The pharmacological assay as a tool to medicinal plants domestication

In Brazil studies with native medicinal plants are usually performed using non-domesticated plants and as a result the genetic variability of wild species could express different levels of active principles changing their therapeutic effect. Based on that, the aim of this study was to demonstrate that extract of different half- sib families Cordia verbenacea (DC), widely used as medicinal plant in Brazil, have different efficacy in the Total Growth Inhibition (TGI) of 5 different human tumor cell lines. Data were statistically analyzed using ANOVA follow by Tuckey test and a heritability estimation of the plant families was performed. The results showed that TGI are different for each plant family according with each human tumor cell line. For instance, extracts obtained from families 3,11 and 12 were more effective to inhibit the U-251 and Ht-29 cell lines compared to the other families, while extracts obtained from the family 32 was more effective against thethe PC-3 line. The heritability coefficient indicated that plant population selection could promote a genetic improvement related to its active principle and their pharmacological effect and could provide the identification of the best families according to their pharmacological efficacy. In conclusion, this study suggests that the domestication of a wild medicinal plant should be better monitored by its pharmacological effect

A múltipla clínica das depressões

The accute increase of depression is a worldwide and complex phenomenon. Its understanding requires the mobilization of several areas of knowledge (Corbanezi, 2021). The objective of this article is less to present extensively the different denominations, aspects, definitions, and understandings concerning depression as a clinical entity, and more to register that they exist, with the intention of revealing, or briefly reiterating, the vast complexity of this area from the point of view of some theoretical bodies, in contrast with the, in our view, simplified and condensed description found in the current diagnostic manuals, especially in the current Disorder and Statistic Manual-DSM. We point to the current number of cases diagnosed as depression, considered of the epidemic order in which, however, a whole range of distinct affections are indistinctly condensed, in the current prevalent diagnostic version. Distinct ranges of sadness, mourning processes, and other affective and physical states clinically similar to those credited as depression, have been steadily increasing numbers that, according to the WHO, are expected to reach the first cause of work impairement by 2030. A projection, or a state of affairs that is still poorly understood and, therefore, as an epidemic, ungoverned?A explosão dos casos de depressão é um fenômeno mundial e complexo. Sua compreensão requer a mobilização de diversas áreas do saber (Corbanezi, 2021). O objetivo deste artigo será menos o de apresentar extensivamente as diferentes denominações, vertentes, definições e compreensões referentes à depressão como entidade clínica, e mais o de registrar que estas existem, com o intuito ainda de revelar, ou reiterar, brevemente, a vasta complexidade desta área a partir do olhar de alguns corpos teóricos, em contraste com a, a nosso ver, simplificada e condensada descrição encontrada nos atuais manuais diagnósticos, em especial, no Manual de Diagnóstico e Estatístico de Transtornos Mentais-DSM vigente. Apontamos para o atual número de casos diagnosticados como depressão, considerado da ordem epidêmica no qual, no entanto, toda uma gama de afetos estão indistintamente aglomerados, na atual versão diagnóstica prevalente. Distintas gamas de tristeza, de processos de luto e de outros estados afetivos e físicos clinicamente semelhantes aos creditados como da depressão, vêm constantemente aumentando os números que, de acordo com a Organização Mundial da Saúde, devem atingir o primeiro lugar na causa de afastamento de trabalho até 2030. Uma projeção, ou um estado de coisas ainda mal compreendido e, portanto, tal qual uma epidemia, desgovernado

Efeito de fermentado (utilizado como alimento funcional) sobre: a citoproteção gástrica, atividade anti-secretória e a motilidade intestinal em animais

Objetivo: Confirmar o mecanismo de ação do fermentado, através da quantificação do muco gastroprotetor e da produção de secreção gástrica ácida em ratos Wistar, além de verificar a interferência na motilidade gastrointestinal em camundongos. Métodos: Nesse estudo foi inicialmente utilizado o modelo de indução de úlcera com administração de solução salina (10mL/kg de peso) como controle negativo, carbenoxolona (200 mg/kg) como controle positivo e o produto fermentado em pó na dose de 2000 mg/kg de peso animal. Em seguida foi utilizado o modelo para determinação quantitativa do muco gastroprotetor e atividade anti-secretória em ratos. Para avaliação da atividade sobre a motilidade intestinal em camundongos cada grupo de animais recebeu, por via oral, solução salina (10mL/kg) como controle negativo, atropina (3mg/kg) como controle positivo e o produto fermentado em pó na dose de 2000mg/kg de peso corporal animal. Resultados: O fermentado apresentou atividade antiulcerogênica de 57,1% e a carbenoxolona de 92,3%. Para a confirmação do mecanismo de ação via prostaglandinas foi realizado a quantificação do muco gástrico no qual o fermentado foi capaz de aumentá-lo em 48,9% e a carbenoxolona em 108,6%. Na avaliação da atividade antisecretória em ratos e da motilidade intestinal em camundongos o fermentado não interferiu na secreção acida gástrica e na motilidade. Conclusão: Com base nos dados obtidos nesse experimento com ratos e camundongos, concluiu-se que o fermentado provavelmente promove a citoproteção da mucosa gástrica, através do aumento da produção de muco gastroprotetor especialmente por meio dos níveis de prostaglandinas

Seven-membered Rings Through Metal-free Rearrangement Mediated By Hypervalent Iodine.

