title: Isobolographically additive anticonvulsant activity between Centella asiatica's ethyl acetate fraction and some antiepileptic drugs.
abstract: OBJECTIVE
  To investigate interaction between orally given Centella asiatica's ethyl acetate fraction (EACA) and intraperitoneally administered antiepileptic drugs (AEDs), namely, phenytoin, valproate and gabapentin.
  
  
  METHODS
  Isobolographic analysis was used to evaluate the interaction between EACA and AEDs in terms of protection of mice in the pentylenetetrazole test. Rotarod test was used to evaluate neurotoxicity.
  
  
  RESULTS
  When given alone, the median effective dose of phenytoin, valproate and gabapentin were found to be 13, 104, and 310 mg/kg BW, respectively, whereas the corresponding values in the presence of EACA were 5, 29 and 79 mg/kg BW. Together with isobolographic analysis, the results obtained indicated an additive effect among all combinations tested. In relation to neurotoxicity, combination of gabapentin and EACA demonstrated a broader margin between the effective dose and the neurotoxic dose while the other two combinations did not.
  
  
  CONCLUSIONS
  The present finding suggested a potential of Centella asiatica to be developed as an adjunctive medication for epileptic patients.
authors.affiliation: PhD Program of Inter-department of Physiology, Graduate School, Chulalongkorn University, Bangkok, Thailand.
authors.forename: Anusara
authors.initials: A
authors.lastname: Vattanajun
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Mayuree H
authors.initials: MH
authors.lastname: Tantisira
authors.forename: Boonyong
authors.initials: B
authors.lastname: Tantisira
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage*; D028041:Centella; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D041743:Herb-Drug Interactions; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage; D012640:Seizures / Q000188:drug therapy*
chemical_list: D000927:Anticonvulsants; D010936:Plant Extracts