{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T19:22:07Z","timestamp":1785439327706,"version":"3.56.0"},"reference-count":97,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T00:00:00Z","timestamp":1741910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","award":["APQ-01288-21 APQ-01915-22"],"award-info":[{"award-number":["APQ-01288-21 APQ-01915-22"]}],"id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["Finance Code 001"],"award-info":[{"award-number":["Finance Code 001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004809","name":"Financiadora de Estudos e Projetos","doi-asserted-by":"publisher","award":["1640-22"],"award-info":[{"award-number":["1640-22"]}],"id":[{"id":"10.13039\/501100004809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["409119\/2023-7 403646\/2021-9 152215\/2022-0"],"award-info":[{"award-number":["409119\/2023-7 403646\/2021-9 152215\/2022-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["16\/07427-8 21\/06009-6"],"award-info":[{"award-number":["16\/07427-8 21\/06009-6"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Neuroinflammation, often driven by the overproduction of reactive oxygen species (ROS), plays a crucial role in the pathogenesis of neurodegenerative diseases such as Alzheimer\u2019s and Parkinson\u2019s diseases. The susceptibility of the brain to oxidative stress is attributed to its high metabolic activity and limited antioxidant defense. This study aimed to evaluate the neuroprotective potential of Benzylidene Digoxin 15 (BD-15) following treatment and pretreatment in a lipopolysaccharide (LPS)-induced neuroinflammation model. Additionally, we examined whether BD-15 enhances the generation of neurons from neural progenitor cells (NPCs).Male Wistar rats were used for acute treatment studies and divided into four groups: control (saline), BD-15 (100 \u03bcg\/kg), LPS (250 \u03bcg\/kg), and LPS + BD-15 (250 \u03bcg\/kg + 100 \u03bcg\/kg). Swiss albino mice were used for chronic pretreatment studies and divided into the following groups: control (saline), BD-15 (0.56 mg\/kg), LPS (1 mg\/kg), and LPS + BD-15 (1 mg\/kg + 0.56 mg\/kg). Behavioral changes were assessed using the open field test, and brain tissues were analyzed for oxidative stress markers, including malondialdehyde (MDA), reduced glutathione (GSH), protein carbonylation, catalase (CAT), superoxide dismutase (SOD), and glutathione S-transferase (GST). To assess neurogenesis, primary NPC cultures derived from the hippocampus of newborn Wistar rats were used, which led to reduced locomotor activity and increased oxidative stress, particularly in the cortex, as indicated by elevated MDA levels and reduced GSH levels. BD-15 treatment reversed these effects, notably by restoring GSH levels and reducing protein carbonylation in the cerebellum. Chronic BD-15 treatment in Swiss mice improved oxidative stress markers including MDA, SOD, CAT, and GST. Furthermore, BD-15 exhibits neuroprotective properties by alleviating oxidative stress and motor dysfunction, suggesting its potential as a therapeutic agent for neuroinflammatory disorders. However, BD-15 did not affect NPC cell proliferation, indicating that this cardiotonic steroid did not alter the cell cycle of these progenitor cells.<\/jats:p>","DOI":"10.3389\/fphar.2025.1537720","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T07:06:17Z","timestamp":1741935977000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Evaluation of the neuroprotective potential of benzylidene digoxin 15 against oxidative stress in a neuroinflammation models induced by lipopolysaccharide and on neuronal differentiation of hippocampal neural precursor cells"],"prefix":"10.3389","volume":"16","author":[{"given":"Gilv\u00e2nia A.","family":"Cordeiro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica A.","family":"Faria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia","family":"Pavan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Israel J. P.","family":"Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduarda P. F. I.","family":"Neves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gustavo Fernando de Frazao","family":"Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hericles M.","family":"Campos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e2mela Y.","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulo C.","family":"Ghedini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa M.","family":"Kawamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maira C.","family":"Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 A. F. P.","family":"Villar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Maria M.","family":"Orellana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leandro