Synergistic antidepressant-like effect of xylopic acid co-administered with selected antidepressants.

Background: Xylopic acid (XA), a kaurene diterpene from the dried fruits of Xylopia aethiopica, has anxiolytic- and antidepressant-like activity in mice and zebrafish. We aimed to assess the potential synergistic antidepressant-like effects of XA when combined with selected antidepressants in the mouse forced-swim test. Materials and methods: The antidepressant-like effect of xylopic acid (XA) (10, 30, 100 mgkg-1), fluoxetine (Flx) (3, 10, 30 mgkg-1), sertraline (Sert) (3, 10, 30 mgkg-1), imipramine (Imi) (10, 30, 100 mgkg-1) and ketamine (Ket) (0.1, 0.3, 1.0 mgkg-1), was evaluated in forced swim test. The dose (ED50) that achieved a 50% reduction in immobility time was determined from the respective log-dose response curves. XA and the selected antidepressants were co-administered in fixed-dose ratio combinations (1/2:1/2, 1/4:1/4, 1/8:1/8) of the ED50 to identify the experimental ED50 (ED50mix). The theoretical ED50(ED50add), of all combinations was determined using isobolograms and compared with the ED50mix to identify the nature of the interaction. The effect of dose combinations on general locomotor activity was assessed in the open-field test. Results: The interaction index (γ) for the following XA combinations, XA/Flx, XA/Sert, XA/Imi and XA/Ket were 0.42, 0.41, 0.31 and 0.34. An independent sample t-test revealed that the experimental ED50 (ED50mix) was significantly lower than the theoretical ED50 (ED50add) in all combinations of XA, indicative of a synergistic antidepressant-like effect. However, combinations of XA with ketamine significantly reduced general locomotor activity at all dose combinations. Conclusion: The co-administration of xylopic acid and fluoxetine, imipramine, sertraline and ketamine produces a synergistic antidepressant-like effect in mice.

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.

Predictors of medication nonadherence among hypertensive clients in a Ghanaian population: Application of the Hill-Bone and Perceived Barriers to Treatment Compliance Scale.

Background and Aim: Nonadherence to antihypertensive medication impairs optimal blood pressure and is influenced by multiple interrelating factors. Knowing the complexity of medication nonadherence and its associated factors is essential for intervention strategies. This study evaluated the predictors of medication nonadherence among hypertensive clients in a Ghanaian population. Methods: This was a hospital-based cross-sectional study conducted at the Hypertensive Clinic of the Kwame Nkrumah University of Science and Technology (KNUST) Hospital, Kumasi, Ghana. A self-designed questionnaire, the Hill-Bone Compliance to High Blood Pressure Therapy and Perceived Barriers to Treatment Compliance Scales, were used for data collection from 246 hypertensives. Data were analyzed using Statistical Package for Social Sciences, version 25. Results: Medication nonadherence was observed among 8.5% of the study participants. In a multivariate regression model perceived noneffectiveness of medication (odds ratio [OR] = 1.76, 95% confidence interval [CI]: 1.34-2.31, p < 0.001) and barriers to alcohol and smoking cessation (OR = 2.83, 95% CI: 1.31-6.13, p = 0.008) were associated increased odds of antihypertensive medication nonadherence. Also, patients who do not know their total prescription (OR = 8.81, 95% CI: 2.28-34.0, p = 0.002) were more likely to be nonadherent to their antihypertensive medications. Moreover, clients who associate signs/symptoms of palpitations (OR = 5.82, 95% CI: 1.31-25.80, p = 0.021), poor sleep (OR = 3.92, 95% CI: 1.09-14.12, p = 0.036) and decreased sexual drive (OR = 4.74, 95% CI: 0.96-23.28, p = 0.055), were more likely to be nonadherent to antihypertensive medication. Conclusion: In conclusion, we observed a lower nonadherence rate among hypertensive clients in a Ghanaian population with correlates being medication-related factors. Most importantly, perceived noneffectiveness of medication, barriers to smoking and alcohol cessation, palpitations, poor sleep, and decreased sexual drive significantly predicted lower adherence and could serve as indicators for high risk of nonadherence to antihypertensive medications.

