Prof. Engidawork, EphremDesalegn, Tesfaye2022-06-202023-11-062022-06-202023-11-062021-11http://etd.aau.edu.et/handle/123456789/32068Epilepsy is one of the most common chronic neurological conditions that affect 70 million people in different parts of the world. The leaves of Ajuga integrifolia Buch.ham ex D Don have been used as anti-convulsant remedy in Ethiopian traditional medicine. However, the evidence supporting this claim is sparse in the literature. This study was conducted to add to the existing body of knowledge about the anti-convulsant activity of the plant. To this effect successive Soxhlet extraction was performed using n-hexane, ethyl acetate, methanol and water. Anti-convulsant activity of the extracts was investigated in both acute (pentylenetetrazole, PTZ; and maximal electroshock, MES) and chronic (PTZ kindling) seizure models. For the acute model, various doses of the extract (100mg/kg, 200mg/kg and 400mg/kg) were administered. Positive controls received sodium valproate (200mg/kg) for PTZ and phenytoin (25mg/kg) for MES. Distilled water or 2% tween 80 was used for negative controls. Kindling was induced by repeated alternate day intra-peritoneal administration of sub-convulsive dose of PTZ (35 mg/kg) for 13 days and the most active extract (ethyl acetate) was tested in this model. Parameters including onset of clonus and duration of hind limb tonic extension were recorded. Moreover, total alkaloid, flavonoid and phenol contents of the most active extract were determined. Treatment of mice with ethyl acetate extract produced a superior effect among all solvent extracts in both PTZ and MES model. The mean latency to clonic seizure was significantly increased (p<0.01) with all doses of ethyl acetate extract in PTZ test compared to control and n.hexane extract ranked next to ethyl acetate extract in increasing onset of clonus. It significantly increased mean onset of clonus compared to controls, with a maximum increase (12.67min, p<0.001) displayed by HA400 mg/kg. Methanol extract at 200mg/kg and 400 mg/kg also significantly delayed onset of clonus (p<0.001) in PTZ model.Once again, all doses of ethyl acetate extract of the study plant significantly reduced (p<0.001) the mean duration of hind limb tonic extension in MES test compared to control. Hexane extract at 200 mg/kg and 400 mg/kg also significantly reduced (p<0.001) duration of hind limb tonic extension. Methanol extract at 200mg/kg and 400 mg/kg also significantly reduced (p<0.01) mean duration of hind limb tonic extension (HLTE) compared to control in MES test. Aqueous extract at all doses was devoid of any anti-convulsant effect in both models. A similar type of study done on the leaf crude extract and solvent fractions collected from different geographical location also reported anti-convulsant activity of the plant in acute seizure models. Treatment of mice with 200mg/kg and 400mg/kg of ethyl acetate extract along with alternate day PTZ injection significantly protected(p<0.01 for 200mg/kg and p<0.001 for 400 mg/kg) against PTZ induced kindling compared to controls in chronic model. Ethyl acetate extract of the plant was found to contain 10.002±0.119 mg atropine equivalent per gram of dry extract of alkaloids, 9.045 ±0.8445 mg quercetin equivalent /g of dry weight extract of flavonoids and 21.928 ±1.118 mg gallic acid equivalent / g of dry weight of extract of phenols. This study indicated that the plant has anti-convulsant activity in both acute and chronic model and it could be a potential source to develop a new anti epileptic drug for pharmacoresistant epilepsy.en-USAjuga integrifolia, Anti-convulsant, Epilepsy, kindling, phytoconstituents, SeizureThesis