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Artemisinin-based combinations (ACTs) are World Health Organization-recommended treatment for malaria. Artemether (A) and lumefantrine (LUM) were the first co-formulated ACT and first-line treatment for malaria globally, artemether is dihydroartemisinin's (DHA's) prodrug. Artemisinins and LUM face low aqueous solubility while artemisinin has low bioavailability and short half-life thus requiring continuous dosage to maintain adequate therapeutic drug-plasma concentration. This study aimed at improving ACTs limitations by nano-formulating DHA-LUM using solid lipid nanoparticles (SLNs) as nanocarrier. SLNs were prepared by modified solvent extraction method based on water-in-oil-in-water double emulsion. Mean particle size, polydispersity index and zeta potential were 308.4 nm, 0.29 and -16.0 mV respectively. Nanoencapsulation efficiencies and drug loading of DHA and LUM were 93.9%, 33.7%, 11.9%, and 24.10% respectively. Nanoparticles were spherically shaped and drugs followed Kors-Peppas release model, steadily released for over 72 h. DHA-LUM-SLNs were 31% more efficacious than conventional oral doses in clearing Plasmodium berghei from infected Swiss albino mice.
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ETHNOPHARMACOLOGICAL RELEVANCE: Solanum incanum L. is commonly used in traditional herbal medicine (THM) in Kenya for treating various ailments. Recent developments in disease treatment have introduced the concept of host-directed therapy (HDT). This approach involves targeting factors within the host cell that can impede the growth or replication of a pathogen. One such host factor is delta aminolevulinate dehydratase (δ-ALAD), the second enzyme in the heme biosynthesis pathway utilized by Plasmodium for growth. Studies using mice models have shown an increase in δ-ALAD expression during Plasmodium berghei infection. Another plant in the Solanum genus, S. guaranticum, has been found to inhibit δ-ALAD in red blood cells in vitro and in the brain in vivo. Is it possible that the bioactive compounds in S. incanum extracts could also be effective in HDT for malaria treatment? AIM OF STUDY: To better assess the effectiveness of S. incanum leaf extracts as a curative and prophylaxis in malaria parasite infection, and to test the plant's ability to decrease δ-ALAD expression. MATERIALS AND METHODS: The leaves of S. incanum were collected, dried, and pulverized before being subjected to a successive extraction protocol to obtain crude, hexane, ethyl acetate, and aqueous extract fractions. Phytochemical analysis was conducted on all extract fractions, followed by GC-MS analysis of the fraction with the most potent antimalarial activity. An acute toxicity study was also performed on the extracted fractions. The potency of the extract fractions as curative and prophylactic antimalarial was then evaluated in THM using Plasmodium berghei-infected mice at a dose of 100 mg/kg. The extract fraction with the highest activity was further evaluated at varying doses and its effect on δ-ALAD was measured using RT-qPCR. The percentage of parasitemia and chemosuppression, and mean survival time were used as indices of activity. RESULTS: Phytochemical analysis revealed that the ethyl acetate and aqueous extract fractions contained high terpenoids, flavonoids, and phenols levels. However, alkaloids were only present in moderate quantities in the aqueous extract, and quinones were found in high levels only in the crude extract. Additionally, all extract fractions contained saponins in high levels but lacked tannins. While the plant extracts were found to be non-toxic, they did not exhibit curative antimalarial activity. However, all extract fractions showed prophylactic antimalarial activity, with the ethyl acetate extract having the highest percentage of chemosuppression even at doses of 250 and 1000 mg/kg. In the negative control, the expression of δ-ALAD was 5.4-fold, but this was significantly reduced to 2.3-fold when mice were treated with 250 mg/kg of the ethyl acetate fraction. GC-MS analysis of the ethyl acetate fraction revealed high percentages of 2-methyloctacosane, tetracosane, and decane. CONCLUSION: The fractions extracted from S. incanum leaves have been found to possess only antimalarial prophylactic properties, with the ethyl acetate extract fraction showing the most effective results. The activity of this fraction may be attributed to its ability to decrease the expression of δ-ALAD, as it contains an alkane compound implicated with enzyme-inhibitory activity.
