Helietta apiculata: a tropical weapon against Chagas disease.

The present study pretends to evaluate the in vivo efficacy of the crude chloroform bark extract of Helietta apiculata, then the activity will be compared with the reference drug, benznidazole, in acute Trypanosoma cruzi infected mice when administered by oral route. The chloroformic extract of Helieta apiculata was administered by oral route at 5, 10 and 50 mg/kg daily for two weeks. This study has shown a moderate efficacy of the H. apiculata bark extract in reducing T. cruzi parasitaemia in 42 to 54% after a monitoring of 60 days post-infection and when compared with control groups. Concerning mice mortality, only two only two mice died, one from the control group and the other one from the group threated with 10 mg of the chlorofom extract of H. apiculata, suggesting the potential of H. apiculta extracts as a safe and inexpensive treatment of Chagas disease.

Phytoelectrochemical analysis of Zanthoxylum chiloperone.

INTRODUCTION: An innovative application of the voltammetry of microparticles methodology to characterize the phytochemical composition of extracts of different parts of Zanthoxylum chiloperone var. angustifolium Engl. is described. OBJECTIVE: Characterize the phytochemical composition of extracts of different parts of plants by electrochemical methodologies. METHODS: The voltammetry of microparticles methodology was applied to alcoholic extracts from leaves, seeds, fruits, roots and stem bark of Zanthoxylum chiloperone. RESULTS: In contact with aqueous phosphate buffer, characteristic cathodic signals of its main natural products (canthin-6-one, 5-methoxycanthin-6-one and trans-avicennol) were recorded. The study of the voltammograns allows the estimation of the relative amounts of canthin-6-one, 5-methoxycanthin-6-one and trans-avicennol from the different parts of Zanthoxylum chiloperone. CONCLUSION: The voltammetric responses of alcoholic extracts from different parts of Zanthoxylum chiloperone var. angustifolium allows their phytochemical characterization without need of sample pretreatment thus illustrating the capabilities of the voltammetry of microparticles methodology to increase the tools applied to phytochemical analysis. Copyright © 2016 John Wiley & Sons, Ltd.

The antiplasmodium effects of a traditional South American remedy: Zanthoxylum chiloperone var. angustifolium against chloroquine resistant and chloroquine sensitive strains of Plasmodium falciparum

Zanthoxylum chiloperone var. angustifolium Engl., Rutaceae, is used in traditional medicine to treat fungal and protozoal infections in the central area of South America. Considering the increasing resistance of Plasmodium falciparum in malarial ridden areas, we explored the anti-plasmodial effects of three compounds isolated from Z. chiloperone. The pyranocoumarin transavicennol and the canthinone alkaloids, canthin-6-one and 5-methoxycanthin-6-one, were found to have IC50 on chloroquine/mefloquine resistant and sensitive strains of P. falciparum of 0.5-2.7, 2.0-5.3 and 5.1-10.4 ƒÊg/mL, respectively. Moreover, the formation of heme adducts by these compounds is described by a novel alternative method based on MS-CID methods. The alkylamide sanshool was also identified, for first time in this plant, in the dichloromethanic and ethanolic extracts and the extracts were found to be notably non-toxic and displayed good anti-plasmodial effects.

