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Diabetes-associated cognitive dysfunction is linked to chronic hyperglycemia, oxidative stress, inflammation, cholinergic dysfunction, and neuronal degeneration. We investigated the antidiabetic and neuroprotective activity of a mixture of Sclerocarya birrea, Nauclea latifolia, and Piper longum (SNP) in type 2 diabetic (T2D) rat model-induced memory impairment. Fructose (10%) and streptozotocin (35 mg/kg) were used to induce T2D in male Wistar rats. Diabetic animals received distilled water, metformin (200 mg/kg), or SNP mixture (75, 150, or 300 mg/kg). HPLC-MS profiling of the mixture was performed. Behavioral testing was conducted using the Y-maze, NORT, and Morris water mazes to assess learning and memory. Biochemical markers were evaluated, including carbohydrate metabolism, oxidative/nitrative stress, pro-inflammatory markers, and acetylcholinesterase activity. Histopathological examination of the pancreas and hippocampus was also performed. Fructose/STZ administration resulted in T2D, impaired short- and long-term memory, significantly increased oxidative/nitrative stress, pro-inflammatory cytokine levels, acetylcholinesterase activity (AChE), hippocampal neuronal loss and degeneration in CA1 and CA3 subfields, and neuronal vacuolation in DG. SNP mixture at 150 and 300 mg/kg significantly improved blood glucose and memory function in diabetic rats. The mixture reduced oxidative/nitrative stress and increased endogenous antioxidant levels. It also reduced serum IL-1β, INF-γ and TNF-α levels and ameliorated AChE activity. Histologically, SNP protected hippocampus neurons against T2D-induced neuronal necrosis and degeneration. We conclude that the aqueous extract of SNP mixture has antidiabetic and neuroprotective activities thanks to active metabolites identified in the plant mixture, which consequently normalized blood glucose, protected hippocampus neurons, and improved memory function in diabetic rats., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pharmacological treatments against Alzheimer disease provide only symptomatic relief and are associated with numerous side effects. Previous studies showed that a concoction of Ziziphus jujuba leaves possesses anti-amnesic effects in scopolamine-treated rats. More recently, an aqueous macerate of Z. jujuba leaves has been shown to reduce short-term memory impairment in D-galactose-treated rats. However, no study on the effect of an aqueous macerate of Z. jujuba on long-term memory impairment was performed. Therefore, this study evaluates the effect of an aqueous macerate of Z. jujuba on long-term spatial memory impairment in D-galactose-treated rats. Long-term spatial memory impairment was induced in rats by administering D-galactose (350 mg/kg/day, s.c.), once dailyfor 21 days. On the 22nd day, the integrity of this memory was assessed using the Morris water maze task. Rats that developed memory impairment were treated with tacrine (10 mg/kg, p.o.), or aspirin (20 mg/kg, p.o.), or extract (41.5, 83, and 166 mg/kg, p.o.), once daily, for 14 days. At the end of the treatment, memory impairment was once more assessed using the same paradigm. Animals were then euthanized, and some pro-inflammatory cytokine markers were analyzed in the hippocampus or blood. The extract at all doses significantly reduced the latency to attain the platforming of the water maze test. The extract (83 mg/kg) also increased the time spent in the target quadrant during the retention phase. The extract markedly reduced the concentration of pro-inflammatory cytokine markers in the hippocampus and blood. Together, these results suggest that this aqueous extract Z. jujuba reduces long-term spatial memory impairment. This effect may be mediated in part by its anti-inflammatory activity., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Parkia biglobosa (Jacq.) R. Br. (Fabaceae) is a widely distributed tree, used in traditional medicine to treat amebiasis, hookworm infection, ascariasis, asthma, sterility, dental pain, headaches, cardiac disorders, and epilepsy. To date, no study on the effect of an aqueous extract of P. biglobosa on epileptogenesis and associated neuropsychiatric disorders has been undertaken. Therefore, this study aimed to investigate antiepileptogenic-, antiamnesic-, and anxiolytic-like effects of an aqueous extract of P. biglobosa using pentylenetetrazole (PTZ)-induced kindling in mice. Animals were divided into six groups of