Isolation, characterisation and complement fixation activity of acidic polysaccharides from Argemone mexicana used as antimalarials in Mali.

CONTEXT: Global studies on Argemone mexicana L. (Papaveraceae) traditionally used against malaria in Mali are limited to its low-mass compounds activities, and little information on its bioactive polysaccharides is available. OBJECTIVE: This study determines the structure and the immunomodulatory activity of polysaccharides from aerial parts of A. mexicana. MATERIALS AND METHODS: Acidic polysaccharides from this plant material named HMAmA1 and HMAmA2 were isolated from water extracts. Their monosaccharide composition was determined by gas chromatography. Glycosidic linkages were determined using GC-MS. NMR was also applied. The polymers were tested for effects on the human complement system in vitro at different doses. RESULTS: The monosaccharide composition showed that the two polysaccharides contained in different amounts the following monomers: arabinose, rhamnose, galactose, and galacturonic acid. Overall structural analysis showed the presence of a low ratio of 1,2-linked rhamnose compared to 1,4-linked galacturonic acid with arabinogalactans substituted on position 4 of rhamnose. NMR data showed the presence of galacturonans alternated by rhamnogalacturonans bearing arabinose and galactose units. α-Linkages were found for l-arabinose, l-rhamnose and d-galacturonic acid, while ß-linkages were found for d-galactose. The two polysaccharides exhibited strong complement fixation activities, with HMAmA1 being the highest potent fraction. ICH50 value of HMAmA1 was 5 µg/mL, compared to the control BPII being 15.9 µg/mL. DISCUSSION AND CONCLUSIONS: Polysaccharides form A. mexicana presented a complement fixation effect. The complement system is an important part of the immune defense, and compounds acting on the cascade are of interest. Therefore, these polymers may be useful as immunodulatory agents.

Anti-plasmodial Effects of Zanthoxylum zanthoxyloides.

Zanthoxylum zanthoxyloides, syn. Fagara zanthoxyloides, is a tree growing in West Africa and is used in traditional medicine against a variety of diseases, including malaria. In the work reported here, root bark and stem bark extracts of this tree, as well as compounds isolated from the extracts, have been investigated for activity in vitro against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum. In addition, toxicity against nauplii of the brine shrimp Artemia salina has been studied. Dichloromethane extracts of the root bark and stem bark, and a methanol extract of the stem bark, showed anti-parasitic activity towards chloroquine-sensitive as well as chloroquine-resistant P. falciparum, with IC50 values between 1 and 10 µg/mL. Among the isolated compounds, bis-dihydrochelerythrinyl ether, buesgenine, chelerythrine, γ-fagarine, skimmianine, and pellitorine were the most active, with IC50 values of less than 5 µg/mL. The dichloromethane extracts were toxic to brine shrimp nauplii, with LC50 values of less than 1 µg/mL. Methanol extracts were much less toxic (LC50 between 50 and 100 µg/mL). Among the isolated substances, bis-dihydrochelethrinyl ether was the most toxic (LC50 ca. 2 µg/mL).

Human resources for primary health care in sub-Saharan Africa: progress or stagnation?

BACKGROUND: The World Health Organization defines a "critical shortage" of health workers as being fewer than 2.28 health workers per 1000 population and failing to attain 80% coverage for deliveries by skilled birth attendants. We aimed to quantify the number of health workers in five African countries and the proportion of these currently working in primary health care facilities, to compare this to estimates of numbers needed and to assess how the situation has changed in recent years. METHODS: This study is a review of published and unpublished "grey" literature on human resources for health in five disparate countries: Mali, Sudan, Uganda, Botswana and South Africa. RESULTS: Health worker density has increased steadily since 2000 in South Africa and Botswana which already meet WHO targets but has not significantly increased since 2004 in Sudan, Mali and Uganda which have a critical shortage of health workers. In all five countries, a minority of doctors, nurses and midwives are working in primary health care, and shortages of qualified staff are greatest in rural areas. In Uganda, shortages are greater in primary health care settings than at higher levels. In Mali, few community health centres have a midwife or a doctor. Even South Africa has a shortage of doctors in primary health care in poorer districts. Although most countries recognize village health workers, traditional healers and traditional birth attendants, there are insufficient data on their numbers. CONCLUSION: There is an "inverse primary health care law" in the countries studied: staffing is inversely related to poverty and level of need, and health worker density is not increasing in the lowest income countries. Unless there is money to recruit and retain staff in these areas, training programmes will not improve health worker density because the trained staff will simply leave to work elsewhere. Information systems need to be improved in a way that informs policy on the health workforce. It may be possible to use existing resources more cost-effectively by involving skilled staff to supervise and support lower level health care workers who currently provide the front line of primary health care in most of Africa.

