{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:56:41Z","timestamp":1775804201021,"version":"3.50.1"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"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. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Epilepsy is a complex neurological disorder characterized by recurrent seizures. Neuroinflammation and excessive neuronal excitation are key pathogenic factors, but current therapies fail to target these mechanisms effectively, highlighting the need for novel therapeutic agents. Zingerone, a bioactive compound derived from ginger (\n                      <jats:italic>Zingiber officinale Roscoe<\/jats:italic>\n                      ), exhibits anti-inflammatory, antioxidant, and neuroprotective properties. However, its acute anticonvulsant efficacy and underlying mechanism in temporal lobe epilepsy (TLE) remain unclear. This study aimed to investigate whether zingerone exerts anticonvulsant effects by modulating neuronal excitability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A lithium chloride-pilocarpine-induced acute TLE rat model was established. Rats were randomly assigned to control, pilocarpine, and zingerone treatment groups (75, 150, and 300 mg\/kg, i.p.). Seizure activity was evaluated via behavioral scoring (Racine scale) and electroencephalography (EEG). Immunohistochemistry (IHC), hematoxylin-eosin (HE) staining, and immunofluorescence were used to assess hippocampal microglial\/astrocytic activation and neuronal damage. Whole-cell patch-clamp recordings were performed to analyze intrinsic neuronal excitability and synaptic transmission in hippocampal CA1 pyramidal neurons.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Acute administration of zingerone (150 and 300 mg\/kg) significantly reduced the number and duration of Racine stage IV\/V generalized seizures. Zingerone dose-dependently inhibited microglial (IBA1\n                      <jats:sup>+<\/jats:sup>\n                      ) and astrocytic (GFAP\n                      <jats:sup>+<\/jats:sup>\n                      ) activation (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.01 for 150 mg\/kg;\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001 for 300 mg\/kg) and preserved neuronal integrity in the hippocampal CA1 region, as evidenced by reduced neuronal shrinkage, pyknosis, and increased NeuN\n                      <jats:sup>+<\/jats:sup>\n                      neuron density. Electrophysiological recordings revealed that zingerone (10 \u03bcM) decreased the firing frequency of CA1 pyramidal neurons (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.05), prolonged the inter-spike interval (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0026), reduced the action potential peak (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.041), increased the rheobase current (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.042), and increased afterhyperpolarization amplitude (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0001). Furthermore, Zingerone also modulated excitatory synaptic transmission onto CA1 neurons.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Zingerone exerts acute anticonvulsant and neuroprotective effects in a TLE rat model by suppressing hippocampal neuroinflammation and reducing the intrinsic excitability of pyramidal neurons. These findings highlight zingerone as a promising natural compound for developing novel adjuvant therapies for drug-resistant TLE.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnins.2026.1809792","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:01:19Z","timestamp":1775800879000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Zingerone alleviates acute seizures by reducing intrinsic hippocampal neuronal excitability in a rat model of temporal lobe epilepsy"],"prefix":"10.3389","volume":"20","author":[{"given":"Hong","family":"Ni","sequence":"first","affiliation":[{"name":"Laboratory of Brain and Psychiatric Disease, Bengbu Medical University, Bengbu","place":["Anhui, China"]},{"name":"Functional Experiment Center, School of Basic Medical Sciences, Bengbu Medical University, Bengbu","place":["Anhui, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenkang","family":"Yang","sequence":"additional","affiliation":[{"name":"Laboratory of Brain and Psychiatric Disease, Bengbu Medical University, Bengbu","place":["Anhui, China"]},{"name":"Department of Pathology, Handan Central Hospital, Handan","place":["Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu","family":"Han","sequence":"additional","affiliation":[{"name":"Laboratory of Brain and Psychiatric Disease, Bengbu Medical University, Bengbu","place":["Anhui, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Brain and Psychiatric Disease, Bengbu Medical University, Bengbu","place":["Anhui, China"]},{"name":"Functional