Isobolographically Additive Anticonvulsant Activity between Centella asiaticaûs Ethyl Acetate Fraction and some Antiepileptic Drugs Anusara Vattanajun MSc*, ** Hiroshi Watanabe PhD***, Mayuree H Tantisira PhD****, Boonyong Tantisira PhD****
* PhD Program of Inter-department of Physiology, Graduate School, Chulalongkorn University
** Department of Physiology, Phramongkutklao College of Medicine
*** Department of Pharmacology, Institute of Natural Medicine, Toyama Medical and Pharmaceutical
University, Toyama Japan
**** Research Unit of Neurophysiology and Neuropharmacology, Faculty of Pharmaceutical Sciences,
Chulalongkorn University
Objective : To investigate interaction between orally given Centella asiaticaûs ethyl acetate fraction (EACA)
and intraperitoneally administered antiepileptic drugs (AEDs), namely, phenytoin, valproate and gabapentin.
Materials and 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.
Conclusion : The present finding suggested a potential of Centella asiatica to be developed as an adjunctive
medication for epileptic patients.
Affiliation :
Centella asiatica, Anticonvulsant activity, Isobologram
Keywords :
