Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Exp Pharmacol ; 16: 231-242, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39045603

RESUMO

Background: Sclerocarya birrea (A. Rich). Hochst, popularly known as Morula, is a plant in the Anacardiaceae family. The bark, fruits, and leaves have traditionally been used to manage a variety of health conditions, most especially diabetes. Unfortunately, there is a scarcity of data and publications on the toxicity and safety of this plant. Purpose: The current study was designed to assess the acute and chronic toxicity of a hydro-ethanolic extract of Sclerocarya birrea in albino rats. Materials and Methods: Sclerocarya birrea was extracted using an 80-20% hydro-ethanolic solution. For the acute toxicity study, female Wistar albino rats were treated with hydro-ethanolic leaf extract at a dose of 5000 mg/kg body weight and followed-up for 14 days. In the chronic toxicity study, 40 healthy Wistar albino rats were divided in 4 groups. The three treatment groups were administered the leaf hydro-ethanolic extract orally at dosages of 30, 150, and 1000 mg/kg once day for 90 days and the fourth group was a control group. Body and organs weights, haematological, serum biochemical, and histopathological parameters were measured at the end of the experiment. Results: Single-dose oral administration of hydro-ethanolic leaf extract of Sclerocarya birrea at 5000 mg/kg produced no mortality indicating the LD50 is greater than 5000 mg/kg body weight. Following 90 days of administration of a hydro-ethanolic extract of Sclerocarya birrea leaves, there was no significant change in body and organs weights. Furthermore, biochemical, haematological and histopathological parameters did not vary significantly. Conclusion: This data indicates neither acute or chronic toxicity in rats and is consistent with the widespread and long-term usage of Sclerocarya birrea in African traditional medicine.

2.
Malar J ; 22(1): 363, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38017455

RESUMO

BACKGROUND: Dual hrp2/hrp3 genes deletions in P. falciparum isolates are increasingly reported in malaria-endemic countries and can produce false negative RDT results leading to inadequate case management. Data on the frequency of hrp2/hrp3 deleted parasites are rarely available and it has become necessary to investigate the issue in Burkina Faso. METHODS: Plasmodium falciparum-positive dried blood spots were collected during a cross-sectional household survey of the malaria asymptomatic children from Orodara, Gaoua, and Banfora. Amplicons from the target regions (exon 2 of hrp2 and hrp3 genes) were generated using multiplexed nested PCR and sequenced according to Illumina's MiSeq protocol. RESULTS: A total of 251 microscopically positive parasite isolates were sequenced to detect hrp2 and hrp3 gene deletions. The proportion of RDTs negative cases among microscopy positive slides was 12.7% (32/251). The highest prevalence of negative RDTs was found in Orodara 14.3% (5/35), followed by Gaoua 13.1%(24/183), and Banfora 9.1% (3/33). The study found that 95.6% of the parasite isolates were wild type hrp2/ hrp3 while 4.4% (11/251) had a single hrp2 deletion. Of the 11 hrp2 deletion samples, 2 samples were RDT negative (mean parasitaemia was 83 parasites/ µL) while 9 samples were RDT positive with a mean parasitaemia of 520 parasites /µL (CI95%: 192-1239). The highest frequency of hrp2 deletion 4/35 (11.4%) was found in Orodara, while it was similar in the other two sites (< 3.5%). No single deletion of the hrp3 or dual deletion hrp2/3 gene was detected in this study. CONCLUSION: These results demonstrate that P. falciparum isolates lacking hrp2 genes are present in 4.4% of samples obtained from the asymptomatic children population in three sites in Burkina Faso. These parasites are circulating and causing malaria, but they are also still detectable by HRP2-based RTDs due to the presence of the intact pfhrp3 gene.


