Obtenção de novas moléculas com atividade analgésica e antiinflamatória a partir de plantas medicinais brasileiras

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências Físicas e MatemáticasO presente trabalho descreve os resultados fitoquímicos e farmacológicos obtidos a partir de três plantas medicinais brasileiras: Mandevilla illustris, Rubus imperialis e Sebastiania schottiana. Utilizando-se procedimentos cromatográficos e espectroscópicos, foram isolados e identificados vários compostos de interesse químico-medicinal como: ácido cafeico, illustrol, heterosil illustrol, acetil illustrol, ácido tormêntico, ácido-23-hidroxi tormêntico, Niga-ichigosídeo F1, xantoxilina, 2,4-dihidroxi-6-metoxi-acetofenona, ácido protocatético, quercetina e luteolina. Experimentos de raio-x permitiram conhecer a fórmula isomérica e determinar a unidade incomum 8-metil-2,5,9-trioxatriciclo[4.2.1.0 3,7] nonano, do acetil illustrol. Alguns destes compostos revelaram importante ação antiedematogênica, inibindo a formação de edemas de pata de ratos causados pela dextrana, carragenina e bradicinina, quando injetados localmente. Quando avaliados frente a dois modelos de dor em camundongos: formalina e contorções abdominais, alguns foram mais efetivos do que alguns fármacos analgésicos usados clinicamente (aspirina e paracetamol). Estes resultados são importantes sob o ponto de vista medicinal, visto que alguns compostos ativos foram detectados nas plantas estudadas, os quais confirmam em parte o uso popular no tratamento de processos dolorosos e inflamatório

Isolamento e identificação de compostos de Phyllanthus Corcovadensis (Euphorbiaceae) com efeito analgesico; correlação estrutura-atividade

Dissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciencias Fisicas e MatematicasAtravés de métodos cromatográficos, foi possível separar do Phyllanthus corcovadensis quatro frações. No entanto, apenas uma apresentou signicante atividade analgésica que analisada por Cromatografia Gasosa de Alta Resolução Computadorizada acoplada à Espectometria de Massa (CGAR-C-MS) revelou a presença de três fitoesteróis identificados como: estigmasterol, -sitosterol e campesterol. Como o estigmasterol apresentou atividade significante, foram realizadas algumas modificações estruturais e correlacionada sua estrutura com atividade farmacológica. Foi verificado nestas modificações que quando se introduziu o grupamento benzoíla a atividade aumentou consideravelmente. Além disso, ensaios farmacológicos indicam que o estigmasterol apresenta um mecanismo de ação analgésica semelhante ao mostrado anteriormente para o extrato bruto do Phyllanthus corcovadensis sendo diferente aos observados em analgésicos conhecidos como aspirina e morfina

Melia azedarach L. Fruit Extract as a potencial candidate in controlling the Neuraeschna Hagen, 1867 (Odonata: Aeshnidae), predominant predators for fish fingerlings

Odonata larvae in fishponds prey on fish fingerlings and decrease the profits from production. With the goal of eliminating these larvae from fishponds, large quantities of pesticides are applied. These products are toxic to fish and have unpredictable effects on the food chain. The objective of this study is to evaluate the effect of the plant extract of fruits of Melia azedarach (CEE) and of methyl parathion (MP) adsorbed in silica in the control of Neuraeschna larvae (Odonata: Aeshnidae). The LC50-18h for CEE was 0.57 mg L-1, and for MP the LC50-12h was 0.17 mg L-1. Two compounds  with the highest concentration were isolated and identified from CEE, linoleic acid and melianone. The latter is a triterpene precursor of limonoids, compounds with insecticide properties. The substitution of synthetic pesticides for natural products is a path towards the sustainability of fish farming

Pharmacological mechanisms underlying the anti-ulcer activity of methanol extract and canthin-6-one of Simaba ferruginea A. St-Hil. in animal models

