Preclinical evidence of a rapid-onset antidepressant-like effect of Pseudospondias microcarpa hydroethanolic leaf extract in a chronic depression model

Background: Depression is a widespread, devastating mental illness and currently available treatments have significant limitations including low response rates and delayed onset of action. N-methyl-D-aspartate (NMDA) receptor antagonists exert fast-acting antidepressant effects. Pseudospondias microcarpa produces an antidepressant-like effect via inhibition of the glycine/NMDA receptor complex, and could therefore possess a rapid onset of action. Therefore, the present study investigated the possible rapid-onset antidepressant action of P. microcarpa in mice.Methods: In this study, rapid-onset and sustained antidepressant effects of the hydroethanolic leaf extract of P. microcarpa (PME) was investigated in the open-space swim test, a chronic model of depression. Antidepressant effect was further assessed in the tail suspension test (TST). In addition, the effect of the extract on cognitive function in the Morris water maze (MWM) test was investigated.Results: Depressed mice showed a significant increase in immobility and decrease in distance swum. However, treatment with PME and the classical antidepressants significantly decreased immobility time and increased distance swum. Furthermore, unlike the classical antidepressants which required 10-14 days to significantly improve mobility behaviour, PME treatment significantly decreased immobility time (P<0.001) on the first day of treatment (day 5 of stress procedure). This effect was also sustained for the remainder of the experiment. The extract also significantly decreased immobility time in the TST (F3,16=4.881, P=0.0135) and decreased escape latency (F4,24=12.07, P<0.0001) in the MWM procedure.Conclusions: The leaves of P. microcarpa exhibits rapid and sustained antidepressant effects and improve cognitive function in depressed mice

Antidepressant-like properties of Antiaris toxicaria aqueous extract

Background: Depression is a global burden whose therapy is plagued with inconsistent efficacy. Hence, the need for the discovery of newer therapies.Methods: In this study, Antiaris toxicaria extract (200, 400 and 800 mg/kg, p.o.), was evaluated for antidepressant activity using behavioral tests battery particularly the forced swim test (FST) and tail suspension test (TST). In order to investigate its mechanism of action, animals groups were pretreated with α-methyldopa (α-MD), para-chlorophenylalanine (PCPA), reserpine, D-serine and 5-hydroxytryptophan.Results: It increased the mobility periods and decreased immobility periods significantly in both the FST and the TST when compared to the control group. But the TST showed more promising effect than the FST. Pre-treatment with α-MD reversed the antidepressant property of A. toxicaria aqueous extract as did PCPA, reserpine and reserpine combined with α-MD. The extract increased the number of head twitches produced by 5-hydroxytryptophan confirming the involvement of serotonin in the antidepressant property and inhibited carbachol-induced contractions on the isolated rat uterus, which was non-competitively antagonized by propranolol.Treatment with D-serine produced no significant increase in the immobility time produced by the extract at the doses studied. This excludes the involvement of N-methyl-d-aspartate in the possible mechanisms of action.Conclusion: A. toxicaria possesses antidepressant-like action in rodents

Subchronic toxicity studies of cocoa pod husk pectin intended as a pharmaceutical excipient in Sprague Dawley rats

Context: Excipients play a key role in the quality of medicines and contribute to viable delivery systems. This has intensified the search for new natural polymer pharmaceutical excipients. Cocoa pod husks (CPHs) are a rich source of pectin. A study of CPH pectin showed that it possesses the requisite physicochemical properties to be employed as a multi-functional pharmaceutical excipient. However, the safety of this natural polymer has not been evaluated. Aims: To conduct sub-chronic toxic effects of CPH pectin in Sprague Dawley rats to assess its safety as a pharmaceutical grade excipient. Methods: CPH pectin at doses of 0.714, 7.14, and 71.4 mg/kg were administered to male and female Sprague-Dawley rats by oral gavage over a 90-day period. Parameters assessed were food and water intake, urinalysis, serum biochemistry, wet organ weights, histopathology and pentobarbital-induced sleeping time. Results: CPH pectin at the orally administered doses had no significant effects on feed and water intake nor on biochemical parameters, except elevations in alkaline phosphatase at the medium and high dose in the female rat. There were also reductions in creatine kinase in both male and female rats at the medium dose after 60 days, suggesting a potential cardioprotective effect of CPH pectin. Conclusions: There were no adverse effects of CPH pectin on the kidneys, wet organ weights and histopathology of the rat tissues. Subchronic administration of cocoa pod husk pectin therefore, has no significant toxic effects

Synedrella nodiflora extract depresses excitatory synaptic transmission and chemically-induced in vitro seizures in the rat hippocampus

