Synedrella nodiflora Extract Depresses Excitatory Synaptic Transmission and Chemically-Induced In Vitro Seizures in the Rat Hippocampus

Patrick Amoateng 1, Thomas A Tagoe 2, Thomas K Karikari 3, Kennedy K E Kukuia 4, Dorcas Osei-Safo 5, Eric Woode 6, Bruno G Frenguelli 7, Samuel B Kombian 8 9

Affiliations

08 March 2021

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doi: 10.3389/fphar.2021.610025

Abstract

Extracts of the tropical Cinderella plant Synedrella nodiflora are used traditionally to manage convulsive conditions in the West African sub-region. This study sought to determine the neuronal basis of the effectiveness of these plant extracts to suppress seizure activity. Using the hippocampal slice preparation from rats, the ability of the extract to depress excitatory synaptic transmission and in vitro seizure activity were investigated. Bath perfusion of the hydro-ethanolic extract of Synedrella nodiflora (SNE) caused a concentration-dependent depression of evoked field excitatory postsynaptic potentials (fEPSPs) recorded extracellularly in the CA1 region of the hippocampus with maximal depression of about 80% and an estimated IC50 of 0.06 mg/ml. The SNE-induced fEPSP depression was accompanied by an increase in paired pulse facilitation. The fEPSP depression only recovered partially after 20 min washing out. The effect of SNE was not stimulus dependent as it was present even in the absence of synaptic stimulation. Furthermore, it did not show desensitization as repeat application after 10 min washout produced the same level of fEPSP depression as the first application. The SNE effect on fEPSPs was not via adenosine release as it was neither blocked nor reversed by 8-CPT, an adenosine A1 receptor antagonist. In addition, SNE depressed in vitro seizures induced by zero Mg2+ and high K+ -containing artificial cerebrospinal fluid (aCSF) in a concentration-dependent manner. The results show that SNE depresses fEPSPs and spontaneous bursting activity in hippocampal neurons that may underlie its ability to abort convulsive activity in persons with epilepsy.

Keywords: SNE; adenosine; field excitatory postsynaptic potentials; hippocampal slices; seizure.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1 High performance liquid chromatography chromatogram of SNE monitored at 315 nm.

FIGURE 1 High performance liquid chromatography chromatogram of SNE monitored at 315 nm.

FIGURE 2 (A) Effect of SNE (0.01, 0.1 and 1.0 mg/ml) on slope of fEPSPs in rat hippocampal slices after a stable baseline perfused with normal aCSF. (B) The bar graph represents the total effect (calculated as AUCs from the graph above). (C) Concentration-response curve from SNE (0.01, 0.1, and 1.0 mg/ml) on slope of fEPSPs. Data is mean ± SEM (n = 5). ***p < 0.001 compared with baseline, one-way ANOVA followed by a Dunnett’s multiple comparison test. show full caption

FIGURE 2 (A) Effect of SNE (0.01, 0.1 and 1.0 mg/ml) on slope of fEPSPs in rat hippocampal slices after a stable baseline perfused with normal aCSF. (B) The bar graph represents the total effect (calculated as AUCs from the graph above). (C) Concentration-response curve from SNE (0.01, 0.1, and 1.0 mg/ml) on slope of fEPSPs. Data is mean ± SEM (n = 5). ***p < 0.001 compared with baseline, one-way ANOVA followed by a Dunnett’s multiple comparison test. show full caption

FIGURE 3 (A) A typical recording of paired fEPSP showing pair-pulse facilitation (B) Effect of SNE (0.01, 0.1, and 1.0 mg/ml) on paired pulse ratio in rat hippocampal slices after a stable baseline perfused with normal aCSF. Data is mean ± SEM (n = 5). ***p < 0.001 compared with baseline, one-way ANOVA followed by a Dunnett’s multiple comparison test.

FIGURE 3 (A) A typical recording of paired fEPSP showing pair-pulse facilitation (B) Effect of SNE (0.01, 0.1, and 1.0 mg/ml) on paired pulse ratio in rat hippocampal slices after a stable baseline perfused with normal aCSF. Data is mean ± SEM (n = 5). ***p < 0.001 compared with baseline, one-way ANOVA followed by a Dunnett’s multiple comparison test.

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