Ameliorative effects of Albizia adianthifolia aqueous extract against pentylenetetrazole-induced epilepsy and associated memory loss in mice: Role of GABAergic, antioxidant defense and anti-inflammatory systems.

Albizia adianthifolia (Schumach.) (Fabaceae) is a medicinal herb used for the treatment of epilepsy and memory impairment. This study aims to investigate the anticonvulsant effects of Albizia adianthifolia aqueous extract against pentylenetetrazole (PTZ)-induced spontaneous convulsions in mice; and determine whether the extract could mitigate memory impairment, oxidative/nitrergic stress, GABA depletion and neuroinflammation. Ultra-high performance liquid chromatography/mass spectrometry analysis was done to identify active compounds from the extract. Mice were injected with PTZ once every 48 h until kindling was developed. Animals received distilled water for the normal group and negative control groups, doses of extract (40, 80, or 160 mg/kg) for the test groups and sodium valproate (300 mg/kg) for the positive control group. Memory was measured using Y maze, novel object recognition (NOR) and open field paradigms, while the oxidative/nitrosative stresses (MDA, GSH, CAT, SOD and NO), GABAergic transmission (GABA, GABA-T and GAD) and neuro-inflammation (TNF-α, IFN-γ, IL- 1β, and IL-6) were determined. Brain photomicrograph was also studied. Apigenin, murrayanine and safranal were identified in the extract. The extract (80-160 mg/kg) significantly protected mice against seizures and mortality induced by PTZ. The extract significantly increased the spontaneous alternation and the discrimination index in the Y maze and NOR tests, respectively. PTZ kindling induced oxidative/nitrosative stress, GABA depletion, neuroinflammation and neuronal cells death was strongly reversed by the extract. The results suggest that the anticonvulsant activity of Albizia adianthifolia extract is accompanied by its anti-amnesic property, and may be supported by the amelioration of oxidative stress, GABAergic transmission and neuroinflammation.