Pharmaceutical properties of 'sucupira' (Pterodon spp.)

The plant of the genus Pterodon (Fabaceae, Leguminosae), commonly known as 'sucupira' or 'faveira', are disseminated throughout the central region of Brazil and has frequently been used in popular medicine for its anti-rheumatic, analgesic, and anti-inflammatory properties. In recent years, interest in these plants has increased considerably. The biological effects of different phytoextracts and pure metabolites have been investigated in several experimental models in vivo and in vitro. The literature describes flavonoids, triterpene and steroids, while one paper presented studies with proteins isolated from the genus. This review provides an overview of phytochemical and pharmacological research in Pterodon, showing the main chemical compounds studied to date, and focusing on the relationship between these molecules and their biological activity. Furthermore, this study paves the way for more in-depth investigation, isolation and characterization of the molecules of this plant genus.As plantas do gênero Pterodon (Fabaceae/Leguminosae), conhecidas popularmente como "sucupira branca" ou "faveira", encontram-se distribuídas pela região central do Brasil e são frequentemente utilizadas na medicina popular por suas propriedades antirreumáticas, analgésicas e antiinflamatórias. Nos últimos anos, o interesse por estas plantas tem aumentado consideravelmente. Os efeitos biológicos dos diferentes fitoextratos e metabólitos puros têm sido investigados em vários modelos experimentais in vivo e in vitro. A literatura descreve flavonóides, triterpenos, esteróides e apenas um trabalho mostra estudos com proteínas isoladas do gênero. Esta revisão apresenta de maneira geral as investigações farmacológicas e fitoquímicas de Pterodon, mostrando os principais compostos já estudados, sua composição química, focando na relação entre estas moléculas e sua atividade biológica. Mais ainda, nós abrimos as portas para maior investigação, isolamento e caracterização de moléculas deste gênero de plantas

Estudos espectroscópicos de inibidores de serinoproteinases isolados de sementes de bauhinia bauhinioides: estimativa de estrutura secundária e estudos de pH

Os inibidores de proteinases estão amplamente distribuídos na natureza. A sua atividade biológica nas plantas pode relacionar-se com a armazenagem de proteínas e com mecanismos de defesa contra agentes patogênicos e predadores. Estudos mostraram que estes inibidores podem desempenhar um importante papel na fisiopatologia de doenças humanas, como nas inflamações, hemorragias e câncer. Inibidores do gênero Bauhinia foram isolados, dentre eles, o inibidor de calicreína plasmática (BbKI) e o inibidor de elastase (BbCI), extraídos de sementes de B. bauhinioides. Eles possuem homologia com os inibidores do tipo Kunitz, porém não apresentam as pontes dissulfeto. Neste trabalho foi realizado um estudo comparativo estrutural entre estes, com o intuito de relacionar a estrutura e a especificidade. Foram utilizadas as técnicas espectroscópicas de dicroísmo cicular (CD) e fluorescência, que possibilitaram estimar o conteúdo de estrutura secundária e monitorar as alterações conformacionais destes inibidores em função do pH. O conteúdo estimado para os inibidores foi muito similar (2% de hélices-a, 36% de folhas-b, 23% de voltas-b e 39% de desordenada). A ausência de diferenças significativas nos espectros de CD e fluorescência dos inibidores, em ampla faixa de pH (2,0-10,5), sugere a grande estabilidade conformacional desse inibidor

Modulation of neuropeptide Y levels is impaired in crack withdrawal patients

Introduction: The dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has a key role in drug addiction susceptibility. In addition to the well-known relationship between cortisol and the HPA axis, other molecules are involved with stress response and could modify the HPA activation, such as the neuropeptide Y (NPY), which has anxiolytic proprieties. There are few studies evaluating the effect of NPY levels on addiction, especially in crack cocaine dependence. Objective: To evaluate NPY in crack users during early withdrawal to determine its relationship with drug use and cortisol levels. Methods: We analyzed 25 male inpatient crack users. Serum NPY levels were measured at admission and discharge (mean of 24 days). Morning salivary cortisol was measured at admission. Results: Serum NPY levels at admission and discharge were very similar. Lower NPY levels at discharge were associated with higher lifetime crack use. Also, a negative correlation was found between morning cortisol and delta NPY (NPY discharge – NPY admission). Conclusion: These preliminary findings indicate that crack use influences the modulation of NPY levels and modifies stress response. The NPY pathway may play an important role in the pathophysiology of crack addiction, and the anxiolytic effect of NPY may be impaired in crack users. Future studies should consider NPY as a measurable indicator of the biological state in addiction

Inflammatory cytokines and alcohol use disorder : systematic review and meta-analysis

