Elvis Ofori Ameyaw

Anti-allodynic and Anti-hyperalgesic effects of an ethanolic extract and xylopic acid from the fruits of Xylopia aethiopica in murine models of neuropathic pain

Background: Fruit extracts of Xylopia aethiopica are used traditionally in the management of pain disorders including headache and neuralgia. An animal model of vincristine-induced sensory neuropathy was developed after repeated intraperitoneal injection in rats and used in the present work to study the effects of the ethanolic extract of X. aethiopica (XAE) and its diterpene xylopic acid (XA) in vincristine-induced neuropathic pain. Materials and Methods: Vincristine (0.1 mg kg-1 day-1) was administered during two cycles of five consecutive days to induce chemotherapy-induced neuropathic pain. Static tactile anti-allodynic, anti-hyperalgesic, and cold anti-allodynic effects of XAE (30-300 mg kg-1) and XA (10-100 mg kg-1) were assessed using Von Frey filaments of bending forces of 4, 8, and 15 g, the Randall-Selitto paw pressure test, and cold water (4.5°C), respectively. Results: Administration of vincristine caused the development of allodynia and hyperalgesia with no significant motor deficit, spontaneous pain, and foot deformity. XAE (30-300 mg kg-1) and XA (10-100 mg kg-1) exhibited anti-hyperalgesic, tactile, and cold anti-allodynic properties with XA exhibiting greater potency than XAE. Pregabalin (10-100 mg kg-1) used as control produced similar effect. Conclusion: These findings establish the anti-allodynic and anti-hyperalgesic effects of the ethanolic fruit XAE and its major diterpene XA in vincristine-induced neuropathtic pain.

Xylopia aethiopica fruit extract exhibits antidepressant-like effect via interaction with serotonergic neurotransmission in mice

ETHNOPHARMACOLOGICAL RELEVANCE Xylopia aethiopica has been used traditionally to treat some central nervous system disorders including epilepsy. AIM OF THE STUDY Despite the central analgesic and sedative effects, there is little evidence for its traditional use for CNS disorders. This study thus assessed the antidepressant potential of Xylopia aethiopica ethanolic fruit extract (XAE). MATERIAL AND METHODS Antidepressant effect was assessed in the forced swim test (FST) and tail suspension test (TST) models in mice. The role of monoamines in the antidepressant effects of XAE was evaluated by selective depletion of serotonin and noradrenaline, whereas involvement of NMDA/nitric oxide was assessed with NMDA receptor co-modulators; d-serine and d-cycloserine and NOS inhibitor, l-NAME. RESULTS Xylopia aethiopica (30, 100, 300mgkg(-1)) dose dependently reduced immobility in both FST and TST. The reduced immobility was reversed after 5-hydroxytryptamine (5-HT) depletion with tryptophan hydroxylase inhibitor-p-chlorophenylalanine (pCPA) and after monoamine depletion with vesicular monoamine transporter inhibitor-reserpine. The observed antidepressant effect was not affected by catecholamine depletion with the tyrosine hydroxylase inhibitor, α-methyl-p-tyrosine (AMPT). Similarly XAE did not potentiate the toxicity of a sub-lethal dose of noradrenaline. XAE had a synergistic effect with the glycineB receptor partial agonist, d-cycloserine and nitric oxide synthase inhibitor, l-NAME. However established antidepressant effects of XAE were abolished by NMDA and NOS activation with d-serine and l-arginine. CONCLUSION This study shows that Xylopia aethiopica has antidepressant potential largely due to effects on 5-HT neurotransmission with possible glutamatergic effect through the glycineB co-binding site and nitric oxide synthase inhibition.

Antidiabetic Effect of Young and Old Ethanolic Leaf Extracts of Vernonia amygdalina: A Comparative Study

The young leaves of Vernonia amygdalina are often utilized as vegetable and for medicinal purpose compared to the old leaves. This study was designed to evaluate and compare the antidiabetic effects between ethanolic leaf extracts of old and young V. amygdalina on streptozotocin (STZ) induced diabetic rat for four weeks. Preliminary screening of both young and old ethanolic extracts revealed the presence of the same phytochemicals except flavonoids which was only present in the old V. amygdalina. Difference in antioxidant power between the young and old leaf extracts was statistically significant (p < 0.05). Both leaf extracts produced a significant (p < 0.05) antihyperglycaemic effect. Also results from treated rats revealed increasing effect in some haematological parameters. Similarly, the higher dose (300 mg/kg) of both extracts significantly (p < 0.05) reduced serum ALT, AST, and ALP levels as compared to the diabetic control rats. Results also showed significant (p < 0.05) decrease in LDL-C and VLDL-C in the extract-treated rats with a corresponding increase in HDL-C, as compared to the diabetic control rats. Moreover histopathological analysis revealed ameliorative effect of pathological insults induced by the STZ in the pancreas, liver, and spleen, most significantly the regeneration of the beta cells of the islets of Langerhans in treated rats.