Zanthoxylum chiloperone leaves extract: first sustainable Chagas disease treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: Zanthoxylum chiloperone var. angustifolium Engl. (Rutaceae) stem bark is used traditionally in Paraguay for its antiparasitic properties. Canthin-6-one is main compound isolated from Zanthoxylum chiloperone var angustifolium with broad spectrum antifungal, leishmanicidal and trypanocidal activities. AIM OF THE STUDY: The qualitative and quantitative characterization and the isolation of main alkaloidal components of different organs of Zanthoxylum chiloperone are investigated by HPLC-UV-MS. The in vitro biological activity of each extract against trypomastigote and amastigote forms of Trypanosoma cruzi parasites were evaluated, then comparison the in vivo efficacy of the ethanolic leaves extract of Zanthoxylum chiloperone with reference drug, benznidazole, in acute Trypanosoma cruzi infected mice when administered by oral route. We have also evaluated the mutagenic and cytotoxic activity of the main component of Zanthoxylum chiloperone, i.e. canthin-6-one, by mouse bone marrow micronucleus test. MATERIALS AND METHODS: The compositions of the ethanol extracts obtained after the maceration process were studied by HPLC-UV-MS methods. The quantitation analysis was performed by external standard method, using a calibration curve constructed utilizing solutions containing different concentrations of the reference samples. The anti-trypomastigote activity was evaluated by the lysis effect on mouse blood trypomastigotes (Y strain Trypanosoma cruzi). The anti-amastigote Trypanosoma cruzi activity was evaluated by a modified colorimetric method with chlorophenol red-ß-d-galactopyranoside (CPRG). The cytotoxicity of extracts and compounds was performed on NCTC 929 cells. The in vivo efficacy of the ethanolic leaves extract of Zanthoxylum chiloperone and benznidazole, in acute Trypanosoma cruzi (two different strains) was evaluated in Trypanosoma cruzi infected mice; the drugs were administered by oral route. The mortality rates were recorded and parasitaemias in control and treated mice were determined once weekly for 70 days. The mutagenic and cytotoxic activity of the main component of Zanthoxylum chiloperone, canthin-6-one, by mouse bone marrow micronucleus test. RESULTS: Canthin-6-one was the main compound of stem and root bark and 5-methoxy-canthin-6-one in leaves and fruits. The ethanolic leaves extract, canthin-6-one and benznidazole presented, approximately, the same level of in vitro activity against trypomastigote and amastigote forms of Trypanosoma cruzi. We have also evaluated the mutagenic and cytotoxic effects of canthin-6-one by micronucleus test in mice. This test showed any mutagenic and cytotoxic damages. The effects of oral or subcutaneous treatments at 10 mg/kg daily for 2 weeks with the ethanolic extract of leaves of Zanthoxylum chiloperone were examined in Balb/c mice infected acutely with Trypanosoma cruzi (CL or Y strain) and compared with benznidazole at 50 mg/kg for 2 weeks. In these experiments, 70 days after infection, parasitaemia and serological response were significantly reduced with the oral ethanolic extract treatment compared with reference drug. CONCLUSIONS: This study have shown the efficacy of the leaves extract of Zanthoxylum chiloperone in reducing Trypanosoma cruzi parasitaemia in vivo assays and could be welcomed by scientific and rural communities of Paraguay because it could help them towards the use of local resources to treat an endemic infection, Chagas disease, affecting 20% of the population of this country.

Antileishmanial activity of furoquinolines and coumarins from Helietta apiculata.

UNLABELLED: The bark infusion of H. apiculata are used to treat wound healing related to cutaneous leishmaniasis and as anti-inflammatory. AIM OF THE STUDY: To isolate, purify active constituents of H. apiculata stem bark, and evaluate their in vitro and in vivo antileishmanial activities. MATERIALS AND METHODS: Isolation by chromatographic methods and chemical identification of furoquinoline alkaloids and coumarins, then evaluation of the in vitro leishmanicidal activity of these compounds against three strains of Leishmania sp. promastigotes and in vivo against Leishmania amazonensis in Balb/c mice. RESULTS: Furoquinoline alkaloids and coumarins presented a moderate in vitro activity against promastigote forms of Leishmania sp. with IC(50) values in the range between 17 and >50 microg/ml. Balb/c mice infected with Leishmania amazonensis were treated with gamma-fagarine by oral route, or with 3-(1'-dimethylallyl)-decursinol or (-)-heliettin by subscutaneous route for 14 days at 10mg/kg daily. In these conditions, gamma-fagarine, 3-(1'-dimethylallyl)-decursinol and (-)-heliettin showed the same efficacy as the reference drug reducing by 97.4, 95.6 and 98.6% the parasite loads in the lesion, respectively. CONCLUSION: These compounds showed significant efficacy in L. amazonensis infected mice, providing important knowledge to improve its potential role for a future use in the treatment of cutaneous leishmaniasis.

Phytochemical and antiprotozoal activity of Ocotea lancifolia.

Thirteen known isoquinoline alkaloids were isolated from Ocotea lancifolia, popularly known as << canela pilosa >> in Brasil and << laurel né >> by the Guarani people which means smell laurel. Their activities against the promastigote forms of three Leishmania strains and the bloodstream form of Trypanosoma cruzi were evaluated, as well as their hepatocytotoxicity. Among them, the noraporphine alkaloid (-) caaverine has shown the most interesting antiprotozoal activity against Leishmania and T. cruzi parasites.

Antiparasitic activity of some New Caledonian medicinal plants.

