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1.
Artigo em Inglês | MEDLINE | ID: mdl-28573218

RESUMO

BACKGROUND: Saraphi (Mammea siamensis) is a Thai traditional herb. In this study, the cytotoxic effects of crude ethanolic and fractional extracts including hexane, ethyl acetate, and methanol fractions from M. siamensis flowers were investigated in order to determine their effect on WT1 expression in Molt4 and K562 cells and Bcr/Abl expression in K562 cells. MATERIALS AND METHODS: The flowers of M. siamensis were extracted using ethanol. The ethanol flower extract was further fractionated with hexane, ethyl acetate, and methanol. Cytotoxic effects were measured by the MTT assay. Bcr/Abl and WT1 protein levels after treatments were determined by Western blotting. The total cell number was determined via the typan blue exclusion method. RESULTS: The hexane fraction showed the strongest cytotoxic activity on Molt4 and K562 cells, with IC50 values of 2.6 and 77.6 µg/ml, respectively. The hexane extract decreased Bcr/Abl protein expression in K562 cells by 74.6% and WT1 protein expressions in Molt4 and K562 cells by 68.4 and 72.1%, respectively. Total cell numbers were decreased by 66.2 and 48.7% in Molt4 and K562 cells, respectively. Mammea E/BB (main active compound) significantly decreased both Bcr/Abl and WTlprotein expressions by 75 and 49.5%, respectively when compared to vehicle control. CONCLUSION: The hexane fraction from M. siamensis flowers inhibited cell proliferation via the suppression of WT1 expression in Molt4 and K562 cells and Bcr/Abl expression in K562 cells. The active compound may be mammea E/BB. Extracts from M. siamensis flowers show promise as naturally occurring anti-cancer drugs.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Proteínas de Fusão bcr-abl/metabolismo , Leucemia/tratamento farmacológico , Mammea , Fitoterapia , Extratos Vegetais/uso terapêutico , Proteínas WT1/metabolismo , Antineoplásicos Fitogênicos/farmacologia , Proliferação de Células , Flores , Humanos , Células K562 , Leucemia/metabolismo , Medicina Tradicional , Proteínas Oncogênicas v-abl/metabolismo , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-bcr/metabolismo , Tailândia
2.
Food Chem ; 234: 269-275, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28551236

RESUMO

Our objective was to compare fruit morphology, physico-chemistry and bioactive compounds content of the edible pulp of six Mammea americana accessions. The results showed that this fruit was rather big, weighing on average 600 to 1100g depending on the accession, and spherical to oblate-shaped. The pulp represented between 50 and 70% of the weight of the whole fruit. The pulp adhered only partially to the seeds in 5 of the 6 accessions studied, while the last one exhibited full adherence. The fresh pulp was acidic, sweet, succulent and crunchy. The fruits studied had a variety of qualities, providing various opportunities for post-harvest uses: fruit salads, nectar preparation, jams and jellies, or export. We have established for the first time the total phenolic compounds and total flavonoids contents in the pulp of mamey apple fruits. The pulp colour was highly correlated with total phenolic compounds and total carotenoids contents.


Assuntos
Carotenoides/química , Flavonoides/química , Frutas/química , Mammea/química , Fenóis/química
3.
J Med Food ; 20(5): 485-490, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28504908

RESUMO

The methanol extract of Mammea longifolia Planch. and Triana (M. longifolia) fruit was studied for anticancer and apoptotic effects in the SW480 colon cancer cell line. The apoptotic and necrotic effects of M. longifolia were detected by 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) and lactate dehydrogenase assays, respectively. One hundred µg/mL of the extract killed ∼82.4% of the cells; however, 2% of the death was related to necrosis. The morphological changes in M. longifolia-stimulated SW480 cells were observed directly by light microscopy. DNA fragmentation assay was employed to analyze the apoptosis induction. M. longifolia-treated SW480 cells promoted the expression of Bax, Bad, cleaved-poly-ADP-ribose polymerase (PARP), and p53 proteins and decreased the protein expression of pro-caspases Bcl-2 and Bcl-XL. The ratios of Bax/Bcl-2 and cleaved-PARP/PARP, predictive markers of apoptotic stimuli in cancer, increased and may play an important role in regulating the progression of apoptosis. The results suggested that M. longifolia induces cell death via mitochondrial-related apoptosis in SW480 cells.


