Bioprospection for antiplasmodial activity, and identification of bioactive metabolites of native plants species from the Mata Atlântica biome, Brazil.

A total of 33 extracts of eleven different plants species from Mata Atlântica biome, Brazil, and different fractions of the bioactive extracts were evaluated against chloroquine-resistant Plasmodium falciparum W2 strain by PfLDH method and cytotoxicity to HepG2 cells by the MTT assay, and chemically characterized by LC-DAD-ESI-MS/MS analysis. The results allowed the identification of Alchornea glandulosa, Miconia latecrenata, and Psychotria suterella as the most active plant species. Different flavonoids and tannins in Alchornea glandulosa and Miconia latecrenata besides alkaloids in Psychotria suterella were identified. Bioguided fractionation of A. glandulosa and M. latecrenata leaves extracts led to fractions exhibiting high parasite growth inhibition. Seven known alkaloids were identified in the P. suterella extract, and of these, only 5-carboxystrictosidine had been assayed for antiplasmodial activity what points to this species as the most promising among the eleven one assayed.

Phytochemistry and antiplasmodial activity of Xylopia sericea leaves.

Aiming to investigate the antiplasmodial activity and the phytochemical composition of Xylopia sericea leaves, the essential oil and dichloromethane extract were analyzed by gas and liquid chromatography, respectively, both of them coupled to mass spectrometry, and were evaluated against the chloroquine-resistant Plasmodium falciparum strain (W2) and for cytotoxicity to HepG2 cells. Low growth inhibition of P. falciparum as well as low cytotoxicity to HepG2 cells were observed for the essential oil. The leaves dichloromethane extract showed moderate growth inhibition of P. falciparum and low cytotoxicity to HepG2 cells. Bioguided chromatographic fractionation of this extract led to fractions with increased antiplasmodial activity from which liriodenine (IC50 6.1 ± 0.1 µg/mL, CC50 > 1000.0 µg/mL, SI > 164), an aporphine alkaloid, and an acetogenin-rich fraction containing mainly isomers of annomontacin and 4-deoxy-annomontacin (IC50 22.7 ± 1.9 µg/mL, CC50 336.1 ± 15.5 µg/mL, SI = 15) might be highlighted for their antiplasmodial activity.

Efficacy of lapachol on treatment of cutaneous and visceral leishmaniasis.

Leishmaniasis is one of the most important neglected diseases worldwide. It is a life-threatening disease and causes significant morbidity, long-term disability, and early death. Treatment involves disease control or use of intervention measures, although the currently used drugs require long-lasting therapy, and display toxicity and reduced efficacy. The use of natural products isolated from plants, such as lapachol, an abundant naphthoquinone naturally occurring in South American Handroanthus species (Tabebuia, Bignoniaceae), is a promising option for the treatment of leishmaniasis. In this study, we investigated the leishmanicidal activity of lapachol in vitro and in vivo against Leishmania infantum and L. amazonensis, causative agents of visceral and cutaneous leishmaniasis, respectively. Low cytotoxicity in HepG2 cells (3405.8 ±â€¯261.33 µM), good anti-Leishmania activity, and favorable selectivity indexes (SI) against promastigotes of both L. amazonensis (IC50 = 79.84 ±â€¯9.10 µM, SI = 42.65) and L. infantum (IC50 = 135.79 ±â€¯33.04 µM, SI = 25.08) were observed. Furthermore, anti-Leishmania activity assays performed on intracellular amastigotes showed good activity for lapachol (IC50 = 191.95 µM for L. amazonensis and 171.26 µM for L. infantum). Flow cytometric analysis demonstrated that the cytotoxic effect of lapachol in Leishmania promastigotes was caused by apoptosis-like death. Interestingly, the in vitro leishmanicidal effect of lapachol was confirmed in vivo in murine models of visceral and cutaneous leishmaniasis, as lapachol (25 mg/kg oral route for 24 h over 10 days) was able to significantly reduce the parasitic load in skin lesions, liver, and spleen, similar to amphotericin B, the reference drug. These results reinforce the therapeutic potential of lapachol, which warrants further investigations as an anti-leishmaniasis therapeutic.

