The antiepileptic potential of Vateria indica Linn in experimental animal models: Effect on brain GABA levels and molecular mechanisms

Abstract

Background: Epilepsy is a neurodegenerative condition characterized by uncontrollable convulsions caused by a misalignment of the central nervous system's inhibitory and excitatory branches. Vateria indica is a medicinal herb with anti-inflammatory, anthelmintic, antiulcer, antitumor, and anticancer properties.

Objectives: To investigate the antiepileptic activity of Vateria indica using maximal electrical shock (MES), pentylenetetrazole (PTZ), and isoniazid (INH) induced experimental animal models.

Methodology: Vateria indica bark was subjected to Soxhlet extraction using ethanol and quantitative and qualitative analysis was performed. The antiepileptic activity of Vateria indica bark extract (VIE) was investigated using different animal models in mice. GABA levels in the brain and antioxidant capacity in vitro were estimated.

Results: Treatment of mice with VIE significantly reversed the MES-induced convulsions, which was reflected by the decrease in the duration (sec) of all the phases of MES-induced convulsions, with an increment in the GABA levels. In the PTZ and INH models, pretreatment with VIE delayed the latency to clonic convulsions (p 0.001), reduced the intensity and duration of clonic convulsions, and reduced the mortality rate in the treatment groups in a dose-dependent manner. VIE intervention dose-dependently restored brain GABA levels. VIE also exhibited significant in-vitro antioxidant activity.

Conclusion: Overall, the findings imply that Vateria indica has substantial antiepileptic activities, mediated by positive GABAergic neurotransmission and antioxidant capabilities. To summarize, Vateria indica may provide adequate protection against epileptic seizures, suggesting that it could be used to treat petitmal and grandmal epilepsy. We plan to provide pure lead compounds derived from Vateria indica in the future in order to better understand the role it could play in the development of natural anticonvulsant drugs.

Keywords: Antiepileptic; Antioxidant; Epilepsy; GABA; Vateria indica.

Fig. 1

FTIR and Mass spectra of Vateria indica ethanolic extract.

Fig. 2

Effect of VIE on MES-induced convulsions and GABA. Values are expressed as Mean ± SEM for 6 animals per group.*P < 0.05; **P < 0.01; ***P < 0.001 compared with positive control; # P < 0.001 compared to normal control.

Fig. 3

Effect of VIE on INH-induced seizure activity and GABA levels in mice. Values are expressed as Mean ± SEM for 6 animals per group.*P < 0.05; **P < 0.01; ***P < 0.001 compared with positive control; # P < 0.001 compared to normal control.

Fig. 4

Effect of VIE on PTZ-induced seizure activity and GABA. Values are expressed as Mean ± SEM for 6 animals per group.*P < 0.05; **P < 0.01; ***P < 0.001 compared with positive control; # P < 0.001 compared to normal control.

Fig. 5

Photomicrographs of mice brain tissue (40x) in PTZ-model (A-series); INH-model (B-series); MES-model (C-series). 1) Normal control; 2) Positive control; 3) Standard; 4) VIE 250 mg/Kg; 5) VIE 500 mg/Kg.