Avaliação farmacológica do produto fitoterápico - CPV (extrato seco de Crataegus oxyacantha L., Passiflora incarnata L. e Valeriana officinalis L.) em animais de laboratório

The aim of the present study was to evaluate the central effects of the phytotherapeutic product-CPV (dry extract of Crataegus oxyacantha, Passiflora incarnata and Valeriana officinalis) in animals models. In order to investigate the psychopharmacological profile of CPV extract, an evaluation toward anxiolytic effect of this extract on the elevated plus-maze (EPM) was carried out. Other effects such as neuroleptic (blockade of the stereotyped behavior induced by apomorphine), analgesic (hot plate; acetic acid writhing and tail-flick tests) and on the memory (passive avoidance test) were also analyzed. CPV extract (430 and 860 mg/ kg) presented an anxiolytic effect on rats (increased the number of entries into the open arms in the EPM) and, furthermore, a tendency of slight amnesic effect for the doses (430 and 860 mg/kg), but less intense when compared to diazepam (1.5 mg/kg). The extract did not show neuroleptic or analgesic effects.O presente estudo teve por objetivo avaliar em modelos animais, os possíveis efeitos do produto fitoterápico CPV (extrato seco de Crataegus oxyacantha, Passiflora incarnata e Valeriana officinalis) quanto à sua ação ansiolítica avaliada no modelo do labirinto em cruz elevado (LCE). Outros efeitos como neuroléptico (bloqueio da estereotipia por apomorfina), analgésico (testes: placa quente; retirada da cauda e contorções abdominais), bem como sobre a memória (esquiva passiva) também foram considerados. O extrato CPV (430 e 860 mg/kg) apresentou um efeito ansiolítico (aumento do número de entradas nos braços abertos do LCE) em ratos e uma tendência de efeito amnésico para ambas as doses (430 e 860 mg/kg), embora menos intenso quando comparado com o diazepam (1,5 mg/kg). O extrato não apresentou efeitos neuroléptico ou analgésico.Universidade Federal de São Paulo (UNIFESP) Departamento de PsicobiologiaUNIFESP, Depto. de PsicobiologiaSciEL

Flavonóides glicosídeos encontrados no extrato hidroalcoólico de Tilia cordata, espécie usada como ansiolítico

Tilia species, among which is Tilia cordata Mill. (Tiliaceae), have been used in folk medicine as anxiolytic. The hydroethanolic extract was analyzed by using liquid chromatography with mass spectrometry HPLC-DAD-ESI-MS/MS in negative ion mode, and its chemical composition was compared to flavonoids reported as anxiolytics. The major flavonoids found were: quercetin-3,7-di-O-rhamnoside, kaempferol-3,7-di-O-rhamnoside and kaempferol 3-O-(6-p-coumaroyl glucoside) or tiliroside. The anxiolytic activity of the genus Tilia has been attributed to the presence of quercetin and kaempferol derivatives, while the anxiolytic activity of T. americana var. Mexicana was attributed to tiliroside, which was also found among the major constituents of this species.As espécies de Tilia, entre elas, a Tilia cordata Mill. (Tiliaceae) são utilizadas como ansiolíticas na medicina popular. O extrato hidroalcoólico foi analisado usando cromatografia líquida acoplada à espectrometria de massas HPLC-DAD-ESI/MS/MS no modo negativo e a sua composição química foi comparada com os flavonóides já reportados como ansiolíticos. Os principais flavonóides encontrados foram: quercetina-3,7-di-O-rhamnosideo, canferol-3,7-di-O-rhamnosideo, e canferol 3-O-(6-p-cumaroil glucosideo) ou tilirosideo. A atividade ansiolítica do gênero Tília tem sido atribuída à presença de derivados de canferol e quercetina, enquanto que a atividade ansiolítica da T. americana var. Mexicana foi atribuída ao tilirosideo, o qual também foi encontrado entre os principais constituintes desta espécie.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Federal University of São Paulo Department of PsychobiologyUNIFESP, Department of PsychobiologySciEL

