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1.
EXCLI J ; 14: 1-20, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26417349

RESUMO

The aim of this study was to investigate the antioxidant activity of the methanolic extracts of Filipendula hexapetala Gilib. aerial parts (FHA) and roots (FHR) and their potential in different model systems, as well as antimicrobial activity. According to this, a number of assays were employed to evaluate the antioxidant and antimicrobial potential of F. hexapetala extracts. In addition, the antioxidant activity assays in different model systems were carried out, as well as pH, thermal and gastrointestinal stability studies. The phenolic compounds contents in FHA and FHR were also determined. The results showed that F. hexapetala extracts had considerable antioxidant activity in vitro and a great stability in different conditions. The extracts exhibited antimicrobial activity against most of the tested bacterial and fungal species. Also, the extracts contain high level of phenolic compounds, especially aerial parts extract.

2.
Food Funct ; 5(8): 1795-803, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24912992

RESUMO

The objective of this work was to investigate the effects of the methanol extracts of Gentiana cruciata L. aerial parts (GCA) and roots (GCR) against carbon tetrachloride-induced liver injury in rats. Pretreatment with GCA and GCR, containing sweroside, swertiamarin and gentiopicrin in high concentrations, dose-dependently and significantly decreased the levels of serum transaminases, alkaline phosphatase and total bilirubin, whereas an increase in the level of total protein was found compared with the CCl4-treated group. Moreover, oral administration of extracts significantly enhanced antioxidant enzyme activities (superoxide dismutase and catalase), increased the content of glutathione and decreased the content of TBARS. Microscopic evaluations of the liver revealed CCl4-induced lesions and related toxic manifestations that were minimal in the liver of rats pretreated with extracts at the dose of 400 mg per kg b.w. The results suggest that the use of G. cruciata extracts has a merit as a potent candidate in protecting the liver against chemical induced toxicity.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Gentiana/química , Iridoides/farmacologia , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Antioxidantes/farmacologia , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Biomarcadores/sangue , Tetracloreto de Carbono/toxicidade , Catalase/metabolismo , Relação Dose-Resposta a Droga , Glutationa/metabolismo , Glucosídeos Iridoides/farmacologia , Fígado/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Raízes de Plantas/química , Pironas/farmacologia , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
3.
Chem Biodivers ; 11(1): 140-9, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24443434

RESUMO

The chemical composition and the antimicrobial activity of the essential oil isolated from the aerial parts of Hypericum maculatum Crantz were determined. In total, 109 compounds were identified, with germacrene D (21.5%), nonane (6.5%), (E)-ß-farnesene (5.3%), δ-cadinene (4.5%), and ledol (4.4%) as the main constituents. The chemical compositions of this oil and of four previously studied H. maculatum oils were compared using multivariate statistical analyses, viz., agglomerative hierarchical cluster and principal component analyses. Based on the results, the interrelationship among the hitherto studied H. maculatum oil samples, including the oil characterized here, was discussed. The study of the antimicrobial potential of the oil against five bacterial and two fungal strains showed that the oil had mainly moderate antimicrobial effects.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Bactérias/efeitos dos fármacos , Fungos/efeitos dos fármacos , Hypericum/química , Óleos Voláteis/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antifúngicos/química , Antifúngicos/isolamento & purificação , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Relação Estrutura-Atividade
4.
Eur J Pharm Sci ; 55: 20-35, 2014 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-24468630

RESUMO

Eight synthesized 3-(1-aminoethylidene)chroman-2,4-diones and 4-hydroxy-3-(1-iminoethyl)-2H-chromen-2-ones were evaluated as in vivo anticoagulants by intraperitoneal application to adult male Wistar rats in order to examine their pharmacological potential, evaluate ther toxicity and propose the mechanism of action. Two of them, 2f and 2a, in concentration of 2mg/kg of body weight, presented remarkable activity (PT=130s; PT=90s) upon seven days of continuous application. The results of rat serum and liver biochemical screening, as well those of histopathological studies, proved the compounds to be non-toxic. Activity of the compounds was further examined on the molecular level. Here, molecular docking studies were performed to position the compounds in relation to the active site of VKORC1 and determine the bioactive conformations. Docking results suggested a non-covalent mode of action during which the proton transfer occurs from Cys135 SH towards 4-carbonyl group of anticoagulant. All crucial interactions for anticoagulant activity were confirmed in generated structure-based 3-D pharmacophore model, consisted of hydrogen bond acceptor and hydrophobic aromatic features, and quantified by a best correlation coefficient of 0.97.


