{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T05:10:33Z","timestamp":1781154633622,"version":"3.54.1"},"reference-count":83,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T00:00:00Z","timestamp":1647993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Instytut Medycyny Wsi im. Witolda Chod\u017aki","award":["DS 20030\/2020-2022"],"award-info":[{"award-number":["DS 20030\/2020-2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Umbelliferone (7-hydroxycoumarin; UMB) is a coumarin with many biological properties, including antiepileptic activity. This study evaluated the effect of UMB on the ability of classical and novel antiepileptic drugs (e.g., lacosamide (LCM), levetiracetam (LEV), phenobarbital (PB) and valproate (VPA)) to prevent seizures evoked by the 6-Hz corneal-stimulation-induced seizure model. The study also evaluated the influence of this coumarin on the neuroprotective properties of these drugs in two in vitro models of neurodegeneration, including trophic stress and excitotoxicity. The results indicate that UMB (100 mg\/kg, i.p.) significantly enhanced the anticonvulsant action of PB (p &lt; 0.01) and VPA (p &lt; 0.05), but not that of LCM orLEV, in the 6-Hz test. Whether alone or in combination with other anticonvulsant drugs (at their ED50 values from the 6-Hz test), UMB (100 mg\/kg) did not affect motor coordination; skeletal muscular strength and long-term memory, as determined in the chimney; grip strength; or passive avoidance tests, respectively. Pharmacokinetic characterization revealed that UMB had no impact on total brain concentrations of PB or VPA in mice. The in vitro study indicated that UMB has neuroprotective properties. Administration of UMB (1 \u00b5g\/mL), together with antiepileptic drugs, mitigated their negative impact on neuronal viability. Under trophic stress (serum deprivation) conditions, UMB enhanced the neurotrophic abilities of all the drugs used. Moreover, this coumarin statistically enhanced the neuroprotective effects of PB (p &lt; 0.05) and VPA (p &lt; 0.001) in the excitotoxicity model of neurodegeneration. The obtained results clearly indicate a positive effect of UMB on the anticonvulsant and neuroprotective properties of the selected drugs.<\/jats:p>","DOI":"10.3390\/ijms23073492","type":"journal-article","created":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T12:20:25Z","timestamp":1648038025000},"page":"3492","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Influence of Umbelliferone on the Anticonvulsant and Neuroprotective Activity of Selected Antiepileptic Drugs: An In Vivo and In Vitro Study"],"prefix":"10.3390","volume":"23","author":[{"given":"Miros\u0142aw","family":"Zagaja","sequence":"first","affiliation":[{"name":"Isobolographic Analysis Laboratory, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Zagaja","sequence":"additional","affiliation":[{"name":"Chair and Department of Humanities and Social Medicine, Medical University of Lublin, Chod\u017aki 7, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2277-1140","authenticated-orcid":false,"given":"Joanna","family":"Szala-Rycaj","sequence":"additional","affiliation":[{"name":"Isobolographic Analysis Laboratory, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Szewczyk","sequence":"additional","affiliation":[{"name":"Isobolographic Analysis Laboratory, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9367-0684","authenticated-orcid":false,"given":"Marta Kinga","family":"Lemieszek","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7327-5473","authenticated-orcid":false,"given":"Grzegorz","family":"Raszewski","sequence":"additional","affiliation":[{"name":"Department of Toxicology and Food Protection, Institute of Rural Health, Jaczewskiego 2, 20-950 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Andres-Mach","sequence":"additional","affiliation":[{"name":"Isobolographic Analysis Laboratory, Institute of Rural Health, Jaczewskiego 2, 20-090 Lublin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1111\/j.0013-9580.2005.66104.x","article-title":"Epileptic seizures and epilepsy: Definitions proposed by the International League Against Epilepsy (ILAE) and the International Bureau for Epilepsy (IBE)","volume":"46","author":"Fisher","year":"2005","journal-title":"Epilepsia"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1016\/S1474-4422(12)70153-9","article-title":"Adverse effects of antiepileptic drugs","volume":"11","author":"Perucca","year":"2012","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"15089","DOI":"10.1073\/pnas.222550499","article-title":"Antiepileptic drugs and apoptotic neurodegeneration in the developing brain","volume":"99","author":"Bittigau","year":"2002","journal-title":"Proc. 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