Evaluation of packaging, labels, and some physicochemical properties of herbal antimalarial products on the Ghanaian market.

Introduction: Malaria is a parasitic disease that is endemic in tropical areas and can be life-threatening. There has been a decrease in the prevalence of malaria in Ghana but the burden of the disease is still high in the country. Many Ghanaians depend on herbal products for malaria treatment. This study aimed to survey and evaluate commercial herbal antimalarials in the Volta Region of Ghana. Methods: A survey of finished herbal antimalarials was done at herbal shops, pharmacies, and over-the-counter medicine seller shops. Products available on shelves were purchased and their details were recorded, after which they were examined using a visual inspection tool. The density, pH, and extract weight per dose of each sample were also determined. Results: Thirty-four liquid formulations (A-1-34) containing 1-9 different herbs were found. The majority of the product labels had errors in consumer age classifications. Unconventional ways of stating doses were found on two products (A-13, "tot"; A-19, cupful). Six products did not have dosing devices. No duration of treatment was indicated on 24 products. Dose errors were found on A-14 and A-22. Samples A-17 and A-28 did not have registration or batch numbers. Product A-28 did not have its herbs listed on it and was indicated for persons aged 3-8 years at a dose of 45 mL. The relative density range for the products was 0.997-1.015. From the pH investigation, no product was extremely erosive; however, 10 samples were deemed erosive (pH, 3.0-3.99), whereas 24 were minimally erosive (pH, ≥4.0). The extract weight per dose volume (20-90 mL) was 0.048-1.766 g, indicating that unit dose capsules or tablets could be formulated from the products. Conclusion: The findings clearly show that Ghanaian authorities responsible for regulating herbal products must enforce guidelines for the formulation, label details, and sale of antimalarial products. Additionally, the unpleasant taste of liquid herbal mixtures can affect patient compliance and dosing convenience; therefore, it is recommended that oral solid dosage forms of herbal antimalarials are produced as alternatives to the liquid mixtures.

Anxiolytic-like effects of Pseudospondias microcarpa hydroethanolic leaf extract in zebrafish: Possible involvement of GABAergic and serotonergic pathways.

Pseudospondias microcarpa is used in ethnomedicine to manage central nervous system diseases. The hydroethanolic extract (PME) from the leaves of the plant has shown anxiolytic-like properties in mice anxiety models. However, its effects in chronic anxiety models and possible mechanism(s) of action were not studied. Therefore, the current study evaluated the anxiolytic-like mechanisms of PME in zebrafish models of anxiety. The zebrafish light dark test (LDT) and novel tank test (NTT) were employed to assess the anxiolytic-like effects of PME (0.1, 0.3, 1.0 mg mL-1), fluoxetine (3 × 10-5 mg mL-1) and diazepam (1.5 × 10-7 mg mL-1). The chronic unpredictable stress (CUS) test was used to further evaluate the extract's anxiolytic-like properties. The potential mechanisms of anxiolytic action of the extract was evaluated after pre-treated with flumazenil, granisetron, methysergide, or pizotifen, all at 1 × 10-3 mg mL-1. The extract significantly decreased anxiety behaviours in the NT and LD tests. These observed effects of the extract were however counteracted by flumazenil, granisetron, methysergide and pizotifen pre-treatment. In addition, PME treatment significantly reversed CUS-induced anxiety behaviours in zebrafish. Results show that PME possesses anxiolytic-like effects possibly through interaction with serotonergic and gamma-aminobutyric acid mediated pathways.

Fast-onset effects of Pseudospondias microcarpa (A. Rich) Engl. (Anacardiaceae) hydroethanolic leaf extract on behavioral alterations induced by chronic mild stress in mice.