Assuntos
Anticoagulantes/síntese química , Anticoagulantes/farmacologia , Coagulação Sanguínea/efeitos dos fármacos , Desenho de Fármacos , Imidazóis/síntese química , Imidazóis/farmacologia , Simulação de Acoplamento Molecular , Vitamina K Epóxido Redutases/antagonistas & inibidores , Animais , Anticoagulantes/metabolismo , Anticoagulantes/toxicidade , Sítios de Ligação , Relação Dose-Resposta a Droga , Imidazóis/metabolismo , Imidazóis/toxicidade , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Conformação Molecular , Estresse Oxidativo/efeitos dos fármacos , Tempo de Protrombina , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Vitamina K Epóxido Redutases/química , Vitamina K Epóxido Redutases/metabolismo
5.
Biochem Pharmacol ; 86(9): 1376-96, 2013 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-23973524

RESUMO

Considering the controversial results concerning the antimutagenicity of some phenolic compounds recorded in the literature, the antigenotoxic effects of four selected phenolic compounds, myricetin, quercetin, rutin, and rosmarinic acid, against DNA damage induced by alkylation with ethyl methanesulfonate (EMS), were evaluated in Drosophila melanogaster males using the sex-linked recessive lethal (SLRL) test. To assess the protective effects against DNA damage, D. melanogaster males were exposed to a monofunctional alkylating agent EMS in concentration of 0.75 ppm, 24 h prior to one of the selected phenolic compounds in the concentration of 100 ppm. The possible differences in mechanisms of protection by selected compounds were determined by molecular docking, after which structure-based 3-D pharmacophore models were generated. EMS induced considerable DNA damage as shown by significant increase in the frequency of germinative mutations. The frequency decreased with high significance (p<0.001***) after post-treatments with all selected phenolic compounds. Further, docking analysis revealed EMS pre-bond conformations against guanine and thymine as a necessary condition for alkylation, after which resulting O6-ethylguanine and O4-ethylthimine were docked into the active site of O6-alkylguanine-DNA alkyltransferase to confirm that particular lesions are going to be repaired. Finally, myricetin and quercetin protected dealkylated nucleotides from further EMS alkylation by forming the strong hydrogen bonds with O6-guanine and O4-thymine via B ring hydroxyl group (bond lengths lower than 2.5 Å). On the other side, rutin and rosmarinic acid encircled nucleotides and by fulfilling the EMS binding space they made an impermeable barrier for the EMS molecule and prevented further alkylation.


Assuntos
Antimutagênicos/farmacologia , Cinamatos/farmacologia , Depsídeos/farmacologia , Flavonoides/farmacologia , Quercetina/farmacologia , Rutina/farmacologia , Alquilantes/química , Alquilantes/toxicidade , Animais , Antimutagênicos/química , Sítios de Ligação , Domínio Catalítico , Cinamatos/química , Dano ao DNA/efeitos dos fármacos , Depsídeos/química , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/genética , Metanossulfonato de Etila/toxicidade , Flavonoides/química , Guanina/análogos & derivados , Guanina/química , Guanina/metabolismo , Masculino , Simulação de Acoplamento Molecular , Método de Monte Carlo , Mutação , O(6)-Metilguanina-DNA Metiltransferase/química , O(6)-Metilguanina-DNA Metiltransferase/metabolismo , Quercetina/química , Rutina/química , Timina/análogos & derivados , Timina/química , Timina/metabolismo , Ácido Rosmarínico
6.
Mutat Res ; 755(2): 81-9, 2013 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-23830930

