Journal of ethnopharmacology | 2021
Pergularia daemia hydro-ethanolic extract protects against pentylenetetrazole kindling-induced seizures, oxidative stress, and neuroinflammation in mice.
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE\nCurrent antiepileptic drugs fail to control approximately 30% of epilepsies. Therefore, there is a need to develop more effective antiepileptic drugs, and medicinal plants provide an attractive source for new compounds. Pergularia daemia (Asclepiadaceae) is used in Cameroon traditional medicine to treat stroke, anemia, inflammation, and epilepsy. Recently, traditional healers claim that the hydro-ethanolic extract of the roots of P. daemia is more effective than the aqueous extract on refractory seizures.\n\n\nAIM OF THE STUDY\nThe antiepileptic effect of P. daemia hydro-ethanolic extract was investigated on the pentylenetetrazole kindling model of temporal lobe epilepsy in mice.\n\n\nMATERIALS AND METHODS\nMice were divided into 8 groups treated as follows: normal group with distilled water (10\u202fml/kg, p.o.), control group with distilled water (10\u202fml/kg, p.o.), ethanol group with ethanol (5%, p.o.), positive control with sodium valproate (300\u202fmg/kg, p.o.), and test groups with P. daemia hydro-ethanolic (HE) extract (1.6, 4, 8 and 16\u202fmg/kg, p.o.). All groups were kindled by 11 injections of pentylenetetrazole (PTZ) (35\u202fmg/kg, i.p.), once every alternate day (48\u202f±\u202f2\u202fh), until the development of kindling, i.e., the occurrence of stage 5 seizures for two consecutive trials. In the 12th injection, mice were challenged with PTZ (25\u202fmg/kg, i.p.) to assess their susceptibility to seizures. After completion of the kindling procedure, Morris water maze, passive avoidance, and open field tests were performed. Afterward, animals were euthanized, and hippocampi were removed for the estimation of the levels of GABA-transaminase (GABA-T), L-glutamate decarboxylase (L-GAD), and γ-aminobutyric acid (GABA). Oxidative stress and neuroinflammation markers also were quantified. Finally, histological analysis of the hippocampus was carried out.\n\n\nRESULTS\nThe HE extract of P. daemia (4-16\u202fmg/kg), compared to sodium valproate, significantly protected mice against myoclonic jerks and generalized tonic-clonic seizures. Also, the HE extract (1.6-16\u202fmg/kg) significantly increased the seizure score. Furthermore, the HE extract of P. daemia significantly reduced seizure-induced cognitive impairments. PTZ-kindling induced significant alterations in GABA, GABA-T, and L-GAD contents as well as oxidative stress, and neuroinflammation, and the HE extract significantly reversed these effects, suggesting possible mechanisms. All these activities of the HE extract were confirmed by its protective effect against neuronal loss in the hippocampus.\n\n\nCONCLUSIONS\nThe HE extract of P. daemia protected mice against kindled seizures and cognitive impairments when compared to sodium valproate. These effects may be mediated by neuromodulatory, anti-oxidant, and anti-inflammatory activities, thus suggesting a neuroprotective effect. These findings help to explain the beneficial use of these HE extracts of P.daemia in traditional medicine to treat epilepsy in Cameroon.