In vitro leishmanicidal, antibacterial and antitumour potential of anhydrocochlioquinone A obtained from the fungus Cochliobolus sp

The bioassay-guided fractionation of the ethyl acetate extract of the fungus Cochliobolus sp. highlighted leishmanicidal activity and allowed for anhydrocochlioquinone A (ANDC-A) isolation. MS, 1D and 2D NMR spectra of this compound were in agreement with those published in the literature. ANDC-A exhibited leishmanicidal activity with EC50value of 22.4 \uc2\ub5g/mL (44 \uce\ubcM) and, when submitted to the microdilution assay against Gram-positive and Gram-negative bacteria, showed a minimal inhibitory concentration against Staphylococcus aureus ATCC 25295 of 128 \uce\ubcg/mL (248.7 \uce\ubcM). It was also active against five human cancer cell lines, showing IC50values from 5.4 to 20.3 \uce\ubcM. ANDC-A demonstrated a differential selectivity for HL-60 (SI 5.5) and THP-1 (SI 4.3) cell lines in comparison with Vero cells and was more selective than cisplatin and doxorubicin against MCF-7 cell line in comparison with human peripheral blood mononuclear cells. ANDC-A was able to eradicate clonogenic tumour cells at concentrations of 20 and 50 \uce\ubcM and induced apoptosis in all tumour cell lines at 20 \uce\ubcM. These results suggest that ANDC-A might be used as a biochemical tool in the study of tumour cells biochemistry as well as an anticancer agent with durable effects on tumours

The outcome of acute schistosomiasis infection in adult mice with postnatal exposure to maternal malnutrition

Maternal malnutrition during the lactation period in early development may have long-term programming effects on adult offspring. We evaluated the combined effects of parasitological behaviour and histopathological features and malnutrition during lactation. Lactating mice and their pups were divided into a control group (fed a normal diet of 23% protein), a protein-restricted group (PR) (fed a diet containing 8% protein) and a caloric-restricted group (CR) (fed according to the PR group intake). At the age of 60 days, the offspring were infected with Schistosoma mansoni cercariae and killed at nine weeks post-infection. Food intake, body and liver masses, leptinaemia, corticosteronaemia, collagen morphometry and neogenesis and the cellular composition of liver granulomas were studied. PR offspring showed reduced weight gain and hypophagia, whereas CR offspring became overweight and developed hyperphagia. The pre-patent period was longer (45 days) in both programmed offspring as compared to controls (40 days). The PR-infected group had higher faecal and intestinal egg output and increased liver damage. The CR-infected group showed a lower number of liver granulomas, increased collagen neogenesis and a higher frequency of binucleate hepatocytes, suggesting a better modulation of the inflammatory response and increased liver regeneration. Taken together, our findings suggest that neonatal malnutrition of offspring during lactation affects the outcome of schistosomiasis in mice

Effect of myriadenolide isolated fromAlomia myriadenia (Asteraceae) on Ehrlich tumor in its ascitic form