Antiplasmodial activity and cytotoxicity, isolation of active alkaloids, and dereplication of Xylopia sericea leaves ethanol extract by UPLC-DAD-ESI-MS/MS.

OBJECTIVES: To assess the antiplasmodial activity of the ethanol extract of Xylopia sericea leaves, Annonaceae, often associated with antimalarial use and to perform a bioguided isolation of active compounds. METHODS: Dereplication of ethanol extract by the UPLC-DAD-ESI-MS/MS technique allowed the identification of the major constituents, isolation and identification of alkaloids. The antiplasmodial and cytotoxic activity of the extract, fractions and isolated compounds was evaluated against the chloroquine-resistant W2 strain Plasmodium falciparum and HepG2 cells, respectively. KEY FINDINGS: Ethanol extract showed high reduction of parasitemia as well as moderate cytotoxicity (86.5 ± 3.0% growth inhibition at 50 µg/ml and CC50 72.1 ± 5.1 µg/ml, respectively). A total of eight flavonoids were identified, and two aporphine alkaloids, anonaine and O-methylmoschatoline, were isolated. Anonaine disclosed significant antiplasmodial effect and moderate cytotoxicity (IC50 23.2 ± 2.7 µg/ml, CC50 38.3 ± 2.3 µg/ml, SI 1.6) while O-methylmoschatoline was not active against P. falciparum and showed a low cytotoxicity (33.5 ± 1.9% growth inhibition at 50 µg/ml, CC50 274.4 ± 0.5 µg/ml). CONCLUSIONS: Characterization of Xylopia sericea leaves ethanol extract by UPLC-DAD-ESI-MS/MS as well as its antiplasmodial activity and the occurrence of anonaine and O-methylmoschatoline in this Xylopia species are reported by the first time.

Phytochemical characterization and antioxidant, antibacterial and antimutagenic activities of aqueous extract from leaves of Alchornea glandulosa.

Plant extracts exist as a complex matrix which serves as a source of numerous bioactive metabolites. The ultra performance liquid chromatography with diode-array detection-coupled electrospray ionization-mass spectrometry/mass spectrometry technique was used to characterize the aqueous extract from leaves of Alchornea glandulosa (EAG), a species popularly used to treat gastrointestinal problems as an antiulcer agent. Quantification of phenolic derivatives was determined using Folin-Ciocalteu and aluminum trichloride (AlCl3) methods. In addition, antioxidant (2,2-diphenyl-1-picrylhydrazyl [DPPH•] radical scavenging, ß-carotene-linoleic acid, and lipid peroxidation), antibacterial (agar well diffusion method and minimum inhibitory concentration), antimutagenic (Ames test), and antigenotoxic (plasmid cleavage) assays were also performed on this plant extract. The ellagitannin tris-galloyl-hexahydroxydiphenic acid-glucose was identified as the predominant compound along with tannins as majority metabolites. EAG showed high antioxidant activity accompanied by moderate antibacterial activity against Staphylococcus aureus. The highest antimutagenic activity was observed for TA97 strain without metabolic activation (S9) and with metabolic activation, TA100 and TA102 were completely inhibited. In addition, EAG exhibited potential signs of antigenotoxic action. The high antioxidant and antimutagenic activity observed for EAG suggests important therapeutic uses that still need to be verified in future studies.

Structure-based drug design studies of the interactions of ent-kaurane diterpenes derived from Wedelia paludosa with the Plasmodium falciparum sarco/endoplasmic reticulum Ca²âº-ATPase PfATP6.

