Antimalarial properties of SAABMAL (®): an ethnomedicinal polyherbal formulation for the treatment of uncomplicated malaria infection in the tropics.

BACKGROUND & OBJECTIVES: Malaria is a serious problem in the countries of the developing world. As the malaria parasite has become resistant to most of the antimalaria drugs available currently, there is a need to search for newer drugs. This study reports the pharmaceutical quality and in vivo antimalarial activities of a polyherbal formulation (SAABMAL ® ) used as malarial remedy in Nigeria. METHODS: The antiplasmodial activity of SAABMAL ® was determined by using the 4-day suppressive test in Plasmodium berghei-infected mice. The formulation was tried on three different experimental animal models for in vivo antimalarial activities, which are prophylactic, suppressive and curative in mice. Chloroquine and pyrimethamine were used as standard drugs for comparison. RESULTS: The suppressive study showed that, SAABMAL ® (200 and 400 mg/kg/bw) significantly (p <0.01) produced a suppression (29.39 - 100%) of parasitaemia in a dose-dependent manner, while the curative study showed that SAABMAL ® at 400 mg significantly (p <0.01) reduced (95.80%) parasitaemia compared with controls. The mean survival time of SAABMAL ®-treated groups (100 and 200 mg/kg) was higher than that of the chloroquine-treated group. Histopathologically, no changes were found in the spleen of both untreated and treated groups. SAABMAL ® capsules were of good mechanical properties with low weight variation and high degree of content mass uniformity. INTERPRETATION & CONCLUSIONS: The results obtained in this study showed the efficacy of SAABMAL ® , a herbal antimalarial formulation against chloroquine sensitive malaria and its potential use in the treatment of uncomplicated malaria infection. Further studies need to be done in humans to test its efficacy and safety for its potential use as an antimalarial drug.

Antiplasmodial activity-aided isolation and identification of quercetin-4'-methyl ether in Chromolaena odorata leaf fraction with high activity against chloroquine-resistant Plasmodium falciparum.

The present study was undertaken to evaluate the antiplasmodial activity of Chromolaena odorata leaf extract and gradient fractions through in vivo and in vitro tests, aimed at identifying its antiplasmodial constituents. Sub-fractions obtained from the most active gradient fraction were further tested for cytotoxicity against THP-1 cells, chloroquine-sensitive (HB3) and chloroquine-resistant (FCM29) Plasmodium falciparum. Our results showed the dichloromethane gradient fraction was most effective, significantly (P < 0.05) suppressing infection by 99.46% at 100 mg/kg body weight. Amongst its 13 sub-fractions (DF1-DF13), DF11 was highly active, with IC50 of 4.8 and 6.74 µg/ml against P. falciparum HB3 and FCM29, respectively. Cytotoxicity of DF11 was estimated to be above 50 µg/ml, and its separation by column chromatography yielded a flavonoid which was characterized as 3, 5, 7, 3' tetrahydroxy-4'-methoxyflavone from its spectroscopic data. It significantly suppressed infection (65.43-81.48%) in mice at 2.5-5 mg/kg doses and compared favourably with the effects of chloroquine and artemisinin. It may therefore serve as a useful phytochemical and antiplasmodial activity marker of C. odorata leaves, which exhibit potential for development as medicine against malaria.

Microencapsulation enhances the anti-ulcerogenic properties of Entada africana leaf extract.