eight mice each. Thus, a PTZ group received distilled water (10 ml/kg, per o s), a positive control group received sodium valproate (300 mg/kg, p.o .), and three test groups received the aqueous extract of P. biglobosa (80, 160, and 320 mg/kg, p.o .).In addition, a control group of eight mice receiving distilled water (10 ml/kg, p.o .) was formed. The treatments were administered to mice, 60 min before administration of PTZ (20 mg/kg, i.p.). These co-administrations were performed once daily, for 22 days. The number and duration of seizures (stages 1, 2, 3, and 4 of seizures) exhibited by each mouse were assessed for 30 min during the treatment period. Twenty-four hours following the last administration of the treatments and PTZ, novel object recognition and T-maze tests were performed to assess working memory impairment in mice, while the open field test was performed to assess anxiety-like behavior. After these tests, the animals were sacrificed, and the hippocampi were collected for biochemical and histological analysis. During the period of PTZ-kindling, the extract at all doses completely ( p < 0.001) protected all mice against stages 3 and 4 of seizures when compared to sodium valproate, a standard antiepileptic drug. The extract also significantly ( p < 0.001) attenuated working memory impairment and anxiety-like behavior. In post-mortem brain analyses, the extract significantly ( p < 0.001) increased γ-aminobutyric acid (GABA) level and reduced oxidative stress and inflammation. Histological analysis showed that the aqueous extract attenuated neuronal degeneration/necrosis in the hippocampus. These results suggest that the extract is endowed with antiepileptogenic-, anti-amnesic-, and anxiolytic-like effects. These effects seem to be mediated in part by GABAergic, antioxidant, and anti-inflammatory mechanisms. These results suggest the merit of further studies to isolate the bioactive molecules responsible for these potentially therapeutically relevant effects of the extract., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kandeda, Menvouta, Mabou, Kouamouo and Dimo.)

Temporal lobe epilepsy is the most common drug-resistant epilepsy. To cure epilepsy, drugs must target the mechanisms at the origin of seizures. Thus, the present investigation aimed to evaluate the antiepileptic- and anti-amnesic-like effects of an aqueous extract of Syzygium cumini against kainate-induced status epilepticus in mice, and possible mechanisms of action. Mice were divided into 7 groups and treated as follows: normal group or kainate group received po distilled water (10 mL/kg), four test groups received Syzygium cumini (28.8, 72, 144, and 288 mg/kg, po), and the positive control group treated intraperitoneally (ip) with sodium valproate (300 mg/kg). An extra group of normal mice was treated with piracetam (200 mg/kg, po). Treatments were administered 60 min before the induction of status epilepticus with kainate (15 mg/kg, ip), and continued daily throughout behavioral testing. Twenty-four hours after the induction, T-maze and Morris water maze tasks were successively performed. The animals were then sacrificed and some markers of oxidative stress and neuroinflammation were estimated in the hippocampus. The extract significantly prevented status epilepticus and mortality. In the T-maze, the aqueous extract markedly increased the time spent and the number of entries in the discriminated arm. In the Morris water maze, the extract significantly increased the time spent in the target quadrant during the retention phase. Furthermore, the aqueous extract induced a significant reduction of oxidative stress and neuroinflammation. These results suggest that the aqueous extract of Syzygium cumini has antiepileptic- and anti-amnesic-like effects, likely mediated in part by antioxidant and anti-inflammatory activities., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ethnopharmacological Relevance: Temporal lobe epilepsy is the most common form of drug-resistant epilepsy. Therefore, medicinal plants provide an alternative source for the discovery of new antiepileptic drugs., Aim of the Study: This study was aimed at investigating the antiepileptic- and anxiolytic-like effects of an aqueous extract of Khaya senegalensis ( K. senegalensis ) in kainate-treated rats., Methods: Seventy-two rats received a single dose of kainate (12 mg/kg) intraperitoneally. Those that exhibited two hours of status epilepticus were selected and monitored for the