Vernonia kotschyana roots: therapeutic potential via antioxidant activity.

The roots of Vernonia kotschyana Sch. Bip. ex Walp. (Asteraceae) are used in Malian traditional medicine in the treatment of gastroduodenal ulcers and gastritis. Since oxidative stress is involved in gastric ulceration, the aim of this study was to screen the root extracts for their in vitro antioxidant activity and phenolic content. The roots were extracted successively with chloroform, ethyl acetate, ethanol and water. The antioxidant activity of root extracts was evaluated in both cell-free and cell-based assays. Their chemical characterization was performed by Fourier transform infrared spectroscopy (FT-IR) whereas the total phenolic content was determined by the Folin-Ciocalteu method. The ethyl acetate extract displayed the highest phenolic content and was found to be the most active in the free radical scavenging and lipid peroxidation inhibition assays; it also showed a high antioxidant activity in MCF-12F cells. This study suggests a potential use of the ethyl acetate extract of Vernonia kotschyana not only as an antioxidant agent in gastroduodenal ulcers and gastritis, but also in other disorders characterized by high levels of oxidative stress.

Complement fixing polysaccharides from Terminalia macroptera root bark, stem bark and leaves.

The root bark, stem bark and leaves of Terminalia macroptera were sequentially extracted with ethanol, 50% ethanol-water, and 50 °C and 100 °C water using an accelerated solvent extractor. Ten bioactive purified polysaccharide fractions were obtained from those crude extracts after anion exchange chromatography and gel filtration. The polysaccharides and their native extracts were characterized with respect to molecular weight, chemical compositions and effects in the complement assay. The chemical compositions showed that the polysaccharides are of pectic nature. The results indicated that there was no great difference of the complement fixation activities in the crude extracts from the different plant parts when extracting with the accelerated solvent extraction system. The purified polysaccharide fractions 100WTSBH-I-I and 100WTRBH-I-I isolated from the 100 °C water extracts of stem and root bark respectively, showed the highest complement fixation activities. These two fractions have rhamnogalacturonan type I backbone, but only 100WTSBH-I-I contains side chains of both arabinogalactan type I and II. Based on the yield and activities of the fractions studied those from the root bark gave highest results, followed by those from leaves and stem bark. But in total, all plant materials are good sources for fractions containing bioactive polysaccharides.

α-Glucosidase inhibition, 15-lipoxygenase inhibition, and brine shrimp toxicity of extracts and isolated compounds from Terminalia macroptera leaves.

CONTEXT: Terminalia macroptera Guill. & Perr. (Combretaceae), a tree that grows in West Africa, has been used in traditional medicine against a variety of diseases such as hepatitis, gonorrhea, skin diseases, and diabetes. OBJECTIVE: To investigate enzyme inhibitory activity against α-glucosidase and 15-lipoxygenase (15-LO) and toxicity against brine shrimp of extracts and compounds from T. macroptera leaves. MATERIALS AND METHODS: Methanol extract, ethyl acetate, and butanol extracts obtained from the methanol extract, six isolated polyphenols (chebulagic acid, chebulic acid trimethyl ester, corilagin, methyl gallate, narcissin, and rutin), and shikimic acid were evaluated for enzyme inhibition and toxicity. RESULTS: In enzyme inhibition assays, all extracts showed high or very high activity. Chebulagic acid showed an IC50 value of 0.05 µM towards α-glucosidase and 24.9 ± 0.4 µM towards 15-LO, in contrast to positive controls (acarbose: IC50 201 ± 28 µM towards α-glucosidase, quercetin: 93 ± 3 µM towards 15-LO). Corilagin and narcissin were good 15-LO and α-glucosidase inhibitors, as well, while shikimic acid, methyl gallate, and chebulic acid trimethyl ester were less active or inactive. Rutin was a good α-glucosidase inhibitor (IC50 ca. 3 µM), but less active towards 15-LO. None of the extracts or the isolated compounds seemed to be very toxic in the brine shrimp assay compared with the positive control podophyllotoxin. CONCLUSION: Inhibition of α-glucosidase in the gastrointestinal tract may be a rationale for the medicinal use of T. macroptera leaves against diabetes in traditional medicine in Mali. The plant extracts and its constituents show strong inhibition of the peroxidative enzyme 15-LO.