ETHNOPHARMACOLOGICAL RELEVANCE: The antiulcer potentials of most plants still remain largely unexplored, despite their prospects evidenced by their use as ethnomedicine. Entada africana (Mimosaceae) has been widely used in Africa for the treatment of skin infections, wounds, tonic for stomach troubles and against diphtheria-like throat complaints. The aim of the present study was to evaluate the anti-ulcer properties of Entada africana (EA) ethanol leaf extract and to obtain a novel multiparticulate pharmaceutical formulation (ACE) with it. MATERIALS AND METHODS: Ethanol or Indomethacin was administered to rats after oral administration of EA (200, 400 and 800 mg extract/kg b.w), ACE (400 and 800 mg/kg bw), cimetidine (100mg/kg bw), misoprostol (40 µg/kg bw) or distilled water/saline (vehicle). Anti ulcer property was evaluated by examining and scoring stomach lesions. RESULTS: The extract exhibited significant (P<0.01) cytoprotective effect against ethanol and indomethacin induced gastro ulceration. The microcapsules showed enhanced cytoprotective effect against ethanol and indomethacin induced gastro ulceration. Histopathologically, the effects of EA and ACE on mucus epithelia were mild with reduced neutrophil, eosinophil and lymphocytic infiltration in stomach tissues of rats ulcerated with ethanol. CONCLUSIONS: Our current findings show that EA and its multiparticulate formulation may be a useful preparation in peptic ulcer disease.

Evaluation of the fluid uptake kinetics and drug release from gellan gum tablets containing metronidazole.

In this study, the fluid uptake (swelling) kinetics and disintegrant properties of gellan gum in metronidazole tablets were evaluated in both simulated gastric and intestinal fluids (SGF and SIF respectively) without enzymes. The mechanical properties as well as the disintegration and dissolution profile of the tablets were also assessed and compared with those of two standard disintegrants: maize starch and sodium starch glycolate (Primogel). Results show that, swelling was faster and higher in SIF than SGF with the minimum and maximum swelling rates of the gum being 0.365 and 6.900 mm(3)/min respectively in SGF, while the corresponding values in SIF were 0.277 and 7.600 mm(3)/min respectively. The gum was most effective as a disintegrant for metronidazole tablets at an optimum concentration of 0.2% (w/w) when incorporated extra-granularly.

Effect of Grewia gum on the mechanical properties of Paracetamol tablet formulations

Grewia gum has been evaluated as a binder in paracetamol tablet formulations. Compressional properties of the formulations were analyzed using density measurements and the compression equations of Heckel and Kawakita as assessment parameters. Formulations containing Grewia gum as a binder show a slower onset and lower amount of plastic deformation than those containing PVP. The Db values for formulations containing Grewia gum; increased with increased concentration up to 4w/w. Formulations containing Grewia gum were also found to exhibit higher degree of packing than those containing PVP. Yield values for formulations containing Grewia gum was found to be at variance with the binder concentration. The values increased between 1 and 2w/w and decreased between 2 and 4w/w. A linear relationship was found to exist between N/C and N for formulations containing Grewia gum at all concentrations. Grewia gum was found to improve the fluidity of paracetamol granulation better than PVP. This study suggests that Grewia gum compares favorably with the standard binder PVP used hence could be a useful substitute binder in paracetamol tablet formulations

Some compaction characteristics of the hot water leaf extract og Nauclea latifiola: a potential antimalarial agent.

This study aims to develop a suitable tablet dosage form of Nauclea latifolia, a potential antimalarial agent. The compaction characteristics of the oven dried water extract were studied using the Heckel equation. The mechanical properties of the compacts were also determined. This preliminary information will be useful in developing a suitable dosage form of the extract for use in the management of malaria. The results showed that N. latifolia extract exhibited high densification due to dye filling while the subsequent rearrangement of the granules did not contribute, significantly, to their densification. The granules had enhanced plasticity as shown by the low yield point, Py. The tablets produced from the extract had good mechanical properties, with hardness increasing via compression pressure while the friability decreased. However, the tablets had poor disintegration properties; it is concluded that while tablets of suitable physical properties can be produced from the extract, a disintegrant would need to be included in the formulation to ensure adequate drug release.

Smooth muscle contraction induced by Indigofera dendroides leaf extracts may involve calcium mobilization via potential sensitive channels.

