Clinical efficacy of a tea-bag formulation of cryptolepis sanguinolenta root in the treatment of acute uncomplicated falciparum malaria.

OBJECTIVE: To evaluate the clinical efficacy and safety of a tea bag formulation of the root of C. sanguinolenta DESIGN: This is a prospective descriptive open trial. SETTING: Patients were recruited from Korle-Bu, Mamprobi and Dansoman Polyclinics. SUBJECTS: Forty-four subjects with uncomplicated malaria were recruited for the study. METHOD: Patients presented with clinical symptoms of malaria. Laboratory investigations conducted included malaria parasite counts, haematological indices and biochemical tests which were obtained before, during and after a 5-day treatment period, up to Day 28 posttreatment. All patients in the study were symptomatic with significant parasitaemia. Patients were given one teabag three times a day, that is, morning, noon and night, for five days of treatment. RESULTS: Fifty percent of the patients were cleared of their P. falciparum parasitaemia by 72 hours, and all by Day 7. Presenting symptoms of fever, chills, nausea and vomiting cleared rapidly, all by Day 3, but resolution of haematological and biochemical abnormalities associated with malaria was generally slow, a feature seen in malaria post-treatment. The overall cure rate was 93.5% due to two cases of recrudescence on Days 21 and 28. The laboratory findings did not suggest any toxicity. CONCLUSION: On the basis of fever clearance and disappearance of parasitaemia by Day 7, the formulation has been shown to be non-toxic and highly effective in the treatment of acute uncomplicated malaria.

Antibiotic resistance and genotyping of clinical group B Salmonella isolated in Accra, Ghana.

AIMS: The purpose of this study was to investigate the antibiotic resistance and clonal lineage of serogroup B Salmonella isolated from patients suspected of suffering from enteric fever in Accra, Ghana. METHODS AND RESULTS: Serogroup B Salmonella were isolated from blood (n=28), cerebral spinal fluid (CSF) (n=1), or urine (n=2), and identified based on standard biochemical testing and agglutinating antisera. Isolates were examined for their susceptibility to ampicillin, chloramphenicol, tetracycline and trimethoprim-sulfamethoxazole. Most of the isolates could be classified as multiple-drug resistant. Furthermore, the genetic location of resistance genes was shown to be on conjugative plasmids. Genetic fingerprinting by plasmid profiling, enterobacterial repetitive intergenic consensus (ERIC)-PCR, and repetitive element (REP)-PCR were performed to determine the diversity among the isolates. Plasmid profiling discriminated five unique groupings, while ERIC-PCR and REP-PCR resulted in two and three groupings, respectively. CONCLUSIONS: A high rate of antibiotic resistance was associated with the Salmonella isolates and the genes responsible for the resistance are located on conjugative plasmids. Also, there appears to be minimal diversity associated with the isolates. SIGNIFICANCE AND IMPACT OF THE STUDY: As a result of the increasing antibiotic resistance among bacteria of all genera, surveys to monitor microbial populations are critical to determine the extent of the problem. The inability to treat many infectious diseases with current antibiotic regimens should prompt the medical community to be more prudent with its antibiotic use.

Extract of Ocimum canum lowers blood glucose and facilitates insulin release by isolated pancreatic beta-islet cells.

Aqueous extract of Ocimum canum Sim, (Lamiaceae) is used by some Ghanaians to manage diabetes mellitus. In vivo modulation of levels of fasting blood glucose by 0. canum extract was evaluated in type-II diabetes mellitus using the C57BL/KsJ db/db genetically diabetic animal model, and its effects on glucose-stimulated insulin release in vitro were monitored using isolated rat pancreatic beta-islet cells. The results showed that fasting blood glucose levels and body weight decreased significantly (p < 0.05) in diabetic and non-diabetic C57BL/KsJ mice, which were administered aqueous extract of 0. canum. In vitro, the 0. canum extract significantly enhanced insulin release from isolated rat pancreatic beta-islet cells. Insulin release was found to be dependent on glucose concentration and increased with increasing O. canum concentration in the incubation medium up to an optimum extract concentration of 0.03 mg/ml. Release of the hormone decreased beyond this concentration of extract in the medium. Addition to the medium of Desmodium adscendens, a plant preparation used to manage inflammatory disorders, did not increase but rather inhibited insulin secretion by the pancreatic beta-islet cells. These results could explain the use of 0. canum in Ghanaian folk medicine to manage diabetes mellitus.