RESUMO

The present study was undertaken to investigate the hepatoprotective effect of the methanol extract of Cotinus coggygria Scop. in rats exposed to the hepatotoxic compound pyrogallol. Assessed with the alkaline version of the comet assay, 1000 and 2000mg/kg body weight (bw) of the extract showed a low level of genotoxicity, while 500mg/kg bw of the extract showed no genotoxic potential. Quantitative HPLC analysis of phenolic acids and flavonoids in the methanol extract of C. coggygria showed that myricetin was a major component. To test the hepatoprotective effect, a non-genotoxic dose of the C. coggygria extract and an equivalent amount of synthetic myricetin, as present in the extract, were applied either 2 or 12h prior to administration of 100mg/kg bw of pyrogallol. The extract and myricetin promoted restoration of hepatic function by significantly reducing pyrogallol-induced elevation in the serum enzymes AST, ALT, ALP and in total bilirubin. As measured by the decrease in total score and tail moment, the DNA damage in liver was also reduced by the extract and by myricetin. Our results suggest that pro-surviving Akt activity and STAT3 protein expression play important roles in decreasing DNA damage and in mediating hepatic protection by the extract. These results suggest that myricetin, as a major component in the extract, is responsible for the antigenotoxic and hepatoprotective properties of the methanol extract of C. coggygria against pyrogallol-induced toxicity.


Assuntos
Anacardiaceae/química , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Dano ao DNA/efeitos dos fármacos , Flavonoides/farmacologia , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Pirogalol/toxicidade , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Ensaio Cometa , Flavonoides/isolamento & purificação , Sequestradores de Radicais Livres/isolamento & purificação , Sequestradores de Radicais Livres/farmacologia , Hidroxibenzoatos/isolamento & purificação , Hidroxibenzoatos/farmacologia , Masculino , Metanol , Caules de Planta/química , Plantas Medicinais/química , Ratos , Ratos Wistar , Solventes
7.
Phytochemistry ; 94: 159-70, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23827325

RESUMO

The non polar extract of Centaurea pannonica (Heuff.) Simonk., growing wild in Serbia, was studied and twenty-five compounds including 14 sesquiterpene lactones, 7 flavonoids, 3 lignans and 1 phenylpropanoid glycoside were isolated. All compounds were isolated for the first time from this species. Among them, one germacranolide 2α-hydroxy, 8-dehydroxy 15-O-methacrylate salonitenolide (1) and two guaianolides 2α,8α-dihydroxy-dehydrocostus lactone (2) and pannonin (3) are new natural compounds. The structures of the compounds were established on the basis of spectroscopic analyses (UV, IR, HREIMS and 1D & 2D NMR). The chemical profile of C. pannonica, which belongs to the "Centaurea jacea" group, was compared to previously studied taxa of the same group and used to assess the phylogenetic relationships in the group.


Assuntos
Centaurea/química , Componentes Aéreos da Planta/química , Extratos Vegetais/química , Centaurea/classificação , Centaurea/metabolismo , Flavonoides/análise , Flavonoides/química , Lactonas/análise , Lactonas/química , Espectroscopia de Ressonância Magnética , Conformação Molecular , Estrutura Molecular , Componentes Aéreos da Planta/metabolismo , Extratos Vegetais/análise , Extratos Vegetais/isolamento & purificação , Sérvia , Sesquiterpenos/análise , Sesquiterpenos/química , Sesquiterpenos de Germacrano/análise , Sesquiterpenos de Germacrano/química , Especificidade da Espécie
8.
Food Chem Toxicol ; 52: 83-90, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23146698