A.","family":"Barbosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristoforo","family":"Scavone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline A.","family":"Leite","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9rica L.","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"13474","DOI":"10.3390\/ijms232113474","article-title":"Minocycline attenuates lipopolysaccharide-induced locomotor deficit and anxiety-like behavior and related expression of the BDNF\/CREB protein in the rat medial prefrontal cortex (mPFC)","volume":"23","author":"Abdo Qaid","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1767203","DOI":"10.1155\/2019\/1767203","article-title":"Review on cross talk between neurotransmitters and neuroinflammation in striatum and cerebellum in the mediation of motor behaviour","volume":"2019","author":"Abg Abd Wahab","year":"2019","journal-title":"BioMed Res. Int."},{"key":"B3","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/s0076-6879(84)05016-3","article-title":"Catalase in vitro","volume":"105","author":"Aebi","year":"1984","journal-title":"Methods Enzymol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1080\/10715762.2020.1851027","article-title":"Protein carbonylation: molecular mechanisms, biological implications, and analytical approaches","volume":"55","author":"Akagawa","year":"2021","journal-title":"Free Radic. Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.neucli.2018.10.004","article-title":"Brain imaging of locomotion in neurological conditions","volume":"48","author":"Allali","year":"2018","journal-title":"Neurophysiol. Clin."},{"key":"B6","doi-asserted-by":"publisher","first-page":"e1010681","DOI":"10.1371\/journal.pgen.1010681","article-title":"Identification of gene networks mediating regional resistance to tauopathy in late-onset Alzheimer\u2019s disease","volume":"19","author":"Ayoub","year":"2023","journal-title":"PLoS Genet."},{"key":"B7","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1124\/pr.108.000711","article-title":"Endogenous cardiotonic steroids: Physiology, pharmacology, and novel therapeutic targets","volume":"61","author":"Bagrov","year":"2009","journal-title":"Pharmacol. Rev."},{"key":"B8","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1515\/BC.2009.033","article-title":"Glutathione dysregulation and the etiology and progression of human diseases","volume":"390","author":"Ballatori","year":"2009","journal-title":"Biol. Chem."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1002\/cpt.1710","article-title":"Protein expression and functional relevance of efflux and uptake drug transporters at the blood\u2013brain barrier of human brain and glioblastoma","volume":"107","author":"Bao","year":"2020","journal-title":"Clin. Pharmacol. Ther."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/0471140856.tx1221s59","article-title":"Comparative human and rat \u201cneurosphere assay\u201d for developmental neurotoxicity testing","volume":"1","author":"Baumann","year":"2014","journal-title":"Curr. Protoc. Toxicol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"112720","DOI":"10.1016\/j.bbr.2020.112720","article-title":"Inducible nitric oxide synthase plays a role in depression- and anxiety-like behaviors chronically induced by lipopolysaccharide in rats: evidence from inflammation and oxidative stress","volume":"392","author":"Beheshti","year":"2020","journal-title":"Behav. Brain Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1006\/abio.1976.9999","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"B13","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/s0076-6879(78)52032-6","article-title":"Microsomal lipid peroxidation","volume":"52","author":"Buege","year":"1978","journal-title":"Methods Enzymol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.jneumeth.2016.06.018","article-title":"Neuroinflammation in animal models of traumatic brain injury","volume":"272","author":"Chiu","year":"2016","journal-title":"J. Neurosci. Methods"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.3390\/antiox12071397","article-title":"Antioxidant therapy reduces oxidative stress, restores Na,K-ATPase function and induces neuroprotection in rodent models of seizure and epilepsy: a systematic review and meta-analysis","volume":"12","author":"de Melo","year":"2023","journal-title":"Antioxidants"},{"key":"B16","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1007\/s00232-021-00186-x","article-title":"Implications of synthetic modifications of the cardiotonic steroid lactone ring on cytotoxicity","volume":"254","author":"de Oliveira","year":"2021","journal-title":"J. Membr. Biol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/j.neuropharm.2013.06.006","article-title":"Ouabain activates NF\u03baB through an NMDA signaling pathway in cultured cerebellar cells","volume":"73","author":"De S\u00e1 Lima","year":"2013","journal-title":"Neuropharmacology"},{"key":"B18","doi-asserted-by":"publisher","first-page":"17108","DOI":"10.1002\/jcb.28971","article-title":"Evaluation of neuroprotective activity of digoxin and semisynthetic derivatives against partial chemical ischemia","volume":"120","author":"de Souza Gon\u00e7alves","year":"2019","journal-title":"J. Cell Biochem."