first spontaneous seizure. Then, animals that developed seizures were divided into 6 groups of 8 rats each and treated twice daily for 14 days as follows: negative control group received per os ( p.o. ) distilled water (10 ml/kg); two positive control groups received either sodium valproate (300 mg/kg, p.o. ) or phenobarbital (20 mg/kg, p.o. ); and three test groups received different doses of the extract (50, 100, and 200 mg/kg, p.o .). In addition, a group of 8 normal rats (normal control group) received distilled water (10 ml/kg, p.o. ). During the treatment period, the animals were video-monitored 12 h/day for behavioral seizures. At the end of the treatment period, animals were subjected to elevated plus-maze and open field tests. Thereafter, rats were euthanized for the analysis of γ-aminobutyric acid (GABA) concentration, oxidative stress status, and neuronal loss in the hippocampus., Results: The aqueous extract of K. senegalensis significantly reduced spontaneous recurrent seizures (generalized tonic-clonic seizures) and anxiety-like behavior compared to the negative control group. These effects were more marked than those of sodium valproate or phenobarbital. Furthermore, the extract significantly increased GABA concentration, alleviated oxidative stress, and mitigated neuronal loss in the dentate gyrus of the hippocampus., Conclusion: These findings suggest that the aqueous extract of K. senegalensis possesses antiepileptic- and anxiolytic-like effects. These effects were greater than those of sodium valproate or phenobarbital, standard antiepileptic drugs. Furthermore, these effects are accompanied by neuromodulatory and antioxidant activities that may be related to their behavioral effects. These data justify further studies to identify the bioactive molecules present in the extract for possible future therapeutic development and to unravel their mechanisms of action., Competing Interests: The authors declare no conflict of interest., (© 2022 Published by Elsevier Ltd.)

Background: Epilepsy is a neurological disorder characterized by spontaneous recurrent seizures. Lantana camara (Verbenaceae) is a plant used in Cameroonian traditional medicine to treat dementia, epilepsy, and sleeping disorders. Hence, this study aimed to assess the antiepileptic-like effects of an aqueous extract of L. camara leaves on seizures induced by kainate in mice, and possible mechanisms of action., Methods: Mice were divided into two groups: a normal control group treated with 0.9% saline (10 ml/kg, i.p.), and a kainate group treated with kainate (10 mg/kg, i.p.). All mice that developed status epilepticus were individually observed for spontaneous seizures. Eighteen days after the induction of status epilepticus, mice that exhibited spontaneous seizures were further divided into 6 groups of 7 mice each and treated as follows: a kainate group treated with 0.9% saline (10 ml/kg, p.o.), two positive control groups either treated with sodium valproate (300 mg/kg, p.o.) or with piracetam (200 mg/kg, p.o.), and three test groups received the extract (230, 460, and 917 mg/kg, p.o.). The control group was treated with 0.9% saline (10 ml/kg, p.o.). These treatments lasted 14 days and the animals were observed 6 h per day for behavioral seizures. Subsequently, the animals were evaluated for anxiety disorders and memory impairment. Animals were then sacrificed and the hippocampus or prefrontal cortex was collected for histological and biochemical analyses. Furthermore, the dilacerates of the hippocampi were stored for white blood cell count., Results: The aqueous extract of L. camara (460 mg/kg) remarkably decreased (p < 0.001) the number and duration of seizures compared to sodium valproate. Also, it significantly increased the level of GABA both in the hippocampus and prefrontal cortex and protected these organs from oxidative stress. Furthermore, the extract (230 mg/kg) induced the highest reduction in the number of white blood cells in the hippocampus. Finally, the extract (917 mg/kg) significantly attenuated neuronal loss in the CA1, CA2, and CA3 regions of the hippocampus. All these compared to the negative control., Conclusion: These results suggest that the aqueous extract of L. camara has an antiepileptic-like effect comparable to that of sodium valproate. This, therefore, warrants further investigation into the effect of bioactive molecules present in the extract using in vitro and in vivo models of epilepsy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