Antinociceptive effects of a hydroethanolic stem bark extract of Burkea africana.

INTRODUCTION: Pain is a major symptom of many clinical disorders and its relief has long been a concern for individuals across the globe. There is therefore an unmet need to search for new efficacious agents for the effective management of pain. The stem bark of the savanna tree Burkea africana (Hook) (Family: Leguminosae) is used in the Ghanaian traditional medicine for the treatment and management of various pain-related diseases. METHOD: An acute oral toxicity study in mice was conducted by administering BAE (50-5000 mg kg-1 p.o.). Antinociceptive effect of BAE (50-1000 mg kg-1 p.o.) was evaluated using the acetic acid-induced abdominal constriction, acidic saline-induced muscle pain and formalin-induced pain models. The antinociceptive mechanism of BAE was also assessed using the formalin-induced pain model. RESULTS: The LD50 of BAE was thus estimated to be above 5000 mg kg-1 since none of the animals died in the acute toxicity study. Pretreatment with BAE (50-1000 mg kg-1 p.o.) significantly reduced the number of writhes after acetic-acid administration compared to the vehicle treated group. BAE also produced a significant and dose-dependent reversal of mechanical hyperalgesia induced by the injection of the acidic saline. Administration of BAE was able to significantly suppress both phases of the formalin test. This effect of the extract was however reversed by pretreatment with naloxone and granisetron. CONCLUSIONS: BAE exhibits antinociceptive effects in rodent pain models with a possible involvement of 5-HT3 receptors and opioidergic pathways.

Drug Disposal and Ecopharmacovigilance Practices in the Krowor Municipality, Ghana.

Introduction: The use of medicines is a ubiquitous practice for the management of healthcare conditions. In the delivery of healthcare, medicines may remain unused and may expire within the various stakeholders in the pharmaceutical value chain. If these unused and expired medicines are not disposed of properly, they may result in the concentration of pharmaceuticals in environmental media contaminating food sources for humans and animals. Implementation of ecopharmacovigilance strategies will reduce the quantities of pharmaceuticals in the environmental media, reduce the potential for inadvertent consumption by humans and animals, and reduce potential pharmacological effects on the environment, humans, and animals. The drug disposal flow diagram (DDFD) provides an effective way of assessing the most cost-effective strategies to reduce environmental contamination. Method: A combined method of desk study and questionnaires, both structured and unstructured was used. The desk study reviewed the institutional arrangements for the regulation of disposal of pharmaceutical waste in Krowor. The questionnaires were used to gather information from community members, community pharmacies, and pharmaceutical manufacturers in Krowor. Results: The drug disposal flow diagram shows that up to 96% of pharmaceuticals are handled and disposed of in ways that are harmful to the environment with only 4% being handled in ways that are environmentally friendly. Forty-nine percent (49%) of generated pharmaceutical waste ends up in the local and surrounding areas, 21% contaminates the drainage system and 25% is discharged into receiving waters. Discussion. The DDFD for Krowor shows that engagement with community members and institutional healthcare service providers and strategies that result in separation of pharmaceutical waste from general household waste will reduce the quantities of pharmaceuticals that end up in the environmental media. Conclusion: The DDFD will support the effective implementation of ecopharmacovigilance (EPV) strategies.

The Anticonvulsant Effect of Hydroethanolic Leaf Extract of Calotropis procera (Ait) R. Br. (Apocynaceae).

