Capparis sepiaria's root bark aqueous lyophilisate shows antiamnesic properties on scopolamine induce cognitive impairment in mice.

Capparis sepiaria (Capparaceae) is a plant used in African traditional medicine to treat psychiatic disorders. The aim of this study was to assess the anti-amnesic effect of aqueous lyophilisate of the root bark of Capparis sepiaria (C. sepiaria) on scopolamine-induced animal model of memory impairment using Swiss albino adult mice of both sexes. Memory integrity was assessed by Morris water Maze test, Novel Object Recognition (NOR) and Object-location memory (OLT) tasks were used to assess behavioural components of memory processes and learning. Malondialdehyde (MDA), reduced glutathione (GSH), NO levels and catalase were used to assess oxidative stress while acethylcholinesterase activity was used to evaluate acetylcholine activity in the hippocampus tissues. The quantitative phytochemistry and acute toxicity of the roots of C. sepiaria were also evaluated. The aqueous lyophilisate of C. sepiaria at doses of 10 mg/kg and 40 mg/kg significantly increased the discrimination index in the Morris Water Maze and the objet location tasks. The aqueous lyophilisate of C. sepiaria significantly increased hippocampal GSH and catalase levels and decreased hippocampal MDA, NO levels and achetylcholinesterase (AChE) activities. The aqueous lyophilisate of C. sepiaria showed no acute toxicity with a LD50 > 5000 mg/kg, and revealed a content of flavonoids, tannins and phenols. These results suggest that C. sepiaria improve memory impairment induced by scopolamine and therefore possess antiamnesic properties. These properties would result from a modulation of cholinergic neurotransmission as well as an antioxidant activity of the plant.

Revealing the most effective anticonvulsant part of Malvaviscus arboreus Dill. Ex Cav. and its acute and sub-acute toxicity.

ETHNOPHARMACOLOGY RELEVANCE: Different parts of Malvaviscus arboreus Dill. Ex Cav. (M. arboreus) are traditionally used in the West Region of Cameroon to treat many diseases, including epilepsy. AIM OF THE STUDY: To determine which part of M. arboreus offers the best anticonvulsant effect, and to assess the acute and sub-acute toxicity of the part of interest. MATERIALS AND METHODS: the anticonvulsant effect of the aqueous lyophilisate of the decoction of flowers, leaves, stems and roots of M. arboreus at various doses was evaluated and compared on the model of acute epileptic seizures induced by pentylenetetrazole (PTZ) (70 mg/kg), injected 1 h after oral administration of the various extracts. Out of these plant parts, the leaves were then selected to prepare the hydroethanolic extract and its anticonvulsant effect against PTZ at the doses of 122.5, 245 and 490 mg/kg, as well as its acute toxicity were compared with those of the aqueous lyophilisate of the leaves. The anticonvulsant effect of the aqueous lyophilisate of M. arboreus leaves was further evaluated on models of acute epileptic seizures induced by picrotoxin (PIC) (7.5 mg/kg), strychnine (STR) (2.5 mg/kg) and pilocarpine (350 mg/kg). The 28 days sub-acute toxicity, as well as the quantitative phytochemistry and the in vitro antioxidant potential (FRAP, DPPH, ABTS+) of the aqueous lyophilisate of the leaves of M. arboreus were also evaluated. RESULTS: M. arboreus leaves showed the best anticonvulsant effect and the aqueous lyophilisate was the best extract. The latter significantly protected the animals against convulsions induced by PTZ (71.43%) (p < 0.01), PIC (57.14%) (p < 0.05) and STR (42%) and had no effect on pilocarpine-induced seizures. Furthermore, it showed no acute or sub-acute toxicity, and revealed a high content of flavonoids, saponins, tannins and alkaloids, and antioxidant activity in vitro. CONCLUSION: The aqueous lyophilisate of the leaves of M. arboreus offers the best anticonvulsant effect on the extraction solvent used, and it would act mainly via a potentiation of the inhibitory systems of the brain (GABA, Glycine). In addition, its richness in bioactive compounds gives it an antioxidant potential, and it is not toxic in acute and sub-acute toxicity. All this justifies at least in part its empirical uses, and makes M. arboreus a candidate for the alternative treatment of epilepsy.