Polyherbal Combinations Used by Traditional Health Practitioners against Mental Illnesses in Bamako, Mali, West Africa.

This study explores the traditional knowledge of plants used by traditional health practitioners (THPs) in the treatment of symptoms or syndromes related to mental illnesses in the district of Bamako in Mali, along with the identification of affiliated traditional treating methods. An exploratory and cross-sectional ethnopharmacological survey was conducted in the district of Bamako. The Malian Federation of Associations of Therapists and Herbalists (FEMATH) assisted in the identification and inclusion of the THPs. Data sampling included semi-structured interviews, questionnaires, and in-depth interviews. Quantitative data were evaluated by analysing reports of the use of different medicinal plants and the number of participants. Fifteen THPs belonging to the district of Bamako participated. In total, 43 medicinal plants belonging to 22 plant families were used by the THPs. The most cited plant species was Securidaca longepedunculata (violet tree), followed by Khaya senegalensis (African mahogany) and Boscia integrifolia (rough-leaved shepherds tree). A great number of herbal combinations, preparation methods, and administration routes were used, often with honey as an adjuvant. To our knowledge, this is the first ethnobotanical survey on the use of medicinal plants in the treatment of all types of mental disorders in Bamako.

Inhibition of Seizure-Like Paroxysms and Toxicity Effects of Securidaca longepedunculata Extracts and Constituents in Zebrafish Danio rerio.

Plants used in traditional medicine in the management of epilepsy could potentially yield novel drug compounds with antiepileptic properties. The medicinal plant Securidaca longepedunculata is widely used in traditional medicine in the African continent, and epilepsy is among several indications. Limited knowledge is available on its toxicity and medicinal effects, such as anticonvulsant activities. This study explores the potential in vivo inhibition of seizure-like paroxysms and toxicity effects of dichloromethane (DCM) and ethanol (EtOH) extracts, as well as isolated xanthones and benzoates of S. longepedunculata. Ten phenolic compounds were isolated from the DCM extract. All of the substances were identified by nuclear magnetic resonance spectroscopy. Assays for toxicity and inhibition of pentylenetetrazole (PTZ)-induced seizure-like paroxysms were performed in zebrafish larvae. Among the compounds assessed in the assay for maximum tolerated concentration (MTC), benzyl-2-hydroxy-6-methoxy-benzoate (MTC 12.5 µM), 4,8-dihydroxy-1,2,3,5,6-pentamethoxyxanthone (MTC 25 µM), and 1,7-dihydroxy-4-methoxyxanthone (MTC 6.25 µM) were the most toxic. The DCM extract, 1,7-dihydroxy-4-methoxyxanthone and 2-hydroxy-1,7-dimethoxyxanthone displayed the most significant inhibition of paroxysms by altering the locomotor behavior in GABAA receptor antagonist, PTZ, which induced seizures in larval zebrafish. The EtOH extract, benzyl benzoate, and benzyl-2-hydroxy-6-methoxy-benzoate unexpectedly increased locomotor activity in treated larval zebrafish and decreased locomotor activity in nontreated larval zebrafish, seemingly due to paradoxical excitation. The results reveal promising medicinal activities of this plant, contributing to our understanding of its use as an antiepileptic drug. It also shows us the presence of potentially new lead compounds for future drug development.

Bioactive flavone-C-glycosides of the African medicinal plant Biophytum umbraculum.