RESUMO

This study is an attempt to evaluate the hepatoprotective activity of Gentiana asclepiadea L. against carbon tetrachloride-induced liver injury in rats. Methanol extracts of aerial parts (GAA) and roots (GAR) of G. asclepiadea at doses of 100, 200, and 400mg/ kg b.w. were orally administered to Wistar rats once daily for 7 days before they were treated with CCl(4). The hepatoprotective activity of the extracts in this study was compared with the reference drug silymarin. In CCl(4) treated animals, GAA and GAR significantly decreased levels of serum transaminases, alkaline phosphatase and total bilirubin, and increased the level of total protein. Treatment with the extracts resulted in a significant increase in the levels of catalase, superoxide dismutase and reduced glutathione, accompanied with a marked reduction in the levels of malondialdehyde, as compared to CCl(4) treated group. The histopathological studies confirmed protective effects of extracts against CCl(4)-induced liver injuries. No genotoxicity was observed in liver cells after GAA treatment, while GAR showed only slight genotoxic effects by comet assay. Phytochemical analysis revealed the presence of sweroside, swertiamarin and gentiopicrin in high concentrations in both extracts. It could be concluded that the use of G. asclepiadea extracts in the treatment of chemical-induced hepatotoxicity.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Gentiana/química , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Fosfatase Alcalina/sangue , Animais , Bilirrubina/sangue , Tetracloreto de Carbono/toxicidade , Catalase/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Relação Dose-Resposta a Droga , Glutationa/metabolismo , Glucosídeos Iridoides/análise , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Malondialdeído/metabolismo , Testes de Mutagenicidade , Pironas/análise , Ratos , Ratos Wistar , Silimarina/farmacologia , Superóxido Dismutase/sangue , Superóxido Dismutase/metabolismo , Testes de Toxicidade Aguda
9.
EXCLI J ; 12: 807-23, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-26622219

RESUMO

The aim of this study was to evaluate the antioxidant and antigenotoxic activities of chloroform, ethyl acetate and n-butanol fractions obtained from Gentiana asclepiadea L. roots methanolic extract. The main secondary metabolites sweroside, swertiamarin and gentiopicrine were quantified in G. asclepiadea root extracts using HPLC-DAD analysis. Amount of total phenols, flavonoids, flavonols and gallotannins was also determined. The antigenotoxic potential of extracts from roots of G. asclepiadea was assessed using the standard in vivo procedure for the detection of sex linked recessive lethal mutations in Drosophila melanogaster males treated with ethyl methanesulfonate (EMS). The results showed that the most abundant secoiridoid in G. asclepiadea roots was gentiopicrine and its content in the n-butanol fraction (442.89 mg/g) was the highest. Among all extracts, ethyl acetate fraction showed the highest antioxidant activity, as well as total phenolics (146.64 GAE/g), flavonoids (44.62 RUE/g), flavonols (22.71 RUE/g) and gallotannins (0.99 mg GAE/g) content. All the fractions showed antioxidant activity using in vitro model systems and the results have been correlated with total phenolics, flavonoids, flavonols and gallotannins content. In addition to antioxidant activity, G. asclepiadea root extract fractions possess an antigenotoxic effect against DNA damage induced by alkylation with EMS. The antioxidant activity exhibited by G. asclepiadea depended on the phenolic compounds content of the tested extracts, while there was no significant difference in the antigenotoxic potential between fractions.

10.
J Biochem Mol Toxicol ; 26(8): 322-30, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22777752

RESUMO

The in vivo sex-linked recessive lethal test was carried out in Drosophila melanogaster to investigate whether or not five substituted 4-hydroxy-2H-chromen-2-ones can modulate the genotoxicity of the well-established mutagenic agent ethyl methanesulfonate (EMS). For this purpose, 3 days old Canton S males were treated with the potent mutagen EMS alone in concentration of 0.75 ppm, as well as in combination with one of the five 4-hydroxycoumarins, namely diethyl 2-(1-(4-hydroxy-2-oxo-2H-chromen-3-yl)ethylidene)malonate (2b), 3-(1-(4-hydroxy-2-oxo-2H-chromen-3-yl)ethylidene)pentane-2,4-dione (6b), 4-(4-(4-hydroxy-2-oxo-2H-chromen-3-yl)thiazol-2-ylamino) benzenesulfonic acid (4c), 4-hydroxy-3-(2-(2-nitropheny lamino)thiazol-4-yl)-2H-chromen-2-one (9c), and (E)-4-hydroxy-3-(1-(m-tolylimino)ethyl)-2H-chromen-2-one (5d), in concentration of 70 ppm. The frequency of germinative mutations increased significantly after the treatment with EMS and decreased after treatments with coumarins. The maximum reduction was observed after treatments with 2b, 6b, 4c, and 5d. By the formation of hydrogen bonds or electrostatic interactions with O(6) of DNA guanine, tested coumarins prevent EMS-induced alkylation. The results indicate a protective role of five 4-hydroxycoumarins under the action of a strong mutagen.


