The schistosomicidal activity of ethanolic extracts from branches, leaves, flowers and fruits of Handroanthus impetiginosus (Mart. ex DC.) Mattos (Bignoniaceae) plant and metabolic profile characterization by UPLC-ESI-QTOF analysis.

Schistosomiasis, caused by Schistosoma mansoni Sambon, 1907, is a severe and widely distributed parasitic disease, affecting about 200 million people worldwide. The disease is recognized by elevated mortality rates, especially among those living in areas of poor sanitation. Currently, the chemotherapeutic treatment is solely based on using the praziquantel drug. Therefore, there is a need for the discovery of new medicines for the treatment of this parasitosis. Thus, this work aimed to evaluate the schistosomicidal activity of ethanolic crude extracts from the branches, leaves, flowers, and fruits of Handroanthus impetiginosus (Mart ex DC.) Masttos and characterize its metabolic profile by UPLC-ESI-QTOF analysis. Evaluation of plant extract on S. mansoni was carried out in adult worms in vitro, in which the mortality rate was quantified, and the damages in the tegument of the worms were monitored. All extracts induced changes in the viability of adult males of S. mansoni, causing the death of the parasites, which was directly dependent of the concentration.

Chemical composition, in vitro larvicidal and antileishmanial activities of the essential oil from Citrus reticulata Blanco fruit peel / Composição química, atividades larvicida e leishmanicida in vitro do óleo essencial da casca do fruto de Citrus reticulata Blanco

Numerous studies have investigated the chemical composition and biological activities of essential oils from different Citrus species fruit peel, leaves and flowers. This paper aims to investigate the chemical composition, larvicidal and antileishmanial activities of essential oil from Citrus reticulata fruit peel (CR-EO). CR-EO was obtained by hydrodistillation in a Clevenger-type apparatus and its chemical composition was analyzed by GC-MS and GC-FID. Limonene (85.7%), ɣ-terpinene (6.7%) and myrcene (2.1%) were identified as its major components. CR-EO showed high activity against promastigote forms of Leishmania amazonensis (IC50 = 8.23 µg/mL). CR-EO also exhibited high larvicidal activity against third instar Aedes aegypti larvae at a lethal concentration (LC50 = 58.35 µg/mL) and 100% mortality at 150 µg/mL. This study suggests, for the first time, the potential use of CR-EO against this important mosquito-borne viral disease caused by the genus Aedes.

Numerosos estudos têm investigado a composição química e as atividades biológicas de óleos essenciais extraídos de cascas dos frutos, folhas e flores de diferentes espécies de Citrus. Este trabalho tem como objetivo investigar a composição química e as atividades larvicida e leishmanicida in vitro do óleo essencial das cascas dos frutos de Citrus reticulata (CR-EO). CR-EO foi obtido pela técnica de extração em aparelho Clevenger e sua composição química foi determinada por CG-EM e CG-DIC. Limoneno (85,7%), ɣ-terpineno (6,7%) and mirceno (2,1%) foram identificados como os constituintes majoritários. CR-EO mostrou alta atividade contra as formas promastigota de Leishmania amazonensis (CI50 = 8,23 µg/mL). CR-EO também exibiu alta atividade larvicida contra as larvas do terceiro estágio do Aedes aegypti com concentração letal (CL50 = 58,35 µg/mL) e mortalidade de 100% em 150 µg/mL. Este estudo sugere, pela primeira vez, o uso potencial de CR-EO contra esta importante doença viral transmitida por mosquitos do gênero Aedes.

Chemical composition, in vitro larvicidal and antileishmanial activities of the essential oil from Citrus reticulata Blanco fruit peel

Abstract Numerous studies have investigated the chemical composition and biological activities of essential oils from different Citrus species fruit peel, leaves and flowers. This paper aims to investigate the chemical composition, larvicidal and antileishmanial activities of essential oil from Citrus reticulata fruit peel (CR-EO). CR-EO was obtained by hydrodistillation in a Clevenger-type apparatus and its chemical composition was analyzed by GC-MS and GC-FID. Limonene (85.7%), -terpinene (6.7%) and myrcene (2.1%) were identified as its major components. CR-EO showed high activity against promastigote forms of Leishmania amazonensis (IC50 = 8.23 µg/mL). CR-EO also exhibited high larvicidal activity against third instar Aedes aegypti larvae at a lethal concentration (LC50 = 58.35 µg/mL) and 100% mortality at 150 µg/mL. This study suggests, for the first time, the potential use of CR-EO against this important mosquito-borne viral disease caused by the genus Aedes.

