Pergularia daemia hydro-ethanolic extract protects against pentylenetetrazole kindling-induced seizures, oxidative stress, and neuroinflammation in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Current 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 an hydro-ethanolic extract of the roots of P. daemia is more effective than an aqueous extract on refractory seizures. AIM OF THE STUDY: The antiepileptic effect of P. daemia hydro-ethanolic extract was investigated on the pentylenetetrazole kindling model of temporal lobe epilepsy in mice and possible mechanisms of action. MATERIALS AND METHODS: Mice were divided into 8 groups treated as follows: normal group received distilled water (10 ml/kg, p.o.), control group received distilled water (10 ml/kg, p.o.), ethanol group received ethanol (5%, p.o.), positive control received sodium valproate (300 mg/kg, p.o.), and test groups received P. daemia hydro-ethanolic (HE) extract (1.6, 4, 8 and 16 mg/kg, p.o.). All groups were kindled by 11 injections of pentylenetetrazole (PTZ) (35 mg/kg, i.p.), once every alternate day (48 ± 2 h), until the development of kindling, i.e., the occurrence of stage 5 seizures for two consecutive trials. One week later, i.e., 29th day, mice were challenged with a single and lower dose of PTZ (25 mg/kg, i.p.) that does not induce seizures in normal mice but causes seizures in mice prone to seizures and behavioral alterations. 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. RESULTS: PTZ-kindling induced myoclonic jerks and generalized tonic-clonic seizures in control mice. However, the HE extract of P. daemia (4-16 mg/kg), compared to sodium valproate, significantly protected mice against myoclonic jerks and generalized tonic-clonic seizures. Also, the HE extract (1.6-16 mg/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. CONCLUSIONS: The HE extract of P. daemia protected mice against kindled seizures and cognitive impairments, and these effects were greater than those of sodium valproate, a widely used antiepileptic drug. 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.

Pergularia daemia alters epileptogenesis and attenuates cognitive impairment in kainate-treated mice: Insight into anti-inflammatory mechanisms.

BACKGROUND: About 60% of temporal lobe epilepsies are drug resistant. Thus, medicinal plants are sources of new antiepileptic drugs. Pergularia daemia is used in Cameroon to treat pain, fever, arthritis, infections, and temporal lobe epilepsy. However, there are no scientific reports on the anti-inflammatory activity of P. daemia during epileptogenesis. OBJECTIVE: This study aimed at determining the involvement of the anti-inflammatory activity of P. daemia during epileptogenesis in kainate-treated mice. METHODS: Status epilepticus was induced in mice with kainate (15 mg/kg; i.p.). Those developing status epilepticus for 2 h were divided and treated once daily, for two weeks, with distilled water (10 ml/kg; p.o.), P. daemia extract (4.9, 12.3, 24.5, and 49 mg/kg; p.o.), and sodium valproate (300 mg/kg; i.p.) or aspirin (20 mg/kg; i.p.). One hour following the last treatment, the susceptibility of mice to seizures was assessed during epileptogenesis with pentylenetetrazole (40 mg/kg; i.p.). Then, mice were subjected to morris water maze, object recognition, and open-field tests. After completion of behavioral analysis, hippocampi and blood were collected for pro-inflammatory markers or histological analysis. RESULTS: The extract of P. daemia at all doses significantly reduced the latency and duration of seizures and increased seizure score. P. daemia (24.5 and 49 mg/kg) also prevented SE-induced cognitive impairment. Furthermore, the extract (24.5 and 49 mg/kg) markedly decreased tumor necrosis factor-α, interleukins-1ß, and -6 levels in hippocampi or serum. Histological analysis revealed that P. daemia attenuated neuronal loss in CA1 and CA3 areas of the hippocampus. CONCLUSIONS: These findings suggest that anti-inflammatory mechanisms are involved in the antiepileptogenic effect of P. daemia extract. This justifies therefore its use to treat epilepsy and inflammation in Cameroon traditional folk medicine.

Anticonvulsant effects of Senna spectabilis on seizures induced by chemicals and maximal electroshock.

Senna spectabilis (Fabaceae) is one of the medicinal plants used in Cameroon by traditional healers to treat epilepsy, constipation, insomnia, anxiety. The present study aimed to investigate the anticonvulsant effects of Senna spectabilis decoction on seizures induced by maximal electroshock (MES), pentylenetetrazole (PTZ), pilocarpine (PC) and its possible action mechanisms in animal models using flumazenil (FLU), methyl-ß-carboline-3-carboxylate (BC) and bicuculline (BIC). Senna spectabilis decoction (106.5 and 213.0mg/kg) antagonized completely tonic-clonic hind limbs of mice induced by MES. The lowest plant dose (42.6mg/kg) provided 100% of protection against seizures induced by PTZ (70mg/kg). Administration of different doses of the plant decoction antagonized seizures induced by PC up to 75%, causing a dose dependent protection and reduced significantly the mortality rate induced by this convulsant. Both FLU and BC antagonize strongly the anticonvulsant effects of this plant and are unable to reverse totally diazepam or the plant decoction effects on inhibiting seizures. The animals did not present any sign of acute toxicity even at higher doses of the plant decoction. In conclusion, Senna spectabilis possesses an anticonvulsant activity. We showed that its decoction protects significantly mice against seizures induced by chemicals and MES, delays the onset time and reduces mortality rate in seizures-induced. It also appears that the oral administration of the decoction of S. spectabilis is more active than the intraperitoneal administration of the ethanolic extract on inhibiting seizures induced by MES and PTZ. Moreover, the plant decoction could interact with GABAA complex receptor probably on the GABA and benzodiazepines sites.