Assuntos
Apoptose/efeitos dos fármacos , Neoplasias do Colo/fisiopatologia , Mammea/química , Mitocôndrias/efeitos dos fármacos , Extratos Vegetais/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Linhagem Celular Tumoral , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Fragmentação do DNA/efeitos dos fármacos , Frutas/química , Humanos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Supressora de Tumor p53/genética
4.
BMC Complement Altern Med ; 17(1): 57, 2017 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-28100218

RESUMO

BACKGROUND: The transmission of Dengue virus (DENV) and Chikungunya virus (CHIKV) has increased worldwide, due in part to the lack of a specific antiviral treatment. For this reason, the search for compounds with antiviral potential, either as licensed drugs or in natural products, is a research priority. The objective of this study was to identify some of the compounds that are present in Mammea americana (M. americana) and Tabernaemontana cymosa (T. cymosa) plants and, subsequently, to evaluate their cytotoxicity in VERO cells and their potential antiviral effects on DENV and CHIKV infections in those same cells. METHODS: Dry ethanolic extracts of M. americana and T. cymosa seeds were subjected to open column chromatographic fractionation, leading to the identification of four compounds: two coumarins, derived from M. americana; and lupeol acetate and voacangine derived from T. cymosa.. The cytotoxicity of each compound was subsequently assessed by the MTT method (at concentrations from 400 to 6.25 µg/mL). Pre- and post-treatment antiviral assays were performed at non-toxic concentrations; the resulting DENV inhibition was evaluated by Real-Time PCR, and the CHIKV inhibition was tested by the plating method. The results were analyzed by means of statistical analysis. RESULTS: The compounds showed low toxicity at concentrations ≤ 200 µg/mL. The compounds coumarin A and coumarin B, which are derived from the M. americana plant, significantly inhibited infection with both viruses during the implementation of the two experimental strategies employed here (post-treatment with inhibition percentages greater than 50%, p < 0.01; and pre-treatment with percentages of inhibition greater than 40%, p < 0.01). However, the lupeol acetate and voacangine compounds, which were derived from the T. cymosa plant, only significantly inhibited the DENV infection during the post-treatment strategy (at inhibition percentages greater than 70%, p < 0.01). CONCLUSION: In vitro, the coumarins are capable of inhibiting infection by DENV and CHIKV (with inhibition percentages above 50% in different experimental strategies), which could indicate that these two compounds are potential antivirals for treating Dengue and Chikungunya fever. Additionally, lupeol acetate and voacangine efficiently inhibit infection with DENV, also turning them into promising antivirals for Dengue fever.


Assuntos
Antivirais/uso terapêutico , Febre de Chikungunya/tratamento farmacológico , Dengue/tratamento farmacológico , Mammea/química , Extratos Vegetais/uso terapêutico , Tabernaemontana/química , Animais , Chlorocebus aethiops , Citotoxinas/toxicidade , Mammea/toxicidade , Extratos Vegetais/toxicidade , Tabernaemontana/toxicidade , Células Vero , Replicação Viral/efeitos dos fármacos
5.
Chem Pharm Bull (Tokyo) ; 64(7): 880-5, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27373643