Malaria is responsible for more deaths around the world than any other parasitic disease. Due to the emergence of strains that are resistant to the current chemotherapeutic antimalarial arsenal, the search for new antimalarial drugs remains urgent though hampered by a lack of knowledge regarding the molecular mechanisms of artemisinin resistance. Semisynthetic compounds derived from diterpenes from the medicinal plant Wedelia paludosa were tested in silico against the Plasmodium falciparum Ca2+-ATPase, PfATP6. This protein was constructed by comparative modelling using the three-dimensional structure of a homologous protein, 1IWO, as a scaffold. Compound 21 showed the best docking scores, indicating a better interaction with PfATP6 than that of thapsigargin, the natural inhibitor. Inhibition of PfATP6 by diterpene compounds could promote a change in calcium homeostasis, leading to parasite death. These data suggest PfATP6 as a potential target for the antimalarial ent-kaurane diterpenes.

Structure-based drug design studies of the interactions of ent-kaurane diterpenes derived from Wedelia paludosa with the Plasmodium falciparum sarco/endoplasmic reticulum Ca2+-ATPase PfATP6

Malaria is responsible for more deaths around the world than any other parasitic disease. Due to the emergence of strains that are resistant to the current chemotherapeutic antimalarial arsenal, the search for new antimalarial drugs remains urgent though hampered by a lack of knowledge regarding the molecular mechanisms of artemisinin resistance. Semisynthetic compounds derived from diterpenes from the medicinal plant Wedelia paludosa were tested in silico against the Plasmodium falciparum Ca2+-ATPase, PfATP6. This protein was constructed by comparative modelling using the three-dimensional structure of a homologous protein, 1IWO, as a scaffold. Compound 21 showed the best docking scores, indicating a better interaction with PfATP6 than that of thapsigargin, the natural inhibitor. Inhibition of PfATP6 by diterpene compounds could promote a change in calcium homeostasis, leading to parasite death. These data suggest PfATP6 as a potential target for the antimalarial ent-kaurane diterpenes.

Estudo farmacognóstico comparativo das folhas de Davilla elliptica A. St.-Hil. e D. rugosa Poir., Dilleniaceae / Comparative pharmacognostic study of leaves of Davilla elliptica A. St.-Hil. e D. rugosa Poir., Dilleniaceae

As características farmacognósticas das folhas de Davilla elliptica A. St.-Hil. e D. rugosa Poir., Dilleniaceae, foram determinadas com objetivo de auxiliar na identificação taxonômica e no controle de qualidade das drogas vegetais e de produtos fitoterápicos. A espécie D. elliptica é um arbusto ereto, que ocorre naturalmente no cerrado e D. rugosa é um trepadeira lenhosa de beira de mata. Ambas são conhecidas popularmente como lixeirinha, sambaibinha e cipó-caboclo, empregadas na medicina tradicional como antiinflamatória e antiúlcera. As características microscópicas observadas em D. rugosa tais como tricomas estrelados e esclereídes no mesofilo e em D. elliptica de idioblastos contendo mucilagem e endoderme, são parâmetros que poderão ser utilizados na diferenciação das espécies. Os teores obtidos nos ensaios de pureza e nos doseamentos de taninos (9,4 por cento e 7,2 por cento), flavonoides (0,46 por cento e 0,9 por cento) e mucilagens (2,2 por cento e 4,1 por cento) de ambas as espécies, podem contribuir no controle de qualidade das drogas vegetais uma vez que são usadas indistintamente na produção de fitoterápicos.

The characters pharmacognostics of leaves of Davilla elliptica St. Hil. and Davilla rugosa Poir. of Dilleniaceae family were determinated for aiming in taxonomic and quality control of vegetable drugs and phytotherapic produtcs. The specie of D. elliptica is an erect shrub, that occurs naturally in cerrado and D. rugosa is a scandent shrub of forest edge. Both are populary known as "lixeirinha", "sambaibinha" and "cipó-caboclo" and used in popular medicine as anti-inflammatory and antiulcer. The microscopic characteristics observed like strellate trichomes and sclereids in the mesophyll in D. rugosa and the idioblasts with mucilage and endodermis in D. elliptica are parameter that will be used to differentiate the species. The content obtained in tests of purity and the tannins (9.4 percent and 7.2 percent), flavonoids (0.46 percent and 0.9 percent) and mucilage (2.2 percent and 4.1 percent) of both species help in quality control of vegetable drugs since they are indistinctly used in production of phytotherapics.

