title: Emodin plays an interventional role in epileptic rats via multidrug resistance gene 1 (MDR1).
abstract: OBJECTIVE
  To observe the interventional effects of emodin in epileptic rats and elucidate its possible mechanism of action.
  
  
  METHODS
  Thirty-six female Wistar rats were randomly divided into normal control group, model group (intraperitoneal injection of kainic acid) and emodin group (intraperitoneal injection of kainic acid+emodin intervention). The rat epilepsy model was confirmed by behavioral tests and electroencephalography. The protein levels of P-glycoprotein and N-methyl-D-aspartate (NMDA) receptor in cerebral vascular tissue were analyzed by western blotting, and mRNA levels of multidrug resistance gene 1 (MDR1) and cyclooxygenase-2 (COX-2) were analyzed by real-time PCR. COX-2 and P-glycoprotein levels in the brains were detected by immunohistochemical assay.
  
  
  RESULTS
  The seizures were relieved in emodin group. Laser scanning confocal microscopy showed P-glycoprotein fluorescence increased significantly after seizures, indicating that epilepsy can induce overexpression of P-glycoprotein. Compared with control group, protein levels of P-glycoprotein and NMDA receptor in cerebral vascular tissue were significantly higher in model group, and mRNA levels of MDR1 and COX-2 were also significantly increased. Compared with model group, P-glycoprotein and NMDA receptor levels in cerebral vascular tissue were significantly decreased in emodin group (P<0.05), and the levels of MDR1 and COX-2 were down-regulated (P<0.05). In the rat brain, seizures could significantly increase COX-2 and P-glycoprotein levels, while emodin intervention was able to significantly reduce the levels of both.
  
  
  CONCLUSIONS
  These findings suggest that epileptic seizures are tightly associated with up-regulated MDR1 gene, and emodin shows good antagonistic effects on epileptic rats, possibly through inhibition of MDR1 gene and its associated genes.
authors.affiliation: Department of Neurosurgery, Chengdu Military General Hospital Chengdu 610083, China ; Department of Neurosurgery, Third Military Medical University Chongqing 400037, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Chengdu Military General Hospital Chengdu 610083, China ; Department of Neurosurgery, Third Military Medical University Chongqing 400037, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Kong
authors.affiliation: Department of Neurosurgery, Chengdu Military General Hospital Chengdu 610083, China.
authors.forename: Yongqin
authors.initials: Y
authors.lastname: Kuang
authors.affiliation: Department of Neurosurgery, Chengdu Military General Hospital Chengdu 610083, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Cheng
authors.affiliation: Department of Neurosurgery, Chengdu Military General Hospital Chengdu 610083, China.
authors.forename: Jianwen
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of Neurosurgery, Chengdu Military General Hospital Chengdu 610083, China.
authors.forename: Junhai
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Chengdu Military General Hospital Chengdu 610083, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Shu
authors.affiliation: Department of Neurosurgery, Chengdu Military General Hospital Chengdu 610083, China.
authors.forename: Sixun
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Neurosurgery, Third Military Medical University Chongqing 400037, China ; Department of Emergency, Chengdu Military General Hospital Chengdu 610083, China.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Chengdu Military General Hospital Chengdu 610083, China.
authors.forename: Jingming
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Neurosurgery, Chengdu Military General Hospital Chengdu 610083, China.
authors.forename: Haidong
authors.initials: H
authors.lastname: Huang
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D058256:Brain Waves / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004569:Electroencephalography; D004642:Emodin / Q000494:pharmacology*; D004827:Epilepsy / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D005260:Female; D007608:Kainic Acid; D018613:Microscopy, Confocal; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000927:Anticonvulsants; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; C095122:multidrug resistance protein 3; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D004642:Emodin; D007608:Kainic Acid
keywords: Emodin; MDR1 gene; animal model; epilepsy