Resumo Numerosos estudos têm investigado a composição química e as atividades biológicas de óleos essenciais extraídos de cascas dos frutos, folhas e flores de diferentes espécies de Citrus. Este trabalho tem como objetivo investigar a composição química e as atividades larvicida e leishmanicida in vitro do óleo essencial das cascas dos frutos de Citrus reticulata (CR-EO). CR-EO foi obtido pela técnica de extração em aparelho Clevenger e sua composição química foi determinada por CG-EM e CG-DIC. Limoneno (85,7%), -terpineno (6,7%) and mirceno (2,1%) foram identificados como os constituintes majoritários. CR-EO mostrou alta atividade contra as formas promastigota de Leishmania amazonensis (CI50 = 8,23 µg/mL). CR-EO também exibiu alta atividade larvicida contra as larvas do terceiro estágio do Aedes aegypti com concentração letal (CL50 = 58,35 µg/mL) e mortalidade de 100% em 150 µg/mL. Este estudo sugere, pela primeira vez, o uso potencial de CR-EO contra esta importante doença viral transmitida por mosquitos do gênero Aedes.

Chemical composition, in vitro larvicidal and antileishmanial activities of the essential oil from Citrus reticulata Blanco fruit peel / Composição química, atividades larvicida e leishmanicida in vitro do óleo essencial da casca do fruto de Citrus reticulata Blanco

Abstract Numerous studies have investigated the chemical composition and biological activities of essential oils from different Citrus species fruit peel, leaves and flowers. This paper aims to investigate the chemical composition, larvicidal and antileishmanial activities of essential oil from Citrus reticulata fruit peel (CR-EO). CR-EO was obtained by hydrodistillation in a Clevenger-type apparatus and its chemical composition was analyzed by GC-MS and GC-FID. Limonene (85.7%), ɣ-terpinene (6.7%) and myrcene (2.1%) were identified as its major components. CR-EO showed high activity against promastigote forms of Leishmania amazonensis (IC50 = 8.23 µg/mL). CR-EO also exhibited high larvicidal activity against third instar Aedes aegypti larvae at a lethal concentration (LC50 = 58.35 µg/mL) and 100% mortality at 150 µg/mL. This study suggests, for the first time, the potential use of CR-EO against this important mosquito-borne viral disease caused by the genus Aedes.

Resumo Numerosos estudos têm investigado a composição química e as atividades biológicas de óleos essenciais extraídos de cascas dos frutos, folhas e flores de diferentes espécies de Citrus. Este trabalho tem como objetivo investigar a composição química e as atividades larvicida e leishmanicida in vitro do óleo essencial das cascas dos frutos de Citrus reticulata (CR-EO). CR-EO foi obtido pela técnica de extração em aparelho Clevenger e sua composição química foi determinada por CG-EM e CG-DIC. Limoneno (85,7%), ɣ-terpineno (6,7%) and mirceno (2,1%) foram identificados como os constituintes majoritários. CR-EO mostrou alta atividade contra as formas promastigota de Leishmania amazonensis (CI50 = 8,23 µg/mL). CR-EO também exibiu alta atividade larvicida contra as larvas do terceiro estágio do Aedes aegypti com concentração letal (CL50 = 58,35 µg/mL) e mortalidade de 100% em 150 µg/mL. Este estudo sugere, pela primeira vez, o uso potencial de CR-EO contra esta importante doença viral transmitida por mosquitos do gênero Aedes.

Chemical composition, in vitro larvicidal and antileishmanial activities of the essential oil from Citrus reticulata Blanco fruit peel.

Numerous studies have investigated the chemical composition and biological activities of essential oils from different Citrus species fruit peel, leaves and flowers. This paper aims to investigate the chemical composition, larvicidal and antileishmanial activities of essential oil from Citrus reticulata fruit peel (CR-EO). CR-EO was obtained by hydrodistillation in a Clevenger-type apparatus and its chemical composition was analyzed by GC-MS and GC-FID. Limonene (85.7%), É£-terpinene (6.7%) and myrcene (2.1%) were identified as its major components. CR-EO showed high activity against promastigote forms of Leishmania amazonensis (IC50 = 8.23 µg/mL). CR-EO also exhibited high larvicidal activity against third instar Aedes aegypti larvae at a lethal concentration (LC50 = 58.35 µg/mL) and 100% mortality at 150 µg/mL. This study suggests, for the first time, the potential use of CR-EO against this important mosquito-borne viral disease caused by the genus Aedes.

Assessment of the cytotoxic, genotoxic, and antigenotoxic activities of sucupira oil (Pterodon emarginatus).

The present study aimed to assess the cytotoxic, genotoxic, and antigenotoxic activities of sucupira oil (Pterodon emarginatus), which is commonly used as an anti-rheumatic, analgesic, antimicrobial, anticercariae, and anti-inflammatory. We used the mouse bone marrow micronucleus test as an experimental model. The experimental groups, which consisted of 5 animals, was administered sucupira oil (100 mg/kg body weight) intraperitoneally and evaluated 24 h after the treatment. The negative control group was treated with sterile distilled water, and the positive control group received an intraperitoneal dose of 4 mg/kg mitomycin C, a dose that corresponds to 80% of its median lethal dose. Cytotoxicity was determined by the polychromatic to normochromatic erythrocytes ratio (PCE/NCE). Sucupira oil had no significant effects (P > 0.05) on the frequency of micronucleated polychromatic erythrocytes as compared to the negative control group. However, the difference was significant (P < 0.005) as compared to the positive control group. The PCE/NCE (100 mg/kg oil and 4 mg/kg mitomycin) ratio did not differ between the experimental group and the positive control group, but it differed significantly when compared to the negative control group (P < 0.05). Thus, these findings suggested that the P. emarginatus oil showed no cytotoxic, mutagenic, or antimutagenic activities at a dose of 100 mg/kg.

