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The ethanol extracts of fresh apical stems ofPhyllanthus niruriL.(Euphorbiaceae)cultured on Murashige and Skoog(MS)medium supplemented with IBA/BAP/Coco nuciferaL. milk for 1, 2, 4, and 6 months were phytochemically and biologically investigated and compared to the intact plant part and whole plant extracts. A phytochemical screening revealed the presence of steroids, terpenes, and flavonoids as the major phytochemical groups, but not the same constituents belonging to these groups in all extracts. Alkaloids were detected in whole plant extract and were in traces in the intact apical stem extract and callus extracts. Results from thein vitroantiplasmodial testing indicated that the callus extract 1&ThickSpace;month old(IC 50 &ThickSpace;=&ThickSpace;16.3±2.5&ThickSpace;µg/ml)exhibited activity similar to the intact plant part extract(IC 50 &ThickSpace;=&ThickSpace;18.2±2.5&ThickSpace;µg/ml)(p&ThickSpace;=&ThickSpace;0.05). This activity was significantly higher(p&ThickSpace;<&THICKSPACE;0.001) than that exhibited by extracts from callus cultures 2, 4, and 6 months old(25&ThickSpace;<&ThickSpace;IC 50 &ThickSpace;<&ThickSpace;40&ThickSpace;µg/ml). The activity of these extracts is lower than that displayed by the same extract from the whole plant(IC 50 &ThickSpace;=&ThickSpace;2.5±0.2&ThickSpace;µg/ml). [ABSTRACT FROM AUTHOR]

The ethanolic, dichloromethane and lyophilized aqueous extracts of Cassia occidentalisroot bark, Morinda morindoidesleaves and whole plants of Phyllanthus niruriwere evaluated for their antimalarial activity in vivo, in 4-day, suppressive assays against Plasmodium bergheiANKA in mice. No toxic effect or mortality was observed in mice treated, orally, with any of the extracts as a single dose, of 500 mg/kg body weight, or as the same dose given twice weekly for 4 weeks (to give a total dose of 4 g/kg). No significant lesions were observed, by eye or during histopathological examinations, in the hearts, lungs, spleens, kidneys, livers, large intestines or brains of any mouse. :At doses of 200 mg/kg, all the ethanolic and dichloromethane extracts produced significant chemosuppressions of parasitaemia (of >60% for C. occidentalisroot bark and Ph. niruriwhole plant, and of 30% for M. morindoidesleaves) when administered orally. The most active ethanolic extract, that of Ph. niruri, reduced parasitaemia by 73%. The dichloromethane extracts of M. morindoidesand Ph. niruriproduced similar reductions (74% and 72% chemosuppression, respectively), whereas that of C. occidentaliswas slightly less active (60% chemosuppression). Each lyophilized aqueous extract was less active than the corresponding ethanolic extract. [ABSTRACT FROM AUTHOR]

Unlabelled: Ethnoparmaological relevance: One of the possible methodologies for the discovery of novel drugs is the screening of selected plant extracts for a broad array of pharmacological activities., Materials and Methods: The selection based on enthnomedicinal uses, combined with a follow-up of existing literature on the plants' chemotaxonomic properties, would seem to be the most cost-effective strategy for finding active plant extracts. A bioassay-guided fractionation of the active extracts should subsequently lead to the isolation and identification of the active lead constituent(s)., Results and Discussion: Taking into account the enormous number and the amazing structural diversity of the currently known plant constituents, one might hope that promising model compounds with new structures and/or novel mechanisms of action might be found. In order, however, to optimize such a natural product drug discovery methodology, dereplication and selectivity of activity should be included in the screening system. Dereplication by which known compounds can rapidly be identified from a partially purified mixture prevents a research group from wasting resources by rediscovering known compounds. The use of single-target specific bioassays such as tests on isolated enzymes or on receptor-binding, or multiple target functional bioassays on isolated organs or intact cells must allow at an early stage to isolate compounds with specific pharmacological properties., Conclusions: In this publication, several examples of bioassay-guided isolation and identification of pharmacologically active lead compounds from plants used in Central-African traditional medicine by our research group will be presented and discussed., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Physalis angulata L., an annual herb from the Solanaceae family, is widely used in popular medicine in tropical countries to treat a variety of diseases. Two products, (X) and (Y), were isolated from a crude CH2Cl2 extract of dried Congolese Physalis angulata L. plants and crystallized from acetone for structure elucidation. Compound (X) corresponds to a physalin B dimer acetone solvate hydrate (2C28H30O9·C3H6O·0.22H2O), while compound (Y) crystallizes as a mixed crystal containing two physalin B molecules which overlap with 5β,6β-epoxyphysalin B, also known as physalin F, and one acetone molecule in the asymmetric unit (1.332C28H30O9·0.668C28H30O10·C3H6O). Antiplasmodial activity, cytotoxic activity and selectivity indices were determined for crude extracts and the two isolated products (X) and (Y).