Twenty-nine extracts of 18 medicinal plants used in New Caledonia by traditional healers to treat inflammation, fever and in cicatrizing remedies were evaluated in vitro against several parasites (Leishmania donovani, Trypanosoma brucei brucei, Trichomonas vaginalis and Caenorhabditis elegans). Among the selected plants, Scaevola balansae and Premna serratifolia L. were the most active against Leishmania donovani with IC(50) values between 5 and 10microg/ml. The almond and aril extracts from Myristica fatua had an IC(50) value of 0.5-5microg/ml against Trypanosoma brucei brucei. Only Scaevola balansae extract presented a weak activity against Trichomonas vaginalis. The almond extract from Myristica fatua presented significant activity against Caenorhabditis elegans (IC(50) value of 6.6+/-1.2microg/ml).

Bioassay-guided isolation of antifungal alkaloids from Melochia odorata.

An alkaloidal extract of the leaves of Melochia odorata exhibited antifungal activity against Candida albicans, Cryptococcus neoformans and Saccharomyces cerevisiae using a TLC bioautographic method. Bioassay-guided fractionation of this extract using separation by normal and reverse high-performance liquid chromatography (HPLC) resulted in the isolation of two active compounds identified as frangulanine, a cyclic peptide alkaloid, and waltherione-A, a quinolinone alkaloid.

Effects of canthin-6-one alkaloids from Zanthoxylum chiloperone on Trypanosoma cruzi-infected mice.

Canthin-6-one (1), isolated from Zanthoxylum chiloperone (Rutaceae), possesses a broad sprectum of antifungal and leishmanicidal activities. In this study, we have examined the antiparasitic effects of canthin-6-one (1), 5-methoxycanthin-6-one (2), canthin-6-one N-oxide (3), as well as that of the total alkaloids of Zanthoxylum chiloperone stem bark, in Balb/c mice infected either acutely or chronically with Trypanosoma cruzi. The compounds were administered orally or subcutaneously at 5mg/kg/day for 2 weeks, whereas the alkaloidal extract was given at 50mg/kg/day for 2 weeks. The antiparasitic activity was compared with that of benznidazole given at 50mg/kg/day for 2 weeks. In the case of acute infection, parasiteamia was significantly reduced following oral treatment with canthin-6-one (1). Moreover, the total alkaloids of Zanthoxylum chiloperone stem bark led to high levels of parasitological clearance. Seventy days post-infection, the serological response in the acute model was significantly different between oral canthin-6-one (1) and benznidazole-treated mice. Chronic model of the disease showed that both canthin-6-one (1) and the alkaloidal extract at the above dosage induced 80-100% animal survival compared to untreated controls. These results indicate that canthin-6-one (1) exhibits trypanocidal activity in vivo in the mouse model of acute or chronic infection. This is the first demonstration of anti-Trypanosoma cruzi activity for a member of this chemical group (canthinones). Considering the very low toxicity of canthin-6-one (1), our results suggest that long-term oral treatment with this natural product could prove advantageous compared to the current chemotherapy of Chagas disease.

Extraction, hemisynthesis, and synthesis of canthin-6-one analogues. Evaluation of their antifungal activities.

Zanthoxylum chiloperone var. angustifolium was investigated. Alkaloids 1-3 from the canthin-6-one series were characterized. Derivatives 7-28 were prepared by hemisynthesis or total synthesis. All compounds were tested for in vitro antifungal activities against five pathogenic fungal strains. Analogues of canthin-6-one did not show better antifungal activities.

Antileishmanial and trypanocidal activity of Brazilian Cerrado plants

The side effects and the emerging resistance to the available drugs against leishmaniasis and trypanosomiasis led to the urgent need for new therapeutic agents against these diseases. Thirty one extracts of thirteen medicinal plants from the Brazilian Cerrado were therefore evaluated in vitro for their antiprotozoal activity against promastigotes of Leishmania donovani, and amastigotes of Trypanosoma cruzi. Among the selected plants, Casearia sylvestris var. lingua was the most active against both L. donovani and T. cruzi. Fifteen extracts were active against promastigotes of L. donovani with concentrations inhibiting 50 percent of parasite growth (IC50) between 0.1-10 æg/ml, particularly those of Annona crassiflora (Annonaceae), Himatanthus obovatus (Apocynaceae), Guarea kunthiana (Meliaceae), Cupania vernalis (Sapindaceae), and Serjania lethalis (Sapindaceae). With regard to amastigotes of T. cruzi, extracts of A. crassiflora, Duguetia furfuracea (Annonaceae), and C. sylvestris var. lingua were active with IC50 values between 0.3-10 æg/ml. Bioassay fractionations of the more active extracts are under progress to identify the active antiparasite compounds.

