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

Abstract

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. Lantana camara 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 Lantana camara 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 status epilepticus, 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, p.o.), levetiracetam (80 mg/kg, p.o.), sodium valproate (300 mg/kg, p.o.), ethanolic extract of L. camara (230, 460, 920 mg/kg, p.o.), or an aqueous extract of L. camara (460 mg/kg p.o.). 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 L. camara effectively attenuate seizures and anxiety disorders. Probable mechanisms of action include GABAergic, iron, GSH, and MDA modulations.