AbstractRelevanceSimaba ferruginea A. St-Hil. (Simaroubaceae) is a subshrub typical of the Brazilian Cerrado, whose rhizomes are popularly used as infusion or decoction for the treatment of gastric ulcers, diarrhea and fever.Aim of the studyTo evaluate the pharmacological mechanism(s) of action of the antiulcer effects of the methanol extract of Simaba ferruginea and its alkaloid canthin-6-one.Materials and methodsRhizome of Simaba ferruginea was macerated with methanol to obtain the methanol extract (MESf) from which was obtained, the chloroform fraction. Canthin-6-one alkaloid (Cant) was purified and then isolated from the chloroform fraction (CFSf). The isolated Cant was identified by HPLC. Anti-ulcer assays were determined using ethanol and indomethacin-induced ulcer models in mice and rats respectively. In order to determine the probable mechanisms of actions of MESf and Cant animals were pretreated with l-NAME prior to anti-ulcer agent treatments and ulcer induction and nitric oxide (NO) level determined in order to assess NO involvement in the gastroprotective effects. Assays of malondialdehyde (MDA), myeloperoxidase (MPO), pro-inflammatory cytokines: interleukin 8 (IL-8) and tumor necrosis factor-alpha (TNF-α) and prostaglandin E2 (PGE2) were also carried out according to previously described methods.ResultsThe results indicate that the antiulcerogenic effects of MESf and Cant in ethanol-induced ulcer is mediated in part through increase in the production of protective endogenous NO as the antiulcerogenic activity of MESf and Cant was reduced in animals pre-treated with l-NAME. In indomethacin-induced ulcer pre-treatment with MESf and Cant showed reduction in the levels of MPO and MDA in the gastric tissue, thus indicating the participation of the antioxidant mechanisms on the gastroprotective effects. The plasma levels of IL-8 in ulcerated rats with indomethacin were also reduced by Cant, but not by MESf, indicating that inhibition of this cytokine contributes to the gastroprotective effect of Cant. However MESf and Cant had no effect on the mucosal membrane levels of PGE2, indicating that the gastroprotective effects of these agents is independent of PGE2 modulation.ConclusionThe results obtained in this study with MESf and Cant added insights into the pharmacological mechanisms involved in their mode of antiulcer action. The results indicate that Cant is one of the compounds responsible for these effects. Such findings are of extreme importance in the strive for future development of potent, safer and effective antiulcer agent. The efficacy of MESf and Cant in gastroprotection shows that Simaba ferruginea might be a promising antiulcer herbal medicine, in addition to confirming the popular use of this plant against gastric ulcer models utilised in this study

Evaluation of the proliferative activity of methanol extracts from six medicinal plants in murine spleen cells

A number of natural compounds have been used as immunomodulatory agents, enabling the function of the immune system to be modified by stimulating or suppressing it. There has been increasing interest in the study of therapeutic action of plant extracts regarding their immunomodulatory activity. The aim of this study was to identify and evaluate the action of extracts of the medicinal plants Calophyllum brasiliense, Ipomoea pes-caprae, Matayba elaeagnoides, Maytenus robusta, Rubus imperialis and Vernonia scorpioides on the development of spleen cells from mice, using the in vitro cellular proliferation assay. The cells, obtained by mechanical rupture of mice spleen (5x10(4) cells/mL), were incubated with methanol extracts (10, 50, 100 and 200 µg/mL) and phytohemagglutinin (PHA, 5 µg/mL). The basal control for proliferation consisted of cells alone, while the positive control consisted of cells and PHA. The cell culture was kept at 37 ºC in 5% CO2 for 72 hours, and cell proliferation was revealed by the blue tetrazolium reduction assay (MTT). The results were expressed as percentage of growth and were analyzed using the Kruskal-Wallis and Mann-Whitney tests. The C. brasiliense, I. pes-caprae and M. elaeagnoides extracts showed dose-dependent induction of cell proliferation, with a significant increase in cell proliferation (pVárias substâncias de origem natural têm sido utilizadas como agentes imunomoduladores, permitindo modificar a função do sistema imune e propiciando o estudo de atividades terapêuticas de extratos de plantas. Este trabalho objetivou identificar a atividade imunomodulatória dos extratos de seis plantas medicinais da flora brasileira, Calophyllum brasiliense, Ipomoea pes-caprae, Matayba elaeagnoides, Maytenus robusta, Rubus imperialis e Vernonia scorpioides, sobre a proliferação de células esplênicas de camundongos. As células esplênicas murinas obtidas por ruptura mecânica do baço (5x14³ células/mL) foram incubadas com os extratos metanólicos das plantas (10, 50, 100, 200 µg/mL) e fito-hemaglutinina (PHA, 5 µg/mL). O controle basal de proliferação foi constituído de células apenas e o controle positivo formado por células e PHA. O cultivo celular foi mantido a 37 ºC, 5% de CO2, 72 horas, com quantificação da proliferação celular pelo ensaio de redução do azul de tetrazólio. Os resultados expressos em percentagem de crescimento foram analisados pelos testes de Kruskal-Wallis e Mann-Whitney. Os extratos de C. brasiliense, I. pes-caprae e M. elaeagnoides mostraram indução dose-dependente da proliferação celular (

Seasonal phytochemical study and antimicrobial potential of Vetiveria zizanioides roots

This paper describes the seasonal phytochemical variation and the antimicrobial potential of V. zizanioides roots collected in Brazil. Considering the high levels of chemical constituents and their biological activity in dichloromethane fraction, the plants were grown in different seasons and the respective dichloromethane fractions were analyzed by gas chromatography-mass spectrometry. The antimicrobial activity was evaluated against several pathogenic microorganisms by determining the minimum inhibitory concentration (MIC) by the agar dilution method. The yields of dichloromethane fractions from plants collected in the autumn and spring occurred in a higher proportion than in other seasons. Khusimol (2) was isolated by column chromatography and identified by NMR and CG-MS, along with other sesquiterpenes, including β-vetivenene (1), vetiselinenol (3), isovalencenol (4), vetivenic acid (5), α-vetivone (6) and β-vetivone (7). Some extracts showed promising antimicrobial effects, with MICs ranging from 31.25 to 500 μg mL–1. Kushimol was slightly active against the tested microorganisms

