Anticonvulsant activity of Pseudospondias microcarpa (A. Rich) Engl. hydroethanolic leaf extract in mice: The role of excitatory/inhibitory neurotransmission and nitric oxide pathway

Donatus W Adongo; Priscilla K Mante; Kennedy K E Kukuia; Robert P Biney; Eric Boakye-Gyasi; Charles K Benneh; Elvis O Ameyaw; Eric Woode

doi:10.1016/j.jep.2017.05.017

Anticonvulsant activity of Pseudospondias microcarpa (A. Rich) Engl. hydroethanolic leaf extract in mice: The role of excitatory/inhibitory neurotransmission and nitric oxide pathway

J Ethnopharmacol. 2017 Jul 12:206:78-91. doi: 10.1016/j.jep.2017.05.017. Epub 2017 May 17.

Authors

Donatus W Adongo¹, Priscilla K Mante², Kennedy K E Kukuia³, Robert P Biney⁴, Eric Boakye-Gyasi⁵, Charles K Benneh⁶, Elvis O Ameyaw⁷, Eric Woode⁸

Affiliations

¹ Department of Pharmacology, School of Medicine, University of Health and Allied Sciences, Ho, Ghana. Electronic address: donatusadongo@yahoo.com.
² Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. Electronic address: pkmante.chs@knust.edu.gh.
³ Department of Pharmacology and Toxicology, University of Ghana School of Pharmacy, University of Ghana, Accra, Ghana. Electronic address: edemkennedy@yahoo.com.
⁴ Department of Pharmacology, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana. Electronic address: rpbiney@hotmail.com.
⁵ Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. Electronic address: ebgyasi.pharm@knust.edu.gh.
⁶ Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. Electronic address: benneh.ck@outlook.com.
⁷ Department of Biomedical and Forensic Sciences, School of Biological Science, University of Cape Coast, Cape Coast, Ghana. Electronic address: elvisameyaw@gmail.com.
⁸ Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, College of Health Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. Electronic address: ewoode.pharm@knust.edu.gh.

PMID: 28528187
DOI: 10.1016/j.jep.2017.05.017

Abstract

Ethnopharmacological relevance: Pseudospondias microcarpa (A. Rich) Engl. is a plant used for managing various diseases including central nervous system disorders.

Aim of the study: This study explored the anticonvulsant activity of P. microcarpa hydroethanolic leaf extract (PME) as well as possible mechanism(s) of action in animal models.

Methods: Effects of PME was assessed in electroconvulsive (the maximal electroshock and 6-Hz seizures) and chemoconvulsive (pentylenetetrazole-, picrotoxin-, isoniazid-, 4-aminopyridine-, and strychnine-induced seizures) models of epilepsy. In addition, effect of the extract on the nitric oxide pathway and GABA_A receptor complex was evaluated.

Results: The extract (30, 100 and 300mgkg^-1, p.o.) significantly delayed the onset as well as decreased the duration and frequency of pentylenetetrazole-, picrotoxin- and strychnine-induced seizures. In addition, PME pre-treatment significantly improved survival in the 4-aminopyridine- and isoniazid-induced seizure tests. Furthermore, the extract protected against 6-Hz psychomotor seizures but had no effect in the maximal electroshock test. The anticonvulsant effect of PME (100mgkg^-1, p.o.) was also reversed by pre-treatment with flumazenil, L-arginine or sildenafil. However, L-NAME or methylene blue (MB) augmented its effect.

Conclusion: Results show that PME has anticonvulsant activity and may probably be affecting GABAergic, glycinergic, NMDA, K⁺ channels and nitric oxide-cGMP pathways to exert its effect.

Keywords: 4-AP (PubChem CID: 1727); Anticonvulsant; Carbamazepine (PubChem CID: 2554); Diazepam (PubChem CID: 3016); Isoniazid (PubChem CID: 3767); L-Arginine (PubChem CID: 6322); L-NAME (PubChem CID: 39836); Methylene blue (PubChem CID: 6099); Nitric oxide (NO); Pentylenetetrazole (PTZ); Pentylenetetrazole (PubChem CID: 73422); Picrotoxin (PubChem CID: 5311359); Pseudospondias microcarpa; Psychomotor seizures; Sildenafil (PubChem CID: 5212); Strychnine (PubChem CID: 441079); Valproic acid (PubChem CID: 16760703).

MeSH terms

Anacardiaceae / chemistry*
Animals
Anticonvulsants / pharmacology*
Anticonvulsants / therapeutic use
Dose-Response Relationship, Drug
Ethanol
Male
Mice
Mice, Inbred ICR
Nitric Oxide / metabolism*
Plant Extracts / pharmacology*
Plant Extracts / therapeutic use
Plant Leaves / chemistry*
Seizures / chemically induced
Seizures / drug therapy
Spectroscopy, Fourier Transform Infrared
Synaptic Transmission / drug effects*

Substances

Anticonvulsants
Plant Extracts
Nitric Oxide
Ethanol