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.

The Aqueous Lyophilisate of Alchemilla Kiwuensis Engl. (Rosaceae) Displays Antiepileptogenic and Antiepileptic Effects on PTZ-induced Kindling in rats: Evidence of Modulation of Glutamatergic and GABAergic Pathways Coupled to Antioxidant Properties.

Alchemilla kiwuensis Engl. (Rosaceae) (A. kiwuensis) is an herbaceous plant traditionally used by Cameroonians to treat epilepsy and other central nervous system disorders. The present study evaluated the antiepileptogenic and antiepileptic effects of A. kiwuensis (40 mg/kg, 80 mg/kg) following Pentylenetetrazole (PTZ)-induced kindling as well as its sub-chronic toxicity. Following an initial i.p administration of a challenge dose (70 mg/kg), Wistar rats of both sexes received sub convulsive doses (35 mg/kg) of PTZ every other day, one hour after the oral gavage of animals with treatments, until two consecutive stage 4, in all animals of negative control. Seizure progression, latency, duration, and repetition were noted. Twenty-four hours later, animals were dissected to extract their hippocampi. The resulting homogenates were used to evaluate Malondialdehyde, reduced glutathione, catalase activity, GABA, GABA-Transaminase, glutamate, glutamate transporter 2, IL-1ß and TGF-1 ß. Sub-chronic toxicity was conducted according to OECD 407 guidelines. The lyophilisate of A. kiwuensis significantly increased the latency of seizure appearance, delayed seizure progression and decreased seizure repetition and duration. Biochemical analysis revealed that the lyophilisate significantly increased the catalase activity, reduced glutathione, GABA, glutamate transporter 2 and TGF-1B levels. The lyophilisate equally caused a significant decreased in the GABA-Transaminase activity, malondialdehyde, and IL-1 ß levels. There was no noticeable sign of toxicity. A. kiwuensis possesses antiepileptic and antiepiletogenic effects by enhancing GABAergic neurotransmission and antioxidant properties, coupled to modulation of glutamatergic and neuroinflammatory pathways and is innocuous in a sub-chronic model. These justifies its local use for the treatment of epilepsy.

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.

Alteration of the α5 GABA receptor and 5HTT lead to cognitive deficits associated with major depressive-like behaviors in a 14-day combined stress rat model.

INTRODUCTION: Current models used to study the pathophysiology of major depressive disorder (MDD) are laborious and time consuming. This study examined the effect of a 14-day combined stress model (CS; corticosterone injection and restraint stress) in male Sprague-Dawley rats and also compare the effect of CS versus 28-day corticosterone treatment on depressive-like behaviour and cognitive deficits. MATERIEL AND METHODS: Depressive-like behaviours and cognitive deficits were assessed in the forced swim test (FST), sucrose preference (SPT), Morris water maze (MWM) and novel object recognition (NORT) tests. Real-time PCR and ELISA were respectively used to detect expression of the serotonin transporter (5-HTT), serotonin 1 A receptor (5-HT1A), α5 GABAA receptor, and the concentrations of corticosterone (plasma), GABA and acetylcholinesterase (AChE) in the hippocampus and Prefrontal cortex (PFC).Results CS group showed increased immobility time in the FST, time to reach the MWM platform, higher corticosterone level, and increased expressions of hippocampal and PFC 5-HT1A and α5 GABAA receptors, and AChE compared to their control groups. In contrast, reductions in SPT ratio, discrimination index in NORT, time in target quadrant, and hippocampal 5-HTT expression was noted relative to their control group. Compared to the 28-day corticosterone only group, PFC 5-HT1A, Hippocampal 5-HTT were reduced, while PFC 5-HTT, Hippocampal α5 GABAA receptors, and AChE concentrations were higher in the CS group. CONCLUSION: Our CS model induced depressive-like behaviour with early cognitive deficits in rats affecting both hippocampus and PFC. The CS model may be useful in investigating new and comprehensive treatment strategies for MDD.

Pentylenetetrazole kindling-induced epilepsy rat models: Insight on the severity state, a comparative study.

This study aimed to carry out a comparative study of the main models of chronic epilepsy induced by pentylenetetrazole (PTZ)-kindling method and to assess the efficacy of sodium valproate, one of the main antiepileptics, on the best epilepsy-inducing kindling model. Two sets of 24 animals were divided into 4 groups of 6 animals and treated as follow: Set 1 included: group 1, control; group 2, the classic kindling PTZ group (UKEOD); group 3, PTZ kindling every other day group with challenge (CKEOD); group 4, PTZ kindling every day group, with challenge (CKED); Set 2 included: group 1, control; group 2, CKEOD group; group 3 and 4, receiving either valproate 200 mg/kg or valproate 300 mg/kg + CKEOD procedure. Results show that CKEOD group significantly reduced the number of injections necessary to reach the fully-kindled state, increased the severity of seizures and improved the stability of seizures. In addition, the CKEOD group significantly increased the level of malondialdehyde and GABA transaminase, reduced the level of reduced glutathione, catalase and GABA. Furthermore, it had no impact on plasma levels of alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT). Valproate 300 mg/kg significantly protected animals against kindling induced by CKEOD. The kindling model with a challenge dose administered on day 1 (CKEOD) thus allows to induce more severe, more stable chronic epilepsy and in a shorter period of time, and could thus contribute to a better understanding of epilepsy, as well as its uses in drug discovery.

