YIKI is an antimalarial phytomedicine used by a traditional healer to treat malaria in Bobo-Dioulasso. However, there is no scientific evidence to support its use by local populations. The aim of this study was to identify the medicinal practices of the healer holder of YIKI and assess the clinical evidence of its phytomedicine in the uncomplicated malaria treatment. Ethnomedical survey based on a semi-structured and open questionnaire was conducted from October to December 2019 with the healer. Malaria knowledge and diagnosis methods, patient treatment and monitoring, and recipe formulation steps were surveyed. Moreover, thick and thin blood smears were taken, haemoglobin levels and temperature of consenting patients were measured before treatment, mid-treatment and at the end of treatment. The survey revealed that the healer has a good knowledge of malaria symptoms and his diagnosis is based on observation and physical examination of patients. The healer’s malaria diagnosis was rudimentary and had accuracy problems, with only 62.79% of malaria cases confirmed by microscopy. The formulation of YIKI and its use to treat malaria follow a standard process for plant harvesting, powder quantities and posology, but do not use any reproducible parameters for dose adjustment. Forty-three patients diagnosed and treated by the healer participated in the study. Laboratory results revealed 27 Plasmodium falciparum infection cases, including 2 with parasitaemia ≥ 200,000 p/µl blood. 25 patients were selected for therapeutic evidence assessment. There was a 48% elimination of parasites, a 28% parasitaemia decrease without complete cure, with gametocytogenesis in some patients, and a 24% parasitaemia increase. Haemoglobin and temperature results suggested that YIKI was not cytotoxic and reduced fever. Encouraging preliminary results have been obtained, but in view of the low number of patients, further YIKI efficacy and toxicity studies will be necessary for patient safety.
Zachari KabreRakiswende Serge YerbangaAminata FofanaRoland Nâg-Tiero MedaAnyirekun Fabrice SomeAlassane HaroNatacha A. J. A. BoroFazhira B. YeBenjamin Kouliga KoamaSami Eric KamEliasse ZongoHadidjatou BelèmWindmi KagambègaFlorence FournetGeorges A. OuedraogoJean-Bosco Ouedraogo
Objective:To evaluate the antimalarial activity of noscapine against Plasmodium falciparum 3D7 strain(Pf3D7),its clinical isolate(Pf140/SS),and Plasmodium berghei ANKA(PbA).Methods:Using ring-stage survival assay,phenotypic assessments,and SYBR-green-based fluorescence assay,the antimalarial activities of noscapine were assessed compared with dihydroartemisinin(DHA)in in vivo and in vitro studies.In addition,hemolysis and cytotoxicity tests were carried out to evaluate its safety.RT-PCR assay was also conducted to determine the effect of noscapine on papain-like cysteine protease Plasmodium falciparum falcipain-2(PfFP-2).Results:The antimalarial efficacy of noscapine against Pf3D7 and Pf140/SS was comparable to DHA,with IC50 values of(7.68±0.88)and(5.57±0.74)nM/mL,respectively,and>95%inhibition of PbA infected rats.Noscapine also showed a safe profile,as evidenced by low hemolysis and cytotoxicity even at high concentrations.Moreover,PfFP-2 expression was significantly inhibited in both noscapine-treated Pf3D7 and Pf140/SS(P<0.01).Conclusions:Noscapine has antimalarial properties comparable to standard antimalarial DHA with better safety profiles,which may be further explored as a therapeutic candidate for the treatment of malaria.
Six new ent-abietane diterpenoids,abientaphlogatones A−F(1−6),along with two undescribed ent-abietane diterpenoid glucosides,abientaphlogasides A−B(7−8)and four known analogs were isolated from the aerial parts of Phlogacanthus curviflorus(P.curviflorus).The structures of these compounds were determined using high-resolution electrospray ionization mass spectrometry(HR-ESI-MS),one-dimensional and two-dimensional nuclear magnetic resonance(NMR)spectroscopy,electronic circular dichroism(ECD)spectra,and quantum chemical calculations.Notably,compounds 5 and 6 represented the first reported instances of entnorabietane diterpenoids from the genus Phlogacanthus.In theβ-hematin formation inhibition assay,compounds 2,4,7−10,and 12 displayed antimalarial activity,with IC_(50) values of 12.97−65.01μmol·L−1.Furthermore,compounds 4,5,8,and 10 demonstrated neuroprotective activity in PC12 cell injury models induced by H_(2)O_(2) and MPP+.