Objective: To assess differences in blood inflammatory cytokines between people with alcohol use disorder (AUD) and healthy controls (HC). Methods: Searches were performed from inception through April 14, 2021. Meta-analyses with random-effects models were used to calculate the standardized mean difference ([SMD], 95%CI), and potential sources of heterogeneity were explored trough meta-regressions and subgroup analysis. Results: The meta-analysis included 23 studies on the following 14 cytokines: tumor necrosis factor (TNF)-a, IL-1, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13, IL15, interferon (IFN)-g and sCD14. There were significantly higher concentrations of IL-6 (n=462 AUD and 408 HC; SMD = 0.523; 95%CI 0.136-0.909; p = 0.008) in AUD than HC. No significant differences were found in the other 13 cytokines. Conclusion: We found that IL-6 levels were significantly higher in individuals with AUD than HC and that other cytokines were not altered. This can be explained by the small number of studies, their methodological heterogeneity, and confounding factors (active use, abstinence, quantity, and physical or psychiatric illnesses, for example). Despite a great deal of evidence about alcohol and inflammatory diseases, studies assessing the role of neuroimmune signaling in the development and severity of AUD are still lacking

Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention

Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention. Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits

Isolation an characterization of the rBbCl(recombinant Bauhinia bauhinioides Cruzain inhibitor) and Cruzan(the major cysteine peptidase from T. cruzi) complex: crystallographyc studies and determination of inhibitor and enzyme interactions for drug design

BV UNIFESP: Teses e dissertaçõe

BbCI, a cruzipain inhibitor of the Bauhinia baujinoides: isolation of it's cDNA an heterrologous expression

O BbCI (Bauhinia bauhinioides Cruzipain Inhibitor) e um inibidor de cisteinoproteinase que mostra alta identidade sequencial com inibidores de planta do tipo Kunitz, porem nao apresenta nenhum residuo de cisteina. A inibicao da cruzipaina faz do BbCI um instrumento biotecnologico interessante no desenvolvimento de uma nova geracao de drogas para o combate a infeccoes causadas pelo Trypanossoma crua 0 BbCI tambem apresenta uma atividade inibitoria para HNE (Human Neutrophillus Elastase) enzima envolvida em varios processos fisiopatologicos. 0 gene codificante para BbCI foi clonado por RT-PCR usando oligonucleotideos degenerados, os quais foram sintetizados a partir da sequencia proteica previamente descrita. 0 produto amplificado foi inserido no vetor pGEM-T para sequenciamento. Uma vez confirmada a sequencia, oligonucleotideos internos foram sintetizados para a realizacao do RACE 5' e 3'(Rapid Amplification of cDNA Ends). A informacao gerada mostrou que o BbCI e inicialmente sintetizado como uma pre-pro-proteina apresentando a seguinte estrutura: 19 residuos de aminoacidos na regiao N-terminal, 164 residuos correspondentes a proteina nativa e 10 residuos na regiao C-terminal. A sequencia correspondente a cadeia madura foi subclonada no vetor de expressao pET-28a (Novagen). 0 BbCI foi produzido por expressao heterologa fusionado a uma sequencia de 6 residuos de histidinas com um sitio de clivagem de trombina entre eles. A expressao em E. coli BL21 (DE3) produziu o inibidor em grande escala o qual foi purificado por cromatografia de afinidade em resina Ni-NTA SuperFlow. A proteina de fusao foi submetida a clivagem com trombina e posteriormente purificada em gel filtracao Superdex 75a(au)BV UNIFESP: Teses e dissertaçõe

Identification of toxigenic Aspergillus species from diet dairy goat using a polyphasic approach

Some species of filamentous fungi that infest agricultural commodities are able to produce mycotoxins, contaminating feed and animal products. The aim of this research was to identify the mycoflora present in the feed and forage for dairy goat and to isolate and characterize the Aspergillus flavus and A. parasiticus strains based on a morphological and molecular characterization and mycotoxigenic ability. The goat dairy diets were collected monthly from 11 goat milk farms, totaling 129 and 106 samples of concentrate and forage, respectively. For the isolation of the mycobiota the surface plating method was used. Aspergillus, Penicillium, and Fusarium were the main fungi producing mycotoxins isolated. The morphological and molecular characterization and mycotoxigenic ability were used for A. flavus and A. parasiticus identification. The Aspergillus spp. from feed 39% produced aflatoxins B1 and B2, 17% produced cyclopiazonic acid (CPA), 18% produced both toxins, and 42% had no toxigenic ability. Only 2.0% of the strains produced aflatoxins B1, B2, G1, and G2, but no CPA. The strains from forage were producers of aflatoxins B1 and B2 (37%), CPA (14%), 14% of both mycotoxins, whereas 49% have shown no toxigenic ability. The aflD and aflR genes were used by PCR and PCR-RFLP, respectively. The presence of toxigenic species in samples of feed for lactating goats indicates a potential risk of contamination of dairy products, if they are exposed to environmental conditions favorable to fungal growth and mycotoxin production