{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T07:54:50Z","timestamp":1762761290280,"version":"3.37.3"},"reference-count":27,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,6,15]],"date-time":"2015-06-15T00:00:00Z","timestamp":1434326400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["31070997, 81372382"],"award-info":[{"award-number":["31070997, 81372382"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Phenytoin (<jats:styled-content style=\"fixed-case\">PHT<\/jats:styled-content>) is a commonly prescribed first\u2010line antiepileptic drug. However, long\u2010term administration of <jats:styled-content style=\"fixed-case\">PHT<\/jats:styled-content> can cause memory loss and balance disturbance. Gastrodin (<jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content>) is the major bioactive component in Tianma and has sedative, anticonvulsive, memory strengthening, and neuroprotective effects. To combine the two drugs seems attractive; however, little was known about the efficacy of combination therapy. In this study, convulsive attack was successfully induced by penicillin. Isobolographic analysis, memory and balance behavior test, histopathological examination, and Western blot analysis were used to investigate whether the combination therapy of <jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">PHT<\/jats:styled-content> can enhance anticonvulsive effect and reduce the side effects associated with <jats:styled-content style=\"fixed-case\">PHT<\/jats:styled-content>. The <jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content> alone (950.60\u00a0mg\/kg) and the <jats:styled-content style=\"fixed-case\">PHT<\/jats:styled-content> alone (45.50\u00a0mg\/kg) could produce an anticonvulsive effect, while comparable effect could be produced by <jats:styled-content style=\"fixed-case\">PHT<\/jats:styled-content>\u00a0:\u00a0<jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content>\u00a0=\u00a01\u00a0:\u00a050 (8.59\u00a0:\u00a0429.27\u00a0mg\/kg), which reduce the dose of <jats:styled-content style=\"fixed-case\">PHT<\/jats:styled-content> by 81% and <jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content> by 55%. After the chronic anticonvulsive experiments of 16\u00a0days, the balance disturbance and short\u2010\/long\u2010term memory loss were observed in the <jats:styled-content style=\"fixed-case\">PHT<\/jats:styled-content> group, while the <jats:styled-content style=\"fixed-case\">PHT<\/jats:styled-content>\u00a0+\u00a0<jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content> therapy can protect the normal balance and memory function. The neuron morphology of hippocampus was preserved, and the number of surviving neurons after combination therapy was more than the model group. The amount of <jats:styled-content style=\"fixed-case\">NF<\/jats:styled-content>\u2010\u03baB (p65) expression was increased in combination group. All above suggested the potential of the combination of <jats:styled-content style=\"fixed-case\">PHT<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content> enhances the anticonvulsive effect and the neuroprotective effect and reduces the <jats:styled-content style=\"fixed-case\">PHT<\/jats:styled-content>\u2010associated memory and balance disturbance. The <jats:styled-content style=\"fixed-case\">PHT<\/jats:styled-content>\u00a0+\u00a0<jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content> strategy would provide new possibilities as a novel promising methodology to treat epileptic patients.<\/jats:p>","DOI":"10.1111\/fcp.12127","type":"journal-article","created":{"date-parts":[[2015,5,27]],"date-time":"2015-05-27T15:23:29Z","timestamp":1432740209000},"page":"371-381","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Anticonvulsive and neuroprotective effects of synergetic combination of phenytoin and gastrodin on the convulsion induced by penicillin in mice"],"prefix":"10.1111","volume":"29","author":[{"given":"Ziqi","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Pharmacology Medical College Jinan University Guangzhou 510632 China"},{"name":"Department of Radiation Oncology Peking Union Medical College Hospital Chinese Academy of Medical Sciences Beijing 100730 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanzhu","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Medical College Jinan University Guangzhou 510632 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Medical College Jinan University Guangzhou 510632 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuzhong","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Medical College Jinan University Guangzhou 510632 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haohua","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Medical College Jinan University Guangzhou 510632 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Medical College Jinan University Guangzhou 510632 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Medical College Jinan University Guangzhou 510632 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital Jinan University Guangzhou 510632 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linyan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Medical College Jinan University Guangzhou 510632 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haifeng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology The Second College of Clinic Medicine Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of TCM) Guangzhou 510120 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,6,15]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1979.00500450029003"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410010602"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2013.12.007"},{"key":"e_1_2_7_5_1","first-page":"CD002217","article-title":"Phenobarbitone versus phenytoin monotherapy for partial onset seizures and generalised onset tonic\u2010clonic seizures","volume":"1","author":"Nolan S.J.","year":"2013","journal-title":"Cochrane Database Syst. 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