RESUMO
Background: With the problems of increasing levels of drug resistance and difficulties to afford and access effective antimalarial drugs in poor and remote areas, herbal medicines could be an important and sustainable source of treatment. Argemone mexicana L. (AM) is a medicinal plant known long ago in several countries for treatment of numerous diseases including malaria. The aim of this study was to conduct a survey on the use of AM in the prevention and treatment of uncomplicated malaria in selected districts of Jimma Zone, Oromia Regional state, Ethiopia. Methods: A community-based cross-sectional study was conducted in two selected districts in Jimma Zone, southwest Ethiopia. In total, 552 participants from 17 kebeles (villages/communities) and 18 traditional healers of the districts were interviewed. Data collection was conducted from April 27 to May 18, 2020 using pre-tested structured questionnaires. The data were analyzed using Epi Info 7.0 and the descriptive statistics were used to summarize the results. Results: The study indicated that AM is available, known by 39.8% of the respondents and used for prevention and treatment of malaria by 5.7% of the population. All traditional healers interviewed knew the plant, and 44.4% use it for treatment of malaria. In addition, AM is especially used to treat malaria, amoebiasis, diarrhea, cough, and tuberculosis. Conclusion: The availability and use of AM to treat malaria was verified in both community and traditional healers. AM, which was found effective as antimalarial plant in high Plasmodium falciparum endemicity in Mali, is also well known and accepted in these areas of Ethiopia for the treatment of malaria. Further research is needed to assess wether AM is also effective against malaria in Ethiopia where P. vivax and P. falciparum coexist.
RESUMO
Classical pharmacology has been the basis for the discovery of new chemical entities with therapeutic effects for decades. In natural product research, compounds are generally tested in vivo only after full in vitro characterization. However drug screening using this methodology is expensive, time-consuming and very often inefficient. Reverse pharmacology, also called bedside-to-bench, is a research approach based on the traditional knowledge and relates to reversing the classical laboratory to clinic pathway to a clinic to laboratory practice. It is a trans-disciplinary approach focused on traditional knowledge, experimental observations and clinical experiences. This paper is an overview of the reverse pharmacology approach applied to the decoction of Argemone mexicana, used as an antimalarial traditional medicine in Mali. A. mexicana appeared as the most effective traditional medicine for the treatment of uncomplicated falciparum malaria in Mali, and the clinical efficacy of the decoction was comparable to artesunate-amodiaquine as previously published. Four stages of the reverse pharmacology process will be described here with a special emphasis on the results for stage 4. Briefly, allocryptopine, protopine and berberine were isolated through bioguided fractionation, and had their identity confirmed by spectroscopic analysis. The three alkaloids showed antiparasitic activity in vitro, of which allocryptopine and protopine were selective towards Plasmodium falciparum. Furthermore, the amount of the three active alkaloids in the decoction was determined by quantitative NMR, and preliminary in vivo assays were conducted. On the basis of these results, the reverse pharmacology approach is discussed and further pharmacokinetic studies appear to be necessary in order to determine whether these alkaloids can be considered as phytochemical markers for quality control and standardization of an improved traditional medicine made with this plant.
RESUMO
A classic way of delaying drug resistance is to use an alternative when possible. We tested the malaria treatment Argemone mexicana decoction (AM), a validated self-prepared traditional medicine made with one widely available plant and safe across wide dose variations. In an attempt to reflect the real situation in the home-based management of malaria in a remote Malian village, 301 patients with presumed uncomplicated malaria (median age 5 years) were randomly assigned to receive AM or artesunate-amodiaquine [artemisinin combination therapy (ACT)] as first-line treatment. Both treatments were well tolerated. Over 28 days, second-line treatment was not required for 89% (95% CI 84.1-93.2) of patients on AM, versus 95% (95% CI 88.8-98.3) on ACT. Deterioration to severe malaria was 1.9% in both groups in children aged 5 years) and 0% had coma/convulsions. AM, now government-approved in Mali, could be tested as a first-line complement to standard modern drugs in high-transmission areas, in order to reduce the drug pressure for development of resistance to ACT, in the management of malaria. In view of the low rate of severe malaria and good tolerability, AM may also constitute a first-aid treatment when access to other antimalarials is delayed.
Assuntos
Amodiaquina/administração & dosagem , Antimaláricos/administração & dosagem , Argemone , Artemisininas/administração & dosagem , Malária/tratamento farmacológico , Fitoterapia/métodos , Preparações de Plantas/administração & dosagem , Adolescente , Amodiaquina/efeitos adversos , Antimaláricos/efeitos adversos , Argemone/efeitos adversos , Artemisininas/efeitos adversos , Criança , Pré-Escolar , Combinação de Medicamentos , Resistência a Medicamentos , Feminino , Humanos , Lactente , Malária/epidemiologia , Masculino , Mali/epidemiologia , Adesão à Medicação/estatística & dados numéricos , Fitoterapia/efeitos adversos , Preparações de Plantas/efeitos adversos , Saúde da População Rural , Resultado do Tratamento , Adulto JovemRESUMO
A prospective, dose-escalating, quasi-experimental clinical trial was conducted with a traditional healer using a decoction of Argemone mexicana for the treatment of malaria in Mali. The remedy was prescribed in three regimens: once daily for 3 days (Group A; n=23); twice daily for 7 days (Group B; n=40); and four times daily for the first 4 days followed by twice daily for 3 days (Group C; n=17). Thus, 80 patients were included, of whom 80% were aged<5 years and 25% were aged<1 year. All presented to the traditional healer with symptoms of malaria and had a Plasmodium falciparum parasitaemia>2000/microl but no signs of severe malaria. The proportions of adequate clinical response (ACR) at Day 14 were 35%, 73% and 65% in Groups A, B and C, respectively (P=0.011). At Day 14, overall proportions of ACR were lower in children aged<1 year (45%) and higher in patients aged>5 years (81%) (P=0.027). Very few patients had complete parasite clearance, but at Day 14, 67% of patients with ACR had a parasitaemia<2000/microl. No patient needed referral for severe disease. Only minor side effects were observed. Further research should determine whether this local resource could represent a first-aid home treatment in remote areas.