Experiment Center, School of Basic Medical Sciences, Bengbu Medical University, Bengbu","place":["Anhui, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haihu","family":"Ding","sequence":"additional","affiliation":[{"name":"Functional Experiment Center, School of Basic Medical Sciences, Bengbu Medical University, Bengbu","place":["Anhui, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianren","family":"Song","sequence":"additional","affiliation":[{"name":"Laboratory of Brain and Psychiatric Disease, Bengbu Medical University, Bengbu","place":["Anhui, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingrui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory of Brain and Psychiatric Disease, Bengbu Medical University, Bengbu","place":["Anhui, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiandong","family":"Yu","sequence":"additional","affiliation":[{"name":"Laboratory of Brain and Psychiatric Disease, Bengbu Medical University, Bengbu","place":["Anhui, China"]},{"name":"Department of Neurosurgery, The First Affiliated Hospital of Bengbu Medical University, Bengbu","place":["Anhui, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rongjing","family":"Ge","sequence":"additional","affiliation":[{"name":"Laboratory of Brain and Psychiatric Disease, Bengbu Medical University, Bengbu","place":["Anhui, China"]},{"name":"Department of Pathophysiology, Bengbu Medical University, Bengbu","place":["Anhui, China"]},{"name":"Anhui Engineering Research Center for Neural Regeneration Technology and Medical New Materials, Bengbu Medical University","place":["Bengbu, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"B1","first-page":"1043","article-title":"Mechanisms of natural products as potential antiepileptic drugs.","volume":"35","author":"Ahmad","year":"2022","journal-title":"Pak. J. Pharm. Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/j.fct.2007.09.085","article-title":"Some phytochemical, pharmacological and toxicological properties of ginger (Zingiber officinale Roscoe): A review of recent research.","volume":"46","author":"Ali","year":"2008","journal-title":"Food Chem. Toxicol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1007\/s43440-020-00143-w","article-title":"Role of oxidative stress in epileptogenesis and potential implications for therapy.","volume":"72","author":"Borowicz-Reutt","year":"2020","journal-title":"Pharmacol. Rep."},{"key":"B4","doi-asserted-by":"publisher","first-page":"3296","DOI":"10.1007\/s12035-023-03741-w","article-title":"Protection by nano-encapsulated bacoside A and bacopaside I in seizure alleviation and improvement in sleep- in vitro and in vivo evidences.","volume":"61","author":"C Sekhar","year":"2024","journal-title":"Mol. Neurobiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"150258","DOI":"10.1016\/j.bbrc.2024.150258","article-title":"Hepatoprotective effects of zingerone on sodium arsenite-induced hepatotoxicity in rats: Modulating the levels of caspase-3\/Bax\/Bcl-2, NLRP3\/NF-\u03baB\/TNF-\u03b1 and ATF6\/IRE1\/PERK\/GRP78 signaling pathways.","volume":"725","author":"Eriten","year":"2024","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B6","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.jep.2017.12.019","article-title":"The hidden mechanism beyond ginger (Zingiber officinale Rosc.) potent in vivo and in vitro anti-inflammatory activity.","volume":"214","author":"Ezzat","year":"2018","journal-title":"J. Ethnopharmacol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1111\/epi.13670","article-title":"Operational classification of seizure types by the international league against epilepsy: Position paper of the ILAE commission for classification and terminology.","volume":"58","author":"Fisher","year":"2017","journal-title":"Epilepsia"},{"key":"B8","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1016\/j.phrs.2016.12.026","article-title":"[6]-gingerol and [6]-shogaol, active ingredients of the traditional Japanese medicine hangeshashinto, relief oral ulcerative mucositis-induced pain via action on Na+ channels.","volume":"117","author":"Hitomi","year":"2017","journal-title":"Pharmacol. Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1016\/j.phymed.2015.05.053","article-title":"Glycyrrhizin, silymarin, and ursodeoxycholic acid regulate a common hepatoprotective pathway in HepG2 cells","volume":"22","author":"Hsiang","year":"2015","journal-title":"Phytomedicine"},{"key":"B10","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/j.exger.2010.03.005","article-title":"Modulation of age-related NF-kappaB activation by dietary zingerone via MAPK pathway.","volume":"45","author":"Kim","year":"2010","journal-title":"Exp. Gerontol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2296","DOI":"10.3390\/plants11172296","article-title":"The effect of ginger and its sub-components on