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Acetatos , Antimaláricos , Malária , Plantas Medicinais , Solanum , Animais , Camundongos , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Sintase do Porfobilinogênio/farmacologia , Sintase do Porfobilinogênio/uso terapêutico , Malária/tratamento farmacológico , Malária/parasitologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Plasmodium berghei , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêuticoRESUMO
BACKGROUND: Malaria remains a public health concern globally. Resistance to anti-malarial drugs has consistently threatened the gains in controlling the malaria parasites. Currently, artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP) are the treatment regimens against Plasmodium falciparum infections in many African countries, including Kenya. Recurrent infections have been reported in patients treated with AL or DP, suggesting the possibility of reinfection or parasite recrudescence associated with the development of resistance against the two therapies. The Plasmodium falciparum cysteine desulfurase IscS (Pfnfs1) K65 selection marker has previously been associated with decreased lumefantrine susceptibility. This study evaluated the frequency of the Pfnfs1 K65 resistance marker and associated K65Q resistant allele in recurrent infections collected from P. falciparum-infected individuals living in Matayos, Busia County, in western Kenya. METHODS: Archived dried blood spots (DBS) of patients with recurrent malaria infection on clinical follow-up days after treatment with either AL or DP were used in the study. After extraction of genomic DNA, PCR amplification and sequencing analysis were employed to determine the frequencies of the Pfnfs1 K65 resistance marker and K65Q mutant allele in the recurrent infections. Plasmodium falciparum msp1 and P. falciparum msp2 genetic markers were used to distinguish recrudescent infections from new infections. RESULTS: The K65 wild-type allele was detected at a frequency of 41% while the K65Q mutant allele was detected at a frequency of 22% in the recurrent samples. 58% of the samples containing the K65 wild-type allele were AL treated samples and while 42% were DP treated samples. 79% of the samples with the K65Q mutation were AL treated samples and 21% were DP treated samples. The K65 wild-type allele was detected in three recrudescent infections (100%) identified from the AL treated samples. The K65 wild-type allele was detected in two recrudescent DP treated samples (67%) while the K65Q mutant allele was identified in one DP treated (33%) recrudescent sample. CONCLUSIONS: The data demonstrate a higher frequency of the K65 resistance marker in patients with recurrent infection during the study period. The study underscores the need for consistent monitoring of molecular markers of resistance in regions of high malaria transmission.
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Antimaláricos , Malária Falciparum , Malária , Quinolinas , Humanos , Combinação Arteméter e Lumefantrina/uso terapêutico , Antimaláricos/uso terapêutico , Plasmodium falciparum/genética , Quênia/epidemiologia , Reinfecção/induzido quimicamente , Reinfecção/tratamento farmacológico , Prevalência , Combinação de Medicamentos , Artemeter/uso terapêutico , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Malária Falciparum/parasitologia , Quinolinas/uso terapêutico , Lumefantrina/uso terapêutico , Malária/tratamento farmacológico , MutaçãoRESUMO
Introduction: malaria remains the leading cause of morbidity and mortality in developing tropical and subtropical nations. Due to the emergence and spread of drug resistance to currently available drugs, there is a need for the search of novel, safe, and reasonably affordable anti-malarial medications. The objective of this study was to assess the in vivoanti-malarial effectiveness of Avicennia marina stem bark extracts in a mice model. Methods: guidelines 425 of the Organization for Economic Cooperation and Development were used to determine the extracts' acute toxicity. Mice infected with chloroquine-sensitive Plasmodium berghei (ANKA strain) were tested for in vivoanti-plasmodial activity, and by giving oral doses of 100 mg/kg, 250 mg/kg, and 500 mg/kg body weight of extracts, the plant's suppressive, curative, and preventive effects were assessed. Results: mice treated with dosages of up to 5000 mg/kg showed no evidence of acute toxicity or mortality. Consequently, it was determined that the acute lethal dosage of Avicennia marina extracts in swiss albino mice was greater than 5000 mg/kg. All doses of the extracts exhibited significant (p<0.05) dose-dependent suppression of P. berghei in the suppressive tests compared to the control group. At the highest dose (500 mg/kg), Methanolic crude extracts exerted the highest (93%) parasitemia suppression during the 4-day suppressive test. The extracts also displayed significant (p<0.001) prophylactic and curative activities at all doses compared to the control. Conclusion: results from this study ascertained the safety and promising curative, prophylactic and suppressive anti-plasmodial capabilities of the stem bark extracts of Avicennia marina in mice model.
