Ethanolic and aqueous extracts of Lantana camara show antiepileptic and anxiolytic effects by inhibiting the ferroptosis pathway in kainate-treated mice

In Cameroon, epilepsy is one of the most common neurological diseases. Available anti-epileptic medication, on the other hand, have been associated with pharmacological toxicity and emotional impairment. The identification of a more efficient replacement is critical. Recent research reveals that ferroptosis contributes to the pathophysiology of epilepsy and related anxiety disorders. <i>Lantana camara</i> is a plant with a high neuropharmacological potential, but its mechanisms of action have yet to be understood. The purpose of this study was to determine the effect of ethanolic and aqueous extracts of <i>Lantana camara</i> on the kainate model of epilepsy in mice. The focus was on these extracts' capacity to suppress ferroptosis. Mice were injected with kainate (12 mg/kg, i.p.) to induce epilepsy. After <i>status epilepticus</i>, animals were left for 19 days, which correspond to an epileptogenic period. After the appearance of spontaneous recurrent seizures, mice were treated with distilled water (10 ml/kg, <i>p.o</i>.), levetiracetam (80 mg/kg, <i>p.o.</i>), sodium valproate (300 mg/kg, <i>p.o.</i>), ethanolic extract of <i>L. camara</i> (230, 460, 920 mg/kg, <i>p.o.</i>), or an aqueous extract of <i>L. camara</i> (460 mg/kg <i>p.o.</i>). These treatments lasted for 14 days. During this period, the number and duration of seizures were recorded. The mice were then subjected to elevated zero-maze and open field tests to assess anxiety-like behavior. At the end, mice were sacrificed and hippocampus, amygdala, and striatum were dissected out for biochemical and histological analyses. The extracts alleviated seizure- and anxiety-like behavior in KA-treated mice. Decreased iron levels, reflected by a decrease in ferritin levels and a increase in transferrin levels, were observed in the hippocampus, striatum and amygdala of the extract-treated group compared to the KA-treated group. In addition, increase in GABA and GSH levels, and a decrease in MDA levels were observed in these groups. Hematoxylin-eosin staining revealed less pronounced neuronal degeneration and a more sustained architecture in the brain region of extract-treated mice. These findings indicated that ethanolic and aqueous extracts of <i>L. camara</i> effectively attenuate seizures and anxiety disorders. Probable mechanisms of action include GABAergic, iron, GSH, and MDA modulations.