Antileishmanial and trypanocidal activity of Brazilian Cerrado plants.

The side effects and the emerging resistance to the available drugs against leishmaniasis and trypanosomiasis led to the urgent need for new therapeutic agents against these diseases. Thirty one extracts of thirteen medicinal plants from the Brazilian Cerrado were therefore evaluated in vitro for their antiprotozoal activity against promastigotes of Leishmania donovani, and amastigotes of Trypanosoma cruzi. Among the selected plants, Casearia sylvestris var. lingua was the most active against both L. donovani and T. cruzi. Fifteen extracts were active against promastigotes of L. donovani with concentrations inhibiting 50% of parasite growth (IC50) between 0.1-10 microg/ml, particularly those of Annona crassiflora (Annonaceae), Himatanthus obovatus (Apocynaceae), Guarea kunthiana (Meliaceae), Cupania vernalis (Sapindaceae), and Serjania lethalis (Sapindaceae). With regard to amastigotes of T. cruzi, extracts of A. crassiflora, Duguetia furfuracea (Annonaceae), and C. sylvestris var. lingua were active with IC50 values between 0.3-10 microg/ml. Bioassay fractionations of the more active extracts are under progress to identify the active antiparasite compounds.

Synthesis and biological evaluation of substituted quinolines: potential treatment of protozoal and retroviral co-infections.

We report the synthesis of substituted quinolines and their in vitro biological evaluation against the causal agents of cutaneous leishmaniasis, visceral leishmaniasis, African trypanosomiasis and Chagas' disease. Furthermore, several quinolines have also been tested for their anti-retroviral activity in HIV-1 infected cells. The structure-activity relationships of these new synthetic compounds are discussed and emphasis was placed on the treatment of leishmania/HIV co-infections.

Antifungal compounds from Zanthoxylum chiloperone var. angustifolium.

An alkaloidal extract of the stem barks of Zanthoxylum chiloperone var. angustifolium exhibited antifungal activity against Candida albicans, Aspergillus fumigatus and Trichophyton mentagrophytes var. interdigitale using a TLC bioautographic method. Bioassay-guided fractionation of this extract resulted in the isolation of two active compounds identi fi ed as canthin-6-one and 5-methoxycanthin-6-one. Canthin-6-one exhibited a broad spectrum of activities against Aspergillus fumigatus, A. niger, A. terreus, Candida albicans, C. tropicalis, C. glabrata, Cryptococcus neoformans, Geotrichum candidum, Saccharomyces cerevisiae, Trichosporon beigelii, Trichosporon cutaneum and Trichophyton mentagrophytes var. interdigitale with MICs values between 5.3 and 46 micro mol/L. 5-methoxy-canthin-6-one was active against only Trichophyton mentagrophytes var. interdigitale with a MIC value of 12.3 micro mol/L.

Natural products as trypanocidal, antileishmanial and antimalarial drugs.

Parasitic diseases caused by protozoa as Leishmania, Trypanosome or Plasmodium are responsible for more than three millions deaths annually throughout the developing countries. This review covers recent studies on plant-secondary metabolites isolated from medicinal plants and that have demonstrated moderate to high activity in in vitro and in vivo bioassays against these protozoa. The biological activity of the last promising antiparasitic leads are described.

Inhibiciòn de la agregaciòn plaquetaria por extractos de plantas de uso medicinal en Paraguay / Annual reports 1995 / Inhibition of platelet aggregation by medicinal plants usein Paraguay