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Antimaláricos , Avicennia , Malária , Camundongos , Animais , Plasmodium berghei , Extratos Vegetais/farmacologia , Casca de Planta , Malária/tratamento farmacológicoRESUMO
Moringa oleifera leaf polyphenols (Mopp) were encapsulated with phytosomes to enhance their efficacy on 4T1 cancer cell lines. The Mopp were extracted via microwave-assisted extraction. Moringa oleifera polyphenol-loaded phytosomes (MoP) were prepared with the nanoprecipitation method and characterized using the dynamic light scattering and dialysis membrane techniques. The in vitro cytotoxic and antiproliferative activity were investigated with the (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazole) MTT assay. Acute toxicity was assessed using Swiss albino mice. An MoP particle size of 296 ± 0.29 nm, −40.1 ± 1.19 mV zeta potential, and polydispersity index of 0.106 ± 0.002 were obtained. The total phenolic content was 50.81 ± 0.02 mg GAE/g, while encapsulation efficiency was 90.32 ± 0.11%. The drug release profiles demonstrated biphasic and prolonged subsequent sustained release. In vitro assays indicated MoP had a low cytotoxicity effect of 98.84 ± 0.53 µg/mL, doxorubicin was 68.35 ± 3.508, and Mopp was 212.9 ± 1.30 µg/mL. Moreover, MoP exhibited the highest antiproliferative effect on 4T1 cancer cells with an inhibitory concentration of 7.73 ± 2.87 µg/mL and selectivity index > 3. The results indicated a significant difference (p ≤ 0.001) in MoP when compared to Mopp and doxorubicin. The in vivo investigation showed the safety of MoP at a dose below 2000 mg/kg. The present findings suggest that MoP may serve as an effective and promising formulation for breast cancer drug delivery and therapy.
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Moringa oleifera , Neoplasias , Animais , Doxorrubicina/farmacologia , Humanos , Células MCF-7 , Camundongos , Extratos Vegetais/farmacologia , Folhas de Planta , Polifenóis/farmacologiaRESUMO
Background: Lumefantrine (LM), piperaquine (PQ), and amodiaquine (AQ), the long-acting components of the artemisinin-based combination therapies (ACTs), are a cornerstone of malaria treatment in Africa. Studies have shown that PQ, AQ, and LM resistance may arise independently of predicted modes of action. Protein kinases have emerged as mediators of drug action and efficacy in malaria parasites; however, the link between top druggable Plasmodium kinases with LM, PQ, and AQ resistance remains unclear. Using LM, PQ, or AQ-resistant Plasmodium berghei parasites, we have evaluated the association of choline kinase (CK), pantothenate kinase 1 (PANK1), diacylglycerol kinase (DAGK), and phosphatidylinositol-4 kinase (PI4Kß), and calcium-dependent protein kinase 1 (CDPK1) with LM, PQ, and AQ resistance in Plasmodium berghei ANKA. Methods: We used in silico bioinformatics tools to identify ligand-binding motifs, active sites, and sequence conservation across the different parasites. We then used PCR and sequencing analysis to probe for single nucleotide polymorphisms (SNPs) within the predicted functional motifs in the CK, PANK1, DAGK, PI4Kß, and CDPK1. Using qPCR analysis, we measured the mRNA amount of PANK1, DAGK, and PI4Kß at trophozoites and schizonts stages. Results: We reveal sequence conservation and unique ligand-binding motifs in the CK, PANK1, DAGK, PI4Kß, and CDPK1 across malaria species. DAGK, PANK1, and PI4Kß possessed nonsynonymous mutations; surprisingly, the mutations only occurred in the AQr parasites. PANK1 acquired Asn394His, while DAGK contained K270R and K292R mutations. PI4Kß had Asp366Asn, Ser1367Arg, Tyr1394Asn and Asp1423Asn. We show downregulation of PANK1, DAGK, and PI4Kß in the trophozoites but upregulation at the schizonts stages in the AQr parasites. Conclusions: The selective acquisition of the mutations and the differential gene expression in AQ-resistant parasites may signify proteins under AQ pressure. The role of the mutations in the resistant parasites and their impact on drug responses require investigations using reverse genetics techniques in malaria parasites.
