Anticonvulsant activity of fraction isolated from ethanolic extract of heartwood of Cedrus deodara

The heartwood of Cedrus deodara is traditionally used for the treatment of neurological disorders in India. In this study, the compound 3,4-bis(3,4-dimethoxyphenyl)furan-2,5-dione (BDFD) isolated from the ethanolic extract of C. deodara was evaluated for its anticonvulsant activity. The experimental studies were carried out in albino mice (18-22 g) and rats (180-220 g), employing different models of convulsions. The N-methyl-d-aspartic acid (NMDA)-induced lethality test and estimation of brain gamma-aminobutyric acid (GABA) were carried out to investigate the mechanism of action of this compound. BDFD gave dose-dependent protection against pentylenetetrazole (PTZ)-, pilocarpine- and 6-Hz-induced convulsions but it could not inhibit NMDA-induced lethality. Motor incoordination was displayed when the BDFD dose exceeded 400 mg/kg, whereas the therapeutic dose was below 100 mg/kg in the PTZ, pilocarpine and 6-Hz models (39-90 mg/kg). Furthermore, brain GABA estimation revealed that this compound increases the GABA level. BDFD dose levels up to 150 mg/kg did not prevent NMDA-induced lethality, which proves its weak influence on the excitatory neurotransmitter glutamate. The findings of the experiments on various animal models clearly demonstrated that BDFD possesses anticonvulsant activity by enhancing inhibitory GABAminergic neurotransmission.