Anticonvulsant and Neurobehavioural effects of the aqueous leaf extract of leea guineensis G. Don (Family: Leeaceae)

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Leea guineensis is an evergreen shrub found in tropical forest zones in Africa and other parts of the world and the leaves are used traditionally to treat convulsions and epilepsy. This study investigated the anticonvulsant, anxiolytic, antinociceptive and neuromuscular effects of the aqueous leaf extract of the plant. Three widely used animal models of epilepsy namely the pentylenetetrazole, picrotoxin and maximal electroshock-induced seizure tests were used to evaluate the anticonvulsant effects of the extract, the elevated plus-maze and the light/dark box were used to evaluate its anxiolytic effects and the formalin test used to investigate its antinociceptive effects. The neuromuscular effects of the extract were determined in the beam traversal test, the rotarod test and the isolated toad rectus abdominis muscle. In the pentylenetetrazole-induced seizures, Leea guineensis (30-300 mg/kg p.o) caused marked and dose-dependent delay of the onset of myoclonic jerks (F3,16=6.29, P=0.0051) and decreased the duration of tonic-clonic convulsions (F3,16=9.20, P=0.0009). The extract delayed the onset of tonic convulsions and decreased the frequency of convulsions induced by pentylenetetrazole (F3,16=0.95, P=0.4385 and F3,16=2.39, P=0.1065, respectively). Onset of tonic convulsions induced by picrotoxin was also significantly delayed by Leea guineensis and the frequency and duration of convulsions significantly reduced. The onset of picrotoxin-induced myoclonic jerks was delayed by the extract (F3,16=0.53, P=0.6682). Again, the extract showed marked anticonvulsant activity by significantly reducing the duration (F3,36=7.35, P=0.0006) of maximal electroshock-induced tonic hind limb extension. Administration of Leea guineensis (30-300 mg/kg p.o) in mice caused significant anxiolytic effects similar to that of diazepam (0.1-1.0 mg/kg i.p) and opposite to that of pentylenetetrazole (3-30 mg/kg i.p) in the elevated plus-maze and the light/dark box tests. It caused significant increase in the number of open arm entries and time (F3,16=5.21, P=0.0106 and F3,16=4.18, P=0.0230, respectively), increased the frequency and duration of unprotected stretch-attend postures (F3,16=5.39, P=0.0093 and F3,16=3.47, P=0.0411, respectively) as well as unprotected head dips (F3,16=3.95, P=0.0277 and F3,16=5.15, P=0.0111, respectively). Similar to diazepam and opposite to pentylenetetrazole, Leea guineensis significantly delayed the emergence latency of mice into the light box from the dark box and increased the time spent in the light area of the light/dark box. Leea guineensis caused potent antinociceptive activity in both the early phase and late phase of formalin-induced pain (F3,16=17.18, P<0.0001 and F3,16=40.17, P<0.0001, respectively). Morphine (3-10 mg/kg i.p) also produced antinociceptive activity in both phases similar to the extract. The extract was approximately equipotent in both phases (ED50 =16.37±4.57 and ED50=14.06±4.39, respectively). The effect of morphine was also almost equipotent in both phases. However, Leea guineensis was less potent than morphine in both phases (about 181.88 and 127.82 times respectively). Naloxone and theophylline significantly reversed the antinociceptive activity of the extract in the first phase but had no effect on the second phase. The extract caused concentration-dependent contractions on the isolated toad rectus abdominis muscle similar to ACh and did not impair motor coordination and balance. In conclusion, the results indicate that the leaves of Leea guineensis produces anticonvulsant, anxiolytic and analgesic effects through central mechanisms which support the traditional use of the plant to treat epileptic fits.
A thesis submitted in fulfillment of the requirements for the degree of Master of Philosophy In the Department of Pharmacology.