About 30% of epileptic patients continue to have seizures. The present study investigates the anticonvulsant and sedative effects of an aqueous extract of C. schweinfurthii in mice. Anticonvulsant effects of C. schweinfurthii aqueous extract (0.01-300 mg/kg, p.o.) were tested against 4-aminopyridine (4-AP, 15 mg/kg, i.p.) -, pilocarpine (PILO, 380 mg/kg, i.p.) - and pentylenetetrazole (PTZ, 75 mg/kg, i.p.) -induced seizures, while sedative effects were tested on diazepam (35 mg/kg, i.p.)-induced sleep. Afterward, the most effective dose of the extract (11.9 mg/kg) was antagonized with N-methyl-β-carboline-3-carboxamide or flumazenil. In another set of experiments, mice were sacrificed for the estimation of GABA content and GABA-T activity in the cerebral cortex. The dose of the extract that protected 50% of mice (ED 50 ) against 4-AP, PILO, and PTZ was respectively 4.43 mg/kg (versus 12.01 for phenobarbital), 9.59 mg/kg (vs 8.67 for diazepam), and 2.12 mg/kg (vs 0.20 for clonazepam). Further, the ED 50 of the extract that increased the duration of sleep was 0.24 mg/kg (vs 0.84 for phenobarbital). N-methyl-β-carboline-3-carboxamide or flumazenil antagonized (p < 0.001) the anticonvulsant effect of C. schweinfurthii in PTZ-induced seizures and diazepam-induced sleep when compared to the negative control group. The extract at all doses increased (p < 0.001) the GABA content and decreased (p < 0.001) GABA-T activity. These findings suggest that C. schweinfurthii possesses anticonvulsant and sedative effects. These effects seem to be mediated via the modulation of the GABA neurotransmission. These data explain the use of this plant to treat epilepsy in Cameroon traditional medicine., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Alzheimer's disease is a neurological condition that affects about 44 million people worldwide. The available treatments target symptoms rather than the underlying causes. Ziziphus jujuba (Rhamnaceae) is widely used in traditional Cameroonian medicine to treat diabetes, pain, infections, and dementia. Previous studies reported that Z. jujuba aqueous macerate improves working memory impairment, but no study on the antiamnesic effect of a concoction of Z. jujuba in rats has been performed. Therefore, this study aimed to assess the antiamnesic and neuroprotective effects of an aqueous extract of Z. jujuba on scopolamine-induced cognitive impairments in rats., Methods: Learning and memory impairments were induced in rats by administering scopolamine (1 mg/kg, i.p.) to 58 rats for 15 days. Rats that developed learning and memory impairments in Morris water maze and Y-maze paradigms were divided into 7 groups (8 rats each) and treated daily for 15 days as follows: the normal control group received distilled water (10 ml/kg, p.o.), the negative control group received distilled water (10 ml/kg, p.o.), positive control groups either received donepezil (1.2 mg/kg, p.o.) or tacrine (10 mg/kg, p.o.), and the three test groups were given the extract (29, 57, and 114 mg/kg, p.o.). At the end of treatments, learning and memory impairments were determined using the same paradigms. Animals were then euthanized, and biochemical parameters of oxidative stress, inflammation, and apoptosis were analyzed in the hippocampus and prefrontal cortex., Results: On the 4th day of the acquisition phase in the Morris water maze, Z. jujuba (29 and 114 mg/kg) reduced ( p < 0.001) the latency to reach the platform, while in the retention phase, Z. jujuba (57 and 114 mg/kg) decreased ( p < 0.001) the time to reach the platform and increased the time in the target quadrant ( p < 0.05) compared to control. Surprisingly, the extract failed to affect spontaneous alternations in the Y -maze. Furthermore, the extract (29, 57, and 114 mg/kg) reversed ( p < 0.001) scopolamine-induced oxidative stress, inflammation, and apoptosis. This was supported by the reduction of neuronal alterations in the hippocampus and prefrontal cortex., Conclusions: Compared to donepezil, a standard drug against Alzheimer's disease, these findings suggest that Z. jujuba extract possesses antiamnesic and neuroprotective effects, and these effects are mediated in part through antioxidant, anti-inflammatory, and antiapoptotic activities. These findings help to explain its use in treating psychiatric disorders in Cameroon's folk medicine., Competing Interests: There are no conflicts of interest., (Copyright © 2021 Etienne Djeuzong et al.)