Dichrocephala integrifolia Aqueous Extract Antagonises Chronic and Binges Ethanol Feeding-Induced Memory Dysfunctions: Insights into Antioxidant and Anti-Inflammatory Mechanisms.

Ethanol consumption is widely accepted despite its addictive properties and its mind-altering effects. This study aimed to assess the effects of Dichrocephala integrifolia against, memory impairment, on a mouse model of chronic and binges ethanol feeding. Mice were divided, into groups of 8 animals each, and received distilled water, Dichrocephala integrifolia aqueous extract (25; 50; 100; or 200 mg/kg) or memantine (200 mg/kg) once a day, while fe, with Lieber-DeCarli control (sham group only) or Lieber-DeCarli ethanol diet ad libitum for 28 days. The Y maze and the novel object recognition (NOR) tests were used to evaluate spatial short-term and recognition memory, respectively. Malondialdehyde, nitric oxide, glutathione levels, and proinflammatory cytokines (Il-1ß, TNF-α, and Il-6) were evaluated in brain homogenates following behavioral assessments. The results showed that chronic ethanol administration in mice was associated with a significant (p < 0.001) reduction in the spontaneous alternation percentage and the discrimination index, in the Y maze and the NOR tests, respectively. It significantly (p < 0.01) increased oxidative stress and inflammation markers levels in the brain. Dichrocephala integrifolia (100 and 200 mg/kg) as well as memantine (200 mg/kg) significantly (p < 0.001) increased the percentage of spontaneous alternation and the discrimination index, in the Y maze and NOR tests, respectively. Dichrocephala integrifolia (100 and 200 mg/kg) likewise memantine (200 mg/kg) significantly (p < 0.01) alleviated ethanol-induced increase, in the brain malondialdehyde level, nitric oxide, Il-1ß, TNF-α, and Il-6. From these findings, it can be concluded that Dichrocephala integrifolia counteracted memory impairment, oxidative stress, and neuroinflammation induced by chronic ethanol consumption in mice.

Protective Effects of Anthocleista djalonensis Extracts against Pentylenetetrazole-Induced Epileptic Seizures and Neuronal Cell Loss: Role of Antioxidant Defense System.

Oxidative stress and neurodegeneration are involved in the initiation of epileptogenesis and progression of epileptic seizures. This study was aimed at investigating the anticonvulsant, antioxidant, and neuroprotective properties of active fractions isolated from Anthocleista djalonensis root barks in pentylenetetrazole mouse models of epileptic seizures. Bioactive-guided fractionation of Anthocleista djalonensis (AFAD) extracts using acute pentylenetetrazole (90 mg/kg) induced generalised tonic-clonic seizures, which afforded a potent anticonvulsant fraction (FPool 5). Further fractionation of AFAD was performed by high-performance liquid chromatography, which yielded fifteen subfractions, which were chemically characterised. In addition, AFAD was tested against convulsions or spontaneous kindled seizures induced, respectively, by acute (50 mg/kg) or subchronic (30 mg/kg) injection of pentylenetetrazole. Finally, oxidative stress markers, brain GABA content, and neuronal cell loss were evaluated in AFAD-treated pentylenetetrazole-kindled mice. Administration of AFAD significantly protected mice against acute pentylenetetrazole (90 mg/kg)-induced convulsions. In acute pentylenetetrazole (50 mg/kg)-induced hippocampal and cortical paroxysmal discharges, AFAD significantly decreased the number of crisis, the cumulative duration of crisis, and the mean duration of crisis. Additionally, AFAD significantly decreased the number of myoclonic jerks and improved the seizure score in subchronic pentylenetetrazole-induced kindled seizures. The pentylenetetrazole-induced alteration of oxidant-antioxidant balance, GABA concentration, and neuronal cells in the brain were attenuated by AFAD treatment. This study showed that AFAD protected mice against pentylenetetrazole-induced epileptic seizures possibly through the enhancement of antioxidant defence and GABAergic signalling. These events might be correlated with the amelioration of neuronal cell loss; hence, AFAD could be a potential candidate for the treatment of epilepsy.

