Alkaloidal Extracts from Avicennia africana P. Beauv. (Avicenniaceae) Leaf: An Antiplasmodial, Antioxidant, and Erythrocyte Viable.

Background: The emergence of drug-resistant parasites impedes disease management and eradication efforts. Hence, a reinvigorated attempt to search for potent lead compounds in the mangroves is imperative. Aim: This study evaluates in vitro antiplasmodial activity, antioxidant properties, and cytotoxicity of A. africana leaf alkaloidal extracts. Methods: The A. africana leaves were macerated with 70% ethanol to obtain a total crude extract. Dichloromethane and chloroform-isopropanol (3 : 1, v/v) were used to extract the crude alkaloids and quaternary alkaloids from the total crude. The antiplasmodial activities of the alkaloidal extracts were performed against 3D7 P. falciparum chloroquine-sensitive clone via the SYBR Green I fluorescence assay with artesunate serving as the reference drug. The alkaloidal extracts were further evaluated for antioxidant properties via the total antioxidant capacity (TAC), the total glutathione concentration (GSH), the DPPH (2,2-diphenyl-1-picrylhydrazyl) assay, and the ferric-reducing antioxidant power (FRAP) methods. The cytotoxic activity of the alkaloidal extracts was tested on erythrocytes using a 3-(4,5-dimethylthiazol-2-yl)-5-diphenyltetrazolium bromide-MTT assay with little modification. The phytocompounds in the alkaloidal extracts were identified via gas chromatography-mass spectrometry (GC-MS) techniques. Results: The total crude extract showed good antiplasmodial activity (IC50 = 11.890 µg/mL). The crude and quaternary alkaloidal extracts demonstrated promising antiplasmodial effects with IC50 values of 6.217 and 6.285 µg/mL, respectively. The total crude and alkaloidal extracts showed good antioxidant properties with negligible cytotoxicity on erythrocytes with good selectivity indices. The GC-MS spectral analysis of crude alkaloidal extracts gave indole and isoquinoline alkaloids and several other compounds. Dexrazoxane was found to be the main compound predicted, with an 86% peak area in the quaternary alkaloidal extract. Conclusion: The crude and quaternary alkaloidal extracts exhibited antiplasmodial activities and ability to inhibit oxidative stress with negligible toxicity on erythrocytes. This may be good characteristics to avoid oxidative stress related to Plasmodium infection in the treatment of malaria.

In Vitro and In Vivo Toxicological Evaluation of Avicennia africana P: Beauv. (Avicenniaceae) Leaf Extract in a Rat Model.

Avicennia africana is an important ethnomedicinal plant that has long been used to treat malaria and several other diseases. Despite the plant's antimalarial and other therapeutic properties, there is limited evidence-based data on its potential toxicity. Hence, the purpose of the current study was to assess the safety of A. africana leaf ethanolic extract (AAE). The study was designed to ascertain the cytotoxic effects of the crude extract on red blood cells (RBCs) as well as the acute and subacute toxicity in Wistar albino rats in accordance with Organization for Economic Co-operation and Development (OECD) guidelines "Test No. 423" and CPMW/SWP/1042/99. The pulverized, shade-dried plant leaves were sequentially macerated with 70% ethanol to obtain the crude extract (AAE). The extract's cytotoxic activity (CC50) against the uninfected human red blood cells (RBCs) was determined using the 3-(4,5-Dimethylythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. For the acute toxicity studies, the rats (male and female) were divided randomly into six groups of five rats (n = 5) and dosed orally once with the following dose levels: 100, 300, 1000, 3000, and 5000 mgkg-1, p.o. of the extracted AAE, with the control group receiving only the vehicle. In the repeated dose toxicity studies, the rats (both sexes) were orally administered daily with AAE at 100, 300, and 1000 mgkg-1 for 14 days. Rat body weights were measured, and blood samples were tested for haematological and biochemical markers. Internal organs like the heart, kidney, liver, and spleen were collected, inspected, and weighed, and histological examinations were performed. The median lethal dose (LD50) value is greater than 5000 mgkg-1 body weight, with no significant change in bodyweight or relative organ weight (ROWs) of the extract-treated groups or control group. The extract showed greater cytotoxicity activity (CC50), which was >100 µg/mL, compared to the reference drug (artesunate).The dosage groups of 100 and 300 mgkg-1bwt had neutrophilia and lymphocytopenia (p < 0.05). However, changes in these haematological parameters may not be dose dependent and could be stress related. All the serum biochemical markers studied in rats given AAE did not show any significant change (p > 0.05). Histopathological examination of internal organs of AAE-treated rats did not show any significant abnormalities resulting from the extract treatment compared to the control group. Based on the findings in the present study, the LD50 value of AAE was found to exceed 5000 mgkg-1 in the acute toxicity test, while the no observed adverse effect level (NOAEL) in rats was 1000 mgkg-1 p.o. In the sub-acute toxicity tests. Histopathological analysis revealed no morphological abnormalities in the vital organs.