Anatomia e histoquímica dos órgãos vegetativos de Polygonum hydropiperoides Michx., Polygonaceae / Anatomical and histochemical characters of Polygonum hydropiperoides Michaux, Polygonaceae

Polygonum hydropiperoides Michaux é uma espécie conhecida popularmente como "erva-de-bicho", amplamente utilizada na medicina tradicional como anti-hemorroidal, antiinflamatória e antidiarréica. O presente trabalho tem como objetivo a caracterização anatômica e histoquímica da folha, caule e raiz, que constituem a droga vegetal, visando estabelecer parâmetros para o controle de qualidade. O material vegetal foi fixado e submetido às técnicas usuais de microscopia de luz e aos testes histoquímicos. A folha é anfiestomática, dorsiventral e com estômatos paracíticos e anisocíticos. É comum a presença de estruturas secretoras como: tricomas glandulares capitados e glândulas epidérmicas e subepidérmicas em ambas as faces da lâmina foliar e também no caule. O material secretado pelas glândulas apresenta composição heterogênea de lipídios e flavonóides, segundo análises histoquímicas. Cristais de oxalato de cálcio e grãos de amido são freqüentes em células parenquimáticas da folha e do caule. Compostos fenólicos estão presentes na folha (parênquima paliçádico), no caule (parênquima cortical e floema) e na raiz (parênquima cortical).

P. hydropiperoides is popularly known as "erva-de-bicho", and it is used in traditional medicine as anti-hemorroidal, anti-inflammatory and antidiarrhoeic. The present work has as objective the anatomical and histochemical characterization of leaf, stem and root that are used as drug in order to offer elements for quality control. The botanical material was prepared for the usual optical and histochemical microtechniques. The leaf is amphistomatic, dorsiventral and paracytic and anisocytic stomata. It is common to find the presence of secretory structures as: capitate glandular trichomes and secretory glands on both epidermis, that are also present in stem. The secretion material is heterogeneous composition of lipids and flavonoids. Druses of calcium oxalate and starch are common in parenchyma cells of leaf and stem. Phenolic compounds are present in leaf (palisade parenchyma), in stem (cortical parenchyma and phloem) and root (cortical parenchyma).

Antimicrobial activity of Trembleya laniflora, Xyris platystachia and Xyris pterygoblephara

Trembleya laniflora (D. Don) Cogn. (Melastomataceae), Xyris platystachia Alb. Nilss. (Xyridaceae) and Xyris pterygoblephara Kunth., Brazilian species collected from a biodiversity hotspot for conservation priority, had their antimicrobial activity evaluated against standardized strains of Staphylococcus aureus and Micrococcus luteus, by the agar diffusion assay. All extracts, assayed in the concentration of 2000 µg/disc, were active against M. luteus, whereas S. aureus growth was inhibited only by T. laniflora leaves and X. platystachia aerial parts. Fractionation of the extracts by partition between immiscible solvents resulted in active fractions from extracts originally inactive against S. aureus. Activity was mainly found in low and medium polar fractions. The extract of T. laniflora leaves was also fractionated by silica gel column chromatography and both the HPLC fingerprint and antimicrobial activity of the obtained fractions were distinct of those originated from the partition process.

As espécies Trembleya laniflora (Melastomataceae), Xyris platystachia (Xyridaceae) e Xyris pterygoblephara foram coletadas na Serra do Cipó, região considerada hotspot para conservação de biodiversidade. A atividade antimicrobiana dessas espécies foi avaliada em ensaios in vitro de difusão em ágar frente a linhagens padronizadas de Staphylococcus aureus e Micrococcus luteus. Todos os extratos, avaliados na concentração de 2000 µg/disco, foram ativos contra M. luteus, enquanto a inibição de crescimento de S. aureus somente foi observada para os extratos de T. laniflora (folhas) e X. platystachia (partes aéreas). A partição dos extratos brutos entre solventes imiscíveis resultou na obtenção de frações ativas, oriundas de extratos originalmente inativos frente a S. aureus, observando-se atividade principalmente para as frações de baixa e média polaridade. O extrato de folhas de T. laniflora foi adicionalmente fracionado por cromatografia em coluna de sílica gel e as frações resultantes apresentaram atividade antimicrobiana e perfis por CLAE distintos daquelas obtidas pela partição entre solventes imiscíveis.