RESUMO

A methanol extract of the flowers of Mammea siamensis (Calophyllaceae) was found to inhibit enzymatic activity against aromatase (IC50=16.5 µg/mL). From the extract, two new geranylated coumarins, mammeasins C (1) and D (2), were isolated together with seven coumarins: 8-hydroxy-5-methyl-7-(3,7-dimethyl-octa-2,6-dienyl)-9-(2-methyl-1-oxobutyl)-4,5-dihydropyrano[4,3,2-de]chromen-2-one (9), 8-hydroxy-5-methyl-7-(3,7-dimethyl-octa-2,6-dienyl)-9-(3-methyl-1-oxobutyl)-4,5-dihydropyrano[4,3,2-de]chromen-2-one (10), mammeas A/AA (14), A/AB (15), A/AA cyclo D (18), E/BA (23), and E/BC cyclo D (25). The structures of 1 and 2 were elucidated on the basis of spectroscopic evidence. Among the isolates including 17 previously reported coumarins, 1 (IC50=2.7 µM), 2 (3.6 µM), and mammea B/AB cyclo D (21, 3.1 µM) showed relatively strong inhibitory activities comparable to the activity of the synthetic nonsteroidal aromatase inhibitor aminoglutethimide (2.0 µM).


Assuntos
Inibidores da Aromatase/farmacologia , Aromatase/metabolismo , Cumarínicos/farmacologia , Flores/química , Mammea/química , Inibidores da Aromatase/química , Inibidores da Aromatase/isolamento & purificação , Cumarínicos/química , Cumarínicos/isolamento & purificação , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Proteínas Recombinantes/metabolismo , Relação Estrutura-Atividade
6.
BMC Complement Altern Med ; 16: 130, 2016 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-27193767

RESUMO

BACKGROUND: Wilms' tumor 1 (WT1) is a biological marker for predicting leukemia progression. In this study, mammea E/BB, an active compound from Saraphi (Mammea siamensis) seed extract was examined for its effect on down-regulatory mechanism of WT1 gene expression, WT1 protein and mRNA stability, and cell proliferation in K562 cell line. METHODS: M. siamensis seeds were obtained from the region of Chiang Mai (North of Thailand). Mammea E/BB was extracted from seeds of M. siamensis. WT1 protein expression and stability were evaluated by Western blot analysis. WT1 mRNA stability was assessed by qRT-PCR. WT1-DNA binding and WT1 promoter activity were assayed by ChIP assay and luciferase-reporter assay, respectively. Cell cycle arrest was studied by flow cytometry. RESULTS: Treatment with mammea E/BB led to down-regulation of WT1 expression. The suppression of WT1 expression did not involve protein and mRNA degradation. Rather, WT1 protein was down-regulated through disruption of transcriptional auto-regulation of the WT1 gene. Mammea E/BB inhibited WT1-DNA binding at the WT1 promoter and decreased luciferase activity. It also disrupted c-Fos/AP-1 binding to the WT1 promoter via ERK1/2 signaling pathway and induced S phase cell cycle arrest in K562 cells. CONCLUSION: Mammea E/BB had pleotropic effects on kinase signaling pathways, resulting in inhibition of leukemia cell proliferation.


Assuntos
Cumarínicos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Mammea/química , Extratos Vegetais/farmacologia , Proteínas WT1/biossíntese , Proliferação de Células/efeitos dos fármacos , Cumarínicos/química , Humanos , Células K562 , Estrutura Molecular , Estabilidade de RNA/efeitos dos fármacos , RNA Neoplásico , Proteínas WT1/genética
7.
Nat Prod Res ; 30(4): 443-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25738951

RESUMO

Mammea siamensis is used in traditional Thai medicine. This study was designed to extract and isolate an active compound from the M. siamensis seeds and to investigate its activity on Wilms' tumour 1 (WT1) protein expression in K562 cells. WT1 is a transcription factor that stimulates cell proliferation. The ethanol saraphi seed (ESS) extract was fractionated using n-hexane, ethyl acetate, n-butanol and water to obtain n-hexane saraphi seed (HSS), ethyl acetate saraphi seed (EASS), n-butanol saraphi seed (BSS), and water saraphi seed (WSS) extracts, respectively. The ESS, HSS and EASS extracts had strong cytotoxic effects on K562 cells in the MTT assay. All three fractions decreased WT1 protein levels and decreased total cell numbers. The HSS extract decreased the WT1 protein levels in a time- and dose-dependent manner. HPLC and NMR analyses indicated that the active compound of HSS was mammea E/BB. M. siamensis seeds are thus identified as a promising source of bioactive compounds for potential inhibition of WT1 protein expression.