In vitro and In vivo antimalarial activities of Avicennia africana P. Beauv. (Avicenniaceae) ethanolic leaf extract.

Background: The emergence of widespread drug-resistant strains of the malaria parasites militates against strives for more potent antimalarial drugs. Aim: The present study evaluated the antimalarial activity of A. africana ethanolic crude extract in vitro and in vivo against Plasmodium berghei -infected mice in anticipation of acquiring scientific evidence for it used by mangrove dwellers to treat malaria in Ghana. Methodology: The pulverized dried leaves were extracted with 70% ethanol (v/v) and screened for phytochemicals using standard protocols. The in vitro antimalarial activity was investigated against chloroquine-sensitive Plasmodium falciparum (Pf3D7 clones), MRA-102, Lot:70032033, via SYBR® Green I fluorescent assay method using positive control Artesunate (50-1.56 × 10-3 µg/mL). In the in vivo studies, doses (200-1500 mg/kg) of AAE were used in the 4-day suppressive and curative tests, using P. berghei-infected mice. Artemether/lumefantrine (1.14 mg/kg) and normal saline were used as positive and negative control respectively. Results: The phytochemical analysis revealed the presence of alkaloids, saponins, flavonoids, glycosides, tannins, terpenoids and phytosterols. The extract showed an IC50 of 49.30 ± 4.40 µg/mL in vitro and demonstrated complete parasite clearance at dose 1500 mg/kg in vivo with a suppressive activity of 100% (p < 0.0001) in the 4-day suppressive test. The extract demonstrated high curative activity (p < 0.0001) at 1500 mg/kg with 100% parasite inhibition and the oral LD50 > 5000 mg/kg in mice. Conclusion: The results demonstrated that A. africana crude extract has antimalarial activity both in vitro and in vivo supporting the traditional use of the plant to treat malaria.

In Vitro and In Vivo Effect of Xylopic Acid on Cytochrome P450 Enzymes.

INTRODUCTION: Xylopic acid (XA), the major constituent of the fruit of Xylopia aethiopica, has shown several pharmacological properties. Traditionally, the plant is used to treat several diseases and is being used in the preparation of several local foods despite the lack of information about its safety, food-drug interaction, and other pharmacokinetic properties. This study, therefore, investigated the effect of XA on rat liver cytochrome P450 (CYP) enzymes in vivo and in vitro. METHODS: Inhibition or induction of some isoforms of CYP450 enzymes: CYP 1A1/1A2, 1A2, 2B1/2B2, 3A4, 2D6, and 2C9 were investigated using microsomal fractions of the liver obtained from rats pretreated with a low dose of xylopic acid (LDT) 30 mg/kg, high dose of xylopic acid (HDT) 100 mg/kg, phenobarbitone (PC) 80 mg/kg, and ketoconazole (NC) 100 mg/kg, and a no-treatment group received distilled water, with (n = 5) animals in each group. The in vitro inhibition of CYP 3A4 was assessed by treating rat liver microsomes with XA. RESULTS: Xylopic acid induced CYP 1A1/1A2, 1A2, 2D6, and 2C9, inhibited CYP 3A4, and had no effect on 2B1/2B2. CONCLUSION: The findings would help mitigate toxicity and therapeutic failure especially in cases of coadministration of medications with food containing XA, with metabolism altered by the latter.

A Hydroethanolic Leaf Extract of Persicaria lanigera Possesses Antinociceptive Activity through Cytokine and Glutamatergic Pathways In Vivo.

