ETUDE PHYTOCHIMIQUE ET PHARMACOLOGIQUE DE PLANTES ANTIPALUDIQUES UTILISEES EN MEDECINE TRADITIONNELLE CONGOLAISE PHYTOCHEMICAL AND PHARMACOLOGICAL STUDY OF ANTIMALARIAL

Cette thèse a été réalisée au sein du service de pharmacognosie de l’Université de Liège, dont les travaux de recherche sont principalement axés sur la découverte de nouvelles molécules à potentialité antipaludique.La première partie de ce travail est consacrée à une enquête ethnobotanique réalisée en R.D.Congo et qui s'est intéressée aux plantes utilisées en médecine traditionnelle pour soigner différentes maladies, en particulier le paludisme. De cette étude, cinq plantes utilisées dans le traitement de la fièvre, de l’inflammation, des céphalées, de la malaria ont été présélectionnées. Un criblage antiplasmodial in vitro des différents extraits a été réalisé sur les souches chloroquino-sensible (3D7) et chloroquino-résistante (W2) de Plasmodium falciparum. Il a permis de sélectionner deux de ces cinq plantes qui se sont révélées très actives et qui n’avaient pas encore été étudiées sur la malaria : Anisopappus chinensis (Asteraceae) et Physalis angulata (Solanaceae). L’activité antiplasmodiale de ces deux plantes a été confirmée par un test in vivo sur les souris NMRI et SWISS infestées par le Plasmodium berghei berghei. Des essais de cytotoxicité in vitro sur des fibroblastes de poumons humains (souche WI-38) ont également été réalisés ainsi que la détermination de la DL50 sur les rats wistar (DL50 > 5g/kg pour les deux plantes).La deuxième partie du travail consiste en l’étude phytochimique bio-guidée de ces deux plantes. A partir de Physalis angulata (extrait CH2Cl2, CI50 CI50 < 30 µg/ml). Par ailleurs, plusieurs acides phénols ont également été identifiés dans l’extrait MeOH. Des études complémentaires pourraient aboutir à l’isolement de substances plus actives. Tous ces composés, de classes phytochimiques très différentes, contribuent vraisemblablement à l’activité antipaludique de la plante, ce qui nous fait penser qu’ils agissent en synergie

In vitro and in vivo antimalarial and cytotoxic activity of five plants used in Congolese traditional medicine.

peer reviewedAIM OF THE STUDY: The in vitro antiplasmodial activity and cytotoxicity of methanolic and dichloromethane extracts from five Congolese plants were evaluated. The plants were selected following an ethnobotanical survey conducted in D.R. Congo and focusing on plants used traditionally to treat malaria. The in vivo antimalarial activity of aqueous and methanolic extracts active in vitro was also determined in mice infected by Plasmodium berghei berghei. MATERIALS AND METHODS: The growth inhibition of Plasmodium falciparum strains was evaluated using the measurement of lactate dehydrogenase activity. The extracts (aqueous, CH(3)OH, EtOH and CH(2)Cl(2)) were prepared by maceration and tested in vitro against the 3D7 (chloroquine sensitive) and W2 (chloroquine resistant) strains of Plasmodium falciparum and against the human normal fetal lung fibroblasts WI-38 to determine the selectivity index. Some extracts were also used at the dose of 300mg/kg to evaluate their activity in mice infected since 4 days by Plasmodium berghei. RESULTS: Two plants presented a very high activity (IC(50)10, Anisopappus chinensis). Anisopappus chinensis and Physalis angulata were also active in vivo

Development of a pharmacovigilance system in a resource-limited country : the experience of the Democratic Republic of Congo

Implementation of pharmacovigilance (PV) systems in resource-limited countries is a real endeavor. Despite country- and continent-specific challenges, the Democratic Republic of the Congo (DRC) has been able to develop one of the most active PV systems in the sub-Saharan Africa. The World Health Organization (WHO) regional Office identified the DRC experience to set up a PV system for antimalarial drugs safety monitoring as a 'best practice' that needed to be documented in order to help DRC improve its PV system and to be scaled up in other African countries. In response to the WHO request, a best practices and bottlenecks analysis was conducted in 2015. This analysis was updated in 2018 in the light of the minimum requirements of the WHO to set up a PV system taking into account other guidance for PV systems. The following themes were retained for analysis: (1) creation of the national PV center; (2) implementation of PV in the health system; (3) data collection and analysis; (4) collaboration with public health programs; (5) collaboration with the National Regulatory Authority. Lessons learnt from the DRC experience show that it is possible to implement PV systems in order to promote patients' safety in resource limited sub-Saharan African countries with no guaranteed funding. The ability of national PV centers to collaborate with Public health stakeholders, including public health authorities at all levels as well as public health programs, and to use existing health information systems are considered the main key to success and may substantially reduce the cost of PV activities