Three flavone-C-glycosides-cassiaoccidentalin A (1), isovitexin (2) and isoorientin (3)-were isolated from the ethyl acetate (EtOAc) soluble fraction of the methanol crude extract of the African medicinal plant Biophytum umbraculum, This is the first report of these compounds in this plant. All compounds were identified by spectroscopic analysis and comparison with published data. Isoorientin (3) and the EtOAc extract showed the greatest antioxidant activity in the DPPH assay as well as the strongest inhibition of xanthine oxidase (XO) and 15-lipoxygenase (15-LO). From these results, the extract of B. umbraculum might be a valuable source of flavone C-glycosides.

Climate variability and environmental stress in the Sudan-Sahel zone of West Africa.

Environmental change in the Sudan-Sahel region of West Africa (SSWA) has been much debated since the droughts of the 1970s. In this article we assess climate variability and environmental stress in the region. Households in Senegal, Mali, Burkina Faso, Niger, and Nigeria were asked about climatic changes and their perceptions were compared across north-south and west-east rainfall gradients. More than 80% of all households found that rainfall had decreased, especially in the wettest areas. Increases in wind speeds and temperature were perceived by an overall 60-80% of households. Contrary to household perceptions, observed rainfall patterns showed an increasing trend over the past 20 years. However, August rainfall declined, and could therefore potentially explain the contrasting negative household perceptions of rainfall trends. Most households reported degradation of soils, water resources, vegetation, and fauna, but more so in the 500-900 mm zones. Adaptation measures to counter environmental degradation included use of manure, reforestation, soil and water conservation, and protection of fauna and vegetation. The results raise concerns for future environmental management in the region, especially in the 500-900 mm zones and the western part of SSWA.

A "reverse pharmacology" approach for developing an anti-malarial phytomedicine.

A "reverse pharmacology" approach to developing an anti-malarial phytomedicine was designed and implemented in Mali, resulting in a new standardized herbal anti-malarial after six years of research. The first step was to select a remedy for development, through a retrospective treatment-outcome study. The second step was a dose-escalating clinical trial that showed a dose-response phenomenon and helped select the safest and most efficacious dose. The third step was a randomized controlled trial to compare the phytomedicine to the standard first-line treatment. The last step was to identify active compounds which can be used as markers for standardization and quality control. This example of "reverse pharmacology" shows that a standardized phytomedicine can be developed faster and more cheaply than conventional drugs. Even if both approaches are not fully comparable, their efficiency in terms of public health and their complementarity should be thoroughly considered.

Bioactive arabinogalactans from the leaves of Opilia celtidifolia Endl. ex Walp. (Opiliaceae).

The leaves of the tree Opilia celtidifolia have a long tradition for being used in Mali and other West African countries against various ailments such as for wound healing. Previous studies on polysaccharides from these leaves showed the presence of pectic-like polymers with an effect on the human complement system as well as the ability to activate macrophages. The present study shows that bioactive arabinogalactans isolated by water of 50°C could be separated into two acidic fractions, Oc50A1 and Oc50A2. The former could, by gel filtration on Sephacryl S-400, be separated into two fractions, which were further purified on a Superdex 200 column to give the fractions Oc50A1.I.pur and Oc50A1.II.pur. These fractions were subjected to chemical and biological studies. The polysaccharides consisted mainly of heavily branched type II arabinogalactans and minor amounts of rhamnogalacturonan I regions. The isolated polymers had a high human complement-fixating ability, as well as the ability to stimulate rat macrophages and dendritic cells (DCs) and to induce B cell proliferation. These effects were especially pronounced for the higher molecular weight fraction of Oc50A1.I.pur. The fractions Oc50A1.I.pur and Oc501.II.pur stimulated secretion of pro-inflammatory cytokines from purified B cells or DCs. Collectively, these results indicate that the arabinogalactan type II polymers present in the leaves of O. celtidifolia may be used to develop medical devices for regulating inflammatory processes.

15-Lipoxygenase inhibitory effects of prenylated flavonoids from Erythrina senegalensis.

One new pterocarpan (named erybraedin F) along with seven known prenylated flavonoids were isolated from the stem and root bark of the medicinal plant Erythrina senegalensis. The structures were elucidated by 1D and 2D NMR and MS. The pterocarpans were found to be strong inhibitors of 15-lipoxygenase.