Assuntos
Antimutagênicos/farmacologia , Benzopiranos/farmacologia , DNA/química , Drosophila melanogaster/genética , Animais , Simulação por Computador , Drosophila melanogaster/efeitos dos fármacos , Metanossulfonato de Etila/química , Metanossulfonato de Etila/toxicidade , Feminino , Genes Recessivos , Masculino , Modelos Moleculares , Método de Monte Carlo , Mutagênicos/química , Mutagênicos/toxicidade , Mutação/efeitos dos fármacos , Conformação de Ácido Nucleico , Cromossomos Sexuais/genética
11.
Eur J Med Chem ; 54: 144-58, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22633008

RESUMO

The objective of this study was to investigate in vitro and in vivo anticoagulant activity of sixteen 4-hydroxycoumarin derivatives bearing polar C-3 scaffolds. The activity was evaluated by measuring prothrombin time. Enhanced anticoagulant activity in vitro was observed for all tested compounds. Upon successive administration of 0.5 mg/kg of body weight to adult Wistar rats, over a period of five days, four derivatives (2b, 4c, 5c and 9c) presented anticoagulant activity in vivo. The most active compound was 2b, with PT = 30.0 s. Low or non-toxic effects in vivo were determined based on the catalytic activity of liver enzymes and the concentration of bilirubin, iron and proteins. Metabolic pathways of the most active compounds in vivo were determined after GC/MS analysis of collected rat urine samples. The excretion occurs by glucuronidation of 7-hydroxy forms of tested derivatives. In vivo results were described using PLS-based CoMFA and CoMSIA 3D-QSAR studies, which showed CoMFA-SE (q(2) = 0.738) and CoMSIA-SEA (q(2) = 0.763) to be the statistically most relevant models. Furthermore, molecular docking and DFT mechanistic studies performed on the rat VKORC1 homology model revealed interactions between the 4-OH coumarin group in the form of phenolic anion and the Cys135 catalytic site in the transition state.


Assuntos
Anticoagulantes/química , Anticoagulantes/farmacologia , Cumarínicos/química , Cumarínicos/farmacologia , Animais , Anticoagulantes/administração & dosagem , Anticoagulantes/metabolismo , Cumarínicos/administração & dosagem , Cumarínicos/metabolismo , Desenho de Fármacos , Humanos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Oxigenases de Função Mista/química , Oxigenases de Função Mista/metabolismo , Simulação de Acoplamento Molecular , Conformação Proteica , Teoria Quântica , Ratos , Ratos Wistar , Homologia de Sequência de Aminoácidos , Vitamina K Epóxido Redutases
12.
J Med Food ; 14(12): 1617-23, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21877950

RESUMO

This study was aimed at evaluating the antioxidant activity and efficacy of the ethanolic extract of the endemic plant species Kitaibelia vitifolia in inhibiting the growth of selected fungi and bacteria. Antimicrobial activity was tested using the broth dilution procedure for determination of minimum inhibitory concentration (MIC). MICs were determined for eight selected indicator strains. The highest susceptibility to K. vitifolia ethanolic extract among the bacteria tested was exhibited by Bacillus subtilis ATCC 6633, Staphylococcus aureus ATCC 25923, and Klebsiella pneumoniae ATCC 13883 (MIC=15.62 µg/mL), followed by Escherichia coli ATCC 25922 and Proteus mirabilis ATCC 14153 (MIC=31.25 µg/mL), and Proteus vulgaris ATCC 13315 (MIC=62.50 µg/mL). Of the fungi, Candida albicans ATCC 10231 (MIC=15.62 µg/mL) showed the highest susceptibility, and Aspergillus niger ATCC 16404 (MIC=31.25 µg/mL) had the lowest. Results showed that K. vitifolia extract possesses antioxidant activity, with total antioxidant capacity of 75.45±0.68 µg of ascorbic acid/g and 50% inhibition concentration values of 47.45±0.55 µg/mL for 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity, 35.35±0.68 µg/mL for inhibitory activity against lipid peroxidation, 95.25±0.52 µg/mL for hydroxyl radical scavenging activity, and 31.50±0.35 µg/mL for metal chelating activity. Total phenolics, flavonoids, condensed tannins, and gallotannins were 85.25±0.69 mg of gallic acid (GA)/g, 45.32±0.55 mg of rutin/g, 54.25±0.75 mg of GA/g, and 41.74±0.55 mg of GA/g, respectively. The phenolic composition of K. vitifolia extract was determined by high-performance liquid chromatography. Rosmarinic acid was found to be the dominant phenolic compound of the extract.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Sequestradores de Radicais Livres/farmacologia , Malvaceae/química , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Aspergillus niger , Bacillus subtilis/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Flavonoides/farmacologia , Ácido Gálico/farmacologia , Klebsiella pneumoniae/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Proteus mirabilis/efeitos dos fármacos , Proteus vulgaris/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos
13.
Int J Mol Sci ; 12(7): 4190-205, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21845072

RESUMO

This study deals with total phenolic content, antiproliferative and proapoptotic activity of methanolic extracts from different Teucrium species and the effect on the prooxidant/antioxidant status in HCT-116 cells. The total phenolic content of the extracts was measured spectrophotometricaly and the obtained results ranged from 56.62 mg/g to 172.50 mg GA/g. The antiproliferative activity of methanolic extracts from different Teucrium species was determined using MTT cell viability assay, where IC(50) value was used as a parameter for cytotoxicity. The type of cell death was explored by fluorescence microscopy using the acridin orange/ethidium bromide method. MTT assay showed that all extracts significantly reduced cell viability in a dose-dependent manner, with very low IC(50) values. The highest content of phenolic compounds and the best cytotoxic activity on HCT-116 cells after 24 h of exposure was in T. chamaedrys extract, with IC(50) values of 5.48 × 10(-9) µg/mL. After 72 h, methanolic extract of T. arduini appeared to have the best cytotoxic activity on HCT-116, with IC(50) values of 0.37 µg/mL. Treatments caused typical apoptotic morphological changes in HCT-116 cells and showed a high percentage of apoptotic cells. The results of the presented research indicate that some Teucrium extracts are a very rich source of phenols, which may directly contribute to high antiproliferative and proapoptotic activity.


Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/química , Apoptose/efeitos dos fármacos , Extratos Vegetais/química , Teucrium/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antioxidantes/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Células HCT116 , Humanos , Óxido Nítrico/química , Óxido Nítrico/metabolismo , Fenóis/química , Fenóis/isolamento & purificação , Fenóis/farmacologia , Superóxidos/química , Teucrium/metabolismo
14.
Can J Physiol Pharmacol ; 89(6): 401-11, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21770795

RESUMO

To examine the protective potential of the Cotinus coggygria Scop. methanol extract, Wistar rats were treated with the hepatotoxic compound pyrogallol, which possesses a potent ability to generate free radicals and induce oxidative stress. The ability of the extract to counteract the oxidative stress was examined in rats that were injected with the extract intraperitoneally (500 mg·(kg body weight)(-1)) either 2 or 12 h before the pyrogallol treatment. The extract possesses a reducing activity in vitro and an ability to chelate the ferrous ion both in vivo and in vitro. Application of the extract prior to pyrogallol treatment led to a decrease in the levels of thiobarbituric acid-reactive substances, aspartate aminotransferase, and alanine aminotransferase, increased activities of antioxidant enzymes and attenuation of DNA damage, as well as increased Akt activity and inhibition of NF-κB protein expression. Treatment with the extract 12 h prior to pyrogallol administration was more effective in suppressing pyrogallol-induced oxidative damage than the 2 h pretreatment. Extract administration promoted an increase in acute phase reactants haptoglobin and α(2)-macroglobulin that was short of a full-fledged acute phase response. Administration of the extract considerably improved the markers of oxidative stress, thus revealing a potential hepatoprotective activity. Our results suggest that Akt activation, NF-κB inhibition, and induction of the acute phase play important roles in mediating hepatic protection by the extract. The greater effectiveness of the 12 h pretreatment with extract points to the important role that preconditioning assumes in improving resistance to subsequent exposure to oxidative stress.


Assuntos
Anacardiaceae , Antioxidantes/farmacologia , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Pirogalol/toxicidade , Animais , Catalase/metabolismo , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/enzimologia , Masculino , NF-kappa B/metabolismo , Oxirredução/efeitos dos fármacos , Caules de Planta , Substâncias Protetoras/farmacologia , Pirogalol/farmacologia , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fatores de Tempo
15.
Genet Mol Biol ; 34(2): 298-303, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21734833

RESUMO

The intention was to evaluate the possible in vivo genotoxic potential in different cell-types, of a methanol extract obtained from the plant stem of Cotinus coggygria Scop., using the sex-linked recessive lethal (or SLRL) test and alkaline comet assay. The SLRL test, revealed the genotoxic effect of this extract in postmeiotic and premeiotic germ-cell lines. The comet assay was carried out on rat liver and bone marrow at 24 and 72 h after intraperitoneal administration. For genotoxic evaluation, three concentrations of the extract were tested, viz., 500, 1000 and 2000 mg/kg body weight (bw), based on the solubility limit of the extract in saline. Comet tail moment and total scores in the group treated with 500 mg/kg bw, 24 and 72 h after treatment, were not significantly different from the control group, whereas in the groups of animals, under the same conditions, but with 1000 and 2000 mg/kg bw of the extract, scores were statistically so. A slight decrease in the comet score and tail moment observed in all the doses in the 72 h treatment, gave to understand that DNA damage induced by Cotinus coggygria extract decreased with time. The results of both tests revealed the genotoxic effect of Cotinus coggygria under our experimental conditions.

16.
Int J Mol Sci ; 12(5): 2822-41, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21686153

RESUMO

The series of fifteen synthesized 4-hydroxycoumarin derivatives was subjected to antioxidant activity evaluation in vitro, through total antioxidant capacity, 1,1-diphenyl-2-picryl-hydrazyl (DPPH), hydroxyl radical, lipid peroxide scavenging and chelating activity. The highest activity was detected during the radicals scavenging, with 2b, 6b, 2c, and 4c noticed as the most active. The antioxidant activity was further quantified by the quantitative structure-activity relationships (QSAR) studies. For this purpose, the structures were optimized using Paramethric Method 6 (PM6) semi-empirical and Density Functional Theory (DFT) B3LYP methods. Bond dissociation enthalpies of coumarin 4-OH, Natural Bond Orbital (NBO) gained hybridization of the oxygen, acidity of the hydrogen atom and various molecular descriptors obtained, were correlated with biological activity, after which we designed 20 new antioxidant structures, using the most favorable structural motifs, with much improved predicted activity in vitro.


Assuntos
4-Hidroxicumarinas/química , Antioxidantes/química , Sequestradores de Radicais Livres/química , Compostos de Bifenilo/química , Radicais Livres/química , Peróxidos Lipídicos/química , Modelos Moleculares , Picratos/química , Relação Quantitativa Estrutura-Atividade , Relação Estrutura-Atividade
17.
Genet. mol. biol ; Genet. mol. biol;34(2): 298-303, 2011. tab
Artigo em Inglês | LILACS | ID: lil-587755

RESUMO

The intention was to evaluate the possible in vivo genotoxic potential in different cell-types, of a methanol extract obtained from the plant stem of Cotinus coggygria Scop., using the sex-linked recessive lethal (or SLRL) test and alkaline comet assay. The SLRL test, revealed the genotoxic effect of this extract in postmeiotic and premeiotic germ-cell lines. The comet assay was carried out on rat liver and bone marrow at 24 and 72 h after intraperitoneal administration. For genotoxic evaluation, three concentrations of the extract were tested, viz., 500, 1000 and 2000 mg/kg body weight (bw), based on the solubility limit of the extract in saline. Comet tail moment and total scores in the group treated with 500 mg/kg bw, 24 and 72 h after treatment, were not significantly different from the control group, whereas in the groups of animals, under the same conditions, but with 1000 and 2000 mg/kg bw of the extract, scores were statistically so. A slight decrease in the comet score and tail moment observed in all the doses in the 72 h treatment, gave to understand that DNA damage induced by Cotinus coggygria extract decreased with time. The results of both tests revealed the genotoxic effect of Cotinus coggygria under our experimental conditions.

18.
Nat Prod Commun ; 5(10): 1663-8, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21121269

RESUMO

The chemical composition and antimicrobial activity of the essential oils obtained by hydrodistillation from Centaurea pannonica (Heufel) Simonkai and C. jacea L. (Asteraceae), were investigated. The essential oils were analyzed by GC and GC-MS. Forty five and twenty nine compounds were identified in the two oils, respectively. C. pannonica oil was rich in fatty acids (43.7%), with 9-octadecanoic acid (34.0%) and (Z,Z)-9,12-octadecadienoic acid (8.6%) as the major compounds. In contrast, the essential oil of C. jacea was dominated by oxygenated sesquiterpenes (43.2%), among which caryophyllene oxide (23.5%) and spathulenol (8.9%) were the major constituents. However, the oil was also characterized by an important fatty acid fraction (15.5%), with 9-octadecanoic acid (8.9%) and hexadecanoic acid (6.6%) being the main components. The antimicrobial activities of the essential oils were evaluated by the microdilution method against three Gram-positive and three Gram-negative bacteria, and one yeast. Both oils exhibited significant antimicrobial activity, especially against Gram-positive bacteria.


Assuntos
Anti-Infecciosos/isolamento & purificação , Centaurea/química , Óleos Voláteis/química , Testes de Sensibilidade Microbiana , Óleos Voláteis/isolamento & purificação
19.
Molecules ; 15(6): 4294-308, 2010 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-20657442

RESUMO

This paper presents the design of novel 4-hydroxy-chromene-2 one derivatives, based on previously obtained minimal inhibitory concentration values (MICs), against twenty four microorganism cultures, gram positive and negative bacteria and fungi. Two of our compounds, 3b (MIC range 130-500 microg/mL) and 9c (31.25-62.5 microg/mL), presented high potential antimicrobial activity. The compound 9c had equal activity to the standard ketoconazole (31.25 microg/mL) against M. mucedo. Enlarged resistance of S. aureus, E. coli and C. albicans on the effect of potential drugs and known toxicity of coumarin antibiotics, motivated us to establish SAR and QSAR models of activity against these cultures and correlate biological activity, molecular descriptors and partial charges of functional groups to explain activity and use for the design of new compounds. The QSAR study presents essential relation of antimicrobial activity and dominant substituents, 4-hydroxy, 3-acetyl and thiazole functional groups, also confirmed through molecular docking. The result was ten new designed compounds with much improved predicted inhibition constants and average biological activity.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/síntese química , Cumarínicos/química , Cumarínicos/síntese química , Anti-Infecciosos/farmacologia , Candida albicans/efeitos dos fármacos , Cumarínicos/farmacologia , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Mucor/efeitos dos fármacos , Relação Quantitativa Estrutura-Atividade , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-Atividade
20.
Arch Pharm Res ; 33(1): 5-15, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20191339

RESUMO

Series of imino and amino derivatives of 4-hydroxy coumarins were synthesized via conventional and microwave promoted procedure and evaluated for antioxidant potential through different in vitro models such as (DPPH) free radical scavenging activity, linoleic acid emulsion model system, reducing power assay and phosphomolybdenum method. All prepared compounds possess good antioxidant activity and among them p-nitro-phenyl derivative 6c with IC50 at 25.9 microM possesses radical scavenging activity which is comparable to standard BHT, while the best reducing power was observed in a case of benzyl amino compound 8c (RP50 255.6 microM). Also, observed data indicated that compounds may serve as inhibitors of lipid peroxidation process.


Assuntos
4-Hidroxicumarinas/química , 4-Hidroxicumarinas/síntese química , Antioxidantes/síntese química , Aminas/síntese química , Compostos de Bifenilo/química , Catálise , Emulsões , Sequestradores de Radicais Livres/química , Iminas/síntese química , Indicadores e Reagentes , Ácido Linoleico/química , Peroxidação de Lipídeos , Espectroscopia de Ressonância Magnética , Micro-Ondas , Oxirredução , Picratos/química
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