NANOFORMULATED OMEGA-5 POMEGRANATE SEED OIL ATTENUATES SEIZURE SEVERITY AND GLIAL REACTIVITY IN A PTZ-INDUCED MOUSE MODEL

Pomegranate-derived compounds have emerged as promising neuroprotective agents due to their antioxidant and anti-inflammatory properties. In murine models, pomegranate extracts reduce seizure frequency and severity as well as seizure-associated oxidative stress. Punicic acid, the main omega-5 fatty acid present in pomegranate seed oil, modulates GABAergic neurotransmission and limits neuroinflammatory responses, suggesting a potential role in seizure control. However, poor bioavailability has limited its translational application. Advanced nanoformulations may enhance therapeutic efficacy by improving stability and brain availability. Here, we investigated the effects of a nanoformulated omega-5 pomegranate seed oil, GranaGard® (GRG), on seizure activity and glial reactivity in an acute pentylenetetrazol (PTZ)-induced seizure model. Twenty-eight male CD1 (ICR) mice were randomly assigned to four groups: control, GRG, PTZ, and PTZ + GRG. GRG was administered intragastrically for five weeks prior to seizure induction. Seizure severity was evaluated using a standardized behavioral scale. Astrocytic and microglial activation were assessed by immunofluorescence, together with Western blot analysis of GFAP and Iba1 protein expression. GRG treatment significantly attenuated PTZ-induced seizure severity and markedly reduced astrocytic and microglial reactivity, as evidenced by decreased immunoreactivity and protein expression of GFAP and Iba1. These findings indicate that nanoformulated omega-5 pomegranate seed oil exerts anticonvulsant and anti-neuroinflammatory effects, likely through modulation of glial activation. Overall, our results support nanoformulated pomegranate seed oil as a promising antioxidant and anti-inflammatory strategy to complement current therapeutic approaches for epilepsy.
Acknowledgements: This work was supported by Universidad de Guadalajara and by partial funding from Distribuidora BioLife S.A. de C.V.