Glutamatergic pathway in depressive-like behavior associated with pentylenetetrazole rat model of epilepsy with history of prolonged febrile seizures.

BACKGROUND: Depression is the most significant cause of suicide among neuropsychiatric illnesses. Major depression further affects the quality of life in an individual with epilepsy. The treatment of depression in an epileptic patient could be very challenging because of drug selection or the fact that some antiepileptic drugs are known to cause depression. It has been shown that in addition to the known involvement of the serotonergic pathway in depression, the glutamatergic system is also involved in the evolution of the disease, but this knowledge is limited. This study assessed if induction of epilepsy in rats will cause depressive-like behavior, alters the concentrations of metabotropic receptor 5 (mGluR5), glutamate transport protein (GLAST), glutamate synthase (GS) and brain derived neurotrophic factor (BDNF). MATERIALS AND METHOD: Epilepsy was induced in rats by injecting Pentylenetetrazole at 35 mg/kg every other day. At kindle, rats were subjected to sucrose preference test (SPT) and forced swim test (FST) and decapitated 4 h later. Hippocampal tissue was collected and the BDNF concentration was measured with ELISA; mGluR5 and GS protein expression was measured using western blot while amygdala tissue was used for GLAST expression with flow cytometry. RESULTS: Our results showed that epilepsy leads to depressive-like behavior in rats and alters the glutamatergic system. CONCLUSION: Therefore, we conclude that targeting the glutamate pathway may be a good strategy to alleviate depressive-like behavior associated with epilepsy.

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.

Combined corticosterone treatment and chronic restraint stress lead to depression associated with early cognitive deficits in mice.

Many models, such as chronic mild stress, chronic stress or chronic corticosterone injections are used to induce depression associated with cognitive deficits. However, the induction period in these different models is still long and face constraints when it is short such as in the chronic mild stress done in a minimum period of 21 days. This study aimed to characterize a model of depression with early onset cognitive deficit. 14 days combined chronic injection of corticosterone followed by 2 h restraint stress using a restrainer was used to induce depression with early cognitive deficit onset. The forced swim test, sucrose test and plasma corticosterone concentration were used to assess depression-like characteristics. The Morris water maze, novel object recognition task, as well as hippocampal acetylcholinesterase activity were used to assess cognitive deficit. The combined corticosterone injection + chronic restraint stress group presented with marked depression-like behaviour and a higher plasma corticosterone concentration compared to corticosterone injection alone and restraint stress alone. It also showed an alteration in the learning process, memory deficit as well as increased acetylcholinesterase activity compared to corticosterone injection and restraint stress alone groups. These findings suggest that the combined corticosterone administration and chronic restraint stress can be used not only as an animal model for severe depression, but also for depression with early onset cognitive deficit.

Gladiolus dalenii lyophilisate reverses scopolamine-induced amnesia and reduces oxidative stress in rat brain.

Learning and memory are the most important executive functions performed by the human brain, the loss of which is a prominent feature in dementia. Gladiolus dalenii is traditionally used to treat a number of illnesses such as epilepsy and schizophrenia in Cameroon. This study aims to investigate the anti-amnesia effect of Gladiolus dalenii in scopolamine-induced amnesia in rats and its possible antioxidant properties in this model. Morris water maze, novel object location and recognition tasks were used to assess spatial and working memory. Male rats were treated for 12 days with saline, G. dalenii or Tacrine. Experimental animals were co-treated with scopolamine once daily from day 9 to 12. Acetylcholinesterase activity was measured in the prefrontal cortex and hippocampus. Malondialdehyde and glutathione levels were measured in the hippocampus. G. dalenii reversed memory impairment induced by scopolamine in the Morris water maze, novel object location and recognition tasks. It decreased acetylcholinesterase activity in the hippocampus and prefrontal cortex. It also decreased the level of malondialdehyde and increased the level of glutathione in the hippocampus. The results of this study show that G. dalenii ameliorates the cognitive impairment induced by scopolamine, through inhibition of oxidative stress and enhancement of cholinergic neurotransmission. It can therefore be useful for treatment of conditions associated with memory dysfunction as seen in dementia.

Neuroprotective and Antiamnesic Effects of Mitragyna inermis Willd (Rubiaceae) on Scopolamine-Induced Memory Impairment in Mice.

