title: Anticonvulsant activity of Benkara malabarica (Linn.) root extract: In vitro and in vivo investigation.
abstract: OBJECTIVE
  To systematically investigate the anticonvulsant activity of methanol extract of Benkara malabarica roots and to provide a biochemical basis elucidating its mode of action.
  
  
  METHODS
  The median lethal dose (LD(50)) of Benkara malabarica extract was determined. The anticonvulsant activity of the extract was assessed in strychnine-induced and isoniazide-induced convulsion models; phenytoin (20mg/kg) and diazepam (1mg/kg) were used as standards, respectively. Percentage protection provided by the drug was accounted as decrease in the number of convulsions within 8h of observation. Mechanism of action was studied by performing GABA transaminase (GABA-T) assay, isolated from rat brain. Active constituent was isolated and characterized from the plant extract.
  
  
  RESULTS
  The median lethal dose (LD50) of Benkara malabarica was found to be more than 500 mg/kg. It demonstrated 30% and 35% protection against strychnine-induced convulsions and 60% and 80% protection against isoniazide-induced convulsions, at doses of 25mg/kg and 50mg/kg, respectively. Enzyme assay results revealed that Benkara malabarica extract possesses GABA-T inhibitory activity (IC50=0.721 mg/ml). Scopoletin which was identified as the major constituent of the extract was found to be an inhibitor of GABA-T (IC50=10.57 microM).
  
  
  CONCLUSIONS
  The anticonvulsant activity of the plant extract is predominantly GABA mediated and may be due to the action of scopoletin alone or is a result of synergy of different compounds in the extract in which scopoletin is the major constituent.
authors.affiliation: Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra 835215, Ranchi, India. nmishra@bitmesra.ac.in
authors.forename: Nibha
authors.initials: N
authors.lastname: Mishra
authors.forename: Awadesh
authors.initials: A
authors.lastname: Oraon
authors.forename: Abhimanyu
authors.initials: A
authors.lastname: Dev
authors.forename: Venkatesan
authors.initials: V
authors.lastname: Jayaprakash
authors.forename: Arijit
authors.initials: A
authors.lastname: Basu
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Pattnaik
authors.forename: Satya N
authors.initials: SN
authors.lastname: Tripapthi
authors.forename: Mustari
authors.initials: M
authors.lastname: Akhtar
authors.forename: Sadab
authors.initials: S
authors.lastname: Ahmad
authors.forename: Shreyshri
authors.initials: S
authors.lastname: Swaroop
authors.forename: Mahua
authors.initials: M
authors.lastname: Basu
mesh_terms: D000612:4-Aminobutyrate Transaminase / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D003975:Diazepam / Q000494:pharmacology; D004347:Drug Interactions; D057075:Enzyme Assays; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D010672:Phenytoin / Q000494:pharmacology; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D019666:Rubiaceae / Q000737:chemistry*; D012603:Scopoletin / Q000627:therapeutic use; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D005680:gamma-Aminobutyric Acid / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D010936:Plant Extracts; D005680:gamma-Aminobutyric Acid; D010672:Phenytoin; D000612:4-Aminobutyrate Transaminase; D012603:Scopoletin; D003975:Diazepam