Persicaria lanigera is used traditionally to treat pain. The antinociceptive properties of the hydroethanolic leaf extract of Persicaria lanigera (PLE) were evaluated in rats and mice. Mice were pretreated orally with PLE (30, 100, and 300 mg kg-1) and evaluated for antinociceptive effects in the acetic acid-, glutamate-, and formalin-induced nociception models. Additionally, mechanical hyperalgesia models were used to evaluate PLE's influence on TNF-α- and IL-1ß-induced hyperalgesia in rats. In the acetic acid-induced nociception model, 100 mg kg-1 PLE exhibited the highest antinociceptive activity of 95.13 ± 9.52% at p < 0.0001, followed by the 300 mg kg-1 (85.44 ± 5.75%; p < 0.0001) and then the 30 mg kg-1 (67.95 ± 18.55%; p < 0.01), compared to morphine 3 mg kg-1 i.p. (86.97 ± 9.52; p < 0.0001). PLE (30, 100, and 300 mg kg-1) also showed significant (p < 0.05) antinociceptive effect in phase two of the formalin-induced nociception with % inhibitions of 66.88 ± 12.17, 75.12 ± 9.01, and 89.12 ± 4.32%, respectively, compared to 3 mg/kg morphine (97.09 ± 2.84%). Similarly, PLE (30, 100, and 300 mg kg-1) significantly reduced pain in the glutamate-induced nociception model with % inhibitions of 79.28 ± 8.17, 90.54 ± 5.64, and 96.49 ± 1.43%, respectively, whereas ketamine (5 mg/kg i.p.) reduced nociception to be 59.94 ± 18.14%. All doses of PLE significantly reduced nociceptive scores in TNF-α- and IL-1ß-induced mechanical hyperalgesia (p < 0.01). Similarly, PLE significantly inhibited bradykinin-induced nociception. The hydroethanolic extract of Persicaria lanigera has antinociceptive effects; this is the first scientific report providing evidence to validate its traditional use for the management of pain.

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.

Protective effect of bergapten in acetic acid-induced colitis in rats.

Bergapten (5-methoxysporalen) is a furanocoumarin extracted from several species of citrus and bergamot oil. Bergamot essential oil is used traditionally in the management of inflammatory conditions. Previous studies on bergapten have explored mainly its in vitro anti-inflammatory activities which include suppression of the expression and release of pro-inflammatory cytokines such as TNF-α and interleukins as well as prostaglandins. Bergapten enhances the clearance of neutrophils and macrophages from the site of inflammation and reduces oxidative stress by inhibition of reactive oxygen species (ROS). Bergapten was assessed for its anti-inflammatory properties in acetic acid-induced colitis. Animals were obtained and randomly placed in six (6) groups (n = 5) after acclimatization. Colitis was induced by rectal administration using 4% v/v acetic acid in Sprague Dawley rats after pre-treatment for 5 days. Bergapten was administered at doses of 3, 10, and 30 mg kg-1 p.o. while the control group received saline 5 mL kg-1 p.o. and the standard drug employed was sulphasalazine at a dose of 500 mg kg-1. Assessments made for colon-weight-to-length ratio, colonic injury, and mucosal mast cell degranulation. There were reduced colon-weight-to-length ratios in animals treated with bergapten which was significant (p < 0.5) for doses 10 and 30 mg kg-1 compared to the disease control group Both macroscopic and microscopic damage were reduced as well, with a lesser percentage of degranulated mast cells. Macroscopic damage was reduced for bergapten at doses 10 and 30 mg kg-1 significantly at p < 0.5 and p < 0.001, respectively. Similarly, microscopic damage was reduced at p < 0.01 and p < 0.001 respectively for bergapten 10 and 30 mg kg-1. The reduction of degranulation by bergapten was significant at p < 0.001. There was generally reduced damage at inflammatory sites as well as decreased infiltration of inflammatory cells. Overall, bergapten reduces inflammation in acetic acid-induced colitis.

Structural elucidation and in vivo anti-arthritic activity of ß-amyrin and polpunonic acid isolated from the root bark of Ziziphus abyssinica HochstEx. A Rich (Rhamnaceae).

Two natural products, compounds 1 and 2 were isolated from the root bark of Ziziphus abyssinica for the first time and were structurally elucidated as ß-amyrin and polpunonic acid, respectively. Both compounds were further subjected to an in vivo study in rats to evaluate their anti-arthritic potency. Compared to the arthritic control group, rats treated with different doses of 1 or 2 (3, 10, and 30 mg/kg) exhibited significantly higher total change in body weight as well as lower arthritic scores and total change in paw edema and erythema. Histopathological examinations of the hind paws of the rats further demonstrated the beneficial effects of both compounds as they significantly reversed cartilage erosion, subchondral cyst, and Weichselbaum's lacunae formation. Evidence of bone remodeling was also observed in all groups of rats treated with 1 or 2. Hematological and serum biochemical parameters were not significantly affected by treatment of 1 or 2. Taken together, the results from the present study suggest potential therapeutic benefit of ß-amyrin and polpunonic acid in rheumatoid arthritis and related inflammatory disorders.