The contractile effects of the aqueous extract of the leaves of Indigofera dendroides (ID) were studied on the gastrointestinal motility in mice and isolated smooth muscle preparations obtained from rats and guinea pigs. The contractile effects of 10(-6) M acetylcholine, 80 mM KCl and 1.6 mg/ml ID were measured on the rat ileal smooth muscle exposed to calcium-free buffer or physiological solution, to determine the calcium pools mobilized by extract for activation of contraction. Acute toxicity test (LD(50)) was also carried out in mice. The result showed that ID (0.05-3.2 mg/ml) produced a concentration-dependent contraction of the guinea pig and rat ileum. These responses were not blocked by mepyramine (2.49 x 10(-9) M), verapamil (8.14 x 10(-9) M), or pirenzepine (4.7 x 10(-7) M), but were blocked completely by atropine (2.92 x 10(-9) M). A significant increase in propulsion of gastrointestinal motility was observed. Acetylcholine, KCl and ID produced contractions in Ca(2+) free media. The phasic components of the contractile responses to Ach as well as the tonic component of K(+) and ID-induced contractions were relatively resistant to short periods of calcium-free exposure. Ach, K(+) and ID still caused contractions in the presence of verapamil. The data revealed that ID-induced contractions were not mediated by histaminergic receptors, calcium channels, M1 muscarinic receptors. It also suggests that Ach mobilize Ca from some tightly bound or intracellular pool, whereas high K(+) and ID may mobilize Ca from some superficial or loosely-bound pool.

Effects of the diluent type on compressional characteristics of the mixed stem bark extract of Anogeissus leiocarpus and Prosopis africana tablet formulation.

The hot water extract of a mixture of stem barks of Anogeissus leiocarpus and Prosopis africana was formulated into tablets using the wet granulation method of massing and screening. The Heckel equation was used to study the compaction characteristics of the extract formulated with lactose (water-soluble) or magnesium carbonate (water-insoluble) as diluents. Granules prepared using magnesium carbonate were found to exhibit two stages of deformation - an initial fragmentation followed by plastic flow while those formulated with lactose consolidated mainly by plastic deformation. Compressibility profiles of the formulations were affected by the diluent type. Tensile strength of granules formulated with magnesium carbonate was found to increase as the compression pressure increased from 56.6 to 113.2 MN m(-2) while the tensile strength of tablets formulated with lactose had its maximum at a compression force of 84.9 MN m(-2).

Effect of the aqueous extract of African mistletoe, Tapinanthus sessilifolius (P. Beauv) van Tiegh leaf on gastrointestinal muscle activity.

Effects of the aqueous extract of T. sessilifolius on the gastrointestinal muscle were investigated on smooth muscle preparations isolated from rabbit jejunum, guinea pig ileum and on gastrointestinal transit in mice. Elemental analysis of the extract was also carried out. The aqueous extract of T. sessilifolius evoked a concentration dependent contraction of the rabbit jejunum and guinea pig ileum. The contractions evoked by the extract were not attenuated either by atropine or mepyramine, but they were completely blocked by verapamil. The elemental analysis revealed the presence of Mg, Zn, Fe, Cu, and very high concentration of Ca. The intraperitoneal LD50 in mice was found to be 1500 mg/kg. The aqueous extract of T. sessilifoliius possesses active components that may be mediating the observed biological activity through calcium mobilization.

Spasmolytic activity of methyl angolensate: a triterpenoid isolated from Entandrophragma angolense.

Entandrophragma angolense is a medicinal plant used in folk medicine against several diseases including peptic ulcer. Methyl angolensate was isolated from E. angolense by recrystallization from methanol. The needle-like crystals were characterized and tested on isolated rabbit jejunum, guinea pig ileum and the rat fundus strip. The compound was also evaluated on the gastrointestinal transit in mice. The results showed that the compound exerted significant concentration dependent inhibition of smooth muscle and reduced the propulsive action of the gastrointestinal tract in mice. The relaxation observed did not attenuate acetylcholine and histamine induced contractions, but was found to inhibit contractions induced by serotonin. It is therefore suggested that methyl angolensate may exert its activity on gastrointestinal smooth muscle via serotonergic mechanisms.