The Aqueous Lyophilisate of Alchemilla Kiwuensis Engl. (Rosaceae) Displays Antiepileptogenic and Antiepileptic Effects on PTZ-induced Kindling in rats: Evidence of Modulation of Glutamatergic and GABAergic Pathways Coupled to Antioxidant Properties

Alchemilla kiwuensis Engl. (Rosaceae) (A. kiwuensis) is an herbaceous plant traditionally used by Cameroonians to treat epilepsy and other central nervous system disorders. The present study evaluated the antiepileptogenic and antiepileptic effects of A. kiwuensis (40 mg/kg, 80 mg/kg) following Pentylenetetrazole (PTZ)-induced kindling as well as its sub-chronic toxicity. Following an initial i.p administration of a challenge dose (70 mg/kg), Wistar rats of both sexes received sub convulsive doses (35 mg/kg) of PTZ every other day, one hour after the oral gavage of animals with treatments, until two consecutive stage 4, in all animals of negative control. Seizure progression, latency, duration, and repetition were noted. Twenty-four hours later, animals were dissected to extract their hippocampi. The resulting homogenates were used to evaluate Malondialdehyde, reduced glutathione, catalase activity, GABA, GABA-Transaminase, glutamate, glutamate transporter 2, IL-1 & beta; and TGF-1 & beta;. Sub-chronic toxicity was conducted according to OECD 407 guidelines. The lyophilisate of A. kiwuensis significantly increased the latency of seizure appearance, delayed seizure progression and decreased seizure repetition and duration. Biochemical analysis revealed that the lyophilisate significantly increased the catalase activity, reduced glutathione, GABA, glutamate transporter 2 and TGF-1B levels. The lyophilisate equally caused a significant decreased in the GABA-Transaminase activity, malondialdehyde, and IL-1 & beta; levels. There was no noticeable sign of toxicity. A. kiwuensis possesses antiepileptic and antiepiletogenic effects by enhancing GABAergic neurotransmission and antioxidant properties, coupled to modulation of glutamatergic and neuroinflammatory pathways and is innocuous in a sub-chronic model. These justifies its local use for the treatment of epilepsy.