Isobolographic analysis of co-administration of two plant-derived antiplasmodial drug candidates, cryptolepine and xylopic acid, in Plasmodium berghei.

BACKGROUND: Increasing resistance to current anti-malarial therapies requires a renewed effort in searching for alternative therapies to combat this challenge, and combination therapy is the preferred approach to address this. The present study confirms the anti-plasmodial effects of two compounds, cryptolepine and xylopic acid and the relationship that exists in their combined administration determined. METHODS: Anti-plasmodial effect of cryptolepine (CYP) (3, 10, 30 mg kg-1) and xylopic acid (XA) (3, 10, 30 mg kg-1) was evaluated in Plasmodium berghei-infected male mice after a 6-day drug treatment. The respective doses which produced 50% chemosuppression (ED50) was determined by iterative fitting of the log-dose responses of both drugs. CYP and XA were then co-administered in a fixed dose combination of their ED50s (1:1) as well as different fractions of these combinations (1/2, 1/4, 1/8, 1/16 and 1/32) to find the experimental ED50 (Zexp). The nature of interaction between cryptolepine and xylopic acid was determined by constructing an isobologram to compare the Zexp with the theoretical ED50 (Zadd). Additionally, the effect of cryptolepine/xylopic acid co-administration on vital organs associated with malarial parasiticidal action was assessed. RESULTS: The Zadd and Zexp were determined to be 12.75 ± 0.33 and 2.60 ± 0.41, respectively, with an interaction index of 0.2041. The Zexp was significantly (P < 0.001) below the additive isobole indicating that co-administration of cryptolepine and xylopic acid yielded a synergistic anti-plasmodial effect. This observed synergistic antiplasmodial effect did not have any significant deleterious effect on the kidney, liver and spleen. However, the testis were affected at high doses. CONCLUSION: The co-administration of cryptolepine and xylopic acid produces synergistic anti-malarial effect with minimal toxicity.

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.

Scientific evidence of plant with a rapid-onset and sustained antidepressant effect in a chronic model of depression: Mallotus oppositifolius.

BACKGROUND: One of the major drawbacks of current depression pharmacotherapy is the delay in symptom improvement, aside from the untoward side effects and lack of efficacy against refractory depression. This work therefore investigated a possible rapid-onset and sustained antidepressant effect of Mallotus oppositifolius. METHODS: Onset of the antidepressant effect of hydroalcoholic extract from the leaves of M. oppositifolius was investigated using the open space swim test, a chronic depression model. The possible effects of the extract on cognitive dysfunction measured in the Morris water maze and weight gain were also investigated. RESULTS: M. oppositifolius extract, after the first day of treatment, reversed the state of immobility in mice. This effect was sustained even after drug treatment was halted and the antidepressant effect verified in the tail suspension test. The extract also increased the total distance travelled by the mice and reversed the cognitive impairment induced by the depressed state but had no effect on weight variation. CONCLUSIONS: M. oppositifolius exhibits a rapid-onset and sustained antidepressant effect in mice.

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.

Synergistic anti-malarial action of cryptolepine and artemisinins.

BACKGROUND: Cryptolepine (CPE) is the major indoloquinoline isolated from the popular West African anti-malarial plant, Cryptolepis sanguinolenta. CPE possesses various pharmacological activities with potent anti-malarial activity against both chloroquine (CQ)-resistant and -sensitive strains. The search for safe and novel anti-malarial agents and combinations to delay resistance development to Plasmodium falciparum directed this work aimed at evaluating the anti-malarial interaction and safety of CPE in combination with some artemisinin derivatives. METHODS: The in vitro SYBR Green I, fluorescent-based, drug sensitivity assay using a fixed ratio method was carried out on the CQ-sensitive plasmodial strain 3D7 to develop isobolograms from three CPE-based combinations with some artemisinin derivatives. CPE and artesunate (ART) combinations were also evaluated using the Rane's test in ICR mice infected with Plasmodium berghei NK-65 strains in a fixed ratio combination (1:1) and fractions of their ED50s in order to determine the experimental ED50 (Zexp) of the co-administered compounds. Isobolograms were constructed to compare the Zexp to the Zadd. RESULTS: CPE exhibited promising synergistic interactions in vitro with ART, artemether and dihydroartemisinin. In vivo, CPE combination with ART again showed synergy as the Zexp was 1.02 ± 0.02, which was significantly less than the Zadd of 8.3 ± 0.31. The haematological, biochemical, organ/body weight ratio and histopathology indices in the rats treated with CPE at all doses (25, 50, 100 mg kg(-1) po) and in combination with ART (4 mg kg(-1)) showed no significant difference compared to the control group. CONCLUSION: The combination of CPE with the artemisinin derivatives were safe in the rodent model and showed a synergistic anti-malarial activity in vivo and in vitro. This study supports the basis for the selection of CPE as a prospective lead compound as the search for new anti-malarial combinations continues.