A number of currently used drugs have been obtained from medicinal plants which are a major source of drugs. These drugs are either used in their pure form or modified to a semisynthetic drug. Drug discovery through natural product research has been fruitful over the years. Traditionally, Calotropis procera is used extensively in the management of epilepsy. This study is conducted to explore the anticonvulsant effect of a hydroethanolic leaf extract of Calotropis procera (CPE) in murine models. This effect was evaluated using picrotoxin-induced convulsions, strychnine-induced convulsions, and isoniazid- and pilocarpine-induced status epilepticus in mice of both sexes. The results showed that CPE (100-300 mg/kg) exhibited an anticonvulsant effect against strychnine-induced clonic seizures by significantly reducing the duration (p = 0.0068) and frequency (p = 0.0016) of convulsions. The extract (100-300 mg/kg) caused a profound dose-dependent delay in the onset of clonic convulsions induced by picrotoxin (p < 0.0001) and tonic convulsions (p < 0.0001) in mice. The duration of convulsions was reduced significantly also for both clonic and tonic (p < 0.0001) seizures as well. CPE (100-300 mg/kg), showed a profound anticonvulsant effect and reduced mortality in the pilocarpine-induced convulsions. ED50 (~0.1007) determined demonstrated that the extract was less potent than diazepam in reducing the duration and onset of convulsions but had comparable efficacies. Flumazenil-a GABAA receptor antagonist-did not reverse the onset or duration of convulsions produced by the extract in the picrotoxin-induced seizure model. In isoniazid-induced seizure, CPE (300 mg kg1, p.o.) significantly (p < 0.001) delayed the onset of seizure in mice and prolonged latency to death in animals. Overall, the hydroethanolic leaf extract of Calotropis procera possesses anticonvulsant properties.

Neuropharmacological Assessment of the Hydroethanolic Leaf Extract of Calotropis procera (Ait). R. Br. (Apocynaceae) in Mice.

BACKGROUND: Calotropis procera has been widely used traditionally for its analgesic and anti-inflammatory effects. It is also reportedly used in ethnomedicine for mental health disorders including epilepsy even in the absence of supporting scientific data. Thus, the potential of the plant to affect neurological functions was evaluated. METHODS: Irwin's test was performed to determine the effect of the oral administration of the extract (30-3000 mg kg-1) on gross behaviour and physiological function. The activity meter, rotarod, pentylenetetrazol- (PTZ-) induced convulsion, pentobarbitone-induced sleep test, and the tail immersion tests were used to evaluate the spontaneous activity, neuromuscular function, convulsive threshold, sedation, and analgesic effects of the Calotropis procera extract (30-1000 mg/kg), respectively, in mice. RESULTS: Calotropis procera extract (CPE) exhibited significant (p < 0.0001) anticonvulsant and analgesic effects. There was a significant increase in withdrawal latency of the CPE-treated animals in the tail immersion test for analgesia (p < 0.0001), while latency and duration of PTZ-induced convulsions were positively modulated. Calotropis procera extract showed significant (p < 0.0001) central nervous system depressant effects in pentobarbitone-induced hypnosis at 100-1000 mg/kg and spontaneous activity test (30-1000 mg/kg). The extract also depicted impaired motor coordination at 100-1000 mg/kg dose levels. LD50 was estimated to be above 1000 mg kg-1. CONCLUSIONS: Calotropis procera extract has significant central nervous system depressant and analgesic effects in mice.