In vitro schistosomicidal effects of aqueous and dichloromethane fractions from leaves and stems of Piper species and the isolation of an active amide from P. amalago L. (Piperaceae).

Dichloromethane and aqueous fractions from leaves and stems of Piper arboreum Aubl., P. aduncum L., P. amalago L., P. crassinervium H.B. & K., P. diospyrifolium Kunth, P. hispidum Sw. and P. xylosteoides (Kunth) Steud. were tested against adult worms of Schistosoma mansoni. The in vitro activity was evaluated in terms of mortality, number of separated worms and number of worms with reduced motor activity. Most dichloromethane fractions from all Piper species showed moderate schistosomicidal activity, but aqueous fractions were not active. The dichloromethane fraction of P. amalago leaves (at 100 µg/ml) showed the highest activity, resulting in worm mortality, the separation of worm pairs and reduced motor activity. Chromatographic fractionation of the dichloromethane fraction of P. amalago leaves led to the isolation of its major compound, which was also tested against adults of S. mansoni. The isolated piperamide N-[7-(3',4'-methylenedioxyphenyl)-2(Z),4(Z)-heptadienoyl] pyrrolidine, at 100 µ m, resulted in the mortality of all adult worms after 24 h of incubation. The findings suggest that species of Piper are potential sources of schistosomicidal compounds.

Chemical composition and in vitro schistosomicidal activity of the essential oil from the flowers of Bidens sulphurea (Asteraceae).

In this study, the chemical composition and the in vitro schistosomicidal properties of the essential oil obtained from Bidens sulphurea flowers (Bs-EO) were investigated. Its major constituents were identified as being 2,6-di-tert-butyl-4-methylphenol (44.98%), germacrene D (33.70%) and ß-caryophyllene (10.23%). Bs-EO at 100 µg mL(-1) caused death of all the adult worms and promoted separation of the couple pairs into individual male and female within 48 h, besides leading to a significant decrease in the motility of the parasites. This oil was also responsible for a remarkable reduction in the number of eggs and the percentage of developed eggs produced by adult worms. These results suggest that the Bs-EO can be considered a promising source for the development of new schistosomicidal agents.

Schistosomicidal and trypanocidal structure-activity relationships for (±)-licarin A and its (-)- and (+)-enantiomers.

(±)-Licarin A (1) was obtained by oxidative coupling, and its enantiomers, (-)-licarin A (2) and (+)-licarin A (3), were resolved by chiral HPLC. Schistosomicidal and trypanocidal activities of these compounds were evaluated in vitro against Schistosoma mansoni adult worms and trypomastigote forms of Trypanosoma cruzi. The racemic mixture (1) displayed significant schistosomicidal activity with an LC50 value of 53.57 µM and moderate trypanocidal activity with an IC50 value of 127.17 µM. On the other hand, the (-)-enantiomer (2), displaying a LC50 value of 91.71 µM, was more active against S. mansoni than the (+)-enantiomer (3), which did not show activity. For the trypanocidal assay, enantiomer 2 showed more significant activity (IC50 of 23.46 µM) than enantiomer 3, which showed an IC50 value of 87.73 µM. Therefore, these results suggest that (±)-licarin A (1) and (-)-licarin A (2) are promising compounds that could be used for the development of schistosomicidal and trypanocidal agents.

Characterization and mRNA expression analysis of PI31, an endogenous proteasome inhibitor from Schistosoma mansoni.

The proline-rich inhibitor of 31 kDa (PI31) is highly conserved through metazoan evolution, and its activity in the proteasome inhibition is well-established although the precise mechanism of inhibition is unclear. The coding DNA sequence of Schistosoma mansoni PI31 (SmPI31) was cloned, and the recombinant protein was expressed in bacterial system. The correct amino acid sequence was confirmed by mass spectrometry and circular dichroism suggests that SmPI31 contains both α-helix and non-structured regions. Inhibition assays, using the Suc-Leu-Leu-Val-Tyr-4-MCA substrate for proteasome degradation, showed that the S. mansoni proteasome may be regulated by the inhibitory activity of SmPI31. A gene expression assay using qRT-PCR at various stages during the S. mansoni life cycle has shown that SmPI31 transcripts are expressed in all studied stages, suggesting that PI31 plays an important role during the developmental processes of the parasite. In this study first evidence is presented that PI31 has a conserved structure and plays a role as proteasome inhibitor in adult worms and it is expressed through life cycle.