Extracts of the tropical Cinderella plant Synedrella nodiflora are used traditionally to manage convulsive conditions in the West African sub-region. This study sought to determine the neuronal basis of the effectiveness of these plant extracts to suppress seizure activity. Using the hippocampal slice preparation from rats, the ability of the extract to depress excitatory synaptic transmission and in vitro seizure activity were investigated. Bath perfusion of the hydro-ethanolic extract of Synedrella nodiflora (SNE) caused a concentration-dependent depression of evoked field excitatory postsynaptic potentials (fEPSPs) recorded extracellularly in the CA1 region of the hippocampus with maximal depression of about 80% and an estimated IC50 of 0.06 mg/ml. The SNE-induced fEPSP depression was accompanied by an increase in paired pulse facilitation. The fEPSP depression only recovered partially after 20 min washing out. The effect of SNE was not stimulus dependent as it was present even in the absence of synaptic stimulation. Furthermore, it did not show desensitization as repeat application after 10 min washout produced the same level of fEPSP depression as the first application. The SNE effect on fEPSPs was not via adenosine release as it was neither blocked nor reversed by 8-CPT, an adenosine A1 receptor antagonist. In addition, SNE depressed in vitro seizures induced by zero Mg2+ and high K+ -containing artificial cerebrospinal fluid (aCSF) in a concentration-dependent manner. The results show that SNE depresses fEPSPs and spontaneous bursting activity in hippocampal neurons that may underlie its ability to abort convulsive activity in persons with epilepsy

Psychotropic Effects of an Alcoholic Extract from the Leaves of Albizia zygia

Background. Albizia zygia is used in Ghanaian traditional medicine for the management of mental disorders. The present study tested the hypothesis that an extract of the leaves of Albizia zygia (AZE) may possess antipsychotic and antidepressant properties. Method. The novelty- and apomorphine-induced locomotor and rearing behaviours of AZE in mice were explored in an open-field observational test system. The effects of AZE in apomorphine-induced cage climbing test, extract-induced catalepsy, and haloperidol-induced catalepsy on mice were also investigated. Lastly, the forced swimming and tail suspension tests in mice were employed to screen the possible antidepressant effects of AZE. Results. AZE (100–3000 mg/kg) showed signs of central nervous system (CNS) depression under observation, with no lethality, 24 h after treatment in mice. AZE (100–1000 mg/kg) produced a significant decrease in the frequency of novelty- and apomorphine-induced locomotor activities in mice. The extract also significantly decreased the frequency and duration of apomorphine-induced climbing activities in mice. AZE, while failing to produce any cataleptic event in naïve mice, significantly enhanced haloperidol-induced catalepsy at a dose of 1000 mg/kg. However, AZE did not produce any significant antidepressant effects in the test models employed. Conclusion. The extract of Albizia zygia exhibited an antipsychotic-like activity in mice

Rapid-onset antidepressant-like effect of sub-therapeutic dose of iron in combination with citalopram or imipramine in mice

In this study, we hypothesize that sub-therapeutic dose of iron combined with classical antidepressants such as citalopram and imipramine will produce rapid-onset antidepressant-like effect in mice. First, the study assessed the antidepressant effects of iron, citalopram or imipramine alone in murine behavioral models. Behavioral tests such as forced swim, tail suspension and open space swim tests were used to collect data on depression-related symptoms. We used the open field test to assess locomotor activity. After the first phase of experiments, dose response curves were plotted and the median dose (ED50) of drugs were calculated using non-linear regression analysis of the dose response curves. From this analysis, the sub-therapeutic dose of iron was selected. In phase 2, the effect of sub-therapeutic dose of iron plus imipramine or citalopram on depression was evaluated using the murine models stated previously. After these behavioral tests, the ELISA test was used to assess concentration of brain-derived neurotrophic factor levels while the Golgi-Cox technique provided information on dendritic spine density of treatment mice.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

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

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

Antidepressant Potentials of Components from Trichilia monadelpha (Thonn.) J.J. de Wilde in Murine Models

Trichilia monadelpha is a common medicinal plant used traditionally in treating central nervous system conditions such as epilepsy, depression, pain, and psychosis. In this study, the antidepressant-like effect of crude extracts of the stem bark of T. monadelpha was investigated using two classical murine models, forced swimming test (FST) and tail suspension test (TST). The extracts, petroleum ether, ethyl acetate, and hydroethanolic extracts (30–300 mg/kg, p.o.), standard drug (imipramine; fluoxetine, 3–30 mg/kg, p.o.), and saline (vehicle) were given to mice one hour prior to the acute study. In a separate experiment the components (flavonoids, saponins, alkaloids, tannins, and terpenoids; 30–300 mg/kg, p.o.) from the most efficacious extract fraction were screened to ascertain which components possessed the antidepressant effect. All the extracts and components significantly induced a decline in immobility in the FST and TST, indicative of an antidepressant-like activity. The extracts and some components showed increase in swimming and climbing in the FST as well as a significant enhancement in swinging and/or curling scores in the TST, suggesting a possible involvement of monoaminergic and/or opioidergic activity. This study reveals the antidepressant-like potential of the stem bark extracts and components of T. monadelpha