pain.","volume":"11","author":"Kim","year":"","journal-title":"Plants"},{"key":"B12","doi-asserted-by":"publisher","first-page":"726","DOI":"10.3390\/ph15060726","article-title":"[6]-shogaol attenuates oxaliplatin-induced allodynia through serotonergic receptors and GABA in the spinal cord in mice.","volume":"15","author":"Kim","year":"","journal-title":"Pharmaceuticals"},{"key":"B13","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1007\/s11055-007-0080-x","article-title":"Kindling in the early postnatal period: Effects on the dynamics of age-related changes in electrophysiological characteristics of hippocampal neurons.","volume":"37","author":"Kudryashov","year":"2007","journal-title":"Neurosci. Behav. Physiol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1139\/cjc-2021-0281","article-title":"Anti-excitotoxicity and neuroprotective action of asiaticoside encapsulated polymeric nanoparticles in pilocarpine rodent seizure model.","volume":"100","author":"Kunjumon","year":"2022","journal-title":"Can. J. Chem."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1111\/j.1528-1167","article-title":"Definition of drug resistant epilepsy: Consensus proposal by the ad hoc task force of the ILAE commission on therapeutic strategies.","volume":"51","author":"Kwan","year":"2010","journal-title":"Epilepsia"},{"key":"B16","doi-asserted-by":"publisher","first-page":"3123","DOI":"10.3390\/ijms23063123","article-title":"Zingerone modulates neuronal voltage-gated Na+ and L-Type Ca2+ currents.","volume":"23","author":"Lai","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"512","DOI":"10.3390\/molecules24030512","article-title":"Pharmacokinetics and Tissue distribution of gingerols and shogaols from ginger (Zingiber officinale Rosc.) in rats by UPLC\u2013Q-Exactive\u2013HRMS.","volume":"24","author":"Li","year":"2019","journal-title":"Molecules"},{"key":"B18","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1177\/1535759719842148","article-title":"CRAFTing a new approach to antiepileptic drug discovery.","volume":"19","author":"Lyman","year":"2019","journal-title":"Epilepsy Curr."},{"key":"B19","doi-asserted-by":"publisher","first-page":"185","DOI":"10.3390\/foods8060185","article-title":"Bioactive compounds and bioactivities of ginger (Zingiber officinale Roscoe).","volume":"8","author":"Mao","year":"2019","journal-title":"Foods"},{"key":"B20","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1007\/s10753-020-01320-y","article-title":"Zingerone mitigates carrageenan-induced inflammation through antioxidant and anti-inflammatory activities.","volume":"44","author":"Mehrzadi","year":"2021","journal-title":"Inflammation"},{"key":"B21","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1007\/s11064-023-04043-2","article-title":"Zingerone alleviates morphine tolerance and dependence in mice by reducing oxidative stress-mediated nlrp3 inflammasome activation.","volume":"49","author":"Molavinia","year":"2024","journal-title":"Neurochem. Res."},{"key":"B22","doi-asserted-by":"publisher","first-page":"6111","DOI":"10.3390\/ijms26136111","article-title":"Zingerone as a neuroprotective agent against cognitive disorders: A systematic review of preclinical studies.","volume":"26","author":"Olasehinde","year":"2025","journal-title":"Int. J. Mol. Sci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"323","DOI":"10.2147\/JEP.S519571","article-title":"Zingerone attenuates cadmium-induced neuroinflammation, oxidative stress and cognitive deficit on the prefrontal cortex of adult Wistar rats.","volume":"17","author":"Oviosun","year":"2025","journal-title":"J. Exp. Pharmacol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1038\/s41583-019-0126-4","article-title":"Neuron-glia interactions in the pathophysiology of epilepsy.","volume":"20","author":"Patel","year":"2019","journal-title":"Nat. Rev. Neurosci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/0013-4694(72)90177-0","article-title":"Modification of seizure activity by electrical stimulation. II. Motor seizure.","volume":"32","author":"Racine","year":"1972","journal-title":"Electroencephalogr. Clin. Neurophysiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"695396","DOI":"10.3389\/fpain.2021.695396","article-title":"GPR171 agonist reduces chronic neuropathic and inflammatory pain in male, but not female mice.","volume":"2","author":"Ram","year":"2021","journal-title":"Front. Pain Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"114911","DOI":"10.1016\/j.expneurol.2024.114911","article-title":"Collagen VI: Role in synaptic transmission and seizure-related excitability.","volume":"380","author":"Ramos-Moreno","year":"2024","journal-title":"Exp. Neurol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1186\/s12974-018-1192-7","article-title":"The role of inflammation in the development of epilepsy.","volume":"15","author":"Rana","year":"2018","journal-title":"J. Neuroinflammation"},{"key":"B29","doi-asserted-by":"publisher","first-page":"146","DOI":"10.3390\/ph14020146","article-title":"Zingerone targets status epilepticus by blocking hippocampal neurodegeneration via regulation of redox imbalance, inflammation and apoptosis.","volume":"14","author":"Rashid","year":"2021","journal-title":"Pharmaceuticals"},{"key":"B30","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/S1474-4422(25)00379-5","article-title":"REPO2MSE study group. Seizure-related biomarkers of sudden unexpected death in epilepsy (SUDEP) in drug-resistant focal epilepsy (REPO2MSE): A prospective, multicentre case-control study.","volume":"25","author":"Ryvlin","year":"2026","journal-title":"Lancet Neurol."