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.

Antibacterial and anti-inflammatory activities of an extract, fractions, and compounds isolated from Gochnatia pulchra aerial parts.

This paper reports on the in vitro antibacterial and in vivo anti-inflammatory properties of a hydroethanolic extract of the aerial parts of Gochnatia pulchra (HEGP). It also describes the antibacterial activity of HEGP fractions and of the isolated compounds genkwanin, scutellarin, apigenin, and 3,5-O-dicaffeoylquinic acid, as evaluated by a broth microdilution method. While HEGP and its fractions did not provide promising results, the isolated compounds exhibited pronounced antibacterial activity. The most sensitive microorganism was Streptococcus pyogenes, with minimum inhibitory concentration (MIC) values of 100, 50 and 25 µg/mL for genkwanin and the flavonoids apigenin and scutellarin, respectively. Genkwanin produced an MIC value of 25 µg/mL against Enterococcus faecalis. A paw edema model in rats and a pleurisy inflammation model in mice aided investigation of the anti-inflammatory effects of HEGP. This study also evaluated the ability of HEGP to modulate carrageenan-induced interleukin-1 beta (IL-1ß), tumor necrosis factor alpha (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) production. Orally administered HEGP (250 and 500 mg/kg) inhibited carrageenan-induced paw edema. Regarding carrageenan-induced pleurisy, HEGP at 50, 100, and 250 mg/kg diminished leukocyte migration by 71.43%, 69.24%, and 73.34% (P<0.05), respectively. HEGP suppressed IL-1ß and MCP-1 production by 55% and 50% at 50 mg/kg (P<0.05) and 60% and 25% at 100 mg/kg (P<0.05), respectively. HEGP abated TNF-α production by macrophages by 6.6%, 33.3%, and 53.3% at 100, 250, and 500 mg/kg (P<0.05), respectively. HEGP probably exerts anti-inflammatory effects by inhibiting production of the pro-inflammatory cytokines TNF-α, IL-1ß, and MCP-1.

Enantiomeric HPLC resolution and absolute stereochemistry assignment of a new poligamain derivative.

A new aryltetralin lignan derivative, 1, was obtained by reacting dimethyl succinate and piperonal, furnishing the lactone 4-(3',4'-methylenedioxybenzyl)-4,5-dihydro-2(3H)-furanone, which was reacted once again with piperonal and LDA to give the dibenzylbutirolactone 7-hydroxyhinokinin. The cyclization of 7-hydroxyhinokinin into polygamain occurred in the presence of trifluoroacetic acid. The reduction of the furanic ring of polygamain was done by its reaction with DIBAL in THF, furnishing the diol functionalized lignin derivative 1 as single diastereomer. The enantiomeric fractions of 1 were obtained by preparative enantioselective HPLC. The absolute stereochemistry was assigned by electronic circular dichroism (ECD) and nuclear magnetic resonance (NMR) spectroscopy. An all-trans relative configuration was determined by NMR on the bases of ¹H coupling constants and nuclear Overhauser effect (n.O.e.) experiments. The absolute configuration at C1 was assigned on the basis of the ECD sign at 296 nm by comparison to the ECD spectra of structural analogues with defined stereochemistry. The assignment of the absolute configuration was confirmed by applying the exciton chirality method to the well-defined ECD couplets at 285 and 200 nm allied to the two electronic transitions L(b) and B(b) of the aromatic moieties, respectively. Rac-1 and its enantiomeric isomers were evaluated against important bacteria responsible for dental caries. The best results obtained for the (1R,2S,3S) isomer were against Streptococcus mutans (250 µM), Streptococcus salivarius (250 µM), Streptococcus sobrinus (280 µM) and Streptococcus mitis (280 µM). The (1S,2R,3R) isomer was active only against Streptococcus sanguinis (280 µM). The enantiomeric mixture was less active than the (1R,2S,3S) isomer.

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.

Antimicrobial activity of selected essential oils against cariogenic bacteria.