Antinociceptive effect of the hydroethanolic leaf extract of Calotropis procera (Ait) R. Br. (Apocynaceae): Possible involvement of glutamatergic, cytokines, opioidergic and adenosinergic pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Pain remains real and still a major problem in clinical medicine which requires new agents with improved efficacy for more therapeutic benefits. Plant sources can serve as a basis for the search for some novel drugs hence the analgesic effects of the hydroethanolic extract of Calotropis procera (CPE) which is widespread in Ghana and other tropical areas and used in folkloric medicine for painful and inflammatory conditions was evaluated. MATERIALS AND METHODS: The analgesic properties of orally administered CPE at doses of 30, 100, and 300 mg/kg were evaluated in thermal (tail immersion), chemical (acetic acid-writhing, formalin-induced paw licking, glutamate-induced nociception) and mechanical (Randall-Selitto) tests for analgesia. The involvement of tumour necrosis factor-alpha (TNF-α), interleukin 1ß (IL 1ß), bradykinin, and prostaglandin E2 (PGE2) on the analgesic effects of CPE were also evaluated in hypernociception assays measuring mechanical pain thresholds. RESULTS: The latency of tail withdrawal in the tail immersion test was significantly increased (p = 0.0001) while writhing induced by acetic acid was significantly reduced (p < 0.0001) on treatment with CPE (30-300 mg/kg). The extract also significantly inhibited both phase 1 and phase 2 nociceptive states induced by formalin comparable to morphine (p < 0.0001). Furthermore, the extract significantly attenuated hyper-nociception induced by TNF-α (p < 0.0001), interleukin 1ß (p = 0.0102), bradykinin (p < 0.0001), and prostaglandin E2 (p < 0.0001). Additionally, glutamate-induced paw licking was reduced significantly (p < 0.05). The antinociceptive effects exhibited by CPE (100 mg/kg) in the formalin test was reversed by systemic administration of naloxone (2 mg/kg) and theophylline (5 mg/kg) but not glibenclamide (8 mg/kg), granisetron (2 mg/kg), atropine (3 mg/kg), yohimbine (3 mg/kg, p.o.) nor nifedipine (10 mg/kg). CONCLUSION: Overall, the hydroethanolic leaf extract of Calotropis procera possesses analgesic properties that is mediated possibly through the glutaminergic, opioidergic, and adenosinergic pathways.

Medicinal Plants with Prospective Benefits in the Management of Peptic Ulcer Diseases in Ghana.

BACKGROUND: The growth or multiplication of harmful microorganisms in addition to harmful human activities has led to many disorders in humans. Consequently, there is a search for medications to treat these disorders. Interestingly, medicines of plant origin are known to be among the most attractive sources of new drugs and have shown promising results in the treatment of various diseases including peptic ulcers. This review, therefore, is aimed at obtaining knowledge on some Ghanaian ethnomedicinal plants used to treat peptic ulcers, their folkloric uses, their phytochemicals, and their antiulcer and related pharmacological activities as well as finding areas for prospective studies. METHODS: Published peer-reviewed articles on ethnomedicinal plants used for the management of peptic ulcers in Ghana from 1967 to 2020 were sourced and used for the study. RESULTS: In this review, 13 plants were identified which belong to 10 different families including Sapindaceae, Apocynaceae, and Bignoniaceae. The parts most often used for most preparations were the leaves (53%), followed by stem bark and roots (both having the same percentage of use of 17.6%), the whole plant (5.9%), and the rhizomes (5.9%). Azadirachta indica was the only plant that had undergone some patient studies in addition to animal studies. Conclusion. A discussion of various antiulcer activity studies using ulcer models carried out on selected medicinal plants used for the management of peptic ulcer disease in addition to brief information on their folkloric uses and their phytochemical and other pharmacological properties is presented. These medicinal plants may be used in developing herbal products for the management of peptic ulcer disease.

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.

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.

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.

Antipleuritic and Vascular Permeability Inhibition of the Ethyl Acetate-Petroleum Ether Stem Bark Extract of Maerua angolensis DC (Capparaceae) in Murine.