Assuntos
Malária Falciparum , Plasmodium falciparum , Criança , Humanos , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Antígenos de Protozoários/genética , Antígenos de Protozoários/análise , Histidina/genética , Deleção de Genes , Estudos Transversais , Burkina Faso/epidemiologia , Malária Falciparum/parasitologia , Testes Diagnósticos de Rotina/métodos
3.
Malar J ; 22(1): 213, 2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37474966

RESUMO

BACKGROUND: Artemisinin-based combinations therapy (ACT) is the current frontline curative therapy for uncomplicated malaria in Burkina Faso. Sulfadoxine-pyrimethamine (SP) is used for the preventive treatment of pregnant women (IPTp), while SP plus amodiaquine (SP-AQ) is recommended for children under five in seasonal malaria chemoprevention (SMC). This study aimed to assess the proportions of mutations in the P. falciparum multidrug-resistance 1 (Pfmdr1), P. falciparum chloroquine resistance transporter (Pfcrt), P. falciparum dihydrofolate reductase (pfdhfr), and P. falciparum dihydropteroate synthase (pfdhps), genes from isolates collected during household surveys in Burkina Faso. METHODS: Dried blood spots from Plasmodium falciparum-positive cases at three sites (Orodara, Gaoua, and Banfora) collected during the peak of transmission were analysed for mutations in Pfcrt (codons 72-76, 93, 97, 145, 218, 343, 350 and 353), Pfmdr-1 (codons 86, 184, 1034, 1042 and 1246) dhfr (codons 51, 59, 108, 164) and dhps (at codons 431, 436, 437, 540, 581, 613) genes using deep sequencing of multiplexed Polymerase chaine reaction (PCR) amplicons. RESULTS: Of the 377 samples analysed, 346 (91.7%), 369 (97.9%), 368 (97.6%), and 374 (99.2%) were successfully sequenced for Pfcrt, Pfmdr-1, dhfr, and dhps, respectively. Most of the samples had a Pfcrt wild-type allele (89.3%). The 76T mutation was below 10%. The most frequent Pfmdr-1 mutation was detected at codon 184 (Y > F, 30.9%). The single mutant genotype (NFSND) predominated (66.7%), followed by the wild-type genotype (NYSND, 30.4%). The highest dhfr mutations were observed at codon 59R (69.8%), followed by codons 51I (66.6%) and 108 N (14.7%). The double mutant genotype (ACIRSI) predominated (52.4%). For mutation in the dhps gene, the highest frequency was observed at codon 437 K (89.3%), followed by codons 436 A (61.2%), and 613 S (14.4%). The double mutant genotype (IAKKAA) and the single mutant genotype (ISKKAA) were predominant (37.7% and 37.2%, respectively). The most frequent dhfr/dhps haplotypes were the triple mutant ACIRSI/IAKKAA (23%), the wild-type ACNCSI/ISKKAA (19%) and the double mutant ACIRSI/ISKKAA (14%). A septuple mutant ACIRNI/VAKKGA was observed in 2 isolates from Gaoua (0.5%). CONCLUSION: The efficacy of ACT partner drugs and drugs used in IPTp and SMC does not appear to be affected by the low proportion of highly resistant mutants observed in this study. Continued monitoring, including molecular surveillance, is critical for decision-making on effective treatment policy in Burkina Faso.


Assuntos
Antimaláricos , Malária Falciparum , Malária , Humanos , Criança , Feminino , Gravidez , Plasmodium falciparum , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Burkina Faso , Pirimetamina/farmacologia , Pirimetamina/uso terapêutico , Sulfadoxina/farmacologia , Sulfadoxina/uso terapêutico , Malária Falciparum/epidemiologia , Malária Falciparum/prevenção & controle , Malária Falciparum/tratamento farmacológico , Malária/tratamento farmacológico , Mutação , Tetra-Hidrofolato Desidrogenase/genética , Combinação de Medicamentos , Resistência a Medicamentos/genética , Códon
4.
Drug Des Devel Ther ; 14: 1593-1607, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32425505