A versatile and metal-free approach for the synthesis of carbocycles and of heterocycles bearing seven- and eight-membered rings is described. The strategy is based on ring expansion of 1-vinylcycloalkanols (or the corresponding silyl or methyl ether) mediated by the hypervalent iodine reagent HTIB (PhI(OH)OTs). Reaction conditions can be easily adjusted to give ring expansion products bearing different functional groups. A route to medium-ring lactones was also developed.201475-9

Synthesis, Antiproliferative Activity And Molecular Properties Predictions Of Galloyl Derivatives.

The present study was designed to investigate the in vitro antiproliferative activity against ten human cancer cell lines of a series of galloyl derivatives bearing substituted-1,3,4-oxadiazole and carbohydrazide moieties. The compounds were also assessed in an in silico study of the absorption, distribution, metabolism and excretion (ADME) in the human body using Lipinski's parameters, the topological polar surface area (TPSA) and percentage of absorption (%ABS). In general, the introduction of N'-(substituted)-arylidene galloyl hydrazides 4-8 showed a moderate antitumor activity, while the 2-methylthio- and 2-thioxo-1,3,4-oxadiazol-5-yl derivatives 9 and 10 led to increased inhibition of cancer cell proliferation. The precursor compound methyl gallate 2 and the intermediary galloyl hydrazide 3 showed greater antiproliferative activity with GI50 values < 5.54 µM against all human tumor cell lines tested. A higher inhibition effect against ovarian cancer (OVCAR-3) (GI50 = 0.05-5.98 µM) was also shown, with compounds 2, 3, 9 and 10 with GI50 ≤ 0.89 µM standing out in this respect. The in silico study revealed that the compounds showed good intestinal absorption.205360-537

Incorporación de nuevos ingredientes funcionales a alimentos como contribución a la promoción de la salud y/o a la prevención de enfermedades de la población iberoamericana

Coordinador: Javier Fontecha.-- et al.El desarrollo de nuevos alimentos que incorporen ingredientes funcionales requiere un enfoque multidisciplinar, por lo que se considera esencial la participación conjunta de grupos de investigación internacionalmente reconocidos, entre los que surjan sinergias, colaboraciones e intercambios, que permitan la obtención de resultados de investigación difícilmente alcanzables por un solo grupo. En la presente propuesta, se promueve la interacción, la cooperación y la transferencia de conocimientos y tecnologías relacionadas con compuestos bioactivos, suficientemente caracterizados por los diferentes grupos que componen esta acción, que integren sus tareas mediante la interconexión con empresas especializadas en ingredientes funcionales, permitiendo una mejor transferencia al sector productivo y por tanto, un aumento de su competitividad.PROYECTO CYTED. IBEROFUN. REF: 110AC0386.Peer reviewe

Effects of the Topical Application of Hydroalcoholic Leaf Extract of Oncidium flexuosum Sims. (Orchidaceae) and Microcurrent on the Healing of Wounds Surgically Induced in Wistar Rats

This study evaluated the wound healing activity of hydroalcoholic leaf extract of Oncidium flexuosum Sims. (Orchidaceae), an important native plant of Brazil, combined or not with microcurrent stimulation. Wistar rats were randomly divided into four groups of nine animals: control (C), topical application of the extract (OF), treated with a microcurrent (10 μA/2 min) (MC), and topical application of the extract plus microcurrent (OF + MC). Tissue samples were obtained 2, 6, and 10 days after injury and submitted to structural and morphometric analysis. The simultaneous application of OF + MC was found to be highly effective in terms of the parameters analyzed (P < .05), with positive effects on the area of newly formed tissue, number of fibroblasts, number of newly formed blood vessels, and epithelial thickness. Morphometric data confirmed the structural findings. The O. flexuosum leaf extract contains active compounds that speed the healing process, especially when applied simultaneously with microcurrent stimulation

Synthesis, Dna Binding, And Antiproliferative Activity Of Novel Acridine-thiosemicarbazone Derivatives.

