Investigation of some possible mechanisms involved in the anticonvulsant activity of Tulbaghia violacea harv

Magister Scientiae (Medical Bioscience) - MSc(MBS)Even though Tulbaghia violacea has been used to treat and manage epilepsy in South Africa by traditional medicine practitioners, no evidence in any literature has shown any scientific scrutiny of the effectiveness of the plant species in therapy. This project was intended, therefore, to investigate the anticonvulsant effect of the leaf methanol extract of Tulbaghia violacea by studying its effect against tonic convulsion induced by either pentylenetetrazole (PTZ), bicuculline, picrotoxin, strychnine or N-methyl-DL-aspartic acid (NMDLA) in mice. Qualitative phytochemical analysis, acute toxicity and HPLC studies were also carried out on the plant species. The doses of 200 (mg/kg, i.p.) and 400 (mg/kg, i.p.) of the leaf methanol extract of T. Violacae significantly delayed the onset of PTZ (100 mg/kg, i.p.)-induced tonic convulsion in a dose dependent manner. Leaf methanol extract of the plant species (200 mg/kg, i.p.) did not affect the incidence of PTZ (100 mg/kg, i.p.)-induced tonic convulsion while 400 mg/kg (i.p.) protected only one mouse against the tonic convulsion. Leaf methanol extract of Tulbaghia violacea (100mg/kg, i.p.) did not significantly affect the onset or incidence of PTZ (100 mg/kg, i.p.)- induce tonic convulsion. Phenobarbitone (12 mg/kg, i.p.), diazepam (0.5 mg/kg, i.p.) and muscimol (2mg/kg, i.p.) significantly delayed the onset of PTZ (100 mg/kg, i.p.)-induced tonic convulsion and also significantly reduced the number of animals convulsing. Muscimol (0.2 mg/kg, i.p.) did not significantly affect the onset or incidence of PTZ (100 mg/kg, i.p.)-induced tonic convulsion. However, combined therapy of sub effective doses of the leaf methanol extract of T. Violacea (100 mg/kg, i.p.) and muscimol (0.2 mg/kg, i.p.) significantly delayed the onset of PTZ (100mg/kg, i.p.)-induced tonic convulsion and but did not significantly reduce the number of animals convulsing. The combined therapy of sub effective doses of the leaf methanol extract of T. violacea (100 mg/kg, i.p.) and muscimol (0.2 mg/kg, i.p.) protected two of the mice against the tonic convulsion. Leaf methanol extract of Tulbaghia violacea (100-400 mg/kg, i.p.) significantly and dose dependently delayed the onset of tonic convulsion produced by bicuculline (30 mg/kg, i.p.), picrotoxin (20 mg/kg, i.p.) or NMDLA (400 mg/kg, i.p.)-induced tonic convulsion but did not affect the incidence of any of the convulsions. Phenobarbitone (12 mg/kg, i.p.), diazepam (0.5 mg/kg, i.p.) or muscimol (2 mg/kg, i.p.) significantly delayed the onset of bicuculline (30 mg/kg, i.p.) or picrotoxin (20 mg/kg, i.p.)-induced tonic convulsion and also significantly reduced the number of animals convulsing. Phenobarbitone (12 mg/kg, i.p.) or diazepam (0.5 mg/kg, i.p.) did affect significantly affect the onset or incidence of NMDLA (400 mg/kg, i.p.)-induced tonic convulsion. LY233053 (5 mg/kg, i.p.) significantly delayed the onset of tonic convulsion produced by NMDLA (400 mg/kg, i.p.) and also significantly reduced the number of animals convulsing. Leaf methanol extract of Tulbaghia violacea (200 and 400 mg/kg, i.p.) significantly delayed the onset of strychnine (2 mg/kg, i.p.)-induced tonic convulsion but did not significantly affect the number of mice convulsing. The dose of 100 mg/kg (i.p.) of leaf methanol extract of T. violacea did not significantly affect the onset or incidence of strychnine (2 mg/kg, i.p.)-induced tonic convulsion. Phenobarbitone (12 mg/kg, i.p.) significantly delayed the onset of strychnine (2 mg/kg, i.p.)-induced tonic convulsion and also significantly reduced the number of animals convulsing. Diazepam (0.5 mg/kg, i.p.) did not significantly delay the onset of strychnine (2 mg/kg, i.p.)-induced tonic convulsion and also did not significantly affect the number of mice convulsing. Phenytoin (30 mg/kg, i.p.) or DMSO (0.25 ml, i.p.) did not significantly affect the onset or incidence of bicuculline (30 mg/kg, i.p.), picrotoxin, strychnine or NMDLA-induced tonic convulsion. The qualitative phytochemical analysis of the plant species showed the presence of alkaloids, saponins, cardiac glycosides, flavonoids, triterpene steroids, quinones and tannins. The LD50 value obtained following oral administration of the leaf methanol extract of Tulbaghia violacea may be greater than 4000 mg/kg. The HPLC fingerprint of the leaf methanol extract of Tulbaghia violacea showed distinct peaks at the following retention times, 2.911, 3.269, 4.010, 7.597, and 15.122 min. The results obtained in this study indicate that the leaf methanol extract of Tulbaghia violacea has anticonvulsant activity. The results obtained also indicate that GABA, glutamic acid and glycine mechanisms may probably be involved in the anticonvulsant activity of the plant extract. The relatively high LD50 obtained for the plant species, given orally, indicate that it is safe in mice