},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1080\/21688370.2025.2582881","article-title":"Protective activity of bacopaside I encapsulated polymeric nanoparticles against kainic acid-induced excitotoxicity.","author":"Sekhar","year":"2025","journal-title":"Tissue Barriers"},{"key":"B32","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1016\/j.phytochem.2015.07.012","article-title":"Gingerols and shogaols: Important nutraceutical principles from ginger.","volume":"117","author":"Semwal","year":"2015","journal-title":"Phytochemistry"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1391019","DOI":"10.3389\/fphar.2024.1391019","article-title":"Unraveling the interconversion pharmacokinetics and oral bioavailability of the major ginger constituents: [6]-gingerol, [6]-shogaol, and zingerone after single-dose administration in rats.","volume":"15","author":"Songvut","year":"2024","journal-title":"Front. Pharmacol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1016\/j.jid.2019.07.715","article-title":"A zingerone analog, acetyl zingerone, bolsters matrisome synthesis, inhibits matrix metallopeptidases, and represses IL-17A target gene expression.","volume":"140","author":"Swindell","year":"2020","journal-title":"J. Invest. Dermatol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"603","DOI":"10.22038\/IJBMS.2024.73342.15934","article-title":"Effects of zingerone on rat induced testicular toxicity by sodium arsenite via oxidative stress, endoplasmic reticulum stress, inflammation, apoptosis, and autophagy pathways.","volume":"27","author":"Tuncer","year":"2024","journal-title":"Iran. J. Basic Med. Sci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1007\/s00401-015-1481-5","article-title":"Infections, inflammation and epilepsy.","volume":"131","author":"Vezzani","year":"2016","journal-title":"Acta Neuropathol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1543594","DOI":"10.3389\/fphar.2025.1543594","article-title":"Zingerone alleviates inflammatory pain by reducing the intrinsic excitability of anterior cingulate cortex neurons in a mice model.","volume":"16","author":"Wang","year":"2025","journal-title":"Front. Pharmacol."},{"key":"B38","unstructured":"Epilepsy: Key Facts.\n          \n          2024"},{"key":"B39","doi-asserted-by":"publisher","first-page":"e70873","DOI":"10.1111\/jcmm.70873","article-title":"Zerumbone attenuates lipopolysaccharide-induced acute lung injury by suppressing the NLRP3\/Caspase-1\/GSDMD signalling pathway.","volume":"29","author":"Xu","year":"2025","journal-title":"J. Cell. Mol. Med."},{"key":"B40","doi-asserted-by":"publisher","first-page":"6687185","DOI":"10.1155\/2020\/6687185","article-title":"Antioxidants targeting mitochondrial oxidative stress: Promising neuroprotectants for epilepsy.","volume":"2020","author":"Yang","year":"2020","journal-title":"Oxid. Med. Cell. Longev."},{"key":"B41","doi-asserted-by":"publisher","first-page":"436","DOI":"10.3389\/fncel.2018.00436","article-title":"The Changes of intrinsic excitability of pyramidal neurons in anterior cingulate cortex in neuropathic pain.","volume":"12","author":"Yang","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"904225","DOI":"10.3389\/fneur.2022.904225","article-title":"Role of HMGB1\/TLR4 and IL-1\u03b2\/IL-1R1 signaling pathways in epilepsy.","volume":"13","author":"Zhang","year":"2022","journal-title":"Front. Neurol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"102198","DOI":"10.1016\/j.pneurobio.2021.102198","article-title":"Neuroregenerative gene therapy to treat temporal lobe epilepsy in a rat model.","volume":"208","author":"Zheng","year":"2022","journal-title":"Prog. Neurobiol."}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2026.1809792\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:01:22Z","timestamp":1775800882000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2026.1809792\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,10]]},"references-count":43,"alternative-id":["10.3389\/fnins.2026.1809792"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2026.1809792","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,10]]},"article-number":"1809792"}}