INTRODUCTION: Pseudospondias microcarpa (Anacardiaceae) is a plant widely used traditionally for treating various central nervous system disorders. A previous study in our laboratory confirmed that the hydroethanolic leaf extract (PME) of the plant produces an antidepressant-like effect in rodent models of behavioral despair. However, its effect on depressive-like behavior induced by chronic mild stress (CMS) and its time course of action are still unknown. In this context, the long-term effects of PME on cognitive function and depressive- and anxiety-like behavior caused by CMS were assessed. METHODS: Male ICR mice were exposed to CMS for nine weeks and anhedonia was evaluated by monitoring sucrose intake (SIT) weekly. PME (30, 100, or 300 mg kg-1) or fluoxetine (FLX) (3, 10, or 30 mg kg-1) was administered to the mice during the last six weeks of CMS. Behavioral tests-coat state, splash test, forced swimming test (FST), tail suspension test (TST), elevated plus maze (EPM), open field test (OFT), novelty suppressed feeding (NSF), EPM transfer latency, and Morris water maze (MWM)-were performed after the nine-week CMS period. RESULTS: When the mice were exposed to CMS, their SIT and grooming behavior reduced (splash test), their coat status was poor, they became more immobile (FST and TST), more anxious (OFT, EPM, and NSF), and their cognitive function was compromised (EPM transfer latency and MWM tests). Chronic PME treatment, however, was able to counteract these effects. Additionally, following two (2) weeks of treatment, PME significantly boosted SIT in stressed mice (30 mg kg-1, P<0.05; 100 mg kg-1, P<0.05; and 300 mg kg-1, P<0.001), as compared to four (4) weeks of treatment with FLX. CONCLUSION: The present findings demonstrate that PME produces a rapid and sustained antidepressant-like action and reverses behavioral changes induced by chronic exposure to mild stressors.

Effect of Diclofenac and Andrographolide Combination on Carrageenan-Induced Paw Edema and Hyperalgesia in Rats.

Studies into drug combination at low doses are a promising approach to the management of pain and inflammation. The aim of this study was to evaluate the anti-edema and anti-hyperalgesic effects of a combination of diclofenac and andrographolide. Male Sprague-Dawley rats were first treated with diclofenac or andrographolide alone (3-100 mg/kg), as well as a combination of the 2 drugs. Carrageenan was then injected into the right hind paw of rats, and changes in paw volume and sensitivity to mechanical (von Frey) and thermal (Hargreaves test) stimuli measured. Results showed drug combination produced synergistic effects at reducing paw edema especially at lower doses, with a Loewe synergy score of 13.02 ± 8.75 in SynergyFinder and a combination index of .41 ± .18 after isobolographic analysis. Again synergy scores for decreasing response to 1.0 and 3.6 g force application of von Frey filaments after drug combination were 10.127 ± 5.68 and 8.554 ± 6.53, respectively, in SynergyFinder. Synergistic effects were also seen after drug combination in the Hargreaves test with a synergy score of 5.136 ± 16.38. In conclusion, combination of diclofenac with andrographolide showed better pharmacologic effects after carrageenan injection and was more synergistic at low-dose combinations.

Glycine/NMDA Receptor Pathway Mediates the Rapid-onset Antidepressant Effect of Alkaloids From Trichilia Monadelpha.