According to the promising results of the Phase I and Phase IIA clinical trials with the herbal medicinal product PR 259 CT1 consisting of an 80 % ethanolic extract of the stem bark of Nauclea pobeguinii containing 5.6 % strictosamide, a Phase IIB study was conducted as a single blind prospective trial in 65 patients with proven Plasmodium falciparum malaria to evaluate the effectiveness and safety of this herbal drug. The study was carried out simultaneously using an artesunate-amodiaquine combination (Coarsucam®) as a positive control. This combination is the standard first-line treatment for uncomplicated malaria recommended by the National Programme of Malaria Control in the Democratic Republic of Congo (DR Congo). With regard to PR 259 CT1, patients were treated with a drug regimen of two 500-mg capsules three times daily for three days in the inpatient clinic, followed by out-patient treatment of one 500-mg capsule three times daily during the next four days; the positive control group received two tablets containing 100 mg artesunate and 270 mg amodiaquine (fixed-dose) once daily during three consecutive days. Antimalarial responses were evaluated according to the WHO 2003 guideline for a 14-day test. The results from the physical and laboratory examinations did not show any significant changes in values of vital signs, ECG, biochemical, and haematological parameters. The study showed a significant decreased parasitaemia in patients treated with PR 29 CT1 and artesunate-amodiaquine with adequate clinical parasitological responses (APCR) at day 14 of 87.9 and 96.9 %, respectively. The former product was better tolerated than the latter since more side effects were observed for the artesunate-amodiaquine combination. These results indicated that PR 259 CT1 can be considered as a promising candidate for the development of a herbal medicine for the treatment of uncomplicated falciparum malaria., (Georg Thieme Verlag KG Stuttgart · New York.)

The aim of this phase IIA clinical trial was to assess the efficacy of an 80 % ethanolic quantified extract (containing 5.6 % strictosamide as the putative active constituent) from Nauclea pobeguinii stem bark denoted as PR 259 CT1 in a small group of adult patients diagnosed with uncomplicated falciparum malaria. Results obtained from a phase I clinical trial on healthy male volunteers indicated that the oral administration during meals of two 500 mg capsules three times daily (each eight hours) during seven days was well tolerated and showed only mild and self-resolving adverse effects. This PR 259 CT1 drug regimen was obtained by mathematical conversion of animal doses obtained in several in vivo studies in mice to human equivalent doses as in falciparum malaria patients. The phase IIA study was an open cohort study in eleven appraisable adult patients suffering from proven Plasmodium falciparum malaria. The study was specifically designed to assess the efficacy of PR 259 CT1 administered with a dose regimen of two 500 mg capsules three times daily for three days, followed by outpatient treatment of one 500 mg capsule three times daily for the next four days, in order to prove that this therapeutic dose, which was calculated from animal doses, was effective to treat adult malaria patients and consequently useful for a future Phase IIB clinical trial. This study would then substitute a dose-escalating trial, which in general is used to find the appropriate dose for clinical studies. The phase IIA clinical trial was carried out according to the WHO 2003 14-day test, and the results revealed that all eleven patients were completely cleared of parasitemia and fever on days 3, 7, and 14 except for one patient, who experienced a recurrence of parasitemia at days 7 until 14. Besides this adequate clinical and parasitological response (ACPR), this trial also demonstrated that PR 259 CT1 was well tolerated with only mild and self-resolving adverse effects including fatigue and headache, which were in accordance with those found in the phase I clinical trial. Moreover, all symptoms progressively disappeared, and no symptoms were observed on day 14. Although the number of patients included in this study was rather limited, the statistical analysis nevertheless suggested the efficacy and tolerability of PR 259 CT1, which indicated that this herbal medicinal product might be considered as a putative candidate for a large scale clinical trial., (© Georg Thieme Verlag KG Stuttgart · New York.)

The aim of this study was to evaluate the short-term safety and tolerability of an antimalarial herbal medicinal product (PR 259 CT1) consisting of a quantified 80 % ethanol extract from the stem bark of Nauclea pobeguinii when given orally to healthy adult male volunteers. The amount of the major alkaloid strictosamide in the extract was determined by a validated HPLC method and was shown to be 5.6 %. The herbal preparation was formulated in a gelatine capsule form containing 500 mg of PCR 259 CT1. A sample of 15 healthy male volunteers, selected using the Lot Quality Assurance of Sampling (LQAS) method, was eligible for inclusion after fulfillment of the inclusion criteria and clinical examination by a physician. The volunteers were treated in an outpatient clinic with a drug regimen of two 500 mg capsules three times daily (each eight hours) for seven days, during meals. Safety and tolerability were monitored clinically, haematologically, biochemically and by electrocardiographic (ECG) examination at days 0, 1, 3, 7 and 14. Adverse effects were recorded by self-reporting of the participants or by detection of abnormalities in clinical examinations by a physician. The oral administration of PR 259 CT1 at high doses of 2 × 500 mg/capsule/day for 7 days was found to induce no significant changes in the concentration levels of all investigated haematological, biochemical, electrocardiogram and vital sign parameters and physical characteristics after 14 days of treatment compared to those seen in the baseline data. The concentration levels of all evaluated parameters were within the normal limits as reported in the literature. All adverse events noted were mild and self-resolving including increase of appetite (33 %), headache (20 %) and nausea (20 %). Other minor side effects were insomnia, somnolence and asthenia (7 %). Thus, PR 259 CT1 presented a significant safety and tolerability in healthy volunteers to allow its further development by starting a phase II clinical trial., (© Georg Thieme Verlag KG Stuttgart · New York.)