In vitro screening for the anti-anaphylactic agent in Thonningia sanguinea.

Thonningia sanguinea, used prophylactically against bronchial asthma, is anti-anaphylactic and anti-asthmatic in guinea pigs when given orally. The aqueous extract of the plant and its fractions were screened in vitro for their effects on anaphylactic- and histamine-induced contractions, and the results compared with those obtained in vivo when the whole extract was administered orally. The comparison showed similar anti-anaphylactic properties of the plant material in the two systems of administration, but the effects on histamine-induced contractions differed from the in vivo ones, suggesting that the anaphylactic assay system should be preferred for the screening in vitro. The anti-anaphylactic substance(s) extracted into n-butanol. The active portions of the extracted components appeared to be stable to acid digestion. Thin layer chromatographic analysis of the butanol extract and preliminary chemical analysis suggest that these substances are polyhydroxy/phenolic in nature.

An activator of calcium-dependent potassium channels isolated from a medicinal herb.

Large-conductance calcium-dependent potassium (maxi-K) channels play an important role in regulating the tone of airway smooth muscle and the release of bronchoconstrictive substances from nerves in the lung. Crude extracts of Desmodium adscendens, a medicinal herb used in Ghana as a treatment for asthma, inhibit binding of monoiodotyrosine charybdotoxin (125I-ChTX) to receptor sites in bovine tracheal smooth muscle membranes that have been shown to be associated with maxi-K channels. Using this assay, three active components have been purified and identified by NMR and MS. Comparison with authentic samples revealed the three active components as the known triterpenoid glycosides dehydrosoyasaponin I (DHS-I), soyasaponin I, and soyasaponin III. The most potent of these compounds, DHS-I, is a partial inhibitor of 125I-ChTX binding (Ki = 120 nM, 62% maximum inhibition). Inhibition of 125I-ChTX binding is primarily due to a decrease in the observed maximum number of binding sites, with a smaller decrease in affinity. DHS-I increases the rate of toxin dissociation from its receptor, suggesting that modulation of ChTX binding occurs through an allosteric mechanism. DHS-I reversibly increases the open probability of maxi-K channels from bovine tracheal smooth muscle incorporated into planar lipid bilayers when applied to the intracellular, but not the extracellular, side of the membrane at concentrations as low as 10 nM. In contrast, DHS-I had no effect on several other types of potassium channels or membrane transporters. This natural product is the first example of a high-affinity activator of calcium-dependent potassium channels and is the most potent known potassium channel opener.

Some secondary plant metabolites in Desmodium adscendens and their effects on arachidonic acid metabolism.

The effects of three chemically different groups of compounds, (triterpenoid saponins, beta-phenylethylamines and tetrahydroisoquinolines), known to be present in Desmodium adscendens, on plasma membrane ion channel, cytochrome P450 NADPH-dependent oxygenation of arachidonic acid, and production of prostaglandins by the cyclooxygenase enzyme system, are described. The very high-conductance calcium-activated potassium ion channel, which is responsible for the maintenance of tone in smooth muscles, was activated by the saponins. The cytochrome P450 NADPH-dependent monooxygenase reaction, which produces epoxy- and hydroxylated eicosanoids from arachidonic acid metabolism, was inhibited by an analogue of the tetrahydroisoquinoline present in the plant. This analogue also acted as a reductant in the prostaglandin synthesizing system using microsomes from ram seminal vesicles. The same system was activated by the beta-phenylethylamines found in the plant material, with the formation of more prostaglandins, the type being dependent on the amount of cyclooxygenase enzyme used and the presence or absence of coenzyme.