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.

Antidepressant and anti-amnesic effects of the aqueous lyophilisate of the leaves of Leptadenia arborea on an animal model of cognitive deficit associated depression.

Leptadenia arborea (Asclepiadaceae) is a plant used in traditional medicine to treat syphilis, migraine, and mental illnesses. The aim of our study was to investigate possible antidepressant and anti-amnesic effects of the aqueous lyophilisate of the leaves of Leptadenia arborea in an animal model of cognitive deficit associated depression. Swiss albino adult mice of both sexes were used for this study. A 14-day combined stress model was used to induce depression with early cognitive deficits. The forced swimming test, the open field test and plasma corticosterone level were used to assess antidepressant-like effect. The novel object recognition task (NORT), the Morris Water Maze (MWM) and neurochemical analysis of hippocampal acetylcholinesterase activity was also carried out to assess memory integrity. The aqueous lyophelisate of L. arborea increased swimming time and decreased immobility time in the forced swimming test. In the open field test they was no difference in the number of lines crossed between groups, and the lyophilisate-treated mice spent more time in the centre compared to the control. The lyophilisate decreased the plasma level of corticosterone compared to the control. The lyophilisate decreased the latency to reach the hidden platform and increased the time spent in the target quadrant in the MWM. The lyophilisate also increased the time of exploration of the novel object in the NORT and decreased the acetylcholinesterase activity in the hippocampus. L. arborea effects were decreased when it was co-administered with pCPA. Results suggest that the aqueous lyophilisate of the leaves of L. arborea possess antidepressant-like and anti-amnesic effects.

Quantification of Bioactive Compounds and Evaluation of the Antioxidant Activity of Carissa edulis Valh (Apocynaceae) Leaves.

Carissa edulis is a plant used in the management of oxidative stress and inflammatory related disorders such as malaria, rheumatism inflammation, and cardiovascular diseases. The present study evaluates the total phenolic content, antioxidant capacity (DPPH, ABTS, and FRAP), and the bioactive compounds present in the various extracts of C. edulis (HEC, MEC, AEC, and PC). An HPLC analysis determined the different compounds present in the extracts. High concentration of total phenolic content was observed in aqueous and methanolic extracts more than in the hydroethanolic extract though not significantly different. Flavonoids were higher in the hydroethanolic and methanolic extracts, respectively, with 14.84 mg RE/g extract and 12.02 mg RE/g extract. Tannins were also found in large amounts in the same two extracts with 26.76 mg TAE/g extract and 34.67 mg TEE/g extract. The percentage radical scavenging activity DPPH ranged between 58.63% and 94.67% for aqueous extract and for ABTS between 51.39% and 94.12% for the methanolic extract. The highest FRAP was obtained in the methanolic extract (6.73 g AAE/100 g extract). HPLC analysis revealed the presence of quercetin, rutin, and gallic acid in the different extracts. C. edulis represents a potential source of bioactive components with antioxidant capacity.

Anxiolytic and Antiepileptic Properties of the Aqueous Extract of Cissus quadrangularis (Vitaceae) in Mice Pilocarpine Model of Epilepsy.