Submitted by Nuzia Santos ([email protected]) on 2013-06-05T17:08:24Z No. of bitstreams: 1 57.pdf: 236363 bytes, checksum: c234abd6e9be5ccf631c4d44f32e0929 (MD5)Made available in DSpace on 2013-06-05T17:08:24Z (GMT). No. of bitstreams: 1 57.pdf: 236363 bytes, checksum: c234abd6e9be5ccf631c4d44f32e0929 (MD5) Previous issue date: 2006FAPEMIG/CNPqUniversidade Federal de Minas Gerais. Escola de Veterinária. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou.Laboratório de Biomarcadores de Diagnóstico e Monitoração. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Escola de Veterinária. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Belo Horizonte, MG, BrasilUniversidade Federal de Minas Gerais. Escola de Veterinária Belo Horizonte, MG, BrasilEstudou-se atividade antineoplásica de um produto natural isolado de Alomia myriadenia (miriadenolídeo) no modelo do tumor de Ehrlich em camundongos. Dezoito fêmeas de camundongo Swiss foram inoculadas com 2x107 células viáveis de tumor de Ehrlich via intraperitoneal (0,3ml) e posteriormente distribuídas aleatoriamente em três grupos que receberam: grupo I (controle) - 0,3ml de solução de Hanks; grupo II - 31µg/kg de miriadenolídeo; e grupo III - 139µg/kg de miriadenolídeo. No oitavo dia de experimento, foram realizados exames hematológicos e perfil protéico sérico eletroforético. Coletou-se todo o líquido ascítico para avaliação do volume, aparência, pH, contagem de células viáveis e inviáveis, realização de esfregaços para contagem de células claras e escuras, leucócitos e avaliação das regiões organizadoras de nucléolos argentafins (AgNORs). Foram realizados exames macro e microscópicos do baço, fígado e rins e aspirado o conteúdo da medula óssea dos fêmures direito e esquerdo de cada animal para avaliação da relação mielóide:eritróide. Não houve diferença significativa no volume, pH, contagem de células viáveis e inviáveis entre os três grupos estudados, observando-se valores de 17,6 x 104 células tumorais viáveis no grupo III, 27,7 x 104 no grupo II e 21,1 x 104 no grupo I. As AgNORs apresentaram-se pequenas, com distribuição difusa e incontáveis no grupo I, e em menor quantidade no grupo III. Os animais do grupo III apresentaram a menor concentração protéica total sérica (4,7g/dl) (P<0,05) quando comparados com os do grupo II (5,3g/dl) e do grupo I (5,1g/dl). Os valores de albumina foram semelhantes nos três grupos (2,6g/dl), e as globulinas totais foram maiores (P<0,05) no grupo II (2,71g/dl) quando comparadas com os valores médios do grupo III (2,11g/dl) e semelhantes ao grupo I (2,43g/dl). Não houve diferença entre alfa e beta globulinas entre os três grupos estudados, porém as gamaglobulinas foram maiores (P<0,05) no grupo II (1,72g/dl) quando comparadas com as do grupo III (1,13g/dl). Com relação ao eritrograma e leucograma, não houve diferença significativa entre os grupos tratados. A relação mielóide:eritróide foi maior (P<0,05) no grupo III (1,40) quando comparada com a relação nos grupos I (0,92) e II (0,61). A contagem de reticulócitos também foi maior (P<0,05) (11,2) no grupo III, quando comparada com as dos grupos I (4,3) e II (3,6). Em todos os grupos, observou-se degeneração hepática.Antitumoral activity of a natural product of Alomia myriadenia (myriadenolide) in Ehrlich tumor in mice was studied. Eighteen Swiss female mice were intra-peritoneal inoculated 2x107 viable cells of Ehrlich Tumor (0.3ml) and randomly distributed in three groups receiving via intra-peritoneal on the 3rd and 5th day post-inoculation the following treatments: group I (control) – 0.3ml Hanks solution; group II: 31µg/kg myriadenolide; and group III: 139µg/kg myriadenolide. On the eighth day of the experiment blood profile and protein serum electrophoresis were performed. All ascitic liquid was collected to evaluate the volume and pH; to observe the aspect; to count viable and no viable cells, dark and clear cells, leukocytes and nucleolar organizer regions (NORs). Macro and microscopic exams were performed and bone marrow was aspirated from right and left femurs of each animal to evaluate myeloid:erythroid ratio. It was not observed difference in volume, pH, counts viable and no viable cells in the groups, although group III showed smaller number of viable tumoral cells (17.6 x 104) when compared to the group II (27.7 x 104) and group I (21.1 x 104). The investigation of NORs to evaluate the proliferative capacity of tumoral cells after myriadenolide treatment showed that cells were smaller, uncountable and with diffuse distribution in group I. They were in lower quantity in group III. These results suggest that myriadenolide in dose 139µg/kg (group III) delay the tumoral growing and, probably, cell proliferation. The animals of group III showed lower value of total protein (4.7g/dl) (P<0.05) when compared to animals from group II (5.3g/dl) and group I (5.1g/dl). The values of albumin were similar in all groups (2.6g/dl) and total globulin was higher (P<0.05) in group II (2.71g/dl) when compared to mean values of group III (2.11g/dl) and similar to group I (2.43g/dl). The decrease of total protein in group III occurred by globulin reduction. There was no difference in alpha and beta globulin in the three studied groups, although the immunoglobulins were higher (P<0.05) in group II (1.72g/dl) when compared to group III (1.13g/dl). These results suggest the viable number of tumoral cells in group II could cause the increase response of IgM reflecting on the final value of immunoglobulins. In relation to erythrogram and leukogram there was no statistical difference. The myeloid:erythroid ratio was higher (P<0.05) in group III (1.40) when compared to groups I (0.92) and II (0.61). Reticulocytes count were higher (P<0.05) (11.2) in group III, when compared to groups I (4.3) and II (3.6). In all groups, hepatic degeneration was observed