The antibacterial activity of nine selected essential oils (EOs) against a panel of oral pathogens was investigated in terms of their minimum inhibitory concentrations (MICs) by using the broth microdilution method. Most of the EOs displayed weak activity or were inactive against the selected oral pathogens, with MIC values ranging from 500 to 4000 µg/mL. However, the EO obtained from the leaves of Bidens sulphurea (Asteraceae) was found to display moderate activity against Streptococcus mutans (MIC = 250 µg/mL) and significant activity against Streptococcus mitis (MIC = 31.25 µg/mL). Germacrene D (38.3%), trans-caryophyllene (18.0%), ß-elemene (13.9%) and bicyclogermacrene (13.1%) were identified as the main chemical components of this oil. 2,6-Di-tert-butyl-4-methylphenol, previously described as the major constituent in the EO from the flowers of B. sulphurea, was not detected in this study.

Chemical Analysis and Study of Phenolics, Antioxidant Activity, and Antibacterial Effect of the Wood and Bark of Maclura tinctoria (L.) D. Don ex Steud.

Maclura tinctoria (L.) D. Don ex Steud. has one of the highest qualities among the coefficients for Brazilian woods (up to 9.6) and resistance rates equivalent to Indian teak (Tectona grandis). In this study, the macromolecular constituents and total phenols compounds as well as the antioxidant and antibacterial activities of this wood were evaluated. Total phenols and proanthocyanidin levels were higher in wood when compared with bark levels. The antioxidant activity of wood extracts (IC(50) = 18.7 µg/mL) was more effective than that of bark extracts (IC(50) = 20.9 µg/mL). Wood and bark extracts revealed a high potential for inhibition of aerobic and anaerobic bacteria. The bark extracts were the most active (MIC from 20 to 60 µg/mL). Both antioxidant activity and high potential for bacteria inhibition turn these extracts promising for drug formulations, especially as antibacterial agent.

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.

The effect of the dibenzylbutyrolactolic lignan (-)-cubebin on doxorubicin mutagenicity and recombinogenicity in wing somatic cells of Drosophila melanogaster.

The dibenzylbutyrolactolic lignan (-)-cubebin was isolated from dry seeds of Piper cubeba L. (Piperaceae). (-)-Cubebin possesses anti-inflammatory, analgesic and antimicrobial activities. Doxorubicin (DXR) is a topoisomerase-interactive agent that may induce single- and double-strand breaks, intercalate into the DNA and generate oxygen free radicals. Here, we examine the mutagenicity and recombinogenicity of different concentrations of (-)-cubebin alone or in combination with DXR using standard (ST) and high bioactivation (HB) crosses of the wing Somatic Mutation And Recombination Test in Drosophila melanogaster. The results from both crosses were rather similar. (-)-Cubebin alone did not induce mutation or recombination. At lower concentrations, (-)-cubebin statistically reduced the frequencies of DXR-induced mutant spots. At higher concentrations, however, (-)-cubebin was found to potentiate the effects of DXR, leading to either an increase in the production of mutant spots or a reduction, due to toxicity. These results suggest that depending on the concentration, (-)-cubebin may interact with the enzymatic system that catalyzes the metabolic detoxification of DXR, inhibiting the activity of mitochondrial complex I and thereby scavenging free radicals. Recombination was found to be the major effect of the treatments with DXR alone. The combined treatments reduced DXR mutagenicity but did not affect DXR recombinogenicity.

Antibacterial activity of 15-deoxygoyazensolide isolated from the stems of Minasia alpestris (Asteraceae) against oral pathogens.