Tratamento da dependência de drogas com plantas medicinais brasileiras

The topic Herbal Medicines in the Treatment of Addictions in a country must be preceded by answers to four questions: 1. Does the country in question possess a biodiversity rich enough to allow the discovery of useful medicines? 2. Do local people have tradition and culture to look for and use resources from Nature to alleviate and cure diseases, including drug dependence? 3. Is drug dependence (or addiction) present in the country in question? 4. Do people of that country recognize and diagnose such problem as a serious one? Alcohol is, by far, the most serious health problem when drug abuse is considered, reaching all of Brazilian society, including the Indians. On the contrary, other drugs may be considered as minor problems and they are not the main focus of this manuscript. The people living in Brazilian hinterland don t have access to public health systems. Consequently, these people seek assistance from curandeiros and raizeiros; the Indians are assisted by the shaman. These folk doctors do not know the academic medicine and therapeutics, and resort to the local plants to treat different ailments of their patients. Furthermore, alcohol abuse and dependence are not recognized by them, according to the rules and criteria of academic medicine. We have conducted a survey in many Brazilian books, Thesis concerning phytotherapy, and several databank. The results of such searches were very disappointing. No published papers from Brazilian authors concerning the use of plants for the treatment of addictions were found in the databases and there were only three very short notes in the masterly book written by Shultes and Raffauf (1990). From the Brazilian books on folk medicine employing medicinal plants, ten mentions were disclosed: most of them dealing with treatment of alcohol problems and two to counteract Ayahuasca dependence.O tema Plantas medicinais no tratamento de dependência em um país deve ser precedido pela resposta a quatro questões: 1. O país em questão possui biodiversidade suficiente para permitir a descoberta de remédios naturais úteis? 2. Seus habitantes possuem tradição e cultura de procurar e utilizar recursos da natureza para aliviar e curar doenças, incluindo dependência de drogas? 3. O problema de dependência de drogas está presente no país em questão? 4. Seus habitantes reconhecem e diagnosticam a dependência de drogas como um sério problema? O álcool é, de longe, o mais sério problema de saúde quando o assunto abuso de drogas é considerado, atingindo toda a sociedade brasileira, incluindo os índios. Ao contrário, outras drogas podem ser consideradas como problemas menores e não são o foco principal deste artigo. As pessoas vivendo nas terras brasileiras mais isoladas não têm acesso ao sistema público de saúde. Conseqüentemente, estas pessoas procuram tratamento com curandeiros e raizeiros; ou, no caso dos indígenas, com os shamans. Estes doutores populares não conhecem a medicina e terapêutica acadêmicas e recorrem a plantas locais para tratar as diferentes patologias que acometem seus pacientes. Entretanto, o abuso e dependência de álcool não são vistos por eles como problemas de saúde segundo as regras e critérios da medicina acadêmica. Um levantamento foi feito em diversos livros brasileiros, teses sobre fitoterapia e alguns bancos de dados. Os resultados de tal pesquisa foram frustrantes. Não foram encontrados artigos de autores brasileiros sobre o uso de plantas para o tratamento de dependência de drogas nos bancos de dados consultados e apenas três notas muito curtas em um livro clássico escrito por Shultes e Raffauf (1990). Dos livros brasileiros sobre o uso popular de plantas medicinais, foram obtidas dez menções: a maioria delas sobre o tratamento de problemas relatados ao álcool e duas delas a respeito do tratamento da dependência de Ayahuasca.Universidade Federal de São Paulo (UNIFESP) Departamento de Psicobiologia Centro Brasileiro de Informações sobre Drogas PsicotrópicasUNIFESP, Depto. de Psicobiologia Centro Brasileiro de Informações sobre Drogas PsicotrópicasSciEL

Alternativní zemědělství - informační bulletin č.10

Témata informačního bulletinu č.10 jsou: Ovocnářský ekologický podnik pana Jiřího Kargra, Ekologické ovocnářství, dojmy ze Švýcarska, úvahy o našich možnostech, Hrách v ekologickém zemědělství, Pěstování sladovnického ječmene pro výrobu biopiva, Vyvýšený záhon, Biozahrádka, Biologická ochrana ovocných stromů v sadech, Horské ekologické hospodářství Marianne a Paula Waldera

The promoters of human cell cycle genes integrate signals from two tumor suppressive pathways during cellular transformation

