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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

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Abstract

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-1β and TGF-1 β. 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 β 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.

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Data Availability

The datasets generated during and/or analysed during the current study are adequately contained within the manuscript. Further information will be made available from the corresponding author on request from qualified investigators.

Change history

  • 18 July 2023

    The original article were updated due to removal of co-authors email addresses.

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Acknowledgements

The authors acknowledge the Research Unit of Animal Physiology and Phytopharmacology (URPAP) who hosted the present work.

Funding

Partial financial support was received by the International brain research organisation [IBRO Early Career grant] and the international society for neurochemistry [ISN CAEN − 1B] grants.

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Authors and Affiliations

  1. Animal Physiology and Phytopharmacology Research Unit, Department of Animal Biology, Faculty of Sciences, University of Dschang, P.O BOX: 67, Dschang, Cameroon

    Aurelien Fossueh Foutsop, Gilbert Ateufack, Chretien Mbeugangkeng Noungoua & Gwladys Temkou Ngoupaye

  2. Department of Biological Sciences, Faculty of Sciences, University of Maroua, P.O BOX: 814, Maroua, Cameroon

    Blesdel Maxwell Adassi, Tatiana Diebo Kom & Adolph Petsou

  3. Department of Biological Sciences, Faculty of Sciences, University of Ngaoundéré, P.O BOX: 454, Ngaoundéré, Cameroon

    Francis Bray Yassi

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  1. Aurelien Fossueh Foutsop
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Contributions

A.F.F. co-designed the work, and conducted the laboratory trials, data analysis, and manuscript writing as part of its PhD thesis. G.T. N. designed the work and supervised the experiments, data analysis, and manuscript writing. Material preparation and data collection were performed by A.F.F. assisted by M.B.A., F. B.Y., T. D. K., C.M.N., and A.P., and supervised by G.T.N. and G.A. The first draft of the manuscript was written by A.F.F. and G.T.N. and G. A. commented the previous version of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Gwladys Temkou Ngoupaye.

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The authors have no relevant financial or non-financial interest to disclose.

Ethics approval and consent to participate

Treatment of animals was done following the guidelines of the Cameroon bioethics committee (reg N. FWA IRB00001954) and in accordance with NIH-Care and use of laboratory animals manual, all of which are in line with Directives 2010/63/EU for animal experiments. Briefly, efforts were made to minimise animal suffering and to reduce the number of animal used in the experiment.

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Foutsop, A.F., Ateufack, G., Adassi, B.M. et al. 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. Neurochem Res 48, 3228–3248 (2023). https://doi.org/10.1007/s11064-023-03982-0

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