INTRODUCTION: Major depressive disorder is often associated with suicidal tendencies, and this condition accentuates the need for rapid-acting antidepressants. We previously reported that Alkaloids (ALK) from Trichilia monadelpha possess antidepressant action in acute animal models of depression and that this effect is mediated through the monoamine and L-arginine-NO-cGMP pathways. This study investigated the possible rapid-onset antidepressant effect of ALK from T. monadelpha and its connection with the glycine/NMDA receptor pathway. METHODS: The onset of ALK action from T. monadelpha was evaluated using the Open Space Swim Test (OSST), a chronic model of depression. The modified forced swimming and tail suspension tests were used to assess the effect of the ALK on the glycine/NMDA receptor pathway. The Instutute of Cancer Research (ICR) mice were treated with either ALK (30-300 mg/kg, orally [PO]), imipramine (3-30 mg/kg, PO), fluoxetine (3-30 mg/kg, PO), or saline. To identify the role of glycine/NMDA receptor pathway in the effect of ALK, we pretreated mice with a partial agonist of the glycine/NMDA receptor, D-cycloserine (2.5 mg/kg, intraperitoneally [IP]), and an agonist of glycine/NMDA receptor, D-serine (600 mg/kg, IP), before ALK administration. RESULTS: ALK reversed immobility in mice after the second day of drug treatment in the OSST. In contrast, there was a delay in the effects induced by fluoxetine and imipramine. ALK also increased mean swimming and climbing scores in mice. ALK was more efficacious than imipramine and fluoxetine in reducing immobility and increasing distance traveled. It is noteworthy that ALK was less potent than fluoxetine and imipramine. D-cycloserine potentiated mobility observed in the ALK- and fluoxetine-treated mice. In contrast, D-serine decreased mobility in the ALK-treated mice. CONCLUSION: The study results suggest that ALK from T. monadelpha exhibits rapid antidepressant action in mice, and the glycine/NMDA receptor pathway possibly mediates the observed effect.

Evidence of an antidepressant-like effect of xylopic acid mediated by serotonergic mechanisms.

BACKGROUND: Depression causes significant debilitating symptoms and economic burden. Current management is challenged by slow onset of action and modest efficacies of antidepressants; thus, the search for newer antidepressants remains relevant. We evaluated the antidepressant effects of a kaurene diterpene, xylopic acid (XA), in zebrafish and mouse models. METHODS: The chronic unpredictable stress (CUS) protocol in zebrafish and the tail suspension test (TST), forced swim test (FST), lipopolysaccharide-induced depression-like behaviour test (LID) and repeated open space swimming test (OSST) in mice were used. We further examined the impact of depleting monoamines on XA's antidepressant effects. The contribution of glutamatergic and nitrergic pathways on the antidepressant effect of XA in mice and XA's effects on 5-HT receptors and monoamine oxidase (MAO) enzymes were also evaluated. Finally, XA's influence on neuroprotection was evaluated by measuring BDNF and oxidative stress enzymes in whole brain. XA doses (1-10 µM) in zebrafish and (10, 30, 100 mg kg-1) in mice exerted potent antidepressant-like potential in FST, TST, LID and showed fast-onset antidepressant-like property in the OSST. RESULTS: The antidepressant-like properties in mice were reversed by blocking synthesis/release of serotonin but not noradrenaline using p-chlorophenylalanine and α-methyl-p-tyrosine, respectively. This antidepressant-like effect was potentiated by D-cycloserine and Nω-Nitro-L-arginine methyl ester (L-NAME) but not by D-serine and L-arginine. XA also evoked partial agonist-like effects on 5-hydroxytrptamine receptors on the rat fundus but it did not have MAO inhibition effect. It also increased BDNF, glutathione and antioxidant enzymes. CONCLUSION: Therefore, xylopic acid possesses antidepressant-like effects largely mediated by serotonergic and neuroprotective mechanisms.

Myrianthus libericus: Possible mechanisms of hypoglycaemic action and in silico prediction of pharmacokinetics and toxicity profile of its bioactive metabolite, friedelan-3-one.