},{"key":"B19","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1111\/1467-8624.00117","article-title":"Close interrelation of motor development and cognitive development and of the cerebellum and prefrontal cortex","volume":"71","author":"Diamond","year":"2000","journal-title":"Child. Dev."},{"key":"B20","doi-asserted-by":"publisher","first-page":"e54722","DOI":"10.1371\/journal.pone.0054722","article-title":"Oxidative stress and proinflammatory cytokines contribute to demyelination and axonal damage in a cerebellar culture model of neuroinflammation","volume":"8","author":"di Penta","year":"2013","journal-title":"PLoS One"},{"key":"B21","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.taap.2011.10.007","article-title":"Digitoxin and a synthetic monosaccharide analog inhibit cell viability in lung cancer cells","volume":"258","author":"Elbaz","year":"2012","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.2119\/molmed.2011.00119","article-title":"Severe alterations in lipid composition of frontal cortex lipid rafts from Parkinson\u2019s disease and incidental Parkinson\u2019s disease","volume":"17","author":"Fabelo","year":"2011","journal-title":"Mol. Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"1568","DOI":"10.3390\/cells13181568","article-title":"Evaluation of anti-inflammatory activity of the new cardiotonic steroid \u03b3-benzylidene digoxin 8 (BD-8) in mice","volume":"13","author":"Ferreira","year":"2024","journal-title":"Cells"},{"key":"B24","doi-asserted-by":"publisher","first-page":"644","DOI":"10.1096\/fj.04-2578fje","article-title":"Altered proteasome structure, function, and oxidation in aged muscle","volume":"19","author":"Ferrington","year":"2005","journal-title":"FASEB J."},{"key":"B25","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1046\/j.1471-4159.1998.70010268.x","article-title":"Increased protein oxidation in human substantia nigra pars compacta in comparison with basal ganglia and prefrontal cortex measured with an improved dinitrophenylhydrazine assay","volume":"70","author":"Floor","year":"1998","journal-title":"J. Neurochem."},{"key":"B26","doi-asserted-by":"publisher","first-page":"2156","DOI":"10.1002\/jcb.26377","article-title":"Ouabain attenuates the oxidative stress induced by lipopolysaccharides in the cerebellum of rats","volume":"119","author":"Garcia","year":"2018","journal-title":"J. Cell Biochem."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1007\/s00232-015-9840-7","article-title":"Ouabain modulates the lipid composition of hippocampal plasma membranes from rats with LPS-induced neuroinflammation","volume":"248","author":"Garcia","year":"2015","journal-title":"J. Membr. Biol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"4081","DOI":"10.1002\/jcb.27693","article-title":"Ouabain attenuates oxidative stress and modulates lipid composition in hippocampus of rats in lipopolysaccharide-induced hypocampal neuroinflammation in rats","volume":"120","author":"Garcia","year":"2019","journal-title":"J. Cell Biochem."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1120","DOI":"10.1016\/s0028-3908(03)00279-x","article-title":"MK-801 and 7-Ni attenuate the activation of brain NF-\u03baB induced by LPS","volume":"45","author":"Glezer","year":"2003","journal-title":"Neuropharmacology"},{"key":"B30","doi-asserted-by":"publisher","first-page":"27832","DOI":"10.1074\/jbc.M002951200","article-title":"Involvement of Src and epidermal growth factor receptor in the signal-transducing function of Na+\/K+-ATPase","volume":"275","author":"Haas","year":"2000","journal-title":"J. Biol. Chem."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/s0006-8993(00)02541-5","article-title":"Expression, activity and distribution of Na,K-ATPase subunits during in vitro neuronal induction","volume":"875","author":"Habiba","year":"2000","journal-title":"Brain Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.ejphar.2014.07.031","article-title":"Protective effect of mangiferin against lipopolysaccharide-induced depressive and anxiety-like behaviour in mice","volume":"740","author":"Jangra","year":"2014","journal-title":"Eur. J. Pharmacol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"2407","DOI":"10.1016\/j.bmc.2011.02.016","article-title":"Synthesis and evaluation of cardiac glycoside mimics as potential anticancer drugs","volume":"19","author":"Jensen","year":"2011","journal-title":"Bioorg Med. Chem."