Aim. To assess memory improvement and neuroprotective and antioxidant effects of Mitragyna inermis (M. inermis) leaf decoction on the central nervous system. Methodology. Leaf decoction of M. inermis was tested on learning and memory in normal and scopolamine-induced cognitive impairment in mice using memory behavioral tests such as the Morris water maze, object recognition task, and elevated plus maze. Oxidative stress enzymes-catalase, superoxide dismutase, and the thiobarbituric acid reactive substance, a product of lipid peroxidation-were quantified. In each test, mice 18 to 25 g were divided into groups of 5. Results. The extract reversed the effects of scopolamine in mice. The extract significantly increased discrimination index in the object recognition task test and inflexion ratio in the elevated plus maze test. The times spent in target quadrant in MWM increased while the transfer latency decreased in mice treated by M. inermis at the dose of 196.5 mg/kg. The activity levels of superoxide dismutase and catalase were significantly increased, whereas the thiobarbituric acid reactive substance was significantly decreased after 8 consecutive days of treatment with M. inermis at the dose of 393 mg/kg. Conclusion. These results suggest that M. inermis leaf extract possess potential antiamnesic effects.

Antidepressant properties of aqueous macerate from Gladiolus dalenii corms.

BACKGROUND: Gladiolus dalenii Van Geel (Iridaceae) has been used for the treatment of depression and psychotic disorders in African traditional medicine. The aim of this study was to assess the effect of the aqueous extract from the corm of Gladiolus dalenii and its possible mechanisms of action. MATERIALS AND METHODS: We assessed the antidepressant properties of G. dalenii corm aqueous extract in mice, using the open field, forced swimming, and tail suspension tests. Spontaneous locomotor activity of mice given various doses of G. dalenii extract (per os) was determined in the open field, whereas immobility was evaluated in the other two tests. RESULTS: Extract maximal effect was observed at 15 mg/kg, as mice displayed a marked reduction in immobility time in both the forced swimming test (80%) and the tail suspension test (66%). In further studies aimed at investigating the mechanism of action of G. dalenii extract, the latter significantly antagonized the effect of N-methyl-D-aspartate (NMDA, 75 mg/kg) at both the doses 15 mg/kg (p<0.001) and 150 mg/kg (p=0.004). A significant reduction in immobility time was also observed following treatment with combinations of a sub-effective dose of extract (7.5 mg/kg) with either the NMDA receptor antagonist D-(-)-2-amino-7-phosphonoheptanoic acid (D-AP7, 50 mg/kg, P< 0.001), the serotonin reuptake inhibitor fluoxetine (5 and 10 mg/kg, P< 0.001 and P< 0.001 respectively), and the multi-target antidepressant imipramine (5 and 10 mg/kg, P< 0.001 and P< 0.001 respectively). Moreover, neither G. dalenii extract alone nor its combinations with NMDA ligands imipramine and fluoxetine enhanced mouse spontaneous locomotor activity. CONCLUSION: Altogether, these results suggest that G. dalenii has antidepressant properties, probably mediated through interactions with NMDA, serotonin and/ or noradrenergic systems, and may justify its use in traditional medicine.

Antidepressant-like effects of the aqueous macerate of the bulb of Gladiolus dalenii Van Geel (Iridaceae) in a rat model of epilepsy-associated depression.

BACKGROUND: In Cameroonian traditional medicine various extracts of Gladiolus dalenii Van Geel (Iridaceae) have been used as a cure for various ailments that include headaches, digestive problems, muscle and joint aches, and some central nervous system disorders such as epilepsy, schizophrenia and mood disorders. Owning to this background, the aim of the study was to investigate whether an aqueous macerate of the bulb of Gladiolus dalenii has any antidepressant activity focusing specifically on depression-like behaviours associated with epilepsy. METHOD: We used the combined administration of atropine and pilocarpine to rats as our animal model of epilepsy. The forced swim test and spontaneous locomotor activity in the open field test were the two tools used to assess the presence of depression-like behaviour in epileptic and control animals. The following depression-related parameters were determined: plasma ACTH, plasma corticosterone, adrenal gland weight and hippocampal levels of brain-derived neurotrophic factor (BDNF). The effects of Gladiolus dalenii were compared to that of fluoxetine. RESULTS: Our results showed that we had a valid animal model of epilepsy-induced depression as all 3 measures of construct, predictive and face validity were satisfied. The data indicated that Gladiolus dalenii significantly reduced the immobility times in the forced swim test and the locomotor activity as assessed in the open field. A similar pattern was observed when the HPA axis parameters were analysed. Gladiolus dalenii significantly reduced the levels of ACTH, corticosterone, but not the adrenal gland weight. Gladiolus dalenii significantly increased the level of BDNF in the hippocampus. In all parameters measured the effects of Gladiolus dalenii were significantly greater than those of fluoxetine. CONCLUSION: The results show that Gladiolus dalenii has antidepressant-like properties similar to those of fluoxetine in epilepsy-associated depressive states. The antidepressant activity of Gladiolus dalenii is likely to be mediated by restoring the activity of the HPA axis and increasing the levels of BDNF in the hippocampus.