Structure Elucidation of Two Physalins Isolated from Physalis angulata L. (Solanaceae)

L'identification et la détermination structurale par diffraction aux rayons X de deux stéroïdes extraits d'une solanacée congolaise récoltée au Congo ( RDR) sont décrites en anglais dans cette communication publiée à la page 55 de l'"abstracts book

UV Visible Spectrophotometric Determination of the Quality of Antiretroviral Drugs Distributed in Kinshasa

peer reviewedBackground: Antiretrovirals (ARVs) are the molecules used in the fight against infection by the Human Immunodeficiency Virus (HIV). Their main objective is to stop the virus from replicating and thus allow the immune system to recover. In 2001, the program to fight against HIV/AIDS United Nations (UNAIDS) and its partners has decided to strengthen the pharmaceutical channel and improve access to good quality care. Thus ARV quality control is recommended. Objective: The objective of this work was to monitor the quality of ARVs distributed in Kinshasa. Methodology: In this work, UV-visible spectrophotometry is used for the analysis of ARVs presented in simple form distributed in the city of Kinshasa. Results: The results of this work show that the stated and analyzed ARVs contain active ingredients; there is no placebo. Ten percent of these ARVs are non-compliant with regard to dosing of the active test. Conclusion: These results confirm the need to control these drugs to protect patients from adverse consequences related to their poor quality

Isolation, pharmacological activity and structure determination of physalin B and 5[beta],6[beta]-ep­oxy­physalin B isolated from Congolese Physalis angulata L.

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 5[beta],6[beta]-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)

Blood Lead, Urinary Lead and Urinary δ-Aminolevulinic Acid Levels among Children Living in Kinshasa, D R Congo: A Pilot Biomonitoring Study,

peer reviewedLead exists naturally in the earth's crust and it is widely used as a heavy metal. It is an environment toxicant that may deleteriously affect nervous, hematopoietic, skeletal, renal, endocrine and reproductive systems. So, exposure to lead in the environment continues to be a serious public health problem for all ages. Children are particularly susceptible to lead poisoning. They absorb more lead from their environment and their developing central nervous systems are vulnerable to the toxic. Fifty percent of children aged from 0 to 17-years-old presented blood lead levels above 100 μg/L and forty three percent of the same population presented blood lead levels above 50 μg/L. There was no correlation between urinary lead level and D-ALAU (urinary δ-aminolevulinic acid) with lead blood levels. But it was observed a small correlation between urinary lead and blood lead concentrations

Blood lead, urinary lead , urinary δ-aminolevulinic acid and urinary porphyrins levels among people living in Kinshasa , D.R. Congo : a pilot biomonitoring study

Objectives: Existing naturally in the earth’s crust, Lead is a widely used heavy metal. It is an environment toxicant that may deleteriously affect nervous, hematopoietic, skeletal, renal, endocrine and reproductive systems. Lead is classified in its inorganic form as possible human carcinogen (group 2A) by IARC. Exposure to lead in the environment continues to be a serious public health problem for all ages. Children are particularly susceptible to lead poisoning. They absorb more lead from their environment and their developing central nervous systems are vulnerable to the toxicant. During the last twenty years, important measures of public health were undertaken in several countries to decrease lead exposure. In the best of our knowledge, this is not the case in D.R. Congo. A study indicated a relatively important lead impregnation of the Kinshasa population (mean 120 μg/L). However, there have been no reported studies in the evaluation of the relationship between urinary lead, urinary δ-aminolevulinic acid (δ-AlaU) and urinary porphyrins and lead blood level in Congolese people. This is the aim of this study targeting at first people living in Kinshasa. Methods: Blood lead and urinary lead levels were measured using inductively coupled plasma mass spectrometry. The Bio-Rad ALA/PBG by Column Test and spectrophotometer method were used to quantify the concentration of δ-Ala in urine. The separation of porphyrins was carried out by HPLC coupled with fluorescence detector. Results: 37% of studied population presented blood lead levels above the 100 μg/L threshold (geometric mean: 133.29 μg/L) with a higher concentration in women than in men (140.30 μg/L vs 130.78 μg/L). 50% of children (0-17 years) presented blood lead levels above the 100 μg/L threshold and 43% of the same population presented blood lead levels above 50 μg/L as accepted nowadays in US. In the adult population, some targeted occupations were found to be associated with high blood lead. A small correlation was observed between urinary lead and blood lead, but no correlation was noticed between δ-AlaU and Porphyrins with lead blood levels. Conclusion: This study confirmed a relatively important Pb impregnation of the Kinshasa population and the existence of a major public health issue requiring corrective actions and the implementation of an appropriate regulation. Also, urinary lead, urinary δ-Ala and urinary porphyrins seems to not to be sensitive markers for monitoring exposure to lead.Contribution au développement des capacités d’enseignement et de formation pour l’amélioration de la qualité du médicament (acronyme : DEV-AQM)