The hypoglycaemic and anti-hyperlipidaemic effects of the 70% ethanol stem bark extract of Myrianthus libericus (MLB), used traditionally in the management of diabetes in Ghana, was evaluated in this study using streptozotocin (45 mg/kg)-induced diabetic rats. In vitro hypoglycaemic activities of the extract and one of its principal compounds, friedelan-3-one were then investigated using α-amylase inhibitory and glucose uptake assay in C2C12 myotubes. In silico analysis of the pharmacokinetic and toxicity properties of the compound was also performed. MLB significantly (p < 0.001) reduced the elevated blood glucose levels and corrected considerably (p < 0.01) the altered serum lipid profiles of the diabetic rats which was comparable to glibenclamide (5 mg/kg). Together with friedelan-3-one, the extract markedly inhibited the activity of α-amylase and promoted glucose uptake in C2C12 cells. Whereas MLB significantly (p < 0.001) up-regulated PI3K and PPARγ transcripts with a corresponding increase in GLUT-4 transcripts within the muscle cells, friedelan-3-one only up-regulated PI3K and GLUT-4 transcripts to promote glucose transport. Friedelan-3-one was shown to be non-carcinogenic, non-hepatotoxic, has decent oral bioavailability and a good compound for optimisation into a drug candidate. The study has demonstrated that MLB possess hypoglycaemic and anti-hyperlipidaemic activities and could be used as a therapeutic agent in the management of diabetes mellitus.

Flavanols and triterpenoids from Myrianthus arboreus ameliorate hyperglycaemia in streptozotocin-induced diabetic rats possibly via glucose uptake enhancement and α-amylase inhibition.

Myrianthus arboreus is use traditionally as an antidiabetic agent in Ghana. We reported the in vivo antidiabetic activity of its 70 % ethanol stem bark extract (MAB) which we found to be strongly concentrated in its EtOAc fraction using glucose uptake and enzyme inhibitory assays. The present study sought to investigate the in vivo hypoglycaemic and anti-hyperlipidaemic activity of this ethyl acetate fraction of MAB (MAB-EtOAc, 50 and 100 mg/kg) in streptozotocin (STZ)-induced diabetic rats for 21 days, isolate and evaluate the bioactive constituents responsible for the antidiabetic activity. In silico pharmacokinetic and toxicity properties of the most active compound was also determined. MAB-EtOAc significantly (p < 0.001) reduced the blood glucose levels while normalizing considerably the altered serum lipid parameters of the diabetic rats which was comparable to glibenclamide (5 mg/kg). Chemical investigation of MAB-EtOAc led to the isolation of seven known compounds including three flavanols which are reported for the first time in the plant: epicatechin (1), epigallocatechin (2), dulcisflavan (3), euscaphic acid (4), tormentic acid (5), sitosterol-3-O-ß-d-glucopyranoside (6) and arjunolic acid (7). The compounds markedly inhibited the action of α-amylase and, except for 4 and 6, which stimulated considerably glucose uptake in C2C12 cells. Compounds 2, 3, 5, 6 and 7 which were further evaluated in STZ-induced diabetic rats demonstrated hypoglycaemic and anti-hyperlipidaemic activities which, however, were not comparable with MAB-EtOAc. Compound 3, the most active compound was predicted to be non-toxic, non-mutagenic, has reasonable oral bioavailability and a decent substrate for further drug development. The findings of this study show that the isolated compounds may contribute to the antidiabetic activity of M. arboreus and could serve as marker compounds for the quality control of herbal medicines that would be made from the plant.

Hydroethanolic Stem Bark Extract of Burkea africana Attenuates Vincristine-Induced Peripheral Neuropathy in Rats.