This work reports the isolation of the sesquiterpene lactone 15-deoxygoyazensolide from the stems of Minasia alpestris and the evaluation of its antimicrobial activity against the following oral pathogens: Enterococcus faecalis, Streptococcus salivarius, Streptococcus sobrinus, Streptococcus mutans, Streptococcus mitis, Streptococcus sanguinis, and Lactobacillus casei. Despite the cytotoxicity and genotoxicity of other sesquiterpene lactones of the furanoheliangolide-type, our results revealed that this compound exhibits low antibacterial activity against the evaluated oral pathogens; however, an interesting selectivity against E. faecalis (minimum inhibitory concentration [MIC]=40 µg mL(-1)) and S. sobrinus (MIC=60 µg mL(-1)) was observed.

Estudo fitoquímico preliminar e bioensaio toxicológico frente a larvas de Artemia salina Leach. de extrato obtido de frutos de Solanum lycocarpum A. St.-Hill (Solanaceae) / Phytochemical screening and toxicological bioassay with brine shrimp larvae (Artemia salina Leach) of an extract obtained from fruits of Solanum lycocarpum A. St-Hill

Neste trabalho, avaliou-se o perfil fitoquímico e a toxicidade preliminar frente a larvas de Artemia salina do extrato etanólico de frutos de Solanum lycocarpum. O extrato foi submetido à análise fitoquímica preliminar para identificação das principais classes de metabolitos secundários presentes e testado frente a larvas de A. salina para obtenção das concentrações letais médias (CL50%). Os testes fitoquímicos demonstraram a presença de fenóis, taninos, saponinas, alcalóides e esteroides livres. O extrato foi fracionado em diferentes solventes para a avaliação da toxicidade frente à A. salina, apresentando considerável citotoxicidade na fração hidroalcoólica (CL50% = 285,546 µg/mL).

The phytochemical profile of ethanolic extract of Solanum lycocarpum fruits was analyzed and preliminary toxicity tests were performed against brine shrimp larvae. The extract was subjected to preliminary phytochemical analysis to identify the main classes of secondary metabolites and tested against the larvae of A. salina to obtain the median lethal concentrations (LC50%). The phytochemical tests showed the presence of phenols, tannins, saponins, alkaloids and free steroids. The extract was fractionated with various solvents for toxicity testing against the larvae and the hydroalcoholic fraction showed considerable cytotoxicity (CL50% = 285.546 µg/mL).

In vitro antileishmanial, antiplasmodial and cytotoxic activities of phenolics and triterpenoids from Baccharis dracunculifolia D. C. (Asteraceae).

Baccharis dracunculifolia (Asteraceae), the most important plant source of the Brazilian green propolis (GPE), displayed in vitro activity against Leishmania donovani, with an IC(50) value of 45 microg/mL, while GPE presented an IC(50) value of 49 microg/mL. Among the isolated compounds of B. dracunculifolia, ursolic acid, and hautriwaic acid lactone showed IC(50) values of 3.7 microg/mL and 7.0 microg/mL, respectively. Uvaol, acacetin, and ermanin displayed moderate antileishmanial activity. Regarding the antiplasmodial assay against Plasmodium falciparum, BdE and GPE gave similar IC(50) values (about 20 microg/mL), while Hautriwaic acid lactone led to an IC(50) value of 0.8 microg/mL (D6 clone).

Hypoglicemic effect of Leandra lacunosa in normal and alloxan-induced diabetic rats.

Leandra lacunosa, popularly known as "erva-do-jabuti", is used in Brazilian folkloric medicine for the treatment of diabetes mellitus. Based on this traditional indication, the aim of this work was to evaluate the hypoglycemic activity of the hydroalcoholic extract of L. lacunosa aerial parts (LLH) in normal and alloxan-induced diabetic rats. Chromatographic fractionation of LLH was also carried out by several techniques, affording isolation of the following major compounds: ursolic acid (1), kaempferol (2), luteolin (3), and quercetin (4). The oral administration of LLH (500 mg/kg) in normal rats caused a significant reduction of 24.7% (P<0.05) in the blood glucose levels after 2 h of treatment, while the administration of chlorpropamide (20 mg/kg, p.o.) led to a reduction of 40.2% (P<0.01). After oral administration of glucose (10 g/kg, p.o.), LLH (500 mg/kg, p.o.) significantly inhibited the increase in blood glucose levels compared with the negative control group. The oral treatment with LLH (500 mg/kg) in alloxan-induced diabetic rats significantly reduced the blood glucose levels in 47.8% after 4 h of treatment, while chlorpropamide resulted in a significant reduction of 71.7% in the 4th hour. Our results showed that LLH, displays hypoglycemic activity, which may be related to the effect of the major compounds identified in the crude extract. This study seems to provide biological evidence for the folkloric use of L. lacunosa in the treatment of diabetes mellitus.

Evaluation of piper cubeba extract, (-)-cubebin and its semi-synthetic derivatives against oral pathogens.

The activities of the crude ethanol extract from Piper cubeba seeds, (-)-cubebin and its semi-synthetic derivatives were evaluated against oral pathogens. The crude ethanol extract was more active against Streptococcus salivarius (MIC value of 80 microg/mL). (-)-Cubebin displayed MIC values ranging from 0.20 mm for Streptococcus mitis to 0.35 mm for Enterococcus faecalis. The natural product (-)-cubebin and its semi-synthetic derivative (-)-hinokinin displayed bacteriostatic activity at all evaluated concentrations, as well as fungicidal activity against Candida albicans at 0.28 mm. The O-benzyl cubebin derivative showed fungistatic and fungicidal effects against C. albicans at 0.28 mm and 0.35 mm, respectively. Also, the other dibenzylbutyrolactone derivatives [(-)-6,6'-dinitrohinokinin and (-)-O-(N,N-dimethylaminoethyl)-cubebin] displayed bacteriostatic and fungistatic effects at the evaluated concentrations. Moreover, the semi-synthetic derivative (-)-6,6'-dinitrohinokinin was the most active compound against all the evaluated microorganisms. Therefore, it may be suggested that the presence of the carbonyl group at C-9 plus the introduction of polar groups in the aromatic rings improve the antimicrobial activity of dibenzylbutyrolactone compounds.

Comportamento térmico de alguns fármacos e medicamentos / Thermal studies of some pharmaceutical drugs

A técnica de análise térmica apresenta aplicações em diversos ramos da ciência, entre eles a indústria farmacêutica, a qual pode utilizá-la para caracterização e estudo das matérias primas e produtos finais. Os compostos farmacêuticos apresentam diferentes formas morfológicas ou estruturais,que afetam diretamente na sua estabilidade, ação e liberação. O desenvolvimento e fabricação de medicamentos requerem intenso cuidado devido a pureza, qualidade e estabilidade dos componentes. Um dos itens para se obter uma formulação estável e efetiva depende dos cuidados na escolha dos excipientes utilizados, onde uma de suas propriedades é a de interferir na biodisponibilidade e proteção do fármaco frente a degradação. Neste trabalho foram utilizadas técnicas de análise térmica (TG/DTG/DSC/DTA) e a espectroscopia Raman para estudar possíveis interações entre o fármaco e seus excipientes. Foram selecionados para o estudo os medicamentos Aspirina® e AAS®, comparados com o seu princípio ativo ácido acetil salicílico. As amostras não sofreram pré tratamento e foram analisadas como adquiridas no mercado. Os resultados obtidos através das técnicas de análise térmica evidenciaram uma possível interação entre os diferentes excipientes utilizados e o princípio ativo. Os espectros Raman corroboram com os resultados obtidos das análises térmicas dos medicamentos. Através dos resultados obtidos concluímos que as diferentes composições existentes na formulação dos medicamentos podem promover mudanças em suas propriedades físicas e consequentemente na sua atividade biológica.

Analgesic and anti-inflammatory activity of a crude root extract of Pfaffia glomerata (Spreng) Pedersen.

The anti-inflammatory and antinociceptive effects of the crude hydroalcoholic extract (PE) of Pfaffia glomerata roots was assessed in the carrageenan-induced rat paw edema at the doses of 100, 200 and 300 mg/kg, using different animal models. An anti-inflammatory dose effect response correlation of r=0.997 and Y=11.67x+0.02 was found. At the same doses, the extract-inhibited acetic acid-induced writhing in mice, but no dose response correlation was found. Oral administration of 100 mg/kg of PE and 0.5 mg/kg of dexamethazone inhibited by 29 and 61%, the granulomatous tissue formation (p>0.05), respectively. These results indicate the potential of this plant extract to treat chronic inflammation. At the assayed doses no significant activity was found in the hot plate test, as well as in the cell migration-induced by carrageenan.

Analgesic and anti-inflammatory activities of (-)-o benzyl cubebin, a (-)-cubebin derivative, obtained by partial synthesis.

The anti-inflammatory and antinociceptive effects of the benzylated cubebin derivative, obtained by reaction of (-)-cubebin with benzyl bromide, were investigated using different animal models. The (-)-o-benzyl cubebin showed a low anti-inflammatory effect (16.2%) in relation to cubebin (57%) and indomethacin (77%) in the carrageenin-induced paw edema in rats, but on the other hand it was more effective (80%) than (-)-cubebin (41%) in inhibiting acetic acid-induced writhing in mice, producing dose-response correlation with doses of 10, 20 and 40 mg/kg, respectively. Moreover, this derivative compound did not show activity in both the hot plate and the cell migration test in rats. Overall, the results showed that the benzylation of cubebin were efficient in enhancing only its analgesic activity.

Evaluation of the trypanocidal and leishmanicidal in vitro activity of the crude hydroalcoholic extract of Pfaffia glomerata (Amarathanceae) roots.

Three different concentrations (1, 10 and 50 microg/ml) of lyophilized hydroalcoholic crude extract of Pfaffia glomerata roots were assayed in vitro against strains of Trypanosoma cruzi (Y) and Leishmania braziliensis. It was observed that P. glomerata hydroalcoholic extract was relatively active within the tested concentrations for L. (V) braziliensis, but inactive against T. cruzi. Despite the fact that both protozoans belong to the Trypanosomatidae family, we suggest that the difference observed for activity should be related to the biological differences between the two parasite species.

Evaluation of the analgesic activity of extracts of Miconia rubiginosa (Melastomataceae).

The analgesic effects of the hexane, methylene chloride and ethanol extracts of Miconia rubiginosa were evaluated in mice and rats using the acetic acid-induced writhing and hot plate tests. The extracts (100, 200 and 300 mg/kg body wt.) and indomethacin (5 mg/kg body wt.) produced a significant (p < 0.05 and p < 0.01) inhibition of acetic acid-induced abdominal writhing. These same extracts (200 mg/kg body wt.) showed a significant (p < 0.05) antinociceptive effect, lower than that produced by morphine (4 mg/kg body wt.). The fractionation of the methylene chloride extract yielded ursolic and oleanoic acids as the major compounds. Using only gas chromatography, it was possible to identify the following triterpenes in the hexane extract: alpha-amyrin, beta-amyrin, lupeol and beta-sitosterol.

Analgesic effects of crude extracts of Miconia albicans (Melastomataceae).

The present study describes the analgesic effects of the crude extracts (hexane, methylene chloride and ethanol) obtained from the aerial parts of Miconia albicans (Melastomataceae) using the writhing test and the hot plate models for pain in mice. The extracts in hexane and methylene chloride, given orally, produced significant antinociception in the writhing test. On the other hand, none of the extracts had a significant effect on the hot plate test, a fact suggesting that the substances present in the extracts may rather have peripheral analgesic activity.

Evaluation of the analgesic activity of an ethanol extract of Miconia fallax.

A significant analgesic effect was observed after oral administration of an ethanol extract of Miconia fallax to mice, evaluated using chemical (writhing test) and thermal (hot plate test) stimuli. The extract showed a significant effect compared to control in both algesimetric models, suggesting that it was efficient in increasing the pain threshold.