The Prevalence of α-Thalassemia and Its Relation to Plasmodium falciparum Infection in Patients Presenting to Clinics in Two Distinct Ecological Zones in Ghana.

Thalassemia and sickle cell disease constitute the most monogenic hemoglobin (Hb) disorders worldwide. Clinical symptoms of α(+)-thalassemia (α(+)-thal) are related to inadequate Hb production and accumulation of ß- and/or γ-globin subunits. The association of thalassemia with malaria remains contentious, though from its distribution it appears to have offered some protection against the disease. Data on the prevalence of thalassemia in Ghana and its link with malaria is scanty and restricted. It was an objective of this cross-sectional study to determine the prevalence of thalassemia in areas representing two of Ghana's distinct ecological zones. The relationship between thalassemia and Plasmodium falciparium (P. falciparum) infection was also ascertained. Overall, 277 patients presenting to health facilities in the study areas were recruited to participate. Tests were carried out to determine the presence of α(+)-thal, sickle cell and malaria parasites in the blood samples of participants. The outcome of this study showed an α(+)-thal frequency of 19.9% for heterozygotes (-α/αα) and 6.8% for homozygotes (-α/-α). Plasmodium falciparum was detected in 17.7% of the overall study population and 14.9% in those with α(+)-thal. No association was observed between those with α(+)-thal and the study sites (p > 0.05). A test of the Hardy-Weinberg law yielded no significant difference (p < 0.001). Findings from this study suggest a modest distribution of α(+)-thal in Ghana with no bias to the ecological zones. Although the prevalence and parasite density were relatively low in those with the disorder, no association was found between them.

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.

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

BACKGROUND: After 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. METHODS: Plasmodium 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. RESULTS: Of 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]. CONCLUSION: This 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.

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.

Analgesic effects of an ethanol extract of the fruits of Xylopia aethiopica (Dunal) A. Rich (Annonaceae) and the major constituent, xylopic acid in murine models.

BACKGROUND: Fruit extracts of Xylopia aethiopica are used traditionally in the management of pain disorders including rheumatism, headache, colic pain, and neuralgia. Little pharmacological data exists in scientific literature of the effect of the fruit extract and its major diterpene, xylopic acid, on pain. The present study evaluated the analgesic properties of the ethanol extract of X. aethiopica (XAE) and xylopic acid (XA), in murine models. MATERIALS AND METHODS: XAE and XA were assessed in chemical (acetic acid-induced abdominal writhing and formalin tests), thermal (Tail-flick and Hargreaves thermal hyperalgesia tests), and mechanical (Randall-Selitto paw pressure test) pain models. RESULTS: XAE and XA exhibited significant analgesic activity in all the pain models used. XAE (30-300 mg kg(-1), p.o.) and XA (10-100 mg kg(-1), p.o.) inhibited acetic acid-induced visceral nociception, formalin- induced paw pain (both neurogenic and inflammatory), thermal pain as well as carrageenan-induced mechanical and thermal hyperalgesia in animals. Morphine (1-10 mg kg(-1), i.p.) and diclofenac (1-10 mg kg(-1), i.p.), used as controls, exhibited similar anti-nociceptive activities. XAE and XA did not induce tolerance to their respective anti-nociceptive effects in the formalin test after chronic administration. Morphine tolerance did not also cross-generalize to the analgesic effects of XAE or XA. CONCLUSIONS: These findings establish the analgesic properties of the ethanol fruit extract of X. aethiopica and its major diterpene, xylopic acid.