Cissus quadrangularis (C. quadrangularis) is a plant of the Vitaceae family known for its anticonvulsant effects in traditional medicine. The objective of this study was to elucidate the anxiolytic and antiepileptic effects of aqueous extract of C. quadrangularis. The mice were divided into different groups and treated for seven consecutive days as follows: a negative control group that received distilled water, po, four test groups that received four doses of the plant (37.22, 93.05, 186.11, and 372.21 mg/kg, po), and a positive control group that received sodium valproate (300 mg/kg, ip). One hour after the first treatment (first day), epilepsy was induced by intraperitoneal administration of a single dose of pilocarpine (360 mg/kg). On the seventh day, the anxiolytic effects of the extract were evaluated in the epileptic mice using the elevated plus maze (EPM) and open field (OP) paradigms. Antioxidant activities and the involvement of gabaergic neurotransmission were determined by measuring the levels of malondialdehyde, reduced glutathione (GSH), GABA, and GABA-transaminase (GABA-T) in the hippocampus of sacrificed epileptic mice. The results show that the extract of C. quadrangularis significantly and dose-dependently increased the latency to clonic and generalized tonic-clonic seizures and decreased the number and duration of seizures. In the EPM, the extract of C. quadrangularis significantly increased the number of entries and the time spent into the open arms and reduced the number of entries and the time spent into the closed arms as well as the number of rearing. The extract of C. quadrangularis also increased the number of crossing, and the time spent in the center of the OP. The level of MDA and the activity of GABA-T were significantly decreased by the extract of C. quadrangularis while reduced GSH and GABA levels were increased. The results suggest that the anticonvulsant activities of C. quadrangularis are accompanied by its anxiolytics effects. These effects may be supported by its antioxidant properties and mediated at least in part by the GABA neurotransmission.

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.

Antipsychotic and sedative effects of the leaf extract of Crassocephalum bauchiense (Hutch.) Milne-Redh (Asteraceae) in rodents.

ETHNOPHARMACOLOGICAL RELEVANCE: Crassocephalum bauchiense (Hutch.) Milne-Redh (Asteraceae) has been used as a medicine for the treatment of epilepsy, insomnia, dementia and psychotic disorders in Cameroonian traditional medicine. AIM OF THE STUDY: This study was designed to examine whether the aqueous extract and the alkaloid fraction prepared from the leaves of Crassocephalum bauchiense possess antipsychotic and sedative properties in rodents. MATERIALS AND METHODS: The rectal temperature of mice was recorded with a probe thermometer at a constant depth. Novelty-induced rearing behavior is used to evaluate a central excitatory locomotor behavior in mice. The antipsychotic effects of the extracts were assessed using the apomorphine animal model of psychosis. The catalepsy test was tested based on the ability of the leaves extracts of Crassocephalum bauchiense to alter the duration of akinesia by placing the naive mice with both forelegs over a horizontal bar. The extracts of Crassocephalum bauchiense effects were evaluated on sodium pentobarbital-induced sleeping time. In addition, gamma-aminobutyric acid concentrations in the brain treated mice were also estimated. RESULTS: The aqueous extract and the alkaloid fraction from Crassocephalum bauchiense caused dose-dependent inhibition of novelty-induced rearing behavior, decreased the apomorphine-induced stereotypy and fighting, and had significant fall of the body temperature. The aqueous extract prolonged the sodium pentobarbital sleeping time. This prolongation was not reversed by bicuculline, a light-sensitive competitive antagonist of GABA(A) receptors complex. However, the effect of the aqueous extract on sodium pentobarbital-induced sleeping time was blocked by N-methyl-ß-carboline-3-carboxamide, a partial inverse agonist of the benzodiazepine site in the GABA(A) receptor complex and flumazenil, a specific antagonist of the benzodiazepine site in the GABAA receptor complex. In biochemical experiments, the concentration of the inhibitory amino acid, gamma-aminobutyric acid, was significantly increased in the brain of animals treated with the aqueous extract of Crassocephalum bauchiense and sodium valproate. CONCLUSIONS: The results show that the antipsychotic and sedative properties of Crassocephalum bauchiense are possibly mediated via the blockade of dopamine D-2 receptors and GABAergic activation, respectively. However, pharmacological and chemical studies are continuing in order to characterize the mechanism(s) responsible for these neuropharmacological actions and also to identify the active substances present in the extracts of Crassocephalum bauchiense.