Atividade vasodilatadora In vitro de espécies de Ouratea (Ochanaceae) e de frações de Ouratea semiserrata (Mart) engl / In vitro vasodilator activity of Ouratea (Ochnaceae) species and fractions from Ouratea semiserrata (Mart) engl

Diversas espécies de Ouratea ocorrem no cerrado, sendo utilizadas popularmente como tônico, adstringente e antiflamatório. No presente trabalho, os extratos hidroetanólicos de O. castanaefolia, O. spectabilis e O. semiserrata foram avaliados para atividade vasodilatadora em anéis de aorta pré-contraídos com fenilefrina. Apenas o extrato de caules de O. semiserrata (OS) produziu vasodilatação significativa (63 ñ 3'por cento', n Í 6), na concentração de 100 mg/mL. O fracionamento biomonitorado de OS resultou em uma fração enriquecida em proantocinanidinas, que produziu 100 ñ 5'por cento' de vasodilatação (n Í 6), na concentração de 100 mg/mL. Os teores totais de proantocianidinas foram determinados para OS e para as frações bioativas, por espectroscopia no visível...

Perfil fitoquímico e atividade antibacteriana in vitro de plantas invasoras / Phytochemical screenig and in vitro antibacterial activity of weed plants

Foram colocadas espécies de plantas invasoras usadas popularmente como anti-sépticas e no tratamento de doenças de pele e as espécies Hedychium coronarium e Scoparia dulcis que se mostraram ativas em estudo preliminar. Empregando-se os pós das plantas realizou-se a triagem fitoquímica e fez-se a avaliação da atividade antibacteriana in vitro para os extratos aquosos das espécies. Polifenóis, esteróides, saponinas e flavonóides foram os constituintes químicos mais freqüentes, nas espécies analizadas. A atividade antibacteriana foi avaliada empregando-se o método de difusão em ágar e culturas padronizadas de Staphylococus aureus, Micrococus luteus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa e Salmonela typhumurium. Com excessão dos extratos de Hedychium coronarium (folhas e rizomas), os demais extratos da espécies avaliadas apresentaram atividade para um ou mais microorganismos.

Espermatozóides no ducto deferente de ratos tratados com extrato etanólico de Curarea tecunarum / Spermatozoa in deferens duct of rats treated with Curarea tecunarum extract

Curarea tecunarum é uma planta usada por tribos indígenas como contraceptivo. As informaçöes etnobotânicas sugerem que o efeito seja no homem, embora a mulher também tome o chá. Com o objetivo de testar, em ratos, a hipótese de que o extrato etanólico de Curarea tecunarum pudesse interromper a produçäo de espermatozóide, projetou-se este trabalho. Ratos Wistar, adultos, foram tratados por gavage com 100 mg (dose única) e 50 mg (por 5 dias ou por 10 dias consecutivos) de extrato etanólico de C. tecunarum (tratado). Um lote de animais recebeu volume equivalente ao extrato, de água destilada (controle A) e outro lote recebeu do mesmo modo, de álcool 50% (controle B). Os animais foram sacrificados aos 7, 21 e 45 dias após o início do tratamento e, imediatamente após o sacrificio foram colhidas amostras de sêmen (ductos deferentes), que foram examinadas para identificar espermatozóides e verificar a sua motilidade. Os seguintes órgäos foram removidos e pesados: hipófise, vesícula seminal (com glândula de coagulaçäo), próstata ventral e testículo (par). Os animais foram pesados no ínicio do tratamento e na data do sacrifício. Näo se observam alteraçöes com significado biológico no peso dos animais dos diferentes grupos. Os órgäos pesados näo mostraram alteraçöes importantes após o tratamento. Todas as amostras de sêmen continham espermatozóides móveis. Embora sejam necessários estudos para avaliar as condiçöes funcionais do espermatozóide (habilidade para fertilizar e gerar embriöes normais) pode-se concluir que, nas condiçöes experimentais deste trabalho, o extrato etanólico de C. tecunarum näo apresenta efeito tóxico sobre o sistema reprodutor e o peso corporal de ratos e näo lesa, severamente, as células germinativas.

