Anticonvulsant Effects of Lippia citriodora (Verbenaceae) Leaves Ethanolic Extract in Mice: Role of GABAergic System

Abstract

Background: Lippia citriodora Kunth is one of the Iranian traditional medicines for the treatment
of convulsive disorders. The goal of this study is to investigate the anticonvulsant activity of the
plant’s leave ethanolic extract against electro‑ and chemoconvulsant‑induced seizures in mice.

Methods: The anticonvulsant activity of the extract (200, 400, 800 mg/kg, per os, p.o.) was
investigated in pentylenetetrazole (PTZ) and maximal electroshock (MES)‑induced seizures in
mice. Diazepam (1 mg/kg) and phenytoin (25 mg/kg) intraperitoneally (i.p.) were used as reference
drugs. In addition, for investigating the role of GABAergic system, flumazenil (2 mg/kg, i.p.) was
also injected before L. citriodora.

Results: The extract had not any toxicity and significantly decreased the duration and increased
the latency of the seizures induced by PTZ (90 mg/kg). In the MES test, L. citriodora displayed
statistically significant reduction in hind limb tonic extension duration in a nondose‑dependent
manner. Flumazenil reversed the anticonvulsant activity of the plant’s extract in the PTZ model.

Conclusions: The results propose that L. citriodora leave ethanolic extract has anticonvulsant
activity against convulsive disorders. It seems that this plant’s extract generates its antiseizure
effect through GABAergic system potentiation. Further studies will be needed in order to investigate
the exact mechanisms of it. Moreover, one may conclude that the present results are in accordance
with the positive effect of L. citriodora extract to treat convulsion mentioned in old Iranian literature.

Keywords: Anticonvulsant, Lippia citriodora, maximal electroshock, mice, pentylenetetrazole