title: Anticonvulsive and neuroprotective effects of synergetic combination of phenytoin and gastrodin on the convulsion induced by penicillin in mice.
abstract: Phenytoin (PHT) is a commonly prescribed first-line antiepileptic drug. However, long-term administration of PHT can cause memory loss and balance disturbance. Gastrodin (GD) 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 GD and PHT can enhance anticonvulsive effect and reduce the side effects associated with PHT. The GD alone (950.60 mg/kg) and the PHT alone (45.50 mg/kg) could produce an anticonvulsive effect, while comparable effect could be produced by PHT : GD = 1 : 50 (8.59 : 429.27 mg/kg), which reduce the dose of PHT by 81% and GD by 55%. After the chronic anticonvulsive experiments of 16 days, the balance disturbance and short-/long-term memory loss were observed in the PHT group, while the PHT + GD 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 NF-κB (p65) expression was increased in combination group. All above suggested the potential of the combination of PHT and GD enhances the anticonvulsive effect and the neuroprotective effect and reduces the PHT-associated memory and balance disturbance. The PHT + GD strategy would provide new possibilities as a novel promising methodology to treat epileptic patients.
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou, 510632, China.|Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.
authors.forename: Ziqi
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou, 510632, China.
authors.forename: Yanzhu
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou, 510632, China.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou, 510632, China.
authors.forename: Yuzhong
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou, 510632, China.
authors.forename: Haohua
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Epidemiology, Medical College, Jinan University, Guangzhou, 510632, China.
authors.forename: Siheng
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou, 510632, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Weng
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital, Jinan University, Guangzhou, 510632, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Medical College, Jinan University, Guangzhou, 510632, China.
authors.forename: Linyan
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Pathology, The Second College of Clinic Medicine, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of TCM), Guangzhou, 510120, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Yang
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D001592:Benzyl Alcohols / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005960:Glucosides / Q000627:therapeutic use*; D006624:Hippocampus / Q000473:pathology; D008297:Male; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000523:psychology; D051379:Mice; D009474:Neurons / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010406:Penicillins; D010672:Phenytoin / Q000627:therapeutic use*; D004856:Postural Balance / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D012640:Seizures / Q000139:chemically induced* / Q000188:drug therapy* / Q000523:psychology; D015996:Survival Rate; D051996:Transcription Factor RelA / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000927:Anticonvulsants; D001592:Benzyl Alcohols; D005960:Glucosides; D018696:Neuroprotective Agents; D010406:Penicillins; D051996:Transcription Factor RelA; C045345:gastrodin; D010672:Phenytoin
keywords: NF-κB; balance; gastrodin; memory; phentyoin