Aim of the Study: To evaluate the in vitro and in vivo antiplasmodial activity and toxicity of the aqueous and 80% EtOH extract of the stem bark of Nauclea pobeguinii (Pob. Ex. Pell.) Petit (Rubiaceae), a plant used in traditional medicine in DR Congo against malaria., Materials and Methods: The aqueous and 80% EtOH extract from N. pobeguinii stem bark, and its constituents (5S)-5-carboxystrictosidine, 19-O-methylangustoline, 3-O-beta-fucosylquinovic acid, 3-ketoquinovic acid and strictosamide, were evaluated for their in vitro activity against Plasmodium falciparum (chloroquine-sensitive Ghana-strain). The 80% EtOH extract, containing 5.6% strictosamide, was evaluated in vivo in the 4-day P. berghei mouse model, and in the P. yoelii N67 model., Results: All compounds were inactive or only moderately active in vitro. The aqueous and 80% EtOH extract displayed moderate in vitro activity with IC(50) values of 44 and 32 microg/mL, respectively, without apparent cytotoxicity on MRC-5 cells (CC50>64 microg/mL). Daily oral dosing of the 80% EtOH extract, at 300 mg/kg, resulted in 86% reduction of parasitaemia in the 4-day P. berghei mouse model, and 75% reduction in the P. yoelii N67 model. Prolonging oral dosing to 2 x 5 days, with an interval of 2 days, and oral administration of the 80% EtOH extract at 300 mg/kg induced 92% reduction of parasitaemia, and a mean survival time of 17 days. Strictosamide, the putative active constituent, may be metabolically activated in the gastrointestinal tract after oral administration. Levels of creatinin, urea, ALAT and ASAT remained unchanged after treatment. No acute toxicity was observed in mice after a single 2g/kg oral dose, nor after 4 weekly doses. No significant macroscopic or microscopic lesions were observed in heart, lung, spleen, kidney, liver, large intestine and brain., Conclusions: These results can partly support and justify the use of N. pobeguinii in traditional medicine in the DR Congo for the treatment of uncomplicated malaria., ((c) 2010 Elsevier Ireland Ltd. All rights reserved.)

Problems of drug availability and accessibility remain a major obstacle to the improvement of sanitary conditions in D.R. Congo, where rational drug use is a major concern. This study assesses prescriptions and cost related to the treatment of malaria and gastroenteritis in two hospitals of Kinshasa. The analysis of prescriptions shows that multiple drugs are prescribed, some of them very irrationally. Both factors increase of the cost of treatment. The lack of prescription policies, the shortage of diagnostic tools, the insufficient knowledge of pharmacology and therapeutics are, with economics constraints, key factors in this phenomenon. Training, education and sensitization of health professionals to the use of drugs are essential for improving the quality of and access to appropriate care.

The ethanolic, dichloromethane and lyophilized aqueous extracts of Cassia occidentalis root bark, Morinda morindoides leaves and whole plants of Phyllanthus niruri were evaluated for their antimalarial actvity in vivo, in 4-day, suppressive assays against Plasmodium berghei ANKA in mice. No toxic effect or mortality was observed in mice treated, orally, with any of the extracts as a single dose, of 500 mg/kg body weight, or as the same dose given twice weekly for 4 weeks (to give a total dose of 4 g/kg). No significant lesions were observed, by eye or during histopathological examinations, in the hearts, lungs, spleens, kidneys, livers, large intestines or brains of any mouse. At doses of 200 mg/kg, all the ethanolic and dichloromethane extracts produced significant chemosuppressions of parasitaemia (of > 60% for C. occidentalis root bark and Ph. niruri whole plant, and of 30% for M. morindoides leaves) when administered orally. The most active ethanolic extract, that of Ph. niruri, reduced parasitaemia by 73%. The dichloromethane extracts of M. morindoides and Ph. niruri produced similar reductions (74% and 72% chemosuppression, respectively), whereas that of C. occidentalis was slightly less active (60% chemosuppression). Each lyophilized aqueous extract was less active than the corresponding ethanolic extract.