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Naunyn Schmiedebergs Arch Pharmacol ; 394(3): 437-446, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33034715


Arterial hypertension is a risk factor for various cardiovascular and renal diseases, representing a major public health challenge. Although a wide range of treatment options are available for blood pressure control, many hypertensive individuals remain with uncontrolled hypertension. Thus, the search for new substances with antihypertensive potential becomes necessary. Coumarins, a group of polyphenolic compounds derived from plants, have attracted intense interest due to their diverse pharmacological properties, like potent antihypertensive activities. Braylin (6-methoxyseselin) is a coumarin identified in the Zanthoxylum tingoassuiba species, described as a phosphodiesterase-4 (PDE4) inhibitor. Although different coumarin compounds have been described as potent antihypertensive agents, the activity of braylin on the cardiovascular system has yet to be investigated. To investigate the vasorelaxation properties of braylin and its possible mechanisms of action, we performed in vitro studies using superior mesenteric arteries and the iliac arteries isolated from rats. In this study, we demonstrated, for the first time, that braylin induces potent vasorelaxation, involving distinct mechanisms from two different arteries, isolated from rats. A possible inhibition of phosphodiesterase, altering the cyclic adenosine monophosphate (cAMP)/cAMP-dependent protein kinase (PKA) pathway, may be correlated with the biological action of braylin in the mesenteric vessel, while in the iliac artery, the biological action of braylin may be correlated with increase of cyclic guanosine monophosphate (cGMP), followed by BKCa, Kir, and Kv channel activation. Together, these results provide evidence that braylin can represent a potential therapeutic use in preventing and treating cardiovascular diseases.

Cumarínicos/farmacologia , Artéria Ilíaca/efeitos dos fármacos , Artérias Mesentéricas/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Artéria Ilíaca/fisiologia , Masculino , Artérias Mesentéricas/fisiologia , Canais de Potássio/fisiologia , Ratos Wistar , Vasodilatação/efeitos dos fármacos
Rev. bras. plantas med ; 16(4): 812-818, oct.-dic. 2014. ilus, graf, tab
Artigo em Português | LILACS | ID: lil-729888


A investigação química da espécie Pilocarpus spicatus, popularmente conhecida como jaborandi e usada na medicina tradicional para doenças como estomatite, febre, bronquite e psoríase, teve por objetivo o isolamento e/ou identificação de substâncias ativas e a avaliação da atividade antiparasitária dos extratos frente às formas epimastigotas de Trypanosoma cruzi. O estudo resultou na identificação de nove substâncias, tais como: tridecanona, 2-heptadecanona, espatulenol, aromadendreno, β-cariofileno, ácido 3α-hidroxitirucala-7,24-dien-21-óico, (+)-isoangenomalina, episesamina e sesamina. As estr uturas dos compostos foram elucidadas por análises espectroscópicas e comparação com dados da literatura. Os extratos hexânico e metanólico de folhas e raízes foram testados in vitro contra o Trypanosoma cruzi cepa Y e apresentaram atividade tripanomicida.

The chemical investigation of the species Pilocarpus spicatus - popularly known as jaborandi and used in traditional medicine for diseases, such as stomatitis, fever, bronchitis and psoriasis - aimed to isolate and / or identify the active substances and evaluate the antiparasitic activity of the extracts against the Trypanosoma cruzi epimastigote forms. The study resulted in the identification of nine substances, such as tridecanone, 2-heptadecanone, spathulenol, aromadendrene, β-caryophyllene, 3α-hydroxytirucalla-7,24-dien-21-oic acid, (+)-isoangenomaline, episesamin and sesamin. The structures were elucidated by spectroscopic analysis and comparison with literature data. The hexane and methanol extracts from leaves and roots were tested in vitro against Trypanosoma cruzi Y strain and showed trypanocidal activity.

Jaborandi/farmacologia , Pilocarpus/química , Trypanosoma cruzi/isolamento & purificação , Antiparasitários/farmacologia , Extratos Vegetais/síntese química , Rutaceae/classificação
Food Chem ; 127(2): 404-11, 2011 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-23140679


In this study, we investigated the effects of the flavonoid rutin (3,3',4',5,7-pentahydroxyflavone-3-rutinoside) on glioma cells, using the highly proliferative human cell line GL-15 as a model. We observed that rutin (50-100µM) reduced proliferation and viability of GL-15 cells, leading to decreased levels of ERK1/2 phosphorylation (P-ERK1/2) and accumulation of cells in the G2 phase of the cell cycle. On the other hand, 87.4% of GL-15 cells exposed to 100µM rutin entered apoptosis, as revealed by flow cytometry after AnnexinV/PI staining. Nuclear condensation and DNA fragmentation were also observed, further confirming that apoptosis had occurred. Moreover, the remaining cells that were treated with 50µM rutin presented a morphological pattern of astroglial differentiation in culture, characterised by a condensed cell body and thin processes with overexpression of GFAP. Because of its capacity to induce differentiation and apoptosis in cultured human glioblastoma cells, rutin could be considered as a potential candidate for malignant gliomas treatment.

Toxicon ; 55(1): 105-17, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19615397


Plants of Crotalaria genus (Leguminosae) present large amounts of the pyrrolizidine alkaloid monocrotaline (MCT) and cause intoxication to animals and humans. Therefore, we investigated the MCT-induced cytotoxicity, morphological changes, and oxidative and genotoxic damages to glial cells, using the human glioblastoma cell line GL-15 as a model. The comet test showed that 24h exposure to 1-500microM MCT and 500microM dehydromonocrotaline (DHMC) caused significant increases in cell DNA damage index, which reached 42-64% and 53%, respectively. Cells exposed to 100-500microM MCT also featured a contracted cytoplasm presenting thin cellular processes and vimentin destabilisation. Conversely, exposure of GL-15 cells to low concentrations of MCT (1-10microM) clearly induced megalocytosis. Moreover, MCT also induced down regulation of MAPs, especially at the lower concentrations adopted (1-10microM). Apoptosis was also evidenced in cells treated with 100-500microM MCT, and a later cytotoxicity was only observed after 6 days of exposure to 500microM MCT. The data obtained provide support for heterogenic and multipotential effects of MCT on GL-15 cells, either interfering on cell growth and cytoskeletal protein expression, or inducing DNA damage and apoptosis and suggest that the response of glial cells to this alkaloid might be related to the neurological signs observed after Crotalaria intoxication.

Crotalaria/toxicidade , Monocrotalina/toxicidade , Mutagênicos/toxicidade , Neuroglia/efeitos dos fármacos , Neuroglia/patologia , Sementes/toxicidade , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Forma Celular/efeitos dos fármacos , Tamanho Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Crotalaria/química , Dano ao DNA , Relação Dose-Resposta a Droga , Humanos , Imuno-Histoquímica , Proteínas Associadas aos Microtúbulos/metabolismo , Monocrotalina/análogos & derivados , Monocrotalina/síntese química , Monocrotalina/isolamento & purificação , Monocrotalina/metabolismo , Mutagênicos/isolamento & purificação , Mutagênicos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Sementes/química , Fatores de Tempo , Vimentina/metabolismo
J Microencapsul ; 26(8): 684-91, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19888877


Zanthoxylum tingoassuiba essential oil (EO) is a complex mixture of organic compounds among which methyl-N-methylanthranilate and sesquiterpene alcohol alpha-bisabolol represent the main compounds. The essential oil antimicrobial activity was studied against bacteria and fungi cells by diffusion disk method and significant activity was observed against S. aureus, S. aureus isolated multi-resistant and the dermathophyte fungi. Essential oil from Zanthoxylum tingoassuiba loaded into DPPC multilamellar liposomes (MLV) was successfully produced through a thin film hydration method with mean diameter of 9.37 +/- 4.69 microm. The EO-loaded liposomes showed adequate sphericity and narrower size distribution than empty liposomes. Results also showed that Zanthoxylum tingoassuiba essential oil can be incorporated in appreciable amounts (43.7 +/- 6.0%) in the prepared vesicular dispersions. A strong interaction between essential oil and lipid bilayer was indicated by a significant decrease in T(m) of the EO-loaded liposomes related to empty vesicles. Essential oil showed incomplete release profile from liposomes, suggesting that EO-loaded liposomes will be useful in pharmaceutical applications to enhance essential oil targeting to cells.

Anti-Infecciosos/administração & dosagem , Portadores de Fármacos/química , Lipossomos/química , Óleos Voláteis/administração & dosagem , Zanthoxylum/química , 1,2-Dipalmitoilfosfatidilcolina , Óleos Voláteis/farmacologia , Staphylococcaceae/efeitos dos fármacos
Cell Biol Toxicol ; 24(1): 75-86, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17549591


Astrocyte and microglia cells play an important role in the central nervous system (CNS). They react to various external aggressions by becoming reactive and releasing neurotrophic and/or neurotoxic factors. Rutin is a flavonoid found in many plants and has been shown to have some biological activities, but its direct effects on cells of the CNS have not been well studied. To investigate its potential effects on CNS glial cells, we used both astrocyte primary cultures and astrocyte/microglia mixed primary cell cultures derived from newborn rat cortical brain. The cultures were treated for 24 h with rutin (50 or 100 micromol/L) or vehicle (0.5% dimethyl sulfoxide). Mitochondrial function on glial cells was not evidenced by the MTT test. However, an increased lactate dehydrogenase activity was detected in the culture medium of both culture systems when treated with 100 micromol/L rutin, suggesting loss of cell membrane integrity. Astrocytes exposed to 50 micromol/L rutin became reactive as revealed by glial fibrillary acidic protein (GFAP) overexpression and showed a star-like phenotype revealed by Rosenfeld's staining. The number of activated microglia expressing OX-42 increased in the presence of rutin. A significant increase of nitric oxide (NO) was observed only in mixed cultures exposed to 100 micromol/L rutin. Enhanced TNFalpha release was observed in astrocyte primary cultures treated with 100 micromol/L rutin and in mixed primary cultures treated with 50 and 100 micromol/L, suggesting different sensitivity of both activated cell types. These results demonstrated that rutin affects astrocytes and microglial cells in culture and has the capacity to induce NO and TNFalpha production in these cells. Hence, the impact of these effects on neurons in vitro and in vivo needs to be studied.

Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Microglia/citologia , Microglia/efeitos dos fármacos , Óxido Nítrico/metabolismo , Rutina/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Animais , Bisbenzimidazol , Western Blotting , Morte Celular/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Meios de Cultura , Proteína Glial Fibrilar Ácida/metabolismo , Imuno-Histoquímica , Masculino , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/biossíntese
Toxicon ; 49(5): 601-14, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17241650


Prosopis juliflora is used for feeding cattle and humans. Intoxication with the plant has been reported, and is characterized by neuromuscular alterations and gliosis. Total alkaloidal extract (TAE) was obtained using acid/basic-modified extraction and was fractionated. TAE and seven alkaloidal fractions, at concentrations ranging 0.03-30 microg/ml, were tested for 24h on astrocyte primary cultures derived from the cortex of newborn Wistar rats. The MTT test and the measure of LDH activity on the culture medium, revealed that TAE and fractions F29/30, F31/33, F32 and F34/35 were cytotoxic to astrocytes. The EC(50) values for the most toxic compounds, TAE, F31/33 and F32 were 2.87 2.82 and 3.01 microg/ml, respectively. Morphological changes and glial cells activation were investigated through Rosenfeld's staining, by immunocytochemistry for the protein OX-42, specific of activated microglia, by immunocytochemistry and western immunoblot for GFAP, the marker of reactive and mature astrocytes, and by the production of nitric oxide (NO). We observed that astrocytes exposed to 3 microg/ml TAE, F29/30 or F31/33 developed compact cell body with many processes overexpressing GFAP. Treatment with 30 microg/ml TAE and fractions, induced cytotoxicity characterized by a strong cell body contraction, very thin and long processes and condensed chromatin. We also observed that when compared with the control (+/-1.34%), the proportion of OX-42 positive cells was increased in cultures treated with 30 microg/ml TAE or F29/30, F31/33, F32 and F34/35, with values raging from 7.27% to 28.74%. Moreover, incubation with 3 microg/ml F32, 30 microg/ml TAE, F29/30, F31/33 or F34/35 induced accumulation of nitrite in culture medium indicating induction of NO production. Taken together these results show that TAE and fractionated alkaloids from P. juliflora act directly on glial cells, inducing activation and/or cytotoxicity, stimulating NO production, and may have an impact on neuronal damages observed on intoxicated animals.

Alcaloides/toxicidade , Astrócitos/efeitos dos fármacos , Óxido Nítrico/metabolismo , Prosopis/química , Alcaloides/isolamento & purificação , Análise de Variância , Animais , Animais Recém-Nascidos , Astrócitos/citologia , Astrócitos/metabolismo , Western Blotting , Antígeno CD11b/metabolismo , Fracionamento Químico , Imuno-Histoquímica , L-Lactato Desidrogenase/metabolismo , Ratos , Ratos Wistar , Sais de Tetrazólio , Tiazóis