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BACKGROUND: Vector control is an essential component in prevention and control of malaria in malaria endemic areas. Insecticide treated nets is one of the standard tools recommended for malaria vector control. The objective of the study was to determine physical integrity and insecticidal potency of long-lasting insecticidal nets (LLINs) used in control of malaria vector in Kirinyaga County, Kenya. METHOD: The study targeted households in an area which had received LLINs during mass net distribution in 2016 from Ministry of Health. A total of 420 households were sampled using systematic sampling method, where the household heads consented to participate in the study. A semi-structured questionnaire was administered to assess care and use while physical examination was used to determine integrity. Chemical concentration was determined by gas chromatography mass spectroscopy (GC-MS). Data analysis was done using Statistical Package for Social Sciences (SPSS) version 19. RESULTS: After 18 months of use, 96.9% (95% CI: 95.2-98.6%) of the distributed nets were still available. Regarding net utilization, 94.1% of household heads reported sleeping under an LLIN the previous night. After physical examination, 49.9% (95% CI: 43-52.8%) of the bed nets had at least one hole. The median number of holes of any size was 2[interquartile range (IQR) 1-4], and most holes were located on the lower part of the nets, [median 3 (IQR 2-5)]. Only 15% of the nets with holes had been repaired. The median concentration for α-cypermethrin was 7.15 mg/m2 (IQR 4.25-15.31) and 0.00 mg/g (IQR 0.00-1.99) for permethrin. Based on pHI, Chi-square test varied significantly with the manufacturer (X (6, N = 389) = 29.14, p = 0.04). There was no significant difference between nets with different number of washes (X2(2) = 4.55, p = 0.103). CONCLUSION: More than three-quarters of the nets supplied had survived and insecticidal potency was adequate in vector control. Standard procedure for field evaluation of surface insecticidal content available to a mosquito after landing on a net to rest is recommended.
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Anopheles , Mosquiteiros Tratados com Inseticida , Inseticidas , Malária , Animais , Humanos , Quênia , Malária/prevenção & controle , Controle de Mosquitos , Mosquitos VetoresRESUMO
BACKGROUND: Chemotherapy plays a crucial role in malaria control. However, the main obstacle to treatment has been the rise of parasite resistance to most antimalarial drugs. Artemisinin-based combination therapies (ACTs) remain the most effective antimalarial medicines available today. However, malaria parasite tolerance to ACTs is now increasingly prevalent especially in Southeast Asia presenting the danger of the spread of ACTs resistance to other parts of the world. Consequently, this creates the need for alternative effective antimalarials. Therefore, this study sought out to determine antimalarial potential, safety, and resistance development of the extracts in a mouse model. METHOD: Methanolic and ethyl acetate extracts were obtained by solvent extraction. The extracts were assayed for acute toxicity in vivo. Additionally, the two extracts were evaluated for antimalarial activity in vivo against Plasmodium berghei ANKA strain by the 4-day suppressive test at 500, 250, and 125 mg/kg/day. Packed cell volume was evaluated to determine anemia manifestation. Finally, continuous drug pressure experiment at 500 mg/kg and DNA amplification via PCR were conducted. The amplicons underwent through Sanger sequencing. RESULTS: There was no toxicity realized in the animals at 2000 mg/kg. Importantly, high parasitemia suppression of 75.52% and 75.30% using a dose of 500 mg/kg of methanolic and ethyl acetate extracts, respectively, was noted. The extracts were able to reverse packed cell volume reduction. Nigella sativa-resistant phenotype was selected as delayed parasite clearance. However, there was no change in the nucleotide sequences of PbMDR1 and PbCRT genes. CONCLUSION: The results provide room for future exploitation of the plant as an antimalarial.