Assuntos
Cumarínicos/farmacologia , Mammea/química , Extratos Vegetais/farmacologia , Proteínas WT1/metabolismo , Cromatografia Líquida de Alta Pressão , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Humanos , Células K562/efeitos dos fármacos , Estrutura Molecular , Sementes/química
8.
Molecules ; 20(10): 17735-46, 2015 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-26404214

RESUMO

Through dereplication analysis, seven known Mammea coumarins were identified in a fraction obtained from Mammea neurophylla dichloromethane bark extract selected for its ability to prevent advanced glycation end-product (AGE) formation. Among them, a careful examination of the NMR dataset of pedilanthocoumarin B led to a structural revision. Inspection of LC-DAD-MS(n) chromatograms allowed us to predict the presence of four new compounds, which were further isolated. Using spectroscopic methods (¹H-, (13)C- and 2D-NMR, HRMS, UV), these compounds were identified as new benzoyl substituted 4-phenylcoumarins (iso-pedilanthocoumarin B and neurophyllol C) and 4-(1-acetoxypropyl)coumarins cyclo F (ochrocarpins H and I).


Assuntos
Cumarínicos/química , Mammea/química , Casca de Planta/química , Extratos Vegetais/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular
9.
J Med Assoc Thai ; 97 Suppl 8: S149-55, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25518307

RESUMO

BACKGROUND: Sa-Tri-Lhung-Klod is a Thai traditional medicine remedy for postpartum in the lists of The National Drug List ofHerbal Medicine Products AD. It consists ofseventeen herbs and were obtained by maceration and used in the form of liquor for women's health care such as treatment ofamenorrhea, menopause and blood tonic. In addition, it also usedfor postpartum care for being anti-inflammation in postpartum and prevention of cancer in women. OBJECTIVE: To investigate cytotoxic activity ofSa-Tri-Lhung-Klod remedy extracts and its herbal ingredients against human ovarian carcinoma cell line (SKOV-3) and cervical adenocarcinoma (HeLa) cell line. MATERIAL AND METHOD: Sa-Tri-Lhung-Klod remedy and its plant ingredients were extracted by maceration in 95% ethanol and dried using evaporator. All extracts were testedfor cytotoxic activity by sulforhodamine B (SRB) assay. RESULTS: Ethanolic extract ofSa-Tri-Lhung-Klod remedy displayed cytotoxic activity against SKOV-3 and HeLa with IC50 values of 72.84±1.07 and 47.24±2.83 µg/ml, respectively. It was classified as "less-active" according to the NCI guideline. However, Caesalpinia sappan, Mammea siamensis and Curcuma comosa showed high cytotoxic activity against SKOV-3 with IC50 values of 9.55±1.38 13.45±0.82 and 14.21±1.30 µg/ml, respectively. The ethanolic extracts ofCaesalpiniasappan and Mammea siamensis also exhibited cytotoxic activity against HeLa with IC50 values of 6.30±0.06 and 7.72±0.11 µg/ml, respectively. CONCLUSION: These results support the use of Sa-Tri-Lhung-Klod remedy in Thai traditional medicine for preventing of ovarian cancer and cervical cancer Caesalpinia sappan, Curcuma comosa and Mammea siamensis were strikingly active against ovarian and cervical cancer cells. Their extracts have the potential for developing as new anti-cancer drugs for women health.