},{"key":"B34","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/1749-8546-6-25","article-title":"Neuroprotective and anti-oxidant effects of caffeic acid isolated from Erigeron annuus leaf","volume":"6","author":"Jeong","year":"2011","journal-title":"Chin. Med."},{"key":"B35","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1007\/s12035-012-8297-2","article-title":"The decrease on Na+, K+-ATPase activity in the cortex, but not in hippocampus, is reverted by antioxidants in an animal model of sepsis","volume":"46","author":"Jeremias","year":"2012","journal-title":"Mol. Neurobiol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.3390\/nu4101399","article-title":"Dysregulation of glutathione homeostasis in neurodegenerative diseases","volume":"4","author":"Johnson","year":"2012","journal-title":"Nutrients"},{"key":"B37","doi-asserted-by":"publisher","first-page":"3707","DOI":"10.1021\/acschemneuro.0c00427","article-title":"Neuroinflammation mechanisms and phytotherapeutic intervention: a systematic review","volume":"11","author":"Kaur","year":"2020","journal-title":"ACS Chem. Neurosci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1002\/jnr.22745","article-title":"Influence of N-methyl-D-aspartate receptors on ouabain activation of nuclear factor-\u03baB in the rat hippocampus","volume":"90","author":"Kawamoto","year":"2012","journal-title":"J. Neurosci. Res."},{"key":"B39","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1016\/j.jmgm.2005.02.001","article-title":"Elucidation of the Na+, K+-ATPase digitalis binding site","volume":"23","author":"Keenan","year":"2005","journal-title":"J. Mol. Graph Model"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1038\/s41593-020-0665-z","article-title":"Regulation of autism-relevant behaviors by cerebellar\u2013prefrontal cortical circuits","volume":"23","author":"Kelly","year":"2020","journal-title":"Nat. Neurosci."},{"key":"B41","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1016\/j.tins.2004.05.013","article-title":"Milestones of neuronal development in the adult hippocampus","volume":"27","author":"Kempermann","year":"2004","journal-title":"Trends Neurosci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1512","DOI":"10.1111\/bph.15419","article-title":"The Janus face of ouabain in Na+\/K+-ATPase and calcium signalling in neurons","volume":"179","author":"Kinoshita","year":"2022","journal-title":"Br. J. Pharmacol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1186\/s12974-014-0218-z","article-title":"Signaling function of Na,K-ATPase induced by ouabain against LPS as an inflammation model in hippocampus","volume":"11","author":"Kinoshita","year":"2014","journal-title":"J. Neuroinflammation"},{"key":"B44","doi-asserted-by":"publisher","first-page":"574","DOI":"10.3390\/antiox10040574","article-title":"Accumulation of carbonyl proteins in the brain of mouse model for methylglyoxal detoxification deficits","volume":"10","author":"Koike","year":"2021","journal-title":"Antioxidants"},{"key":"B45","doi-asserted-by":"publisher","first-page":"15249","DOI":"10.1074\/jbc.273.24.15249","article-title":"Multiple signal transduction pathways link Na+\/K+-ATPase to growth-related genes in cardiac myocytes. The roles of Ras and mitogen-activated protein kinases","volume":"273","author":"Kometiani","year":"1998","journal-title":"J. Biol. Chem."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1493","DOI":"10.1007\/s00213-023-06382-y","article-title":"L-theanine attenuates LPS-induced motor deficit in experimental rat model of Parkinson\u2019s disease: emphasis on mitochondrial activity, neuroinflammation, and neurotransmitters","volume":"240","author":"Kumar","year":"2023","journal-title":"Psychopharmacol. Berl."},{"key":"B47","doi-asserted-by":"publisher","first-page":"1755","DOI":"10.1073\/pnas.1422997112","article-title":"Structures and characterization of digoxin- and bufalin-bound Na+,K+-ATPase compared with the ouabain-bound complex","volume":"112","author":"Laursen","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B48","doi-asserted-by":"publisher","first-page":"265798","DOI":"10.1155\/2015\/265798","article-title":"Ouabain modulates zymosan-induced peritonitis in mice","volume":"2015","author":"Leite","year":"2015","journal-title":"Mediat. Inflamm."