Alzheimer's disease is a progressive cognitive dysfunction. However, pharmacological treatments are symptomatic and have many side effects, opening the opportunity to alternative medicine. This study investigated the antiamnesic effect of the aqueous extract of Ziziphus jujuba on D-galactose-induced working memory impairment in rats. Impairment of working memory was induced by subcutaneous (s.c.) injection of D-galactose (350 mg/kg/day) to rats for 21 days. These animals were then subjected to object recognition and Y-maze tests. Rats with confirmed memory impairment were treated per os ( p.o. ) with tacrine (10 mg/kg), aspirin (20 mg/kg, p.o. ), extract (41.5, 83, and 166 mg/kg, p.o. ), and distilled water (10 mL/kg, p.o. ) daily for 14 days. At the end of the treatments, alteration in working memory was assessed using the above paradigms. Afterward, these animals were euthanized, and cholinergic, proinflammatory, and neuronal damage markers were analyzed in the prefrontal cortex. Rats administered D-galactose and treated with distilled water had impaired working memory (evidenced by decreased time spent on the novel object and discrimination index) and decreased spontaneous alternation in the Y-maze. D-galactose also decreased the levels of acetylcholinesterase and acetylcholine and increased the level of glial fibrillary acidic protein, ionized calcium-binding adapter molecule 1, tumor necrosis factor-alpha (TNF- α ), interleukin 1 beta (IL-1 β ), interleukin 6 (IL-6), and interferon-gamma (IFN- γ ). Treatment with the extract (166 mg/kg) reversed the time spent on the novel object and the discrimination index. It equally increased the percentage of spontaneous alternation. Neurochemical analysis revealed that the extract markedly alleviated acetylcholinesterase activity and neuroinflammation. These observations were corroborated by the reduction in neuronal loss. Taken together, these results suggest that Ziziphus jujuba aqueous extract possesses an antiamnesic effect. This effect seems to involve cholinergic and anti-inflammatory modulations. This, therefore, claims using this plant in the treatment of dementia in Cameroon subject to further studies and trials., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2021 Antoine K. Kandeda et al.)

Bridelia atroviridis Müll. Arg. (B. atroviridis ) is a plant used in Cameroonian traditional medicine to manage diabetes. The effects of hydroethanolic barks extract from B. atroviridis were evaluated on diabetes disorders including hematology, inflammatory, and oxidative stress parameters. The in vitro antioxidant capacity of the hydroethanolic bark extract (70 : 30) was evaluated. Nicotinamide-/streptozotocin-induced diabetic rats were daily treated with the B. atroviridis extract for fifteen days. Glycemia were evaluated every 5 days, insulin sensibility test was performed, and haematological, inflammatory, and oxidative stress parameters were analysed. Histomorphometry of the pancreas was realized. The extract was able to scavenge free radicals in vitro and decrease significantly the blood glucose levels. The treatment resulted in a significant alleviation of insulin resistance, anemia, leukocytopenia, and thrombocytopenia observed in untreated diabetic rats. The extract significantly decreased proinflammatory cytokines TNF- α , IL-1 β , and IL-10. The rate of reduced glutathione was increased in the pancreas, whereas the catalase activity and nitrite concentration were decreased. Diabetic control showed a reduced size of Langerhans islet, whereas the size of islets was large in treated groups. The hydroethanolic extract of B. atroviridis was able to improve glycemia and alleviate haematological and inflammatory parameters disorders observed in diabetic conditions, probably due to its antidiabetic, anti-inflammatory, and antioxidant capacities., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2020 Clarice Noussi Djouwoug et al.)

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.

