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.

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 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.

The possible mode of antitussive and expectorant activity of the ethanol seed extracts of Picralima nitida ((Stapf) Th. & H. Durand).

It has been established that Picralima nitida has antitussive effect. This study therefore aimed at determining the possible mode of antitussive and expectorant activity of an ethanolic seed extract of P. nitida (PNE). The muco-suppressant, mast cell stabilization, and the anxiolytic effects of PNE were ascertained using ammonium chloride-induced phenol red secretion in BALB/c mice; compound 48/80-induced mesenteric mast cell degranulation assay; and the open field and the elevated plus maze models respectively. Antibacterial potential was ascertained by the agar plate diffusion method and its antioxidant potential by the 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH) free radical scavenging, linoleic acid lipid peroxidation, reducing power, and total antioxidant assays. Data obtained was analyzed using One-way analysis of variance (ANOVA) with Dunnett's Multiple Comparison post hoc test. PNE (100-500 mg/kg) reduced (P ≤ 0.05-0.001) tracheal phenol red secretion. The extract (100-500 µg/ml) also dose-dependently (P ≤ 0.05-0.0001) stabilized mast cells. PNE (100-500 mg/kg) increased open arm activities in the elevated plus maze (P ≤ 0.05) as well as central zone exploration (P ≤ 0.05) in the open field test. PNE (10-50 mg/ml) showed activity against Staphylococcus aureus, Streptococcus pneumonia, Escherichia coli, Klebsiella pneumonia, and Salmonella typhi. By the assays, PNE showed significant antioxidant effect. The ethanolic seed extract of P. nitida has demonstrated very significant mast cell stabilizing, mucus suppressant, and antioxidant activity as well as substantial antibacterial and anxiolytic properties; all of which could contribute to its antitussive and expectorant property.

Analgesic properties of aqueous leaf extract of Haematostaphis barteri: involvement of ATP-sensitive potassium channels, adrenergic, opioidergic, muscarinic, adenosinergic and serotoninergic pathways.

BACKGROUND: Pain is the most common cause of patients seeking medical advice as a result of its association with different pathologies. This study evaluated the antinociceptive property of Haematostaphis barteri as well as the possible mechanism(s) associated with its antinociceptive property. METHODS: Mice were administered H. barteri (30-300 mg kg-1; p.o.), followed by intraplantar injection of 10 µL of 5% formalin into the hind paws. The pain score was determined for 1 h in the formalin test. The possible nociceptive pathways involved in the antinociceptive action of H. barteri were determined by pre-treating mice with theophylline (5 mg kg-1, a non-selective adenosine receptor antagonist), naloxone (2 mg kg-1, a non-selective opioid receptor antagonist), glibenclamide (8 mg kg-1; an ATP-sensitive K+ channel inhibitor), and atropine (3 mg kg-1; non-selective muscarinic antagonist). RESULTS: H. barteri (30-300 mg kg-1) significantly and dose dependently precluded both first and second phases of nociception. Pre-treatment with naloxone had no effect on the analgesic activities of H. barteri in the first phase. Again, pre-treatment with atropine and glibenclamide did not significantly reverse the neurogenic antinociception of the extract in phase 1. However, theophylline reversed the analgesic effect of the extract in the first phase. In phase 2, theophylline had no effect on the analgesic activities of the extract. Naloxone, atropine, and glibenclamide significantly blocked the antinociception of H. barteri in the inflammatory phase of the formalin test. CONCLUSIONS: H. barteri possesses antinociceptive property mediated via the opioidergic, adrenergic, muscarinic, ATP-sensitive K+ channels, and adenosinergic nociceptive pathways.

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.