},{"key":"B49","doi-asserted-by":"publisher","first-page":"916312","DOI":"10.3389\/fphar.2022.916312","article-title":"Effect of ouabain on calcium signaling in rodent brain: a systematic review of in vitro studies","volume":"13","author":"Leite","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1186\/1742-2094-9-230","article-title":"Neuronal toll-like receptor 4 signaling induces brain endothelial activation and neutrophil transmigration in vitro","volume":"9","author":"Leow-Dyke","year":"2012","journal-title":"J. Neuroinflammation"},{"key":"B51","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1016\/0076-6879(90)86141-h","article-title":"Determination of carbonyl content in oxidatively modified proteins","volume":"186","author":"Levine","year":"1990","journal-title":"Methods Enzymol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.anireprosci.2016.11.012","article-title":"The upregulation of pro-inflammatory cytokines in the rabbit uterus under the lipopolysaccaride-induced reversible immunoresponse state","volume":"176","author":"Liu","year":"","journal-title":"Anim. Reprod. Sci."},{"key":"B53","doi-asserted-by":"publisher","first-page":"e22942","DOI":"10.1002\/jbt.22942","article-title":"Imbalanced GSH\/ROS and sequential cell death","volume":"36","author":"Liu","year":"2022","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-\u03baB signaling in inflammation","volume":"2","author":"Liu","year":"","journal-title":"Springer Nat."},{"key":"B55","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.mam.2008.05.005","article-title":"Regulation of glutathione synthesis","volume":"30","author":"Lu","year":"2009","journal-title":"Mol. Aspects Med."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neures.2013.10.004","article-title":"Neuroinflammation: the role and consequences","volume":"79","author":"Lyman","year":"2014","journal-title":"Neurosci. Res."},{"key":"B57","unstructured":"Ouabain increases neuronal differentiation of hippocampal neural precursor cells Running title: role of Ouabain in neurogenesis\n          \n          \n            \n              Maria Orellana\n              A.\n            \n            \n              Medeiros Port\n              N. S.\n            \n            \n              de S\u00e1 Lima\n              L.\n            \n            \n              Alves Leite\n              J.\n            \n            \n              Zukas Andreotti\n              D.\n            \n            \n              Fernanda Kinoshita\n              P."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1207","DOI":"10.1111\/j.1476-5381.2010.01163.x","article-title":"Animal modelling of traumatic brain injury in preclinical drug development: where do we go from here? Vol. 164","volume":"164","author":"Marklund","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"489","DOI":"10.3233\/JAD-2010-1242","article-title":"Lipid alterations in lipid rafts from Alzheimer\u2019s disease human brain cortex","volume":"19","author":"Mart\u00edn","year":"2010","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"B60","doi-asserted-by":"publisher","first-page":"1839","DOI":"10.3390\/antiox12101839","article-title":"Protein carbonylation as a biomarker of oxidative stress and a therapeutic target in neonatal brain damage","volume":"12","author":"Mart\u00ednez-Orgado","year":"2023","journal-title":"Antioxidants"},{"key":"B61","doi-asserted-by":"publisher","first-page":"1775","DOI":"10.1089\/ars.2006.8.1775","article-title":"Reactive oxygen species-induced activation of the MAP kinase signaling pathways","volume":"8","author":"McCubrey","year":"2006","journal-title":"Antioxidants Redox Signal."},{"key":"B62","doi-asserted-by":"publisher","first-page":"3170","DOI":"10.1016\/s0021-9258(19)45228-9","article-title":"The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase","volume":"247","author":"Misra","year":"1972","journal-title":"J. Biol. Chem."},{"key":"B63","doi-asserted-by":"publisher","first-page":"5317","DOI":"10.1074\/jbc.M211315200","article-title":"The Na,K-ATPase alpha 2 isoform is expressed in neurons, and its absence disrupts neuronal activity in newborn mice","volume":"278","author":"Moseley","year":"2003","journal-title":"J. Biol. Chem."},{"key":"B64","doi-asserted-by":"publisher","first-page":"5343","DOI":"10.1002\/hbm.23718","article-title":"Abnormal functional activation and maturation of ventromedial prefrontal cortex and cerebellum during temporal discounting in autism spectrum disorder","volume":"38","author":"Murphy","year":"2017","journal-title":"Hum. Brain Mapp."},{"key":"B65","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1111\/j.1471-4159.2010.06778.x","article-title":"TLR2 activation inhibits embryonic neural progenitor cell proliferation","volume":"114","author":"Okun","year":"2010","journal-title":"J. Neurochem."