Screening and Fractionation of Plant Extracts with Antiproliferative Activity on Human Peripheral Blood Mononuclear Cells

Three hundred and thirteen extracts from 136 Brazilian plant species belonging to 36 families were tested for their suppressive activity on phytohemaglutinin (PHA) stimulated proliferation of human peripheral blood mononuclear cells (PBMC). The proliferation was evaluated by the amount of [3H]-thymidine incorporated by the cells. Twenty extracts inhibited or strongly reduced the proliferation in a dose-dependent manner at doses between 10 and 100 µg/ml. Three of these extracts appeared to be non-toxic to lymphocytes, according to the trypan blue permeability assay and visual inspection using optical microscopy. Bioassay-guided fractionation of Alomia myriadenia   extract showed that myriadenolide, a labdane diterpene known to occur in this species, could account for the observed activity of the crude extract. Using a similar protocol, an active fraction of the extract from Gaylussacia brasiliensis   was obtained. Analysis of the 1H and 13C NMR spectra of this fraction indicates the presence of an acetylated triterpene whose characterization is underway. The extract of Himatanthus obovatus   is currently under investigation

New cassane diterpenes from caesalpinia echinata

Submitted by Nuzia Santos ([email protected]) on 2014-10-20T14:40:53Z No. of bitstreams: 1 New cassane diterpenes from Caesalpinia echinata.pdf: 322346 bytes, checksum: 005703ead6a099cb8967af34862ebd55 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2014-10-20T14:44:28Z (GMT) No. of bitstreams: 1 New cassane diterpenes from Caesalpinia echinata.pdf: 322346 bytes, checksum: 005703ead6a099cb8967af34862ebd55 (MD5)Made available in DSpace on 2014-10-20T14:44:28Z (GMT). No. of bitstreams: 1 New cassane diterpenes from Caesalpinia echinata.pdf: 322346 bytes, checksum: 005703ead6a099cb8967af34862ebd55 (MD5) Previous issue date: 2011Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Química de Produtos Naturais. Belo Horizonte, MG, BrazilUniversidade Estadual do Sudoeste de Bahia. Jequié, BA, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Química de Produtos Naturais. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Pesquisas Clínicas. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Química de Produtos Naturais. Belo Horizonte, MG, BrazilAn investigation of the ethanolic extract from stems of Caesalpinia echinata Lam Leguminosae-Caesalpinioideae) led to the isolation of five new cassane diterpenes along with known lambertianic acid. Their structures were determined based on spectroscopic methods. A preliminary study on leishmanicidal activity demonstrated that compounds 1, 2 and 6 were found to inhibit the growth of amastigote-like forms of Leishmania amazonensis without affecting mononuclear cells obtained from human peripheral blood

Cytotoxicity and bacterial membrane destabilization induced by Annona squamosa L. extracts

<div><p>ABSTRACT This study aimed to further investigate the cytotoxicity against tumor cell lines and several bacterial strains of Annona squamosa and its mode of action. Methanol extracts of A. squamosa leaves (ASL) and seeds (ASS) were used. ASL showed significant antibacterial activity against S. aureus, K. pneumoniae and E. faecalis with MIC values of 78, 78 and 39 µg/mL respectively. Moreover, ASL exhibited significant biofilm disruption, rapid time dependent kinetics of bacterial killing, increased membrane permeability and significantly reduced the cell numbers and viability. Regarding the cytotoxicity against tumor cell lines, ASS was more active against Jurkat and MCF-7 cells, with CI50 1.1 and 2.1 µg/mL, respectively. ASL showed promising activity against Jurkat and HL60, with CI50 4.2 and 6.4 µg/mL, respectively. Both extracts showed lower activity against VERO cells and reduced the clonogenic survival at higher concentrations (IC90) to MCF-7 and HCT-116 lineages. The alkaloids anonaine, asimilobine, corypalmine, liriodenine nornuciferine and reticuline were identified in extracts by UPLC-ESI-MS/MS analysis. This study reinforced that A. squamosa presents a remarkable phytomedicinal potential and revealed that its antimicrobial mechanism of action is related to bacterial membrane destabilization.</p></div