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Articles

Methanolic Stem Extract of Colebrookea oppositifolia Attenuates Epilepsy in Experimental Animal Models: Possible Role of GABA Pathways

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Pages 44-58 | Received 11 Feb 2020, Accepted 04 Mar 2020, Published online: 03 Apr 2020
 

Abstract

The current study aims to evaluate the methanolic stem extract of Colebrookea oppositifolia (MsCO) for its anticonvulsant property and its role in GABA pathways. Initially, the PsCO (petroleum ether), MsCo, and AsCO (aqueous) extracts of C. oppositifolia were evaluated in Six -hertz seizure test. Later, the potent extract was evaluated on MES, PTZ and NMDA models to explore the possible mechanisms of action. In addition, the potent extract was evaluated for its locomotor deficit inducing potential in actophotometer test. In the Six-hertz (6-Hz) seizure test, MsCO showed the most potent and dose-dependent anticonvulsant activity, and as per the pre-defined criteria, it was further evaluated in other models to explore its mechanisms of action. Interestingly, the MsCO at doses 25 (p<0.05), 50 (p<0.01), 100 (p<0.01) and 200 mg/kg (p<0.01), doses showed significant protection in both MES and PTZ models; however, there was no protection in the NMDA-induced mortality test. Based on these outcomes, the MsCO (25, 50, 100 and 200 mg/kg) was further evaluated in the PTZ model to confirm the involvement of GABA pathways, the levels of GABA in the cortex and hippocampus were measured, and also to confirm the GABA receptor mediated action, the anti-PTZ action of MsCO (100 mg/kg) was evaluated in presence of flumazenil, which is a GABAA receptor antagonist. In the outcomes, the MsCO (100 and 200 mg/kg) administration showed a significant increase in GABA levels in both cortex (p<0.01) and hippocampus (p<0.01), compared to PTZ control. Also, the anticonvulsant action of MsCO was blocked in the presence of flumazenil, thus confirmed the possible role of GABA mechanism. Moreover, actophotometer test revealed that MsCO (25, 50, 100 and 200 mg/kg) is free from locomotor deficit-inducing potential. Thus, the results of the study indicate that MsCO possesses potent anticonvulsant activity through GABA mediated mechanism.

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