Assuntos
Adenocarcinoma , Neoplasias Ovarianas , Extratos Vegetais/farmacologia , Neoplasias do Colo do Útero , Caesalpinia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Curcuma , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Células HeLa , Humanos , Técnicas In Vitro , Mammea , Medicina Tradicional , Plantas Medicinais
10.
Fitoterapia ; 96: 65-75, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24731922

RESUMO

Advanced glycation end-products (AGEs) are associated with many pathogenic disorders such as pathogenesis of diabetes or endothelial dysfunction leading to cardiovascular events. Therefore, the identification of new anti-AGE molecules or extracts aims at preventing such pathologies. Many Clusiaceae and Calophyllaceae species are used in traditional medicines to treat arterial hypertension as well as diabetes. Focusing on these plant families, an anti-AGE plant screening allowed us to select Mammea neurophylla for further phytochemical and biological studies. Indeed, both DCM and MeOH stem bark extracts demonstrated in vitro their ability to prevent inflammation in endothelial cells and to reduce vasoconstriction. A bioguided fractionation of these extracts allowed us to point out 4-phenyl- and 4-(1-acetoxypropyl)coumarins and procyanidins as potent inhibitors of AGE formation, potentially preventing endothelial dysfunction. The fractionation steps also led to the isolation of two new compounds, namely neurophyllols A and B from the DCM bark extract together with thirteen known mammea A and E coumarins (mammea A/AA, mammea A/AB, mammea A/BA, mammea A/BB, mammea A/AA cycloD, mammea A/AB cycloD, disparinol B, mammea A/AB cycloE, ochrocarpin A, mammea A/AA cycloF, mammea A/AB cycloF, mammea E/BA, mammea E/BB) as well as δ-tocotrienol, xanthones (1-hydroxy-7-methoxyxanthone, 2-hydroxyxanthone) and triterpenes (friedelin and betulinic acid). During this study, R,S-asperphenamate, previously described from fungal origin was also purified.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Biflavonoides/farmacologia , Catequina/farmacologia , Cumarínicos/farmacologia , Produtos Finais de Glicação Avançada/efeitos dos fármacos , Mammea/química , Extratos Vegetais/farmacologia , Proantocianidinas/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Biflavonoides/química , Biflavonoides/isolamento & purificação , Catequina/química , Catequina/isolamento & purificação , Sobrevivência Celular/efeitos dos fármacos , Cumarínicos/química , Cumarínicos/isolamento & purificação , Células Endoteliais , Frutas/química , Masculino , Estrutura Molecular , Casca de Planta/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta/química , Proantocianidinas/química , Proantocianidinas/isolamento & purificação , Ratos , Ratos Wistar , Triterpenos/química , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Xantonas/química , Xantonas/isolamento & purificação , Xantonas/farmacologia
11.
J Ethnopharmacol ; 147(1): 259-62, 2013 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-23466248

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The stem bark of Mammea africana is widely distributed in tropical Africa and commonly used in traditional medicine. This study aims to identify the active compound in Mammea africana and to evaluate its antimicrobial and antiproliferative activity. MATERIALS AND METHODS: Methanol extract from the bark of the Mammea africana was separated by liquid-liquid extraction, followed by open column chromatography. A principal antimicrobial compound was purified by high performance liquid chromatography (HPLC) and its structure was elucidated by nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). The antibacterial activity of the purified compound was determined using the broth microdilution method against 7 common pathogenic bacteria. The compound was also evaluated for cytotoxicity by cell proliferation assay (MTS) using the mouse embryonic fibroblast cell line NIH 3T3 and the non-small cell lung cancer cell line A549. RESULTS: The purified active compound was determined to be mammea A/AA and was found to be highly active against Campylobacter jejuni (MIC=0.5 µg/ml), Streptococcus pneumoniae (MIC=0.25 µg/ml), and Clostridium difficile (MIC=0.25 µg/ml). The compound exhibited significant antiproliferative activities against both NIH 3T3 and A549 cell lines. CONCLUSION: Mammea A/AA isolated from Mammea africana exerts specific inhibitory activity against Campylobacter jejuni, Streptococcus pneumoniae, and Campylobacter difficile. Mammea A/AA was also found to exhibit significant cytotoxicity against both cancer and normal cell lines.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Bactérias/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cumarínicos/farmacologia , Mammea , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Antibacterianos/toxicidade , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Bactérias/crescimento & desenvolvimento , Campylobacter jejuni/efeitos dos fármacos , Campylobacter jejuni/crescimento & desenvolvimento , Linhagem Celular Tumoral , Fracionamento Químico , Cromatografia Líquida de Alta Pressão , Clostridium difficile/efeitos dos fármacos , Clostridium difficile/crescimento & desenvolvimento , Cumarínicos/química , Cumarínicos/isolamento & purificação , Cumarínicos/toxicidade , Relação Dose-Resposta a Droga , Humanos , Espectroscopia de Ressonância Magnética , Mammea/química , Espectrometria de Massas , Medicina Tradicional Africana , Metanol/química , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Células NIH 3T3 , Fitoterapia , Casca de Planta , Caules de Planta , Plantas Medicinais , Solventes/química , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pneumoniae/crescimento & desenvolvimento
12.
Bioorg Med Chem Lett ; 23(1): 158-62, 2013 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-23206866