Context. The stem bark of the savanna tree Burkea africana (Hook) (family: Leguminosae) is used in the Ghanaian traditional medicine for the management of various pain-related diseases. OBJECTIVE: This study seeks to investigate the possible antiallodynic and antihyperalgesic effects of the hydroethanolic stem bark extract of B. africana in a vincristine-induced peripheral neuropathy model in rats. Materials and Methods. 0.1 mg kg-1 vincristine was administered intraperitoneally for 5 days followed by 2 days break and continued for another 5 days to establish peripheral neuropathy in Sprague Dawley rats. Effects of Burkea africana (Hook) (family: Leguminosae) is used in the Ghanaian traditional medicine for the management of various pain-related diseases. p.o.) and pregabalin (10-100 mg kg-1, i.p.) were assessed on tactile, intermediate, mechanical, cold, and hot allodynia as well as in the Randall-Sellito test. Moreover, the levels of total proteins, malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) in sciatic nerve tissue homogenates were assayed. RESULTS: BAE (50-1000 mg kg-1 p.o.) showed significant antiallodynic and antihyperalgesic effects similar to pregabalin by increasing paw withdrawal latency and paw withdrawal threshold in all the behavioral tests used. Also, the extract decreased the levels of MDA (a lipid peroxidation product) as well as MPO and caused a significant increase in endogenous antioxidants (GSH) and antioxidant enzymes (SOD and CAT) in tissue homogenates of treated rats. CONCLUSIONS: Results from this study indicate that the hydroethanolic stem bark extract of B. africana exhibits antiallodynic and antihyperalgesic effects in vincristine-induced peripheral neuropathy in rats.B. africana in a vincristine-induced peripheral neuropathy model in rats.

Anxiolytic and Antidepressant Effects of Maerua angolensis DC. Stem Bark Extract in Mice.

INTRODUCTION: The stem bark extract of Maerua angolensis DC. (Capparaceae) is used as a traditional remedy for management of anxiety, psychosis, and epilepsy. AIM OF THE STUDY: We therefore aimed at evaluating the anxiolytic and antidepressant potential of the plant in mice models. METHODS: The dried stem bark was extracted with petroleum ether/ethyl acetate (50:50) mixture to obtain the extract, MAE. We employed Irwin's test to identify the preliminary behavioral and autonomic effects. Subsequently, MAE was administered per os to male mice and subsequently assessed, 1 h later, for anxiety parameters in the elevated plus maze (EPM) and the regular Suok tests. The forced swim (FST) and tail suspension (TST) tests were employed to assess the antidepressant potential of the extract (100-1000 mg kg-1). RESULTS: In our preliminary assay, MAE (100-5000 mg/kg) exhibited analgesic effects and a reduction in fear response in the Irwin's test. The spontaneous locomotor activity was reduced at 1000 mg/kg. Additionally, MAE (1000 mg/kg) increased the latency to PTZ-induced convulsions, and duration to sleep in the pentobarbitone induced sleeping time assay. MAE (1000 mg/kg), similar to diazepam, in the anxiolytic assay, increased the percentage time spent in the open arms while decreasing protected head dips and unprotected stretch attend postures in the EPM. Correspondingly, there was a reduction in anxiety-induced immobility and freezing in the Suok test (300 mg/kg) without loss of sensorimotor coordination. Additionally, there was a significant reduction in immobility duration in the FST (300 mg/kg) and TST (1000 mg/kg). CONCLUSION: The petroleum ether/ethyl acetate fractions of Maerua angolensis stem bark possess anxiolytic and acute antidepressant effects in mice.

Toxicological Assessment of Pseudospondias microcarpa (A. Rich.) Engl. Hydroethanolic Leaf Extract in Rats: Haematological, Biochemical, and Histopathological Studies.

Pseudospondias microcarpa is used traditionally for treating various diseases. However, although parts of the plant are extensively used in African traditional medicine, no scientific study has been reported on its toxicity. Therefore, this study evaluated the acute and subacute toxicity studies of the ethanolic extract of P. microcarpa in rats. Male Sprague-Dawley rats (120-150 g) were treated orally with the extract (30, 100, 300, 1000, and 3000 mg kg-1) or distilled water (10 ml kg-1) for 2 weeks and observed daily for general appearance and signs of toxicity. In addition, blood was collected for both biochemical and haematological assays. Sections of tissues from liver, kidney, spleen, brain, and stomach were also used for histopathological examination. Administration of the extract for 14 consecutive days caused no deaths, with an LD50 above 3000 mg kg-1. Except for lymphocytes (%) that showed a significant decrease (F5,23 = 3.93, P = 0.013), all other haematological parameters remained unaffected by the extract. The extract at 100 mg kg-1 showed a significant decrease in the levels of triglyceride and very-low-density lipoproteins (both at P < 0.05). Weight change as well as histological evaluation of the organs indicated no toxicity. The study demonstrates that an ethanolic extract of P. microcarpa given orally to rats is safe.

