Involvement of the Benzodiazepine Site in the Anticonvulsant Activity of Tapinanthus globiferus against Pentylenetetrazole-induced Seizures in Mice

Christianah A. Elusiyan; Ana Luiza Gonçalves Faria; Ane Emanuelle Queiroga Mendes; Iransé Oliveira Silva; José Luis Rodrigues Martins; Daniel Alves Rosa; Gustavo Rodrigues Pedrino; Elson Alves Costa; Mohamed Ali Ibrahim; Jordan K. Zjawiony; James Oluwagbamigbe Fajemiroye

doi:10.1055/a-1209-1254

Planta Medica, Table of Contents

Planta Med 2020; 86(16): 1204-1215
DOI: 10.1055/a-1209-1254

Biological and Pharmacological Activity

Original Papers

Involvement of the Benzodiazepine Site in the Anticonvulsant Activity of Tapinanthus globiferus against Pentylenetetrazole-induced Seizures in Mice

Christianah A. Elusiyan

¹Drug Research and Production Unit, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria

,

Ana Luiza Gonçalves Faria

²University center, UniEVANGÉLICA, Cidade Universitária, Anápolis, GO, Brazil

,

Ane Emanuelle Queiroga Mendes

²University center, UniEVANGÉLICA, Cidade Universitária, Anápolis, GO, Brazil

,

Iransé Oliveira Silva

²University center, UniEVANGÉLICA, Cidade Universitária, Anápolis, GO, Brazil

,

José Luis Rodrigues Martins

²University center, UniEVANGÉLICA, Cidade Universitária, Anápolis, GO, Brazil

,

Daniel Alves Rosa

³Department of Physiological Sciences, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil

,

Gustavo Rodrigues Pedrino

³Department of Physiological Sciences, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil

,

Elson Alves Costa

⁴Department of Pharmacology Sciences, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil

,

Mohamed Ali Ibrahim

⁵National Center for Natural Products Research, University of Mississippi, University, Mississippi, United States

,

Jordan K. Zjawiony

⁵National Center for Natural Products Research, University of Mississippi, University, Mississippi, United States

⁶Department of Biomolecular Sciences, School of Pharmacy, University of Mississippi, University, Mississippi, United States

,

James Oluwagbamigbe Fajemiroye

⁴Department of Pharmacology Sciences, Institute of Biological Sciences, Federal University of Goiás, Goiânia, GO, Brazil

› Author Affiliations

Abstract

Tapinanthus globiferus is often referred to as an all-purpose herb for the treatment of stroke and epilepsy. The present study investigates the anticonvulsant effect of methanolic leaf extract, active fractions, and lupeol (isolate) of Tapinanthus globiferus in mice as well as the underlying mechanisms. Following phytochemical studies of T. globiferus, preliminary assays were performed to evaluate MLE-induced toxic effect and behavioral changes. The pentylenetetrazol (70 mg/kg, i. p.)-induced seizure was evaluated in mice that were pretreated orally with vehicle 10 mL/kg, MLE (4, 20, or 100 mg/kg), fractions (F1 to F6), lupeol 10 mg/kg or diazepam (3 mg/kg). Methanolic leaf extract preserved neuron viability as well as the relative organ weight, and hematological and biochemical parameters. The behavioral endpoints, neuromuscular coordination, and sensory response parameters revealed a dose-dependent effect of methanolic leaf extract. This extract, active fractions, lupeol, and diazepam potentiated the hypno-sedative effect of the barbiturate and attenuated PTZ-induced acute seizure. This antiseizure effect was completely reversed by flumazenil 2 mg/kg (benzodiazepine site antagonist). Altogether, the benzodiazepine site-mediated anticonvulsant effects of methanolic leaf extract, active fractions, and lupeol corroborate traditional application of T. globiferus against epilepsy.

Key words

mistletoe - Tapinanthus globiferus - Loranthaceae - lupeol - antiseizure - γ-aminobutyric acid

Full Text

References

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