Maerua angolensis has been used traditionally in the management of pain, arthritis, and rheumatism in Ghana and Nigeria but no scientific evidence is currently available to give credence to its folkloric use. The aim of this study was therefore to evaluate the anti-inflammatory effects of a stem bark extract of Maerua angolensis DC (MAE) in acute inflammatory models. The effects of MAE (30-300 mg kg-1) on neutrophil infiltration, exudate volume, and endogenous antioxidant enzymes in lung tissues and lung morphology were evaluated with the carrageenan induced pleurisy model in Sprague Dawley rats. The effects of MAE (30-300 mg kg-1) on vascular permeability were also evaluated in the acetic acid induced vascular permeability in ICR mice. MAE significantly reduced neutrophil infiltration, exudate volume, and lung tissue damage in carrageenan induced pleurisy. MAE increased the activities of antioxidant enzymes glutathione, superoxide dismutase, and catalase in lung tissues. The extract was also able to reduce myeloperoxidase activity and lipid peroxidation in lung tissues in carrageenan induced rat pleurisy. Vascular permeability was also attenuated by the extract with marked reduction of Evans blue dye leakage in acetic acid induced permeability assay. The results indicated that Maerua angolensis is effective in ameliorating inflammation induced by carrageenan and acetic acid. It also has the potential of increasing the activity of endogenous antioxidant enzymes.

Albizia zygia root extract exhibits antipsychotic-like properties in murine models of schizophrenia.

BACKGROUND: The root extract of Albizia zygia (DC.) J.F. Macbr. (Leguminosae) is used to manage mental disorders in African traditional medicine. However, its value, particularly, against negative and cognitive symptoms of schizophrenia have not been evaluated. AIM: The aim of this study was to evaluate the antipsychotic properties of the hydroethanolic root extract of Albizia zygia (AZE) against positive, negative and cognitive symptoms of schizophrenia in animal models. MATERIALS AND METHODS: The effects of AZE (30-300 mg kg-1) were evaluated against apomorphine-induced cage climbing as well as ketamine -induced hyperlocomotion, -enhanced immobility, -impaired social interaction and novel object recognition. The propensity of AZE to induce catalepsy and to attenuate haloperidol-induced catalepsy were also investigated. RESULTS: AZE 30-300 mg kg-1 significantly reduced apomorphine-induced climbing behaviour as well as ketamine-induced hyperlocomotion, immobility and object recognition deficits (at least P < 0.05). Moreover, the extract showed no cataleptic effect but significantly inhibited haloperidol-induced catalepsy at a dose of 30 mg kg-1 (P < 0.05). CONCLUSION: The root extract of Albizia zygia exhibited an antipsychotic-like activity in mice with potential to alleviate positive, negative and cognitive symptoms of schizophrenia.

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.

An isobolographic analysis of the anti-nociceptive effect of geraniin in combination with morphine or diclofenac.

BACKGROUND: Geraniin, a dehydroellagitannin, is a major component of the aqueous extract of the aerial parts of Phyllanthus muellerianus (Kuntze) Exell. (Euphorbiaceae). Several Phyllanthus species are traditionally used for painful disorders. The anti-nociceptive effects of the aqueous extract of the aerial parts of P. muellerianus and of geraniin have been scientifically established. The aim of the paper is to determine whether a combination of geraniin and diclofenac or geraniin and morphine leads to better anti-nociceptive effects. METHODS: The nature of the interactions of morphine and diclofenac with geraniin was evaluated by undertaking the isobolographic analysis. Mice were treated with geraniin (3-30 mg/kg), morphine (1-10 mg/kg), and diclofenac (10-100 mg/kg) to obtain the ED50 values of the agents in the formalin test. Dose-response curves were then obtained and analyzed after the co-administration of geraniin with morphine or diclofenac in fixed ratio (1:1) combinations based on specific fractions (1/2, 1/4, and 1/8) of their respective ED50 values for the formalin test. RESULTS: Geraniin was less potent than morphine but more potent than diclofenac in the formalin-induced nociception. The isobolographic analysis of geraniin/morphine (G/M) and geraniin/diclofenac combinations (G/D) at different fractions revealed the potentiation of their anti-nociceptive effects. The degrees of potentiation, which were calculated as interaction indices, showed synergism for both combinations in both phase I (G/M: 0.040, G/D: 0.017) and phase II (G/M: 0.004, G/D: 0.002) of the formalin test. CONCLUSIONS: The present study demonstrates synergism for the co-administration of geraniin with both morphine and diclofenac.