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

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

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 extract (BAE) (50–1000 mg kg−1, 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−1p.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

Maerua angolensis

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 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

Correlates of patient satisfaction with pain management at the Ho Teaching Hospital in Ghana: A cross-sectional study

Pain is a symptom that many people who visit the hospital with various illnesses experience. Inadequate pain management has been regularly shown to have a negative impact on patients' health and reduce patient satisfaction. Patients' satisfaction with pain management is therefore important. The aim of this study was therefore to assess patients’ satisfaction and experience with pain management at the Ho Teaching Hospital, Volta Region, Ghana. The study was a prospective cross-sectional investigation and was carried out among 196 adult patients (older than 18 years) at the emergency, medical, and surgical wards. Data was collected using the 2010 version of the patient outcome and satisfaction survey questionnaire developed by the American Pain Society. Descriptive and inferential statistical analysis were employed in analysing the data obtained from the respondents. p-value less than 0.05 was considered as statistically significant.The results revealed that 96% of the respondents were satisfied with their pain management. Expectations for pain treatment (r = 0.221, p-value=0.002), percentage of pain relief in first 48 h (r = 0.439, p-value<0.001) and how helpful the information was (r = 0.158, p-value=0.027) were positively correlated with satisfaction with pain treatment. In addition, the median satisfaction with pain treatment was higher for those with knowledge on pain medication (p-value=0.043), and patients who were allowed to participate in decision-making indicated a higher level of satisfaction.The majority of patients (95% with acute pain and 100% with chronic pain) were satisfied with their pain management. Aside the effective use of analgesics, it was found that patient satisfaction can also be enhanced by good patient-provider relationships, providing patients with helpful information about their pain treatment, and allowing patients to participate in decisions about their pain management. This research is the first to provide such information for pain management in the Volta Region of Ghana

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

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