Maerua angolensis DC. (Capparaceae) Stem Bark Extract Protects against Pentylenetetrazole-Induced Oxidative Stress and Seizures in Rats.

INTRODUCTION: The stem bark of Maerua angolensis DC. (Capparaceae) is traditionally used for management of epilepsy. Our aim was to evaluate the antiseizure potential and identify possible mechanisms by which the effects are registered. METHODS: The petroleum ether/ethyl acetate extract (100-1000 mg kg-1) was administered per os to male Sprague-Dawley rats after pretreatment with flumazenil (0.3 mg kg-1) or L-arginine (150 mg kg-1) or sildenafil (5 mg kg-1) and they subsequently received a subcutaneous injection of pentylenetetrazole (65 mg kg-1). Rats were observed for latency to and duration of myoclonic seizures and additionally the level of protection against oxidant markers and products was assessed in vitro and in vivo. RESULTS: The extract (300 and 1000 mg kg-1, p.o.) significantly delayed the onset and decreased the duration and frequency of PTZ-induced convulsions. The anticonvulsant effect of MAE (300 mg kg-1, p.o.) was reversed by pretreatment with flumazenil, L-arginine, or sildenafil. Also, MAE (300 mg kg-1) treatment reversed significantly PTZ-induced oxidative stress in rat brain tissue. CONCLUSION: The petroleum ether/ethyl acetate fraction exhibits antiseizure activity by affecting GABAergic and nitric oxide-cGMP pathways. In addition, the extract protects against the generation of free radicals and the oxidative products of the PTZ-induced seizures.

Maerua angolensis stem bark extract reverses anxiety and related behaviours in zebrafish-Involvement of GABAergic and 5-HT systems.

ETHNOPHARMACOLOGICAL RELEVANCE: Maerua angolensis DC (Capparaceae) has been employed in the management of several central nervous system (CNS) disorders including anxiety. This study evaluated the anxiolytic effects of the petroleum ether/ethyl acetate fraction stem bark extract and its possible mechanism(s) using zebrafish anxiety models. METHODS: Adult zebrafish, tested in the novel tank and light dark tests, have shown by previous authors to be sensitive to the anxiolytic effects of known anxiolytic drugs. Adult zebrafish were treated with M. angolensis extract, fluoxetine, desipramine, and diazepam followed by testing in the novel tank and light dark tests. We further assessed the effect of the extract on anxiety after inducing an anxiogenic phenotype using the ethanol-withdrawal and chronic unpredictable stress (CUS) tests. The anxiolytic effect was further investigated after pretreatment with flumazenil, granisetron, cyproheptadine, methysergide and pizotifen. RESULTS: M. angolensis extract, similar to fluoxetine and desipramine, demonstrated significant anxiolytic behaviour at doses that did not reduce locomotor activity significantly. Similar anxiolytic effects were recorded in the ethanol withdrawal-induced anxiety test. Furthermore, the anxiogenic effects induced by the CUS paradigm were significantly reversed by treatment M. angolensis extract and fluoxetine. The anxiolytic effects of M. angolensis extract were however reversed after pre-treatment with flumazenil, granisetron, cyproheptadine, methysergide and pizotifen. CONCLUSIONS: Taken together, this suggests that the petroleum ether/ ethyl acetate fraction of M. angolensis possesses significant anxiolytic activity, which could partly be accounted for by an interaction with the serotoninergic system and the GABAA receptor.

Anticonvulsant effects of antiaris toxicaria aqueous extract: investigation using animal models of temporal lobe epilepsy.