Pectic polysaccharides from Biophytum petersianum Klotzsch, and their activation of macrophages and dendritic cells.

The Malian medicinal plant Biophytum petersianum Klotzsch (Oxalidaceae) is used as a treatment against various types of illnesses related to the immune system, such as joint pains, inflammations, fever, malaria, and wounds. A pectic polysaccharide obtained from a hot water extract of the aerial parts of B. petersianum has previously been reported to consist of arabinogalactans types I and II (AG-I and AG-II), probably linked to a rhamnogalacturonan backbone. We describe here further structural characteristics of the main polysaccharide fraction (BP1002) and fractions obtained by enzymatic degradations using endo-alpha-d-(1-->4)-polygalacturonase (BP1002-I to IV). The results indicate that in addition to previously reported structures, rhamnogalacturan type II and xylogalacturonan areas appear to be present in the pectic polymer isolated from the plant. Atomic force microscopy confirmed the presence of branched structures, as well as a polydisperse nature. We further tested whether the BP1002 main fraction or the enzymatically degraded products could induce immunomodulating activity through stimulation of subsets of leukocytes. We found that macrophages and dendritic cells were activated by BP1002 fractions, while there was little response of T cells, B cells, and NK cells. The enzymatic treatment of the BP1002 main fraction gave important information on the structure-activity relations. It seems that the presence of rhamnogalacturonan type I is important for the bioactivity, as the bioactivity decreases with the decreased amounts of rhamnose, galactose, and arabinose. The demonstration of bioactivity by the plant extracts might indicate the mechanisms behind the traditional medical use of the plant.

Sublingual sugar for hypoglycaemia in children with severe malaria: a pilot clinical study.

BACKGROUND: Hypoglycaemia is a poor prognostic indicator in severe malaria. Intravenous infusions are rarely feasible in rural areas. The efficacy of sublingual sugar (SLS) was assessed in a pilot randomized controlled trial among hypoglycaemic children with severe malaria in Mali. METHODS: Of 151 patients with presumed severe malaria, 23 children with blood glucose concentrations < 60 mg/dl (< 3.3 mmol/l) were assigned randomly to receive either intravenous 10% glucose (IVG; n = 9) or sublingual sugar (SLS; n = 14). In SLS, a teaspoon of sugar, moistened with a few drops of water, was gently placed under the tongue every 20 minutes. The child was put in the recovery position. Blood glucose concentration (BGC) was measured every 5-10 minutes for the first hour. All children were treated for malaria with intramuscular artemether. The primary outcome measure was treatment response, defined as reaching a BGC of >or= 3.3 mmol/l (60 mg/dl) within 40 minutes after admission. Secondary outcome measures were early treatment response at 20 minutes, relapse (early and late), maximal BGC gain (CGmax), and treatment delay. RESULTS: There was no significant difference between the groups in the primary outcome measure. Treatment response occurred in 71% and 67% for SLS and IVG, respectively. Among the responders, relapses occurred in 30% on SLS at 40 minutes and in 17% on IVG at 20 minutes. There was one fatality in each group. Treatment failures in the SLS group were related to children with clenched teeth or swallowing the sugar, whereas in the IVG group, they were due to unavoidable delays in beginning an infusion (median time 17.5 min (range 3-40).Among SLS, the BGC increase was rapid among the nine patients who really kept the sugar sublingually. All but one increased their BGC by 10 minutes with a mean gain of 44 mg/dl (95%CI: 20.5-63.4). CONCLUSION: Sublingual sugar appears to be a child-friendly, well-tolerated and effective promising method of raising blood glucose in severely ill children. More frequent repeated doses are needed to prevent relapse. Children should be monitored for early swallowing which leads to delayed absorption, and in this case another dose of sugar should be given. Sublingual sugar could be proposed as an immediate "first aid" measure while awaiting intravenous glucose. In many cases it may avert the need for intravenous glucose.

Polysaccharides with complement fixing and macrophage stimulation activity from Opilia celtidifolia, isolation and partial characterisation.