},{"key":"B66","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3389\/fendo.2016.00010","article-title":"Cardiotonic steroids as modulators of neuroinflammation","volume":"7","author":"Orellana","year":"2016","journal-title":"Front. Endocrinol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1006\/mcne.1996.0595","article-title":"The adult rat hippocampus contains primordial neural stem cells","volume":"8","author":"Palmer","year":"1997","journal-title":"Mol. Cell Neurosci."},{"key":"B68","doi-asserted-by":"publisher","first-page":"6399","DOI":"10.3390\/ijms23126399","article-title":"Neuroprotective effect of bcl-2 on lipopolysaccharide-induced neuroinflammation in cortical neural stem cells","volume":"23","author":"Park","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B69","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1007\/s00232-021-00173-2","article-title":"The \u03b3-benzylidene digoxin derivative BD-15 increases the \u03b13-Na, K-ATPase activity in rat Hippocampus and prefrontal cortex and no change on heart","volume":"254","author":"Parreira","year":"2021","journal-title":"J. Membr. Biol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1080\/14756366.2017.1380637","article-title":"Selectivity analyses of \u03b3-benzylidene digoxin derivatives to different Na,K-ATPase \u03b1 isoforms: a molecular docking approach","volume":"33","author":"Pess\u00f4a","year":"2018","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"B71","doi-asserted-by":"publisher","first-page":"3596","DOI":"10.3390\/molecules25163596","article-title":"Anticancer and antiviral properties of cardiac glycosides: a review to explore the mechanism of actions","volume":"25","author":"Reddy","year":"2020","journal-title":"Molecules"},{"key":"B72","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1007\/s11064-020-02961-z","article-title":"Glial factors regulating white matter development and pathologies of the cerebellum","volume":"45","author":"Revuelta","year":"2020","journal-title":"Neurochem. Res."},{"key":"B73","doi-asserted-by":"publisher","first-page":"e78332","DOI":"10.1371\/journal.pone.0078332","article-title":"N-acetylcysteine prevents spatial memory impairment induced by chronic early postnatal glutaric acid and lipopolysaccharide in rat pups","volume":"8","author":"Rodrigues","year":"2013","journal-title":"PLoS One"},{"key":"B74","doi-asserted-by":"publisher","first-page":"912925","DOI":"10.1155\/2011\/912925","article-title":"Anti-inflammatory and antinociceptive activity of ouabain in mice","volume":"2011","author":"Rodrigues-Mascarenhas","year":"2011","journal-title":"Mediat. Inflamm."},{"key":"B75","doi-asserted-by":"publisher","first-page":"2288","DOI":"10.1152\/jn.00082.2009","article-title":"Anatomical and electrophysiological comparison of CA1 pyramidal neurons of the rat and mouse","volume":"102","author":"Routh","year":"2009","journal-title":"J. Neurophysiol."},{"key":"B76","doi-asserted-by":"publisher","first-page":"1932","DOI":"10.3390\/molecules22111932","article-title":"Anticancer and immunogenic properties of cardiac glycosides","volume":"22","author":"Schneider","year":"2017","journal-title":"Molecules"},{"key":"B77","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.neulet.2014.01.003","article-title":"A fast and simple differentiation protocol to study the pro-neurogenic activity of soluble factors in neurospheres","volume":"562","author":"Schramm","year":"2014","journal-title":"Neurosci. Lett."},{"key":"B78","article-title":"A guide to basic cell culture and applications in biomaterials and tissue engineering","volume-title":"Biomaterials, artificial organs and tissue engineering","author":"Selvakumaran","year":"2005"},{"key":"B79","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1080\/00207454.2016.1212854","article-title":"Neuroinflammation pathways: a general review","volume":"127","author":"Shabab","year":"2017","journal-title":"Int. J. Neurosci."},{"key":"B80","doi-asserted-by":"publisher","first-page":"1361","DOI":"10.1113\/jphysiol.2014.282319","article-title":"Na+\/Ca2+ exchange and Na+\/K+-ATPase in the heart","volume":"593","author":"Shattock","year":"2015","journal-title":"J. Physiology"},{"key":"B81","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.jprot.2015.04.005","article-title":"Redox proteomics identification of specifically carbonylated proteins in the hippocampi of triple transgenic Alzheimer\u2019s disease mice at its earliest pathological stage","volume":"123","author":"Shen","year":"2015","journal-title":"J. Proteomics"},{"key":"B82","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1038\/nature07939","article-title":"Crystal structure of the sodium-potassium pump at 2.4 A resolution","volume":"459","author":"Shinoda","year":"2009","journal-title":"Nature"},{"key":"B83","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.etap.2008.10.003","article-title":"A