Deciphering regulatory events that drive malignant transformation represents a major challenge for systems biology. Here we analyzed genome-wide transcription profiling of an in-vitro transformation process. We focused on a cluster of genes whose expression levels increased as a function of p53 and p16INK4A tumor suppressors inactivation. This cluster predominantly consists of cell cycle genes and constitutes a signature of a diversity of cancers. By linking expression profiles of the genes in the cluster with the dynamic behavior of p53 and p16INK4A, we identified a promoter architecture that integrates signals from the two tumor suppressive channels and that maps their activity onto distinct levels of expression of the cell cycle genes, which in turn, correspond to different cellular proliferation rates. Taking components of the mitotic spindle as an example, we experimentally verified our predictions that p53-mediated transcriptional repression of several of these novel targets is dependent on the activities of p21, NFY and E2F. Our study demonstrates how a well-controlled transformation process allows linking between gene expression, promoter architecture and activity of upstream signaling molecules.Comment: To appear in Molecular Systems Biolog

Human disease locus discovery and mapping to molecular pathways through phylogenetic profiling

Genes with common profiles of the presence and absence in disparate genomes tend to function in the same pathway. By mapping all human genes into about 1000 clusters of genes with similar patterns of conservation across eukaryotic phylogeny, we determined that sets of genes associated with particular diseases have similar phylogenetic profiles. By focusing on those human phylogenetic gene clusters that significantly overlap some of the thousands of human gene sets defined by their coexpression or annotation to pathways or other molecular attributes, we reveal the evolutionary map that connects molecular pathways and human diseases. The other genes in the phylogenetic clusters enriched for particular known disease genes or molecular pathways identify candidate genes for roles in those same disorders and pathways. Focusing on proteins coevolved with the microphthalmia-associated transcription factor (MITF), we identified the Notch pathway suppressor of hairless (RBP-Jk/SuH) transcription factor, and showed that RBP-Jk functions as an MITF cofactor

Wide-Scale Analysis of Human Functional Transcription Factor Binding Reveals a Strong Bias towards the Transcription Start Site

We introduce a novel method to screen the promoters of a set of genes with shared biological function, against a precompiled library of motifs, and find those motifs which are statistically over-represented in the gene set. The gene sets were obtained from the functional Gene Ontology (GO) classification; for each set and motif we optimized the sequence similarity score threshold, independently for every location window (measured with respect to the TSS), taking into account the location dependent nucleotide heterogeneity along the promoters of the target genes. We performed a high throughput analysis, searching the promoters (from 200bp downstream to 1000bp upstream the TSS), of more than 8000 human and 23,000 mouse genes, for 134 functional Gene Ontology classes and for 412 known DNA motifs. When combined with binding site and location conservation between human and mouse, the method identifies with high probability functional binding sites that regulate groups of biologically related genes. We found many location-sensitive functional binding events and showed that they clustered close to the TSS. Our method and findings were put to several experimental tests. By allowing a "flexible" threshold and combining our functional class and location specific search method with conservation between human and mouse, we are able to identify reliably functional TF binding sites. This is an essential step towards constructing regulatory networks and elucidating the design principles that govern transcriptional regulation of expression. The promoter region proximal to the TSS appears to be of central importance for regulation of transcription in human and mouse, just as it is in bacteria and yeast.Comment: 31 pages, including Supplementary Information and figure

Small RNA pathway genes identified by patterns of phylogenetic conservation and divergence

Genetic and biochemical analyses of RNA interference (RNAi) and microRNA (miRNA) pathways have revealed proteins such as Argonaute/PIWI and Dicer that process and present small RNAs to their targets. Well validated small RNA pathway cofactors, such as the Argonaute/PIWI proteins show distinctive patterns of conservation or divergence in particular animal, plant, fungal, and protist species. We compared 86 divergent eukaryotic genome sequences to discern sets of proteins that show similar phylogenetic profiles with known small RNA cofactors. A large set of additional candidate small RNA cofactors have emerged from functional genomic screens for defects in miRNA- or siRNA-mediated repression in C. elegans and D. melanogaster1,2 and from proteomic analyses of proteins co-purifying with validated small RNA pathway proteins3,4. The phylogenetic profiles of many of these candidate small RNA pathway proteins are similar to those of known small RNA cofactor proteins. We used a Bayesian approach to integrate the phylogenetic profile analysis with predictions from diverse transcriptional coregulation and proteome interaction datasets to assign a probability for each protein for a role in a small RNA pathway. Testing high-confidence candidates from this analysis for defects in RNAi silencing, we found that about half of the predicted small RNA cofactors are required for RNAi silencing. Many of the newly identified small RNA pathway proteins are orthologues of proteins implicated in RNA splicing. In support of a deep connection between the mechanism of RNA splicing and small RNA-mediated gene silencing, the presence of the Argonaute proteins and other small RNA components in the many species analysed strongly correlates with the number of introns in that species