Anticonvulsant activity of Benkara malabarica (Linn.) root extract: In vitro and in vivo investigation.
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.
Mishra
Nibha
N
Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra 835215, Ranchi, India. nmishra@bitmesra.ac.in
Oraon
Awadesh
A
Dev
Abhimanyu
A
Jayaprakash
Venkatesan
V
Basu
Arijit
A
Pattnaik
Ashok K
AK
Tripapthi
Satya N
SN
Akhtar
Mustari
M
Ahmad
Sadab
S
Swaroop
Shreyshri
S
Basu
Mahua
M
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
D000927:Anticonvulsants; D010936:Plant Extracts; D005680:gamma-Aminobutyric Acid; D010672:Phenytoin; D000612:4-Aminobutyrate Transaminase; D012603:Scopoletin; D003975:Diazepam