AIM OF THE STUDY: The present study is aimed to determine the bioactivity and structure of polysaccharides present in the leaves from the Malian medicinal plant Opilia celtidifolia [Guill. & Perr. Endl. ex Walp (Opiliaceae)]. MATERIALS AND METHODS: The polysaccharides from the leaves of Opilia celtidifolia were isolated from water extracts of the leaves using gelfiltration and anion exchange chromatography giving the fractions Oc50A1 and Oc50A2. Monosaccharide composition was determined by gas chromatography of the derived TMS-derivatives of the methyl-glycosides. Linkages were determined of the partly methylated, partly acetylated alditol acetates obtained after a process including reduction, methylation, hydrolysis, reduction and acetylation followed by GC-MS. Effects on the complement system and the macrophages were determined using specific methods aimed for studying those activities. RESULTS: The polysaccharide fractions isolated from the leaves of Opilia celtidifolia has high complement fixing activity and induce nitrite oxide release from macrophages in a dose dependent manner. The fractions had an ICH50 of 0.5 and 0.9 microg/ml respectively in the complement fixing assay. They induced the release of 7.2 and 7.3 microM of nitrite oxide from macrophages respectively at a dose of 100 microg/ml. The monosaccharide composition in Oc50A1 and Oc50A2, analysed, showed the presence of arabinose (26.7 and 13.2%), galactose (31.5 and 28%) and galacturonic acid (5.3 and 7.8%) respectively. The Yariv test confirmed the presence of arabinogalactan type II in both fractions. Structural analyses did also show the presence of terminal and 1-4 linked galacturonic acid and terminal and 1-2 linked rhamnose. Endo-polygalacturonanase treatment was performed to isolate the heavily substituted parts of the polysaccharides. These parts contained the same monosaccharides in similar proportion, and showed stronger dose dependent complement fixing activity and also stimulated macrophages to release nitrite oxide. CONCLUSIONS: The leaves of Opilia celtidifola contains polysaccharides of pectic type that have both complement fixing and macrophage stimulating activity.

Circumstances of child deaths in Mali and Uganda: a community-based confidential enquiry.

BACKGROUND: Interventions to reduce child deaths in Africa have often underachieved, causing the Millennium Development Goal targets to be missed. We assessed whether a community enquiry into the circumstances of death could improve intervention effectiveness by identifying local avoidable factors and explaining implementation failures. METHODS: Deaths of children younger than 5 years were ascertained by community informants in two districts in Mali (762 deaths) and three districts in Uganda (442 deaths) in 2011-15. Deaths were investigated by interviewing parents and health workers. Investigation findings were reviewed by a panel of local health-care workers and community representatives, who formulated recommendations to address avoidable factors and, subsequently, oversaw their implementation. FINDINGS: At least one avoidable factor was identified in 97% (95% CI 96-98, 737 of 756) of deaths in children younger than 5 years in Mali and 95% (93-97, 389 of 409) in Uganda. Suboptimal newborn care was a factor in 76% (146 of 194) of neonatal deaths in Mali and 64% (134 of 194) in Uganda. The most frequent avoidable factor in postneonatal deaths was inadequate child protection (mainly child neglect) in Uganda (29%, 63 of 215) and malnutrition in Mali (22%, 124 of 562). 84% (618 of 736 in Mali, 328 of 391 in Uganda) of families had consulted a health-care provider for the fatal illness, but the quality of care was often inadequate. Even in official primary care clinics, danger signs were often missed (43% of cases in Mali [135 of 396], 39% in Uganda [30 of 78]), essential treatment was not given (39% in Mali [154 of 396], 35% in Uganda [27 of 78]), and patients who were seriously ill were not referred to a hospital in time (51% in Mali [202 of 396], 45% in Uganda [35 of 78]). Local recommendations focused on quality of care in health-care facilities and on community issues influencing treatment-seeking behaviour. INTERPRETATION: Local investigation and review of circumstances of death of children in sub-Saharan Africa is likely to lead to more effective interventions than simple consideration of the biomedical causes of death. This approach discerned local public health priorities and implementable solutions to address the avoidable factors identified. FUNDING: European Union's 7th Framework Programme for research and technological development.