RESUMO

On the search for anti-cancer compounds from Thai traditional herb medicines, a bioassay-guided fractionation and chemical investigation of the methanol extract of Mammea siamensis flower resulted in the isolation and identification of eight compounds (1-8) including a novel geranylated coumarin, namely mammeanoyl (2), and seven known compounds (1 and 3-8). The structure of new compound 2 was elucidated based on the extensive spectroscopic and chemical methods. Among the isolated compounds, three structurally related coumarins 3, 4, and 5 showed significant antiproliferative activities against human leukemia and stomach cancer cell lines. However, these compounds did not affect the cell viabilities of colon cancer, hepatoma, and normal skin fibroblast cell lines. Further analysis demonstrated that the morphological features of apoptosis including DNA fragmentation and chromatin condensation were observed in human leukemia HL-60 cells treated with compounds 3, 4, and 5. In addition, compound 3 led to caspase-3 activation and cleavage of poly (ADP-ribose) polymerase (PARP), and compound 3-induced DNA fragmentation was inhibited by caspase-specific inhibitors. These results suggest that compound 3, 4, and 5 exert antiproliferative actions through apoptotic cell death in leukemia cells and these compounds may have the potential to be developed into new anti-cancer drug candidates.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cumarínicos/química , Mammea/química , Antineoplásicos/síntese química , Antineoplásicos/química , Caspase 3/metabolismo , Linhagem Celular Tumoral , Cumarínicos/isolamento & purificação , Cumarínicos/farmacologia , DNA/metabolismo , Fragmentação do DNA , Ensaios de Seleção de Medicamentos Antitumorais , Flores/química , Células HL-60 , Humanos , Espectroscopia de Ressonância Magnética , Conformação Molecular , Poli(ADP-Ribose) Polimerases/metabolismo
13.
Bioorg Med Chem ; 20(16): 4968-77, 2012 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-22831798

RESUMO

A methanol extract of the flowers of Mammea siamensis (Calophyllaceae) was found to inhibit nitric oxide (NO) production in lipopolysaccharide-activated RAW264.7 cells. From the extract, two new geranylated coumarins, mammeasins A (1) and B (2), were isolated together with 17 known compounds including 15 coumarins. The structures of 1 and 2 were determined on the basis of their spectroscopic properties as well as of their chemical evidence. Among the isolates, 1 (IC(50) = 1.8 µM), 2 (6.4 µM), surangins B (3, 5.0 µM), C (4, 6.8 µM), and D (5, 6.2 µM), kayeassamins E (7, 6.1 µM), F (8, 6.0 µM), and G (9, 0.8 µM), mammea A/AD (11, 1.3 µM), and mammea E/BB (16, 7.9 µM) showed NO production inhibitory activity. Compounds 1, 9, and 11 were found to inhibit induction of inducible nitric oxide synthase (iNOS). With regard to mechanism of action of these active constituents (1, 9, and 11), suppression of STAT1 activation is suggested to be mainly involved in their suppression of iNOS induction.


