Donatus Wewura Adongo

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 activity of Pseudospondias microcarpa (A. Rich) Engl. hydroethanolic leaf extract in mice: The role of excitatory/inhibitory neurotransmission and nitric oxide pathway

ETHNOPHARMACOLOGICAL RELEVANCE Pseudospondias microcarpa (A. Rich) Engl. is a plant used for managing various diseases including central nervous system disorders. AIM OF THE STUDY This study explored the anticonvulsant activity of P. microcarpa hydroethanolic leaf extract (PME) as well as possible mechanism(s) of action in animal models. METHODS Effects of PME was assessed in electroconvulsive (the maximal electroshock and 6-Hz seizures) and chemoconvulsive (pentylenetetrazole-, picrotoxin-, isoniazid-, 4-aminopyridine-, and strychnine-induced seizures) models of epilepsy. In addition, effect of the extract on the nitric oxide pathway and GABAA receptor complex was evaluated. RESULTS The extract (30, 100 and 300mgkg-1, p.o.) significantly delayed the onset as well as decreased the duration and frequency of pentylenetetrazole-, picrotoxin- and strychnine-induced seizures. In addition, PME pre-treatment significantly improved survival in the 4-aminopyridine- and isoniazid-induced seizure tests. Furthermore, the extract protected against 6-Hz psychomotor seizures but had no effect in the maximal electroshock test. The anticonvulsant effect of PME (100mgkg-1, p.o.) was also reversed by pre-treatment with flumazenil, L-arginine or sildenafil. However, L-NAME or methylene blue (MB) augmented its effect. CONCLUSION Results show that PME has anticonvulsant activity and may probably be affecting GABAergic, glycinergic, NMDA, K+ channels and nitric oxide-cGMP pathways to exert its effect.

Antidepressant Effects of Mallotus oppositifolius in Acute Murine Models

Objective. Hydroalcoholic extract of leaves of Mallotus oppositifolius (MOE), a plant used for CNS conditions in Ghana, was investigated for acute antidepressant effects in the forced swimming (FST) and tail suspension tests (TST). Results. In both FST and TST, MOE (10, 30, and 100 mg kg−1) significantly decreased immobility periods and frequencies. A 3-day pretreatment with 200 mg kg−1, i.p., para-chlorophenylalanine (PCPA), a tryptophan hydroxylase inhibitor, reversed the decline in immobility and the increase of swimming score induced by MOE in the modified FST. Pretreatment with reserpine alone (1 mg kg−1), α-methyldopa alone (400 mg kg−1, i.p.), or a combination of both drugs failed to reverse the decline in immobility or the increase in swimming score caused by the extract in the modified FST. The extract potentiated the frequency of head twitch responses induced by 5-hydroxytryptamine. Pretreatment with d-serine (600 mg kg−1, i.p.), glycine/NMDA agonist, abolished the behavioural effects of MOE while d-cycloserine (2.5 mg kg−1, i.p.), a glycine/NMDA partial agonist, potentiated it in both TST and modified FST. Conclusion. The extract exhibited antidepressant effects in mice which is mediated by enhancement of serotoninergic neurotransmission and inhibition of glycine/NMDA receptor activation.

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.

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.

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.

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

Abstract 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.

Scientific evidence of plant with a rapid-onset and sustained antidepressant effect in a chronic model of depression: Mallotus oppositifolius.

Abstract Background: One of the major drawbacks of current depression pharmacotherapy is the delay in symptom improvement, aside from the untoward side effects and lack of efficacy against refractory depression. This work therefore investigated a possible rapid-onset and sustained antidepressant effect of Mallotus oppositifolius. Methods: Onset of the antidepressant effect of hydroalcoholic extract from the leaves of M. oppositifolius was investigated using the open space swim test, a chronic depression model. The possible effects of the extract on cognitive dysfunction measured in the Morris water maze and weight gain were also investigated. Results: M. oppositifolius extract, after the first day of treatment, reversed the state of immobility in mice. This effect was sustained even after drug treatment was halted and the antidepressant effect verified in the tail suspension test. The extract also increased the total distance travelled by the mice and reversed the cognitive impairment induced by the depressed state but had no effect on weight variation. Conclusions: M. oppositifolius exhibits a rapid-onset and sustained antidepressant effect in mice.

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.

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.