BACKGROUND: Antiaris toxicaria has previously shown anticonvulsant activity in acute animal models of epilepsy. The aqueous extract (AAE) was further investigated for activity in kindling with pentylenetetrazole and administration of pilocarpine and kainic acid which mimic temporal lobe epilepsy in various animal species. RESULTS: ICR mice and Sprague-Dawley rats were pre-treated with AAE (200-800 mg kg-1) and convulsive episodes induced using pentylenetetrazole, pilocarpine and kainic acid. The potential of AAE to prevent or delay onset and alter duration of seizures were measured. In addition, damage to hippocampal cells was assessed in kainic acid-induced status epilepticus test. 800 mg kg-1 of the extract suppressed the kindled seizure significantly (P < 0.05) as did diazepam. AAE also produced significant effect (P < 0.01) on latency to first myoclonic jerks and on total duration of seizures. The latency to onset of wet dog shakes was increased significantly (P < 0.05) by AAE on kainic acid administration. Carbamazepine and Nifedipine (30 mg kg-1) also delayed the onset. Histopathological examination of brain sections showed no protective effect on hippocampal cells by AAE and nifedipine. Carbamazepine offered better preservation of hippocampal cells in the CA1, CA2 and CA3 regions. CONCLUSION: Antiaris toxicaria may be effective in controlling temporal lobe seizures in rodents.

Enhancement of inhibitory neurotransmission and inhibition of excitatory mechanisms underlie the anticonvulsant effects of Mallotus oppositifolius.

CONTEXT: Mallotus oppositifolius is a shrub that is used traditionally to treat epilepsy, but its potential has not been scientifically validated. AIMS: This study investigated the anticonvulsant properties and possible mechanism of action of the 70% v/v hydroalcoholic extract of the leaves of M. oppositifolius. MATERIALS AND METHODS: Inprinting control region (ICR) mice (25-30 g) were pretreated with the M. oppositifolius leaf extract (10-100 mg/kg) before administering the respective convulsants (pentylenetetrazole [PTZ], picrotoxin [PTX], strychnine [STR], 4-aminopyridine [4-AP], and pilocarpine). The effect of the extract in maximal electroshock seizure (MES) model was investigated also. STATISTICAL ANALYSIS: Data were presented as mean ± standard error of the mean and were analyzed with one-way analysis of variance (ANOVA) or two-way ANOVA where appropriate with Newman-Keuls or Bonferroni post hoc test respectively. P < 0.05 was considered significant. RESULTS: In both PTX and PTZ test, extract delayed the onset of seizures and reduced the frequency and duration of seizures. In the STR-induced seizure test, the extract significantly delayed the onset of seizures and reduced the duration of seizures. The extract also delayed the onset of clonic and tonic seizures as well as increasing the survival of mice in the 4-AP-induced seizure test. It further reduced the duration of tonic limb extensions in the MES test. In the pilocarpine-induced status epilepticus, the extract significantly delayed the onset of clonic convulsions and reduced the frequency and duration of seizures. Moreover, the anticonvulsant effect of the extract was attenuated by flumazenil, a benzodiazepine/gamma-aminobutyric acid (GABA) receptor antagonist. CONCLUSION: These findings show that the extract has anticonvulsant effect possible mediated by GABAergic, glycinergic neurotransmission, and potassium channel conductions. It may also be acting by antagonizing muscarinic receptor activation and N-Methyl-D-aspartate receptor activation.

Anxiolytic-like effect of the leaves of Pseudospondias microcarpa (A. Rich.) Engl. in mice.