comparative study on oxidative stress induced by LPS and rotenone in homogenates of rat brain regions","volume":"27","author":"Swarnkar","year":"2009","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"B84","doi-asserted-by":"publisher","first-page":"49","DOI":"10.3390\/antiox9010049","article-title":"Neuroprotective mechanisms of three natural antioxidants on a rat model of Parkinson\u2019s disease: a comparative study","volume":"9","author":"Tancheva","year":"2020","journal-title":"Antioxidants"},{"key":"B85","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1016\/j.physbeh.2018.02.034","article-title":"Neuroprotective effect of melatonin against lipopolysaccharide-induced depressive-like behavior in mice","volume":"188","author":"Taniguti","year":"2018","journal-title":"Physiol. Behav."},{"key":"B86","doi-asserted-by":"publisher","first-page":"5954","DOI":"10.3390\/ijms23115954","article-title":"Neurotransmitters-key factors in neurological and neurodegenerative disorders of the central nervous system","volume":"23","author":"Teleanu","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B87","doi-asserted-by":"publisher","first-page":"1732","DOI":"10.1016\/j.str.2011.10.016","article-title":"First crystal structures of Na +,K +-ATPase: new light on the oldest ion pump","volume":"19","author":"Toyoshima","year":"2011","journal-title":"Structure"},{"key":"B88","doi-asserted-by":"publisher","first-page":"1281932","DOI":"10.3389\/fncel.2023.1281932","article-title":"Different responses of mice and rats hippocampus CA1 pyramidal neurons to in vitro and in vivo-like inputs","volume":"17","author":"Vitale","year":"2023","journal-title":"Front. Cell Neurosci."},{"key":"B89","doi-asserted-by":"publisher","first-page":"e51225","DOI":"10.3791\/51225","article-title":"One mouse, two cultures: isolation and culture of adult neural stem cells from the two neurogenic zones of individual mice","author":"Walker","year":"2014","journal-title":"J. Vis. Exp."},{"key":"B90","doi-asserted-by":"publisher","first-page":"318","DOI":"10.1038\/cr.2015.12","article-title":"FXYD2, a \u03b3 subunit of Na\u207a, K\u207a-ATPase, maintains persistent mechanical allodynia induced by inflammation","volume":"25","author":"Wang","year":"2015","journal-title":"Cell Res."},{"key":"B91","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3389\/fnagi.2010.00012","article-title":"Selective neuronal vulnerability to oxidative stress in the brain","volume":"2","author":"Wang","year":"2010","journal-title":"Front. Aging Neurosci."},{"key":"B92","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1002\/iub.1229","article-title":"Regulation of renal function and structure by the signaling Na\/K-ATPase","volume":"65","author":"Xie","year":"2013","journal-title":"IUBMB Life"},{"key":"B93","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1007\/s10495-016-1342-2","article-title":"Activation of Na+-K+-ATPase with DRm217 attenuates oxidative stress-induced myocardial cell injury via closing Na+-K+-ATPase\/Src\/Ros amplifier","volume":"22","author":"Yan","year":"2017","journal-title":"Apoptosis"},{"key":"B94","doi-asserted-by":"publisher","first-page":"104814","DOI":"10.1016\/j.nbd.2020.104814","article-title":"Neuroprotection by dihydrotestosterone in LPS-induced neuroinflammation","volume":"140","author":"Yang","year":"2020","journal-title":"Neurobiol. Dis."},{"key":"B95","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.bbabio.2008.12.019","article-title":"P-type ATPases as drug targets: tools for medicine and science","volume":"1787","author":"Yatime","year":"2009","journal-title":"Biochimica Biophysica Acta - Bioenergetics"},{"key":"B96","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/j.biopha.2008.01.017","article-title":"Glutathione and Parkinson\u2019s disease: is this the elephant in the room?","volume":"62","author":"Zeevalk","year":"2008","journal-title":"Biomed. Pharmacother."},{"key":"B97","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1111\/j.1472-8206.2008.00620.x","article-title":"Na+\/K+-ATPase-mediated signal transduction and Na+\/K+-ATPase regulation","volume":"22","author":"Zhang","year":"2008","journal-title":"Fundam. Clin. Pharmacol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1537720\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T07:06:24Z","timestamp":1741935984000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1537720\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,14]]},"references-count":97,"alternative-id":["10.3389\/fphar.2025.1537720"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1537720","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,14]]},"article-number":"1537720"}}