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BACKGROUND: Use of chloroquine, an otherwise safe and relatively affordable anti-malarial drug, was discontinued due to widespread prevalence of resistant parasites. Many entrant anti-malarial drugs for treatment of chloroquine resistant malaria raises the concerns of cost and safety among other challenges. Innovative ways of circumventing chloroquine resistance is of paramount importance. Such may include nanoparticulate delivery strategies and targeting. This study evaluated physicochemical properties and in vitro antiplasmodial activity of chloroquine encapsulated heparin functionalized solid lipid nanoparticles (CQ-Hep-SLNs) and non-heparin functionalized SLNs (CQ-SLN) against Plasmodium falciparum. METHODS: The modified double-emulsion solvent evaporation technique was used to prepare the nanoparticles. HPLC/UV was used to determine the in vitro drug release. The semi-automated micro-dilution technique was adapted in assessing the in vitro antiplasmodial activity to give drug concentration capable of inhibiting 50% of the P. falciparum (IC50), as a function of antiplasmodial efficacy. RESULTS: Prepared nanoparticles were below 500 nm in size with % drug loading (%DL) between 21 and 25% and encapsulation efficiency (%EE) of 78-90%. The drug-loaded SLN exhibited a biphasic drug release profile at pH 7.4, with an initial burst release during the first 24 h followed by sustained release in both formulations. Nanoformulated CQ-SLN (4.72 ± 0.14 ng/mL) and CQ-Hep-SLN (2.41 ± 0.27 ng/mL), showed enhanced in vitro antiplasmodial activities against chloroquine sensitive (D6) strain of P. falciparum, albeit with no activity against the chloroquine resistant W2 strain, compared to free CQ standard (5.81 ± 0.18 ng/mL). CONCLUSIONS: These findings suggest that the nanoformulated drugs displayed enhanced anti-malarial activities against chloroquine sensitive (D6) strains of P. falciparum compared to the free CQ standard. There is some form of potential dual synergistic effect of CQ-loaded heparinized solid lipid nanoparticles (Hep-SLN), meaning that combining heparin and CQ in SLNs has beneficial effects, including potential for specific targeting of parasitized red blood cells as afforded by heparin. Thus, the study has produced SLNs nanoparticles that have superior in vitro activities than CQ on CQ-sensitive parasites.
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Antimaláricos/farmacologia , Cloroquina/farmacologia , Heparina/farmacologia , Nanopartículas/química , Plasmodium falciparum/efeitos dos fármacos , Antimaláricos/química , Células Cultivadas , Cloroquina/química , Eritrócitos/parasitologia , Heparina/química , Humanos , Lipídeos/química , Testes de Sensibilidade ParasitáriaRESUMO
Effective use of dihydroartemisinin (DHA) is limited by poor water-solubility, poor pharmacokinetic profile and unsatisfactory clinical outcome especially in monotherapy. To reduce such limitations, we reformulated DHA into solid lipid nanoparticles (SLNs) as a nanomedicine drug delivery system. DHA-SLNs were characterized for physical parameters and evaluated for in vitro and in vivo antimalarial efficacy. DHA-SLNs showed desirable particle characteristics including particle size (240.7 nm), particle surface charge (+17.0 mV), drug loadings (13.9 wt %), encapsulation efficacy (62.3%), polydispersity index (0.16) and a spherical appearance. Storage stability up to 90 days and sustained release of drug over 20 h was achieved. Enhanced in vitro (IC50 0.25 ng/ml) and in vivo (97.24% chemosuppression at 2mg/kg/day) antimalarial activity was observed. Enhancement in efficacy was 24% when compared to free DHA. These encouraging results show potential of using the described formulation for DHA drug delivery for clinical application. FROM THE CLINICAL EDITOR: Malaria still poses a significant problem worldwide. One of the current drugs, artemisinin has been shown to be effective, but has poor water-solubility. The authors here described their formulation of making dihydroartemisinin (DHA) into solid lipid nanoparticles, with subsequent enhancement in efficacy. These results would have massive potential in the clinical setting.
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Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Portadores de Fármacos/química , Lipídeos/química , Malária/tratamento farmacológico , Nanopartículas/química , Plasmodium/efeitos dos fármacos , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Humanos , Nanopartículas/ultraestrutura , Plasmodium berghei/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacosRESUMO
Primaquine (PQ) is one of the most widely used antimalarial drugs and is the only available drug that combats the relapsing form of malaria. PQ use in higher doses is limited by severe tissue toxicity including hematological- and gastrointestinal-related side effects. Nanoformulation of drugs in an appropriate drug carrier system has been extensively studied and shown to have the potential to improve bioavailability, thereby enhancing activity, reducing dose frequency, and subsequently reducing toxicity. The aim of this work was to design, synthesize, and characterize PQ-loaded solid lipid nanoparticles (SLNs) (PQ-SLNs) as a potential drug-delivery system. SLNs were prepared by a modified solvent emulsification evaporation method based on a water-in-oil-in-water (w/o/w) double emulsion. The mean particle size, zeta potential, drug loading, and encapsulation efficiency of the PQ-SLNs were 236 nm, +23 mV, 14%, and 75%, respectively. The zeta potential of the SLNs changed dramatically, from -6.54 mV to +23.0 mV, by binding positively charged chitosan as surface modifier. A spherical morphology of PQ-SLNs was seen by scanning electron microscope. In vitro, release profile depicted a steady drug release over 72 hours. Differential scanning calorimeter thermograms demonstrated presence of drug in drug-loaded nanoparticles along with disappearance of decomposition exotherms, suggesting increased physical stability of drug in prepared formulations. Negligible changes in characteristic peaks of drug in Fourier transform infrared spectra indicated absence of any interaction among the various components entrapped in the nanoparticle formulation. The nanoformulated PQ was 20% more effective as compared with conventional oral dose when tested in Plasmodium berghei-infected Swiss albino mice. This study demonstrated an efficient method of forming a nanomedicine delivery system for antimalarial drugs.
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Antimaláricos/química , Portadores de Fármacos/química , Lipídeos/química , Nanopartículas/química , Primaquina/química , Animais , Antimaláricos/farmacocinética , Antimaláricos/uso terapêutico , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/uso terapêutico , Emulsões , Lipídeos/farmacocinética , Lipídeos/uso terapêutico , Malária/tratamento farmacológico , Camundongos , Parasitemia/tratamento farmacológico , Plasmodium berghei , Primaquina/farmacocinética , Primaquina/uso terapêuticoRESUMO
Two bisbenzylisoquinoline and one hasubanane alkaloids: (-)-pseudocurine (1), (-)-pseudoisocurine (2) and (-)-10-oxoaknadinine (3), were isolated from leaf extract of Stephania abyssinica, a plant used in traditional medicine in South Nyanza region of Kenya. They were characterized using 1D ((1)H, (13)C and DEPT) and 2D (COSY, NOESY, HMQC and HMBC) NMR techniques. (-)-Pseudocurine (1) and (-)-pseudoisocurine (2) exhibited strong to moderate anti-plasmodial activity while (-)-10-oxoaknadinine (3) showed moderate to mild activity.