An immunomodulating pectic polymer from Glinus oppositifolius.

An immunomodulating pectic polymer, GOA1, obtained from the aerial parts of the Malian medicinal plant Glinus oppositifolius (L.) Aug. DC. (Aizoaceae) has previously been reported to consist of arabinogalactans type I and II, probably linked to a rhamnogalacturonan backbone. To further elucidate the structure of the polymer GOA1, enzymatic degradation studies and weak acid hydrolysis were performed. Five different glycosidases were used, endo-alpha-D-(1-->4)-polygalacturonase, exo-alpha-L-arabinofuranosidase, endo-alpha-L-(1-->5)-arabinanase, endo-beta-D-(1-->4)-galactanase and exo-beta-D-galactosidase. It appears that GOA1 may contain a structural moiety consisting of a 1,3-linked galactopyranosyl (Galp) main chain with 1,6-linked Galp side chains attached to position 6 of the main chain. The 1,6-linked Galp side chain may be branched in position 3 with arabinofuranosyl (Araf) side chains. A 1,4-linked Galp backbone which might carry side chains or glycosyl units attached to position 3 is also a structural element in the polymer. We further show that GOA1 induce proliferation of B cells and the secretion of IL-1beta by macrophages, in addition to a marked increase of mRNA for IFN-gamma in NK-cells. To elucidate structure-activity relations the native polymer and the digested fractions were tested for complement fixing activity and intestinal immune stimulating activity. The partial removal of Araf residues after enzymatic degradations did not affect the bioactivities, while the acid hydrolysed fraction showed reduced complement fixing activity. A decrease in Araf units, 1,3,6-linked Galp units and a partial hydrolysed rhamnogalacturonan backbone, in addition to a reduction in molecular weight are factors that might have contributed to reduced bioactivity.

Argemone mexicana decoction for the treatment of uncomplicated falciparum malaria.

A prospective, dose-escalating, quasi-experimental clinical trial was conducted with a traditional healer using a decoction of Argemone mexicana for the treatment of malaria in Mali. The remedy was prescribed in three regimens: once daily for 3 days (Group A; n=23); twice daily for 7 days (Group B; n=40); and four times daily for the first 4 days followed by twice daily for 3 days (Group C; n=17). Thus, 80 patients were included, of whom 80% were aged<5 years and 25% were aged<1 year. All presented to the traditional healer with symptoms of malaria and had a Plasmodium falciparum parasitaemia>2000/microl but no signs of severe malaria. The proportions of adequate clinical response (ACR) at Day 14 were 35%, 73% and 65% in Groups A, B and C, respectively (P=0.011). At Day 14, overall proportions of ACR were lower in children aged<1 year (45%) and higher in patients aged>5 years (81%) (P=0.027). Very few patients had complete parasite clearance, but at Day 14, 67% of patients with ACR had a parasitaemia<2000/microl. No patient needed referral for severe disease. Only minor side effects were observed. Further research should determine whether this local resource could represent a first-aid home treatment in remote areas.

Antiplasmodial and GABA(A)-benzodiazepine receptor binding activities of five plants used in traditional medicine in Mali, West Africa.

Extracts of five medicinal plants: Boscia angustifolia, Cissus quadrangularis, Securidaca longipedunculata, Stylosanthes erecta and Trichilia emetica, used traditionally in Malian traditional medicine were screened for in vitro antiplasmodial activity and GABA(A)-benzodiazepine receptor binding activity. Four extracts showed significant antiplasmodial activities, with the dichloromethane extract of leaf of Securidaca longipedunculata being the most active (IC(50) of 7 microg/ml [95% CI: 5-9]). The dichloromethane extract of leaf of Trichilia emetica, in addition to its antiplasmodial activity (IC(50): 12 microg/ml [95% CI: 12-14]), exhibited a good binding activity to the GABA(A)-benzodiazepine receptor, while water and methanol extracts of the same plant did not show any activity. A strong GABA(A)-receptor complex binding activity was observed in the methanol extract of aerial part of Stylosanthes erecta. The results in this study justify some of the traditional indications of the plants investigated and may thus be candidates for Improved Traditional Medicines in Mali.