RESUMO

PURPOSE: Continuous efforts into the discovery and development of new antimalarials are required to face the emerging resistance of the parasite to available treatments. Thus, new effective drugs, ideally able to inhibit the Plasmodium life-cycle stages that cause the disease as well as those responsible for its transmission, are needed. Eight compounds from the Medicines for Malaria Venture (MMV) Malaria Box, potentially interfering with the parasite polyamine biosynthesis were selected and assessed in vitro for activity against malaria transmissible stages, namely mature gametocytes and early sporogonic stages. METHODS: Compound activity against asexual blood stages of chloroquine-sensitive 3D7 and chloroquine-resistant W2 strains of Plasmodium falciparum was tested measuring the parasite lactate dehydrogenase activity. The gametocytocidal effect was determined against the P. falciparum 3D7elo1-pfs16-CBG99 strain with a luminescent method. The murine P. berghei CTRP.GFP strain was employed to assess compounds activities against early sporogonic stage development in an in vitro assay simulating mosquito midgut conditions. RESULTS: Among the eight tested molecules, MMV000642, MMV000662 and MMV006429, containing a 1,2,3,4-tetrahydroisoquinoline-4-carboxamide chemical skeleton substituted at N-2, C-3 and C-4, displayed multi-stage activity. Activity against asexual blood stages of both strains was confirmed with values of IC50 (50% inhibitory concentration) in the range of 0.07-0.13 µM. They were also active against mature stage V gametocytes with IC50 values below 5 µM (range: 3.43-4.42 µM). These molecules exhibited moderate effects on early sporogonic stage development, displaying IC50 values between 20 and 40 µM. CONCLUSION: Given the multi-stage, transmission-blocking profiles of MMV000642, MMV000662, MMV006429, and their chemical characteristics, these compounds can be considered worthy for further optimisation toward a TCP5 or TCP6 target product profile proposed by MMV for transmission-blocking antimalarials.


Assuntos
Antimaláricos/farmacologia , Malária/tratamento farmacológico , Fenil-Hidrazinas/farmacologia , Plasmodium berghei/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos , Animais , Antimaláricos/administração & dosagem , Relação Dose-Resposta a Droga , Injeções Intraperitoneais , Malária/transmissão , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Testes de Sensibilidade Parasitária , Fenil-Hidrazinas/administração & dosagem , Relação Estrutura-Atividade
5.
Phytochemistry ; 174: 112336, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32192964

RESUMO

Targeting the transmissible stages of the Plasmodium parasite that develop in the human and mosquito host is a crucial strategy for malaria control and elimination. Medicinal plants offer a prolific source for the discovery of new antimalarial compounds. The recent identification of the gametocytocidal activity of lophirone E, obtained from the African plant Lophira lanceolata (Ochnaceae), inspired the evaluation of the plant also against early sporogonic stages of the parasite development. The bioassay-guided phytochemical study led to the isolation of two known lanceolins and of a new glycosylated bichalcone, named glucolophirone C. Its stereostructure, including absolute configuration of the bichalcone moiety, was elucidated by means of NMR, HRMS, ECD and computational calculations. Lanceolin B proved to be a potent inhibitor of the development of Plasmodium early sporogonic stages indicating that the plant produces two different stage-specific antimalarial agents acting on transmissible stages in the human and mosquito host.


Assuntos
Antimaláricos , Malária , Ochnaceae , Animais , Humanos , Casca de Planta , Extratos Vegetais , Plasmodium falciparum
6.
Bioorg Chem ; 93: 103321, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31585261

RESUMO

Bioassay-guided fractionation of the organic extract obtained from stem barks of the African plant Lophira lanceolata has led to the isolation of seven biflavonoids, including the new α'-chlorolophirone E (5) and 5'-chlorolophirone D (6). Among the isolated compounds, the bichalcone lophirone E was identified as a potent gametocytocidal agent with an IC50 value in the nanomolar range and negligible cytotoxicity (selectivity index = 570). Lophirone E proved to be about 100 times more active against P. falciparum stage V gametocytes than on asexual blood stages, thus exhibiting a unique stage-specific activity profile. The isolation of structural analogues allowed to draw preliminary structure-activity relationships, identifying the critical positions on the chemical scaffold of lophirone E.


Assuntos
Antimaláricos/química , Ochnaceae/química , Casca de Planta/química , Caules de Planta/química , Antimaláricos/isolamento & purificação , Antimaláricos/farmacologia , Linhagem Celular , Humanos , Concentração Inibidora 50 , Plasmodium falciparum/efeitos dos fármacos , Análise Espectral/métodos , Relação Estrutura-Atividade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA