Evaluation of packaging, labels, and some physicochemical properties of herbal antimalarial products on the Ghanaian market.

Introduction: Malaria is a parasitic disease that is endemic in tropical areas and can be life-threatening. There has been a decrease in the prevalence of malaria in Ghana but the burden of the disease is still high in the country. Many Ghanaians depend on herbal products for malaria treatment. This study aimed to survey and evaluate commercial herbal antimalarials in the Volta Region of Ghana. Methods: A survey of finished herbal antimalarials was done at herbal shops, pharmacies, and over-the-counter medicine seller shops. Products available on shelves were purchased and their details were recorded, after which they were examined using a visual inspection tool. The density, pH, and extract weight per dose of each sample were also determined. Results: Thirty-four liquid formulations (A-1-34) containing 1-9 different herbs were found. The majority of the product labels had errors in consumer age classifications. Unconventional ways of stating doses were found on two products (A-13, "tot"; A-19, cupful). Six products did not have dosing devices. No duration of treatment was indicated on 24 products. Dose errors were found on A-14 and A-22. Samples A-17 and A-28 did not have registration or batch numbers. Product A-28 did not have its herbs listed on it and was indicated for persons aged 3-8 years at a dose of 45 mL. The relative density range for the products was 0.997-1.015. From the pH investigation, no product was extremely erosive; however, 10 samples were deemed erosive (pH, 3.0-3.99), whereas 24 were minimally erosive (pH, ≥4.0). The extract weight per dose volume (20-90 mL) was 0.048-1.766 g, indicating that unit dose capsules or tablets could be formulated from the products. Conclusion: The findings clearly show that Ghanaian authorities responsible for regulating herbal products must enforce guidelines for the formulation, label details, and sale of antimalarial products. Additionally, the unpleasant taste of liquid herbal mixtures can affect patient compliance and dosing convenience; therefore, it is recommended that oral solid dosage forms of herbal antimalarials are produced as alternatives to the liquid mixtures.

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.

Flavanols and triterpenoids from Myrianthus arboreus ameliorate hyperglycaemia in streptozotocin-induced diabetic rats possibly via glucose uptake enhancement and α-amylase inhibition.

Myrianthus arboreus is use traditionally as an antidiabetic agent in Ghana. We reported the in vivo antidiabetic activity of its 70 % ethanol stem bark extract (MAB) which we found to be strongly concentrated in its EtOAc fraction using glucose uptake and enzyme inhibitory assays. The present study sought to investigate the in vivo hypoglycaemic and anti-hyperlipidaemic activity of this ethyl acetate fraction of MAB (MAB-EtOAc, 50 and 100 mg/kg) in streptozotocin (STZ)-induced diabetic rats for 21 days, isolate and evaluate the bioactive constituents responsible for the antidiabetic activity. In silico pharmacokinetic and toxicity properties of the most active compound was also determined. MAB-EtOAc significantly (p < 0.001) reduced the blood glucose levels while normalizing considerably the altered serum lipid parameters of the diabetic rats which was comparable to glibenclamide (5 mg/kg). Chemical investigation of MAB-EtOAc led to the isolation of seven known compounds including three flavanols which are reported for the first time in the plant: epicatechin (1), epigallocatechin (2), dulcisflavan (3), euscaphic acid (4), tormentic acid (5), sitosterol-3-O-ß-d-glucopyranoside (6) and arjunolic acid (7). The compounds markedly inhibited the action of α-amylase and, except for 4 and 6, which stimulated considerably glucose uptake in C2C12 cells. Compounds 2, 3, 5, 6 and 7 which were further evaluated in STZ-induced diabetic rats demonstrated hypoglycaemic and anti-hyperlipidaemic activities which, however, were not comparable with MAB-EtOAc. Compound 3, the most active compound was predicted to be non-toxic, non-mutagenic, has reasonable oral bioavailability and a decent substrate for further drug development. The findings of this study show that the isolated compounds may contribute to the antidiabetic activity of M. arboreus and could serve as marker compounds for the quality control of herbal medicines that would be made from the plant.

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.

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.

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.

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.