Effect of Desmodium adscendens fraction 3 on contractions of respiratory smooth muscle.

The third flash chromatography fraction prepared from an aqueous extract of Desmodium adscendens leaves (DAF3) was evaluated for pharmacological activity using contractions of tracheal spirals and lung parenchymal strips caused by ovalbumin, arachidonic acid, histamine and carbachol. DAF3 inhibited both the early and late phases of antigen-induced contractions of both tissues dose-dependently, but had no effect on arachidonic-induced contractions. With tracheal spirals, the inhibition occurred whether the tissue was pretreated with indomethacin or not. On tracheal spirals, the maximum contraction (Emax) caused by histamine and carbachol were enhanced, but the pD2 value for histamine was not affected while that for carbachol was decreased. DAF3 had no effect on Emax or pD2 values for these agonists on lung parenchymal strips. The results suggest that DAF3 may inhibit the release of free arachidonic acid.

Effect of Desmodium adscendens fractions on antigen- and arachidonic acid-induced contractions of guinea pig airways.

Three fractions (n-butanol, F2, and L5), isolated from an aqueous extract of Desmodium adscendens, a plant used in Ghana for the management of asthma, were evaluated for their pharmacological activity using ovalbumin and arachidonic acid-induced contractions of guinea pig airways. All three fractions inhibited the ovalbumin-induced contractions of indomethacin-pretreated tracheal spirals from sensitized animals dose dependently, but only L5 and n-butanol inhibited such contractions in the absence of indomethacin. The concentrations required to inhibit ovalbumin-induced contractions of lung parenchymal strips were threefold higher than with trachea. The contractile response over a 60-min period was divided into three phases. F2 and n-butanol inhibited all phases, whereas L5 inhibited only the late phase. n-Butanol and L5 inhibited arachidonic acid-induced contractions on indomethacin-pretreated tracheal spirals, a leukotriene-dependent reaction. There was no inhibition of arachidonic acid-induced contractions of lung parenchymal strips, which is largely a thromboxane-dependent reaction. The results suggest that D. adscendens contains several pharmacologically active substances that can inhibit allergic airway smooth muscle contraction at multiple sites, including the synthesis and (or) activity of the bronchoconstrictor leukotrienes.

Dose-response effects of Desmodium adscendens aqueous extract on histamine response, content and anaphylactic reactions in the guinea pig.

Different concentrations of a hot water extract of Desmodium adscendens, a plant used in Ghana to control asthmatic attacks, were used in drinking water to evaluate the plant's anti-anaphylactic properties in guinea pigs. The results show that the extract's inhibition of histamine-induced ileal contraction is largely competitive and that its effect of reducing lung histamine content is dose-dependent. The results also show that the extract causes a dose-dependent reduction in the amount of spasmogens released anaphylactically and in anaphylactic-induced contraction of ileal muscle.

Anti-anaphylactic properties of Thonningia sanguinea.

The anti-anaphylactic properties of extracts of THONNINGIA SANGUINEA, a plant used prophylactically against asthma were investigated using experimental anaphylaxis in the guinea pig. The results show that when administered orally, aqueous extract of the plant material inhibited anaphylactic contractions in isolated ileal pieces, reduced the sensitivity of ileal pieces to exogenous histamine, reduced the amount of histamine and mepyramine-resistant spasmogens released anaphylactically from lung tissues, and reduced the total histamine content of the lung. These properties could be responsible for the prophylactic action of the plant preparation.

Effects of the extracts of Desmodium adscendens on anaphylaxis.

Desmodium adscendens, used by herbalists in Ghana for the treatment of asthma, is anti-anaphylactic in vitro. As the plant material is administered orally, in vivo studies of its anti-anaphylactic property were undertaken using the guinea-pig. The results show that both aqueous and ethanolic extracts of D. adscendens, when taken orally, reduce anaphylactic contractions, interfere with histamine-induced contractions, and reduce the amount of smooth muscle stimulating substances released from lung tissue of guinea pigs.