BACKGROUND: Pseudospondias microcarpa is a plant used for managing various diseases including CNS disorders. Previous studies showed sedative and anticonvulsant effects, suggesting possible anxiolytic activity. This study therefore assessed the anxiolytic effects of P. microcarpa hydroethanolic leaf extract (PME) in mice. METHODS: In the present study, anxiolytic-like effect of the extract in behavioural paradigms of anxiety - the elevated plus maze (EPM), light/dark box (LDB), social interaction test and stress-induced hyperthermia (SIH) - was evaluated. RESULTS: Mice treated with PME (30-300 mg kg-1, p.o.) exhibited anxiolytic-like activity similar to diazepam in all the anxiety models used. The extract increased open arm activity (p<0.05) in the EPM as well as increasing the time spent in the lit area in relation to the time spent in the dark area of the LDB. Sociability and preference for social novelty significantly (p<0.05-0.001) increased in mice treated with PME. In the SIH paradigm in mice, both PME and the benzodiazepine receptor agonist, diazepam, significantly (p<0.05) reduced the stress-induced increase in rectal temperature. The extract did not impair motor coordination and balance in the beam walk test. CONCLUSIONS: Results of the present study indicate that PME possesses anxiolytic-like effects in mice.

Antidepressant-Like Effect of the Leaves of Pseudospondias microcarpa in Mice: Evidence for the Involvement of the Serotoninergic System, NMDA Receptor Complex, and Nitric Oxide Pathway.

Depression continues to be a major global health problem. Although antidepressants are used for its treatment, efficacy is often inconsistent. Thus, the search for alternative therapeutic medicines for its treatment is still important. In this study, the antidepressant-like effect of Pseudospondias microcarpa extract (30-300 mg kg(-1), p.o.) was investigated in two predictive models of depression--forced swimming test and tail suspension test in mice. Additionally, the mechanism(s) of action involved were assessed. Acute treatment with the extract dose dependently reduced immobility of mice in both models. The antidepressant-like effect of the extract (100 mg kg(-1), p.o.) was blocked by p-chlorophenylalanine and cyproheptadine but not prazosin, propranolol, or yohimbine. Concomitant administration of D-cycloserine and the extract potentiated the anti-immobility effect. In contrast, D-serine, a full agonist of glycine/NMDA receptors, abolished the effects. Anti-immobility effects of PME were prevented by pretreatment of mice with L-arginine (750 mg kg(-1), i.p.) and sildenafil (5 mg kg(-1), i.p.). On the contrary, pretreatment of mice with L-NAME (30 mg kg(-1), i.p.) or methylene blue (10 mg kg(-1), i.p.) potentiated its effects. The extract produces an antidepressant-like effect in the FST and TST that is dependent on the serotoninergic system, NMDA receptor complex, and the nitric oxide pathway.

Anticonvulsant Effect of Antiaris toxicaria (Pers.) Lesch. (Moraceae) Aqueous Extract in Rodents.

Antiaris toxicaria (Moraceae) was evaluated for anticonvulsant activity in rodents. Animal models used include maximal electroshock test (MEST); pentylenetetrazole-induced (PTZ) convulsions; picrotoxin-induced (PCT) convulsions; strychnine- (STR-) and 4-aminopyridine-induced convulsions. Increase in latency to seizures as well as reduction in duration and frequency of seizures indicated anticonvulsant activity. The extract was more effective in all models used except the maximal electroshock test and strychnine-induced convulsions. Antiaris toxicaria aqueous extract (200, 400, and 800 mg kg(-1)) significantly (P < 0.05 - 0.01) shortened the duration of convulsions in PTZ- and PCT-induced seizures. Delay in the onset of convulsions in the two tests was significant (P < 0.001). Reduction in the frequency of seizures was also significant (P < 0.05 - 0.001) in both tests. Antiaris further delayed the onset of seizures in 4-aminopyridine model while producing 75% protection against death in mice. Diazepam (0.1, 0.3, and 1 mg kg(-1)), carbamazepine (3, 10, and 30 mg kg(-1)), and sodium valproate (100-400 mg kg(-1)) were used as reference anticonvulsant drugs for various models. Flumazenil blocked the effect of the extract in the PTZ test significantly suggesting that Antiaris toxicaria may be acting by enhancing the effects of the GABAergic system. Antiaris toxicaria aqueous extract therefore possesses anticonvulsant activity.