetic rats subjected to stress","volume":"862","author":"Reagan","year":"2000","journal-title":"Brain Res."},{"key":"B43","doi-asserted-by":"publisher","first-page":"964","DOI":"10.1007\/s10753-016-0311-9","article-title":"Hesperetin Suppresses Inflammatory Responses in Lipopolysaccharide-Induced RAW 264.7 Cells via the Inhibition of NF-kappa B and Activation of Nrf2\/HO-1 Pathways","volume":"39","author":"Ren","year":"2016","journal-title":"Inflammation"},{"key":"B44","doi-asserted-by":"publisher","first-page":"S8","DOI":"10.1016\/S0165-0327(12)70004-6","article-title":"Epidemiology of depression and diabetes: A systematic review","volume":"142","author":"Roy","year":"2012","journal-title":"J. Affect. Disord."},{"key":"B45","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1007\/s40265-015-0347-4","article-title":"Depression in Type 2 Diabetes Mellitus: Prevalence, Impact, and Treatment","volume":"75","author":"Semenkovich","year":"2015","journal-title":"Drugs"},{"key":"B46","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.phrs.2012.03.004","article-title":"Methylglyoxal promotes oxidative stress and endothelial dysfunction","volume":"65","author":"Sena","year":"2012","journal-title":"Pharmacol. Res."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1172\/Jci119885","article-title":"Overexpression of glyoxalase-I in bovine endothelial cells inhibits intracellular advanced glycation endproduct formation and prevents hyperglycemia-induced increases in macromolecular endocytosis","volume":"101","author":"Shinohara","year":"1998","journal-title":"J. Clin. Invest."},{"key":"B48","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1007\/s12576-012-0224-9","article-title":"Glyoxalase 1 and glyoxalase 2 activities in blood and neuronal tissue samples from experimental animal models of obesity and type 2 diabetes mellitus","volume":"62","author":"Skapare","year":"2012","journal-title":"J. Physiol. Sci."},{"key":"B49","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1016\/j.pnpbp.2012.09.003","article-title":"Evidence for the involvement of the serotonergic 5-HT-(1A) receptors in the antidepressant-like effect caused by hesperidin in mice","volume":"40","author":"Souza","year":"2013","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"B50","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1007\/Bf00808119","article-title":"Methylglyoxal, Glyoxalases and the Development of Diabetic Complications","volume":"6","author":"Thornalley","year":"1994","journal-title":"Amino Acids"},{"key":"B51","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1042\/bst0311343","article-title":"Glyoxalase I - structure, function and a critical role in the enzymatic defence against glycation","volume":"31","author":"Thornalley","year":"2003","journal-title":"Biochem. Soc. Trans."},{"key":"B52","doi-asserted-by":"publisher","first-page":"814","DOI":"10.3109\/13880209.2013.870584","article-title":"Hesperidin, a flavanoglycone attenuates experimental diabetic neuropathy via modulation of cellular and biochemical marker to improve nerve functions","volume":"52","author":"Visnagri","year":"2014","journal-title":"Pharm. Biol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"29","DOI":"10.5402\/2012\/479570","article-title":"Hesperidin ameliorates immobilization-stress-induced behavioral and biochemical alterations and mitochondrial dysfunction in mice by modulating nitrergic pathway","volume":"479570","author":"Viswanatha","year":"2012","journal-title":"ISRN Pharmacol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"e0123932","DOI":"10.1371\/journal.pone.0123932","article-title":"Neuroprotective effect of neuroserpin in oxygen-glucose deprivation- and reoxygenation-treated rat astrocytes in vitro","volume":"10","author":"Wang","year":"2015","journal-title":"PloS One"},{"key":"B55","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1042\/Bj201116418","article-title":"Transcriptional control of glyoxalase 1 by Nrf2 provides a stress-responsive defence against dicarbonyl glycation","volume":"443","author":"Xue","year":"2012","journal-title":"Biochem. J."},{"key":"B56","doi-asserted-by":"publisher","first-page":"2282","DOI":"10.2337\/db16-0153","article-title":"Improved Glycemic Control and Vascular Function in Overweight and Obese Subjects by Glyoxalase 1 Inducer Formulation","volume":"65","author":"Xue","year":"2016","journal-title":"Diabetes"},{"key":"B57","doi-asserted-by":"publisher","first-page":"3450","DOI":"10.1080\/14786419.2018.1480019","article-title":"Sikokianin A from Wikstroemia indica protects PC12 cells against OGD\/R-induced injury via inhibiting oxidative stress and activating Nrf2","volume":"33","author":"Yao","year":"2019","journal-title":"Nat. Prod. Res."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1080\/14786419.2017.1346645","article-title":"Thevetiaflavone Protects PC12 Cells Against Neurotoxicity Induced by A beta(1-42) Through Inhibiting Oxidative Stress and Activating Nrf2\/HO-1 Pathway","volume":"37","author":"Yao","year":"2018","journal-title":"Latin Am. J. Pharm."},{"key":"B59","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.pneurobio.2012.09.003","article-title":"Emerging roles of Nrf2 and phase II antioxidant enzymes in neuroprotection","volume":"100","author":"Zhang","year":"2013","journal-title":"Prog. Neurobiol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1016\/j.biopha.2018.06.036","article-title":"Involvement of the TGF beta 1-ILK-Akt signaling pathway in the effects of hesperidin in type 2 diabetic nephropathy","volume":"105","author":"Zhang","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"B61","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1007\/s00210-018-1543-z","article-title":"Enhancement of glyoxalase 1, a polyfunctional defense enzyme, by quercetin in the brain in streptozotocin-induced diabetic rats","volume":"391","author":"Zhu","year":"2018","journal-title":"Naunyn Schmiedebergs Arch. Pharmacol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphar.2020.01325\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,7]],"date-time":"2020-09-07T12:23:32Z","timestamp":1599481412000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fphar.2020.01325\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,28]]},"references-count":61,"alternative-id":["10.3389\/fphar.2020.01325"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2020.01325","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,28]]},"article-number":"1325"}}