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Alcaloides/química , Alcaloides/farmacologia , Antimaláricos/química , Antimaláricos/farmacologia , Benzilisoquinolinas/química , Benzilisoquinolinas/farmacologia , Stephania/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Plasmodium falciparum/efeitos dos fármacosRESUMO
Indigenous rural communities in the tropics manage parasitic diseases, like malaria and leishmaniasis, using herbal drugs. The efficacy, dosage, safety and active principles of most of the herbal preparations are not known. Extracts from 6 selected plant species, used as medicinal plants by indigenous local communities in Kenya, were screened for in vitro anti-plasmodial and anti-leishmanial activity, against 2 laboratory-adapted Plasmodium falciparum isolates (D6, CQ-sensitive and W2, CQ-resistant) and Leishmania major (IDU/KE/83=NLB-144 strain), respectively. The methanol extract of Suregada zanzibariensis leaves exhibited good anti-plasmodial activity (IC(50) 4.66+/-0.22 and 1.82+/-0.07 microg/ml for D6 and W2, respectively). Similarly, the methanol extracts of Albizia coriaria (IC(50) 37.83+/-2.11 microg/ml for D6) and Aspergillus racemosus (32.63+/-2.68 and 33.95+/-2.05 microg/ml for D6 and W2, respectively) had moderate anti-plasmodial activity. Acacia tortilis (IC(50) 85.73+/-3.36 microg/ml for W2) and Albizia coriaria (IC(50) 71.17+/-3.58 microg/ml for W2) methanol extracts and Aloe nyeriensis var kedongensis (IC(50) 87.70+/-2.98 and 67.84+/-2.12 microg/ml for D6 and W2, respectively) water extract exhibited mild anti-plasmodial activity. The rest of the extracts did not exhibit any anti-plasmodial activity. Although the leishmanicidal activity of extracts were lower than for pentosam (80%), reasonable activity was observed for Aloe nyeriensis methanol (68.4+/-6.3%), Albizia coriara water (66.7+/-5.0%), Maytenus putterlickoides methanol (60.0+/-6.23%), Asparagus racemosus methanol and water (58.3+/-8.22 and 56.8+/-6.58%, respectively), Aloe nyeriensis water (53.3+/-5.1%) and Acacia tortilis water (52.9+/-6.55%) extracts at 1000 microg/ml. Leishmania major infected macrophages treated with methanol extracts of Suregada zanzibariensis and Aloe nyeriensis var kedongensis and pentostam had infection rates of 28+/-2.11, 30+/-1.22 and 40+/-3.69%, respectively at 1000 microg/ml, indicating better anti-leishmanial activity for the extracts. The methanol extract of Albizia coriara (44.0+/-3.69%) and aqueous extracts of Asparagus racemosus (42+/-3.84%) and Acacia tortilis (44+/-5.59%) had similar activity to pentosam. Multiplication indices for Leishmania major amastigotes treated with methanol extracts of Albizia coriaria, Suregada zanzibariensis and Aloe nyeriensis var kedongensis, aqueous extract of Acacia tortilis and pentosam were 28.5+/-1.43, 29.4+/-2.15, 31.1+/-2.22, 35.9+/-3.49 and 44.0+/-3.27%, respectively, at 1000 microg/ml, confirming better anti-leishmanial activity for the extracts. Aqueous extracts of Aloe nyeriensis (46.7+/-3.28%) and Albizia coriaria (47.5+/-3.21%) had similar activity level to pentosam. The plant extracts have better inhibitory activity while pentosam has better leishmanicidal activity. All extracts exhibited very low cytotoxicity (CC(50) > 500 microg/ml) against human embryonic lung fibroblast (HELF) cells. The investigations demonstrated the efficacy and safety of some extracts of plants that are used by rural indigenous communities for the treatment of parasitic diseases.