EFEITO DO EXTRATO BRUTO, FRAÇÕES E SUBFRAÇÕES DA GARCINIA ACHACHAIRU RUSBY (CLUSIACEAE) SOBRE A PRESSÃO ARTERIAL DE RATOS ANESTESIADOS

 A Garcinia achachairu é popularmente conhecida como “achachairu”, é utilizada na medicina popular boliviana para o tratamento de gastrite, reumatismo e inflamações. Apesar do seu uso terapêutico generalizado, há ausência de dados sobre os seus efeitos biológicos, principalmente sobre a pressão arterial “in vivo”. No presente estudo, foi avaliado o efeito do extrato bruto metanólico (MeOH), frações e subfrações da G. achachairu sobre a pressão arterial de ratos anestesiados. Protocolo 1: O MeOH foi administrado por via oral, na dose de 300 mg/kg. Após 20 min, os animais foram preparados para registro da pressão arterial média (PAM). Protocolo 2: Os animais foram preparados para o registro PAM. Após a estabilização da pressão arterial, os ratos receberam três doses consecutivas das frações acetato de etila (AE), butanol (BuOH) e diclorometano (DC), nas doses de 3, 10 e 30 mg/kg, i.v. As subfrações foram administradas nas doses de 0,1, 0,3 e 1 mg/kg, i.v. Após a administração da fração AE, os animais receberam L-NAME (20 mg/kg, sc), um inibidor não específico da síntese do óxido nítrico, para verificar o possível mecanismo de ação. Os resultados mostraram que o MeOH reduziu a PAM em cerca de 15 mm Hg (92,3 ± 7,4 mmHg) se comparados aos animais não tratados (107,7 ± 8,7 mmHg). A fração AE apresentou uma redução na PAM, dependente da dose. No entanto, BuOH e DC foram menos eficazes do que a AE. A epicatequina, um composto isolado, não alterou a pressão arterial. Após a administração de L-NAME, o efeito vasodilatador da fração AE foi bloqueado. As análises dos dados sugerem que uma única administração oral do extrato G. achachairu reduziu a PAM. A fração AE foi mais eficaz do que as frações BuOH e DC. Os resultados mostraram que o L-NAME bloqueou parcialmente o efeito vasodilatador da fração AE. Portanto, a capacidade da fração AE em reduzir a pressão arterial é explicada, em parte, por um aumento da produção de óxido nítrico.Palavras-chave: Garcinia achachairu. Pressão arterial. Plantas medicinais

Is there still a place for involutional melancholia nowadays?

Ethnopharmacological relevance: Rubus niveus Thunb. plant belongs to Rosaceae family and have been used traditionally to treat wounds, burns, inflammation, dysentery, diarrhea and for curing excessive bleeding during menstrual cycle. The present study was undertaken to investigate the in vivo genotoxicity of Rubus niveus aerial parts extract and its possible chemoprotection on doxorubicin (DXR)-induced DNA damage. In parallel, the main phytochemicals constituents in the extract were determined.Materials and methods: The animals were exposed to the extract for 24 and 48 h, and the doses selected were 500, 1000 and 2000 mg/kg b.w. administered by gavage alone or prior to DXR (30 mg/kg b.w.) administered by intraperitoneal injection. The endpoints analyzed were DNA damage in bone marrow and peripheral blood cells assessed by the alkaline alkaline (pH > 13) comet assay and bone marrow micronucleus test.Results and conclusion: The results of chemical analysis of the extract showed the presence of tormentic acid, stigmasterol, quercitinglucoronide (miquelianin) and niga-ichigoside F1 as main compounds. Both cytogenetic endpoints analyzed showed that there were no statistically significant differences (p > 0.05) between the negative control and the treated groups with the two higher doses of Rubus niveus extract alone, demonstrating absence of genotoxic and mutagenic effects. Aneugenic/clastogenic effect was observed only at 2000 mg/kg dose. On the other hand, in the both assays and all tested doses were observed a significant reduction of DNA damage and chromosomal aberrations in all groups co-treated with DXR and extract compared to those which received only DXR. These results indicate that Rubus niveus aerial parts extract did not revealed any genotoxic effect, but presented some aneugenic/clastogenic effect at higher dose; and suggest that it could be a potential adjuvant against development of second malignant neoplasms caused by the cancer chemotherapic DXR. (C) 2015 Elsevier Ireland Ltd. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP