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.

Avaliação da atividade antimicobacteriana da lignana diidrocubebina extraída da Piper cubeba e de seus derivados semissintéticos / Evaluation of antimycobacterial activity of dihydrocubebin lignan extracted from Piper cubeba and its semisynthetic derivatives

RESUMO: A atividade antimicobacteriana de diidrocubebina (1), uma lignana dibenzilbutanodioica obtida a partir de extrato etanólico de sementes da Piper cubeba, e seus derivados foram avaliados in vitro contra três diferentes cepas de Mycobacterium utilizando o método de microdiluição. Dentre as lignanas avaliadas 3 e 4 foram as mais ativas, exibindo valores de CIM de 62,5 µg/mL contra M. avium e M. tuberculosis, respectivamente. Os derivados 2-6 obtidos por síntese parcial possuem diferentes substituintes nos carbonos 9 e 9 ', que alteram polaridade, solubilidade e limitam as rotações livres entre C8-C8' em relação de material (1) de partida. As diferenças estruturais entre estes compostos podem fornecer informações importantes sobre a relação estrutura-atividade antimicobacteriana do esqueleto dibenzilbutanodioico, obtido a partir de fonte natural, como um possível alvo para o desenvolvimento de drogas mais potentes contra a tuberculose

ABSTRACT: Evaluation of antimycobacterial activity of dihydrocubebin lignan extracted from Piper cubeba and its semisynthetic derivatives. The antimycobacterial activity of the dihydrocubebin (1), a dibenzylbutanedioiclignan obtained from ethanolic extract of Piper cubeba seeds, and its derivatives were examined in vitro against three different strains of Mycobacterium using amicrodilution method. Among the lignans evaluated, the 3 and 4 samples were the most active ones, displaying MIC values of 62.5 µg/mL against M. avium and M. tuberculosis, respectively. The derivatives 2-6, obtained for partial synthesis, had different substituents in the carbons 9 and 9', fact thatalters the polarity, solubility and restricts the free rotations between the bonds C8-C8' in relation to the starting material (1). The structural differences among these compounds provide important information about the antimycobacterial structure-activity relationship of the dibenzylbutanodioic skeleton, obtained from natural source, such as a possible target for the development of more powerful drugs against tuberculosis

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.

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.

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 evaluation of (-)-O-acetyl, (-)-O-methyl, (-)-O-dimethylethylamine cubebin and their preparation from (-)-cubebin.

The anti-inflammatory and antinociceptive effects of the acetylated (2), methylated (3) and aminated (4) derivatives of cubebin (1), obtained by its reaction with acetic anhydride, methyl iodide and dimethylethylamine chloride, respectively, were investigated, using different animal models. The compound (2) was the most effective anti-inflammatory one in the carrageenin-induced paw edema in rats and was the only one which showed dose-response correlation for this assay with r = 0.993 and Y = 64.58x + 0.22. Besides, compounds (2) and (4) were more effective than cubebin in inhibiting acetic acid-induced writhing in mice, producing dose-response correlation with doses of 10, 20 and 30 mg/kg, respectively. Regarding the hot plate and the cell migration tests in rats, none of the four tested compounds showed activity. Overall, the results showed that the acetylation and amination of cubebin were efficient in enhancing its analgesic activity, as well as its anti-inflammatory 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.