Antimalarial Activity of Ethanol Extract of Kelakai Leaves (Stenochlaena palustris) to Parasitemia and Splenomegaly in BALB/c Mice Infected with Plasmodium berghei ANKA

Introduction: Malaria is one of global health problems. Splenomegaly is one of malaria symptoms. Antimalarial drug resistance had been reported. Alternative treatment is by using traditional medicinal plants such as kelakai (Stenochlaena palustris). Kelakai contains alkaloid and flavonoid which had been reported to have antimalarial activity. The aim of this study was to discover antimalarial activity of ethanol extract of kelakai leaves to parasitemia and splenomegaly of Plasmodium berghei ANKA in infected BALB/c mice.Methods: This study was based on a modified Peter test using BALB/c mice infected with P. berghei ANKA treated with ethanol extract of kelakai leaves, with chloroquine diphosphate as a positive control. The negative control was P. berghei ANKA infected mice without any additional treatment. Administration of ethanol extract of kelakai leaves was performed for 4 days with a serial doses of 100, 10, and 1 mg/kg body weight. The positive control was given chloroquine diphosphate 20 mg/kg body weight. Parasitemia was observed daily prior to the calculation of the percentage of parasite growth and parasite growth inhibition. At the end of the test, the mice were sacrificed and spleens were isolated to measure their sizes. Probit analysis was performed to obtain ED50 to find the effect of extract in parasite killing by 50%. Spearman test was performed to analyze the correlation of doses of extract and splenomegaly.Results: Parasitemia growth inhibition was directly proportional to the dose. Higher parasitemia inhibition was obtained at higher doses and vice versa. Result of probit analysis showed an ED50 was 77.05 mg/kg body weight. Statistical analysis resulted in insignificant correlation between doses and splenomegaly p = 1.0 (significancy < 0.05).Conclusion: Ethanol extract of kelakai leaves possessed good antimalarial activity and there was no correlation between extract doses and splenomegaly in Plasmodium berghei ANKA-infected mice.

Dependence of Viscosity and Diffusion on β-Cyclodextrin and Chloroquine Diphosphate Interactions

Mutual diffusion coefficients of chloroquine diphosphate (CDP) in aqueous solutions both without and with β-cyclodextrin (β-CD) were measured at concentrations from (0.0000 to 0.0100) mol dm−3 and 298.15 K, using the Taylor dispersion technique. Ternary mutual diffusion coefficients (Dik) measured by the same technique are reported for aqueous CDP + β-CD solutions at 298.15 K. The presence of β CD led to relevant changes in the diffusion process, as showed by nonzero values of the cross-diffusion coefficients, D12 and D21. β-CD concentration gradients produced significant co-current coupled flows of CDP. In addition, the effects of β-CD on the transport of CDP are assessed by comparing the binary diffusion coefficient of aqueous CDP solutions with the main diffusion coefficient (D11) measured for ternary {CDP(1) + β-CD(2)} solutions. These observations are supported by viscosity analysis. All data allow to have a better interpretation on the effect of cyclodextrin on the transport behavior of CDP.

PET Imaging of Translocator Protein as a Marker of Malaria-Associated Lung Inflammation

Purpose. Malaria-associated acute respiratory distress syndrome (MA-ARDS) is a severe complication of malaria despite effective anti-malarial treatment. Currently, non-invasive imaging procedures such as chest X-rays are used to assess oedema in established MA-ARDS but earlier detection methods are needed to reduce morbidity and mortality. The early stages of MA-ARDS are characterized by the infiltration of leukocytes, in particular monocyte/macrophages, thus monitoring of immune infiltrates may provide a useful indicator of early pathology. Procedures. Plasmodium berghei ANKA-infected C57BL/6 mice, a rodent malaria model of MA-ARDS, were longitudinally imaged using the TSPO imaging agent [ 18 F]FEPPA as a marker of macrophage accumulation during the development of pathology and response to combined artesunate and chloroquine diphosphate therapy (ART+CQ). [ 18 F]FEPPA uptake was compared to blood parasitemia levels and pulmonary immune cell infiltrates using flow cytometry. Results. Infected animals showed rapid increases lung retention of [ 18 F]FEPPA, correlating well with increases in blood parasitemia and pulmonary accumulation of interstitial inflammatory macrophages and MHC II+ alveolar macrophages. Treatment with ART+CQ therapy abrogated this increase in parasitemia and significantly reduced both lung uptake of [ 18 F]FEPPA and macrophage infiltrates. Conclusions. Retention of [ 18 F]FEPPA in the lungs is well correlated with changes in blood parasitemia and lung associated macrophages during disease progression and in response to ART+CQ therapy. With further development TSPO biomarkers may have the potential to be able to accurately assess early onset of MA-ARDS.