Con el propòsito de identificar extractos y luego aislar productos on actividad inhibidoria sobre la agregaciòn plaquetaria in vitro fueron probados 21 extractos alcohòlicos de plantas antitrombòlicos y en transtornos circulatorios e inmunològicos. La inhibiciòn de la agregaciòn se determinò mediante el mètodo turbo-densitomètrico (coagulòmetro AccuStasisTM 1000) midiendo el tiempo de agregaciòn del plasma rico en plaquetas inducido por adenosina 5 difosfato (ADP), colàgeno y epinefrina a las concentraciones iniciales de 2x10-4mo1/L, 2 mg/ml y 1x10-4mo1/L respectivamente y como control positivo de la inhibiciòn de la agregaciòn plaquetaria se usò aspirina a la concentraciòn de 0,1g/ml. La evaluaciòn cualitativa se realizò por apreciaciòn microscòpica (A 100x) de frotis teñidos con Giemsa del agregado plaquetario o nò por los extractos y los controles. Del screening resultò activo el extracto de una planta medicinal perteneciente a la familia Myrtaceae a la concentraciòn de 272ug/ml con los porcentajes de inhibiciòn de 96 por ciento a la concentraciòn de 0,18x10-4mo1/L de ADP y 94,4 por ciento a la concentraciòn de 0,045x10-4mo1/L de ADP. Tambièn resultò activo el extracto de una planta medicinal perteneciente a la familia Flacourtiaceae con un porcentaje de inhibiciòn de 92 por ciento al ser inducido por ADP a la concentraciòn de 0,045x10-4mo1/L. Este estudio indica el potencial de algunos extractos estudiados y justifica el aislamiento de compuestos puros de los extractos activos con mejores propiedades.

Inhibiciòn de la agregaciòn plaquetaria por extractos de plantas de uso medicinal en Paraguay / Annual reports 1995 / Inhibition of platelet aggregation by medicinal plants usein Paraguay

Con el propòsito de identificar extractos y luego aislar productos on actividad inhibidoria sobre la agregaciòn plaquetaria in vitro fueron probados 21 extractos alcohòlicos de plantas antitrombòlicos y en transtornos circulatorios e inmunològicos. La inhibiciòn de la agregaciòn se determinò mediante el mètodo turbo-densitomètrico (coagulòmetro AccuStasisTM 1000) midiendo el tiempo de agregaciòn del plasma rico en plaquetas inducido por adenosina 5 difosfato (ADP), colàgeno y epinefrina a las concentraciones iniciales de 2x10-4mo1/L, 2 mg/ml y 1x10-4mo1/L respectivamente y como control positivo de la inhibiciòn de la agregaciòn plaquetaria se usò aspirina a la concentraciòn de 0,1g/ml. La evaluaciòn cualitativa se realizò por apreciaciòn microscòpica (A 100x) de frotis teñidos con Giemsa del agregado plaquetario o nò por los extractos y los controles. Del screening resultò activo el extracto de una planta medicinal perteneciente a la familia Myrtaceae a la concentraciòn de 272ug/ml con los porcentajes de inhibiciòn de 96 por ciento a la concentraciòn de 0,18x10-4mo1/L de ADP y 94,4 por ciento a la concentraciòn de 0,045x10-4mo1/L de ADP. Tambièn resultò activo el extracto de una planta medicinal perteneciente a la familia Flacourtiaceae con un porcentaje de inhibiciòn de 92 por ciento al ser inducido por ADP a la concentraciòn de 0,045x10-4mo1/L. Este estudio indica el potencial de algunos extractos estudiados y justifica el aislamiento de compuestos puros de los extractos activos con mejores propiedades

Actividad tripanocida de productos naturales contra formas sanguineas tripomasrigotes de Trypanosoma Cruzi / Trypanocidal activity of natural products against blood Trypomastigote forms of Trypanosoma cruzi / Annual Reports 1991

Blood trnasfusion is the second most importnatmechanism of transmission of Chagas'disease in both endemic and non-endemic areas. In Latin America, more than 20,000 cases of transmission of the disease, trough blood transfusion, may be occurring. Gentian Violet is currently the only available trypanicidal agent used for treating blood before transfusion. The main disadvantages of this treatment are the time required to allow drug action before transfusion and the coloring of the blood. In vitro trypanocidal effect of plant extracts and that of pure compounds are assessed against trypomastigote blood forms of T. cruzi. The induction of sister chromatid exchange (SCE) in human lypocytes was performed to evaluate mutagenic effects of these compounds. Eight compounds had a high activity against blood forms of T. cruzi at a concentration of 250 mg/ml; namely, daphnandrine, limacine, pheantine, daphnoline and cocsuline. Plumbagin (a naphthoquinone) also showed high trypanicidal activity and has previously been recognized as a leismaniacidal, bactericidal and fungicidal, compound. Daphnoline showed low values for both LC50 (8mg/ml) and LC90 (50mg/ml) and was the only tested compound which did not induce sister chromatid exchange below 10 mg/ml. Therefore, deeper evaluations of these compounds should be considered