Aframomum melegueta mitigates seizure severity and neuroinflammation via gut-brain axis modulation in PTZ-induced kindling

Abstract Background This study investigates the anticonvulsant properties of Aframomum melegueta in pentylenetetrazole (PTZ)-induced kindling in rats, emphasizing on its effects on the gut-brain axis, inflammatory pathways, and metabolomic profiles. Given the established links between the brain and gut through bidirectional communication and their collective role in epilepsy pathophysiology, this research aims to explore the therapeutic potential of the ethanolic extract of Aframomum melegueta (AM) in modulating these interactions. Results PTZ (40 mg/kg) was given to rats to induce kindling. Animals also, underwent chronic drug treatments of AM and sodium valproate (VPA) which were administered during the induction of kindling. Animals were observed for stages of seizure development. Inflammatory mediators, neurotransmitters, and cortisol concentration were assessed in the brain and serum of the rats post-kindling using NMR-based metabolomics and ELISA assays. Findings suggest that seizures were less severe and less frequent in Aframomum melegueta treated rats. Pretreatment with AM at doses, 30, 100, and 300 mg/kg delayed the effect of PTZ on seizure development (P < 0.05). AM treatment also reversed neuroinflammatory changes by lowering (p < 0.0001) IL-6 and TNF-α levels. In addition, metabolomic profiling established that Aframomum melegueta affected neurotransmitter synthesis of glutamate as well as serotonin, acetate, propionate and cortisol, similar to what was observed in VPA (p < 0.05). Conclusion Therefore, the findings of the present study suggest that AM may be useful in the management of epilepsy through its influence on the brain-gut axis and by suppressing inflammation and other metabolic processes in PTZ-induced kindling.