In this work, the acridine nucleus was used as a lead-compound for structural modification by adding different substituted thiosemicarbazide moieties. Eight new (Z)-2-(acridin-9-ylmethylene)-N-phenylhydrazinecarbothioamide derivatives (3a-h) were synthesized, their antiproliferative activities were evaluated, and DNA binding properties were performed with calf thymus DNA (ctDNA) by electronic absorption and fluorescence spectroscopies. Both hyperchromic and hypochromic effects, as well as red or blue shifts were demonstrated by addition of ctDNA to the derivatives. The calculated binding constants ranged from 1.74 × 10(4) to 1.0 × 10(6) M(-1) and quenching constants from -0.2 × 10(4) to 2.18 × 10(4) M(-1) indicating high affinity to ctDNA base pairs. The most efficient compound in binding to ctDNA in vitro was (Z)-2-(acridin-9-ylmethylene)-N- (4-chlorophenyl) hydrazinecarbothioamide (3f), while the most active compound in antiproliferative assay was (Z)-2-(acridin-9-ylmethylene)-N-phenylhydrazinecarbothioamide (3a). There was no correlation between DNA-binding and in vitro antiproliferative activity, but the results suggest that DNA binding can be involved in the biological activity mechanism. This study may guide the choice of the size and shape of the intercalating part of the ligand and the strategic selection of substituents that increase DNA-binding or antiproliferative properties.1613023-1304

Antimicrobial and antiproliferative activities of stingless bee Melipona scutellaris geopropolis

Background\ud Geopropolis is a type of propolis containing resin, wax, and soil, collected by threatened stingless bee species native to tropical countries and used in folk medicine. However, studies concerning the biological activity and chemical composition of geopropolis are scarce. In this study, we evaluated the antimicrobial and antiproliferative activity of the ethanolic extract of geopropolis (EEGP) collected by Melipona scutellaris and its bioactive fraction against important clinical microorganisms as well as their in vitro cytotoxicity and chemical profile.\ud \ud Methods\ud The antimicrobial activity of EEGP and fractions was examined by determining their minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against six bacteria strains as well as their ability to inhibit Streptococcus mutans biofilm adherence. Total growth inhibition (TGI) was chosen to assay the antiproliferative activity of EEGP and its bioactive fraction against normal and cancer cell lines. The chemical composition of M. scutellaris geopropolis was identified by reversed-phase high-performance liquid chromatography and gas chromatography–mass spectrometry.\ud \ud Results\ud EEGP significantly inhibited the growth of Staphylococcus aureus strains and S. mutans at low concentrations, and its hexane fraction (HF) presented the highest antibacterial activity. Also, both EEGP and HF inhibited S. mutans biofilm adherence (p < 0.05) and showed selectivity against human cancer cell lines, although only HF demonstrated selectivity at low concentrations. The chemical analyses performed suggest the absence of flavonoids and the presence of benzophenones as geopropolis major compounds.\ud \ud Conclusions\ud The empirical use of this unique type of geopropolis by folk medicine practitioners was confirmed in the present study, since it showed antimicrobial and antiproliferative potential against the cancer cell lines studied. It is possible that the major compounds found in this type of geopropolis are responsible for its properties.The authors are grateful to Mr. José Emídio Borges de Souza for providing the geopropolis samples. This research was supported by FAPESP (#2009/12354-6 and #2010/20214-7)

Chitosan-tripolyphosphate Nanoparticles As Arrabidaea Chica Standardized Extract Carrier: Synthesis, Characterization, Biocompatibility, And Antiulcerogenic Activity.

Natural products using plants have received considerable attention because of their potential to treat various diseases. Arrabidaea chica (Humb. & Bonpl.) B. Verlot is a native tropical American vine with healing properties employed in folk medicine for wound healing, inflammation, and gastrointestinal colic. Applying nanotechnology to plant extracts has revealed an advantageous strategy for herbal drugs considering the numerous features that nanostructured systems offer, including solubility, bioavailability, and pharmacological activity enhancement. The present study reports the preparation and characterization of chitosan-sodium tripolyphosphate nanoparticles (NPs) charged with A. chica standardized extract (AcE). Particle size and zeta potential were measured using a Zetasizer Nano ZS. The NP morphological characteristics were observed using scanning electron microscopy. Our studies indicated that the chitosan/sodium tripolyphosphate mass ratio of 5 and volume ratio of 10 were found to be the best condition to achieve the lowest NP sizes, with an average hydrodynamic diameter of 150±13 nm and a zeta potential of +45±2 mV. Particle size decreased with AcE addition (60±10.2 nm), suggesting an interaction between the extract's composition and polymers. The NP biocompatibility was evaluated using human skin fibroblasts. AcE-NP demonstrated capability of maintaining cell viability at the lowest concentrations tested, stimulating cell proliferation at higher concentrations. Antiulcerogenic activity of AcE-NP was also evaluated with an acute gastric ulcer experimental model induced by ethanol and indomethacin. NPs loaded with A. chica extract reduced the ulcerative lesion index using lower doses compared with the free extract, suggesting that extract encapsulation in chitosan NPs allowed for a dose reduction for a gastroprotective effect. The AcE encapsulation offers an approach for further application of the A. chica extract that could be considered a potential candidate for ulcer-healing pharmaceutical systems.103897-390