Alteraçäo do desenvolvimento embrionário de ratos após tratamento com extratos aquosos de diferentes orgäos de Petiveria alliacea / Alteration of rat embrionic development after treatment with aqueous extract of different organs of Petiveria alliacea

A pesquisa teve por objetivo verificar, em testes controlados, o efeito abortivo atribuido popularmente à Petiveria alliacea. Ratas grávidas foram tratadas, por via oral, com extratos aquosos da folha (100mg/animal), do caule (200mg) ou da raiz (200mg) de Petiveria alliacea no 3§ ou no 5§ dia após inseminaçäo. O grupo controle recebeu, pela mesma via, volume de água destilada equivalente ao extrato administrado. Os animais foram sacrificados no 14§ dia após inseminaçäo. Contaram-se corpos lúteos, implantes viáveis, reabsorçöes. Observou-se que os extratos da raiz e folha de Petiveria alliacea demonstraram ter efeito anti-implantaçäo, enquanto que o caule parece ter efeito zigotóxico.

Avaliaçäo do potencial contraceptivo de plantas da regiäo amazônica / Evaluation of the contraceptive potencial of plants from the amazon region

Apresentam-se resultados sobre efeito inibidor da fertilidade em ratas, tratadas com plantas usadas por populaçöes da regiäo amazônica. Nos testes inciais com oito plantas, as seguintes revelaram efeito zigotóxico ou de inibiçäo da implantaçäo e desenvolvimento embrionário: Cusparia toxicaria, Petiveria alliacea, Inga edulis e Endopleura uichi

Efeito biológico de extratos das folhas de Petiveria alliacea na gestaçäo de ratas / Biological effect of the Petiveria alliacea leaft extract on rat pregnancy

A Petiveria alliacea L. (Fitolacacea) é considerada como abortiva pela populaçäo nativa e como anticoncepcional pelos índios caritianos de Rondônia. Extratos aquosos demonstraram efeito abortivo em ratas. Neste trabalho estuda-se o efeto interceptivo de diferentes extratos, administrados no 3§ ou no 5§ dia de gestaçäo da rata (espermatozóide no esfregaço vaginal = dia 1 de gestaçäo). Os animais foram injetados com diferentes doses e diferentes extratos e foram sacrificados no 14§ dia de gestaçäo . Os cornos uterinos foram examinados para observaçäo e contagem de implantes viáveis e reabsorçöes. Ovários foram removidos para observaçäo e contagem dos corpos lúteos. Os resultados mostram que o extratos hidroalcoólico (18 mg) de P, illiacea possui efeito zigotóxico e a fraçäo solúvel em água (20 mg) efeito abortivo

Antifertility effects of (3R)-claussequinone in rats

Com o objetivo de verificar-se o efeito zigotóxico da (3R)-claussequinona em ratas, foram administradas 200 micron/100g de peso corporal/via intraperitoneal do composto a animais no 4§ dia de gestaçäo. A (3R)-claussequinona mostrou efeito zigotóxico causando 32,3% de abortos em embriöes implatados

Estudo da atividade antimicrobiana de extrato de folha de Aristolochia gigantea Mart e Zucc / Study of the antimycrobial activity of extracts from the leaves of Aristolochia gigantea Mart and Zucc

Foram investigadas as atividades antibacteriana e antifúngica dos extratos éter de petróleo e alcaloídico de folhas de Aristolochia gigantea Mart e Zucc, pelo método de difusäo em agar. O extrato éter de petróleo mostrou atividade contra uma bactéria Gram-positiva. O extrato alcaloídico apresentou atividade contra duas bactérias Gram-positivas. Uma Gram-negativa, näo apresentando qualquer atividade antifúngica.