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.

Use of proscribed chloroquine is associated with an increased risk of pfcrt T76 mutation in some parts of Ghana

BackgroundAfter years of disuse of chloroquine (CQ) as first-line anti-malarial drug in Ghana, reports from molecular studies conducted in parts of the country indicate varying prevalence of T76 mutation in the pfcrt gene. This situation has several health implications, one being that mutations that confer resistance to CQ have been reported to show substantial cross-resistance to other anti-malarial drugs. It is important to identify some of the factors contributing to the continuous presence of CQ resistance markers in the country. This study determined the prevalence of T76 mutation in pfcrt gene of Plasmodium falciparum isolates collected from selected areas of the Central region of Ghana and correlated with the level of CQ use in these areas.MethodsPlasmodium falciparum DNA was extracted from collected blood-blot filter paper samples in the study sites. The prevalence of T76 point mutation in pfcrt gene was assessed using nested PCR followed by RFLP. CQ from pharmacy and chemical shops was obtained using mystery buying method. The extent of CQ use by the participants was determined by measuring the level of the drug in their urine samples using the Saker-Solomon method.ResultsOf the 214 P. falciparum isolates analysed, 71.9% were found to have T76 mutation of pfcrt gene. The study revealed that 14.49% of community pharmacies and chemical shops had stocks of CQ for sale while 16.9% of the participants had CQ in their urine samples. There is five times more risks of becoming infected with CQ resistant strain for staying in an area where CQ is stocked for sale [RR = 0.20, p < 0.0001] and thirteen times more risks of having CQ-resistant mutant from those who still use CQ than non-users [OR = 0.08, p < 0.0001].ConclusionThis study has shown that high variation in the prevalence of T76 mutations of P. falciparum is linked with the level of CQ stocking and usage within study area.

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.

An isobolographic analysis of the antinociceptive effect of xylopic acid in combination with morphine or diclofenac.

Background: A common practice of managing pain globally is the combination of analgesics and this is aimed at facilitating patient compliance, simplifying prescription, and improving efficacy without increasing adverse effects. Fruit extracts of Xylopia aethiopica are used traditionally in the management of pain disorders and xylopic acid (XA) present in the fruit extract have been shown to possess analgesic properties in animals. There is the likelihood of concomitant use of XA and the commonly used analgesics in traditional settings. This study, therefore, evaluated the pharmacologic interaction between XA/morphine and xylopic/diclofenac combinations. Methods: The formalin test and acetic acid writhing test were used to study the antinociceptive activity of XA, morphine, and diclofenac. The isobolographic analysis was used to study the antinociceptive interactions between XA co-administered with morphine or diclofenac. Results: Results obtained revealed that XA (10–100 mg/kg), morphine (1–10 mg/kg), and diclofenac (1–10 mg/kg) produced dose-related antinociception with different potencies in the formalin and acetic acid writhing tests. Isobolographic analysis of XA/morphine and XA/diclofenac combinations revealed potentiation of their antinociceptive effects. The degree of potentiation calculated as interaction index showed synergism for both combinations in all the nociceptive tests. Conclusion: In conclusion, the present study demonstrated synergism for the co-administration of XA with morphine or diclofenac.

Hypotensive effect of an aqueous extract of Heliotropium indicum Linn (Boraginaceae)

A simple, rapid, accurate and precise isocratic reverse phase high performance liquid chromatography (RP - HPLC) method has been developed for simultaneous estimation of febuxostat and diclofenac potassium in combined dosage form by using phenomenex C18 column (statio nary phase) having dimension of 4.6 × 250 mm and particle size of 5 μm and mobile phase containing a mixtur e of 0.02 M potassium dihydrogen orthophosphate buffer (adjusted to pH 7 with sodium hydroxide): acetonitrile: methanol (35:9:56 v/v/v) at a flow rate of 1 ml/min and detection was carried out at 290 nm. The retention times of febuxostat and diclofenac pot assium were 6.01 ± 0.02 minutes and 7.10 ± 0.02 minutes respectively. The developed method was validated as per ICH guideline for specificity, linearity, accuracy and precision , limit of detection and limit of quantification. Linearity studies for the deve loped method were found in the range of 5 to 30 μg/ml for febuxostat and 12.5 to 75 μg/ml for diclofenac potassium respectively. The accuracy of the method was studied by recovery study and found to be in the range of 98 % - 102 %. The % RSD for intraday a nd inter day precision was found less than 2. The new RP - HPLC method was successfully applied to marketed formulation of Febuxostat and Diclofenac potassium without any interference from excipients.

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.