Heme Polymerization Inhibitory Activity And Phytochemical Screening Of Ethyl Acetate Fraction In Manuran (Coptosapelta tomentosa Valeton ex K. Heyne) Stem

The native Indonesian plant that is empirically used as an antimalarial agent is manuran (Coptosapelta tomentosa Valeton ex K. Heyne). This study aims to determine chemical compound and heme polymerization inhibitory activity of ethyl acetate fraction of C. Tomentosa stem based on IC50 value. The method identification of chemical compound used tube test, and the method of heme polymerization inhibitory activity was Basilico through in vitro method. The results of chemical compound identification of the ethyl acetate fraction of C. Tomentosa showed the presence of flavonoids, terpenoids, saponins, tannins, and anthraquinones. The average percentages of heme polymerization inhibitory activity of ethyl acetate fraction of C. Tomentosa stem from concentration 20; 10; 5; 2.5; 1.25; 0.625; 0.3125 mg / mL were 98.507; 97,872; 96,407; 93,560; 88,419; 80,680; and 45.467%.The averages of IC50 of ethyl acetate fraction and chloroquine diphosphate were 0.24 ± 0.018 mg/mL and 0.214 ± 0.012 mg/mL. This shows that the ethyl acetate fraction of C. Tomentosa stem has heme polymerization inhibitory activity. The result of the independent sample t-Test obtained the significance value of 0.111 (p more than 0.05) that there was no significant difference. It means that the ethyl acetate fraction of C. Tomentosa stem has heme polymerization inhibitory activity as well as chloroquine diphosphate. This suggests the potentiation of the methyl acetate fraction of the stem C. Tomentosa as anti-malarial.

Metabolite profiling of endophytic Streptomyces spp. and its antiplasmodial potential

Background Antiplasmodial drug discovery is significant especially from natural sources such as plant bacteria. This research aimed to determine antiplasmodial metabolites of Streptomyces spp. against Plasmodium falciparum 3D7 by using a metabolomics approach. Methods Streptomyces strains’ growth curves, namely SUK 12 and SUK 48, were measured and P. falciparum 3D7 IC50 values were calculated. Metabolomics analysis was conducted on both strains’ mid-exponential and stationary phase extracts. Results The most successful antiplasmodial activity of SUK 12 and SUK 48 extracts shown to be at the stationary phase with IC50 values of 0.8168 ng/mL and 0.1963 ng/mL, respectively. In contrast, the IC50 value of chloroquine diphosphate (CQ) for antiplasmodial activity was 0.2812 ng/mL. The univariate analysis revealed that 854 metabolites and 14, 44 and three metabolites showed significant differences in terms of strain, fermentation phase, and their interactions. Orthogonal partial least square-discriminant analysis and S-loading plot putatively identified pavettine, aurantioclavine, and 4-butyldiphenylmethane as significant outliers from the stationary phase of SUK 48. For potential isolation, metabolomics approach may be used as a preliminary approach to rapidly track and identify the presence of antimalarial metabolites before any isolation and purification can be done.

Antiplasmodial activity of Ethanolic extract of Cassia spectabilis DC leaf and its inhibition effect in Heme detoxification

Background In previous studies, Cassia spectabilis DC leaf has shown a good antiplasmodial activity. Therefore, this study is a follow-up study of the extract of leaf of C. spectabilis DC on its in vitro and in vivo antiplasmodial activity and mechanism as an antimalarial. Methods The extract was fractionated, sub-fractionated and isolated to obtain the purified compound. In vitro antiplasmodial activity test against Plasmodium falciparum to find out the active compound. In vivo test against P. berghei ANKA-infected mice was conducted to determine prophylactic activity and antiplasmodial activity either alone or in combination with artesunate. The inhibition of heme detoxification test as one of the antimalarial mechanisms was carried out using the Basilico method. Results The results showed that active antimalarial compound isolated from C. spectabilis DC leaf had a structural pattern that was identical to (−)-7-hydroxycassine. Prophylactic test of 90% ethanolic extract of C. spectabilis DC leaf alone against P. berghei ANKA-infected mice obtained the highest percentage inhibition was 68.61%, while positive control (doxycycline 13 mg/kg) was 73.54%. In combination with artesunate, 150 mg/kg three times a day of C. spectabilis DC (D0-D2) + artesunate (D2) was better than the standard combination of amodiaquine + artesunate where the inhibition percentages were 99.18 and 92.88%, respectively. The IC50 of the extract for the inhibitory activity of heme detoxification was 0.375 mg/ml which was better than chloroquine diphosphate (0.682 mg/ml). Conclusion C. spectabilis DC leaf possessed potent antiplasmodial activity and may offer a potential agent for effective and affordable antimalarial phytomedicine.