Present research on the antimalarial mechanisms of artemisinin(ART)is mainly focused on covalent drug binding targets alkylated by free radicals,while non-covalent binding targets have rarely been reported.Here,we developed a novel photoaffinity probe of ART to globally capture and identify the antimalarial target proteins of ART through chemical proteomics.The results demonstrated that ART can bind to par-asite proteins by both covalent and non-covalent modification,and these may jointly contribute to the antimalarial effects.Our work enriches the research on the antimalarial targets of ART,and provides a new perspective for further exploring the antimalarial mechanism of ART.
Background: Malaria remains a major cause of morbidity and mortality in Zambia, affecting all levels of society, with children under the age of five and pregnant women being most at risk of serious illness. The availability of antimalarial medicines is one of the key interventions of malaria management. This study assessed the availability of antimalarial medicines in community pharmacies in Lusaka district, Zambia. Materials and Methods: This was a cross-sectional study that was conducted among 210 community pharmacies from September to November 2022 using a well-structured checklist in selected areas of Lusaka district. The availability was verified by a physical check of the product. The checklist contained the medicines listed both in the guidelines for diagnosis and treatment of malaria in Zambia as well as in the World Health Organization (WHO) malaria treatment guidelines. Results: This study found that all antimalarials listed in the local treatment guidelines for malaria were available in community pharmacies, though with the varying distribution. Of the 210 community pharmacies, 209 (99.5%) had artemether/lumefantrine in stock. The lowest available antimalarial was quinine/clindamycin, which was only available in 3 (1.4%) of the outlets. Conversely, 3 out of 16 (18.8%) antimalarials that were available in community pharmacies were not listed in the local treatment guidelines of malaria in Zambia, despite being listed in the WHO malaria treatment guidelines. This translated into a compliance level of 81.2% based on the local malaria treatment guidelines. Conclusion: This study concluded that antimalarials were available for all categories of malaria management in community pharmacies, though with a varying distribution. The presence of antimalarials not listed in the Zambian treatment guidelines is of public health concern which may have an impact on antimicrobial resistance in the future.
Artemisinins tested against W-2 strains of malaria falciparum are investigated with molecular electrostatic potential (MEP), in an attempt to identify key features of the compounds that are necessary for their activities, as well as to investigate likely interactions with the receptor in a biological process and to use that information to propose new molecules. In order to discover the best geometry involving the ligand-receptor complexes (heme) studied and help in the proposition of the new derivatives, molecular simulations of interactions between the most negative charged region around the peroxide and heme locates (the ones around the Fe2+ ion) were carried out. In addition, PCA (principal components analysis), HCA (hierarchical cluster analysis), SDA (stepwise discriminant analysis), and KNN (K-nearest neighbor) multivariate models were employed to investigate which descriptors are responsible for the classification between the higher and lower antimalarial activity of the compounds, and also this information was used to propose new potentially active molecules. The information accumulated in studies of MEP, molecular docking, and multivariate analysis supported the proposal of new structures with potential antimalarial activities. The multivariate models constructed were applied to the new structures and indicated numbers 19 and 20 as the most prominent for syntheses and biological assays.
Josué de Jesus Oliveira AraújoRicardo Morais de MirandaJeferson Stiver Oliveira de CastroAntonio Florêncio de FigueiredoAna Cecília Barbosa PinheiroSílvia Simone dos Santos MoraisMarcos Antonio Barros dos SantosAndréia de Lourdes Ribeiro PinheiroAndréia de Lourdes Ribeiro PinheiroFábio dos Santos GilHeriberto Rodrigues BitencourtGustavo Nery Ramos AlvesJosé Ciríaco Pinheiro