In this study, we investigated antiepileptogenic and neuroprotective effects of the aqueous extract of Pergularia daemia roots (PDR) using in vivo and in vitro experimental models. In in vivo studies, status epilepticus caused by pilocarpine injection triggers epileptogenesis which evolves during about 1-2 weeks. After 2 h of status epilepticus, mice were treated during the epileptogenesis period for 7 days with sodium valproate and vitamin C (standards which demonstrated to alter epileptogenesis), or Pergularia daemia . The animals were then, 1 week after status epilepticus, challenged with acute pentylenetetrazole (PTZ) administration to test behaviorally the susceptibility to a convulsant agent of animals treated or not with the plan extract. Memory was assessed after PTZ administration in the elevated plus maze and T-maze paradigms at 24 and 48 h. Antioxidant and acetylcholinesterase activities were determined in the hippocampus after sacrifice, in vitro studies were conducted using embryonic rat primary cortical cultures exposed to L-glutamate. Cell survival rate was measured and apoptotic and necrotic cell death determined. The results showed that chronic oral administration of PDR significantly and dose-dependently increased the latency to myoclonic jerks, clonic seizures and generalized tonic-clonic seizures, and the seizure score. In addition, PDR at all doses (from 4.9 to 49 mg/kg) significantly decreased the initial and retention transfer latencies in the elevated plus maze. Interestingly PDR at the same doses significantly increased the time spent and the number of entries in T-maze novel arm. PDR significantly increased the activities of acetylcholinesterase and antioxidant enzymes superoxide dismutase, catalase, and total glutathione and proteins, and decreased malondialdehyde level. Furthermore, PDR increased viability rate of primary cortical neurons after L-glutamate-induced excitotoxicity, in a dose dependent manner. Altogether these results suggest that PDR has antiepileptogenic and neuroprotective effects, which could be mediated by antioxidant and antiapoptotic activities.

Extracts of Feretia apodanthera Del. (Rubiaceae) have been extensively used in traditional Cameroonian medicine to treat a variety of diseases, including some neurological disorders. The present study was aimed to tests the anticonvulsant properties of the aqueous extract and the alkaloid fraction of the stem barks of Feretia apodanthera. The anticonvulsant investigation was carried out against bicuculline-, picrotoxin-, pentylenetetrazol-, Methyl-β-carboline-3-carboxylate-, N-Methyl-D-aspartate-, 4-aminopyridine-, and maximal electroshock-induced seizures or turning behavior in mice. The aqueous extract protected mice against bicuculline-, picrotoxin-, pentylenetetrazol-, Methyl-β-carboline-3-carboxylate-, N-methyl-D-aspartate -, 4-aminopyridine- and maximal electroshock-induced seizures or turning behavior. Also, N-Methyl-D-aspartate-, 4-aminopyridine- and maximal electroshock- induced seizures or turning behavior, were significantly antagonized by the alkaloid fraction (80mg/kg) from Feretia apodanthera. The total protection of mice provided by the aqueous extract against convulsions induced by pentylenetetrazol or picrotoxin was anagonized by flumazenil, a specific antagonist of the benzodiazepine site in the GABA A receptor complex. The aqueous extract of Feretia apodanthera (but not the alkaloid fraction) increased the brain GABA content and inhibited the GABA transaminase activity. In conclusion, Feretia apodanthera was revealed possessing anticonvulsant effects in mice, likely via the GABAergic neurotransmission., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Feretia apodanthera Del. (Rubiaceae) is extensively used in ethnomedicine in Cameroon and Nigeria for epilepsy, febrile convulsions, and rheumatic pains and for enhancing cognitive performance. The aim of the present study was to examine the effects of a lyophilized aqueous extract of F. apodanthera on the course of kindling development, kindling-induced learning deficit, oxidative stress markers, and cholinesterase activity in pentylenetetrazole (PTZ)-kindled mice. Pentylenetetrazole, 30mg/kg, induced kindling in mice after 30.00±1.67days. The aqueous extract of F. apodanthera showed dose-dependent antiseizure effects. Feretia apodanthera (150-200mg/kg) significantly increased the latency to myoclonic jerks, clonic seizures, and generalized tonic-clonic seizures. The extract also improved the seizure score and decreased the number of myoclonic jerks. Pentylenetetrazole kindling induced significant oxidative stress and cognitive impairment which were reversed by pretreatment with F. apodanthera in a dose-dependent manner. The significant decrease in cholinesterase activity observed in the PTZ-kindled mice was reversed by pretreatment with the F. apodanthera extract. The results indicated that pretreatment with the aqueous extract of F. apodanthera antagonizes seizures, oxidative stress, and cognitive impairment in PTZ-kindled mice. The aqueous extract of F. apodanthera also showed anxiolytic activities, but the inhibition of memory impairment was not attributed to the anxiolytic activities of the plant. These results thus suggest the potential of F. apodanthera as an adjuvant in epilepsy both to prevent seizures as well as to protect against seizure-induced oxidative stress and memory impairment., (Copyright © 2014 Elsevier Inc. All rights reserved.)