Assuntos
Cumarínicos/farmacologia , Inibidores Enzimáticos/farmacologia , Mammea/química , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Animais , Células Cultivadas , Cumarínicos/química , Cumarínicos/isolamento & purificação , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Flores/química , Camundongos , Estrutura Molecular , Óxido Nítrico Sintase Tipo II/biossíntese , Óxido Nítrico Sintase Tipo II/metabolismo , Estereoisomerismo , Relação Estrutura-Atividade
14.
Clin Infect Dis ; 55(1): 61-6, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22423132

RESUMO

BACKGROUND: Fifty-four outbreaks of domestically acquired typhoid fever were reported between 1960 and 1999. In 2010, the Southern Nevada Health District detected an outbreak of typhoid fever among persons who had not recently travelled abroad. METHODS: We conducted a case-control study to examine the relationship between illness and exposures. A case was defined as illness with the outbreak strain of Salmonella serotype Typhi, as determined by pulsed-field gel electrophoresis (PFGE), with onset during 2010. Controls were matched by neighborhood, age, and sex. Bivariate and multivariate statistical analyses were completed using logistic regression. Traceback investigation was completed. RESULTS: We identified 12 cases in 3 states with onset from 15 April 2010 to 4 September 2010. The median age of case patients was 18 years (range, 4-48 years), 8 (67%) were female, and 11 (92%) were Hispanic. Nine (82%) were hospitalized; none died. Consumption of frozen mamey pulp in a fruit shake was reported by 6 of 8 case patients (75%) and none of the 33 controls (matched odds ratio, 33.9; 95% confidence interval, 4.9). Traceback investigations implicated 2 brands of frozen mamey pulp from a single manufacturer in Guatemala, which was also implicated in a 1998-1999 outbreak of typhoid fever in Florida. CONCLUSIONS: Reporting of individual cases of typhoid fever and subtyping of isolates by PFGE resulted in rapid detection of an outbreak associated with a ready-to-eat frozen food imported from a typhoid-endemic region. Improvements in food manufacturing practices and monitoring will prevent additional outbreaks.


Assuntos
Frutas/microbiologia , Mammea/imunologia , Salmonella typhi/isolamento & purificação , Febre Tifoide/epidemiologia , Adolescente , Adulto , Bebidas/microbiologia , California/epidemiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Busca de Comunicante , Surtos de Doenças , Feminino , Microbiologia de Alimentos , Guatemala , Hispano-Americanos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nevada/epidemiologia , Oregon/epidemiologia , Fatores de Risco , Salmonella typhi/classificação , Salmonella typhi/genética , Inquéritos e Questionários , Febre Tifoide/etnologia , Febre Tifoide/microbiologia
15.
J Nat Prod ; 74(2): 240-8, 2011 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-21214226

RESUMO

In an effort to identify natural product-based molecular-targeted antitumor agents, mammea-type coumarins from the tropical/subtropical plant Mammea americana were found to inhibit the activation of HIF-1 (hypoxia-inducible factor-1) in human breast and prostate tumor cells. In addition to the recently reported mammea E/BB (15), bioassay-guided fractionation of the active extract yielded 14 mammea-type coumarins including three new compounds, mammea F/BB (1), mammea F/BA (2), and mammea C/AA (3). The absolute configuration of C-1' in 1 was determined by the modified Mosher's method on a methylated derivative. These coumarins were evaluated for their effects on mitochondrial respiration, HIF-1 signaling, and tumor cell proliferation/viability. Acetylation of 1 afforded a triacetoxylated product (A-2) that inhibited HIF-1 activation with increased potency in both T47D (IC(50) 0.83 µM for hypoxia-induced) and PC-3 cells (IC(50) 0.94 µM for hypoxia-induced). Coumarins possessing a 6-prenyl-8-(3-methyloxobutyl) substituent pattern exhibited enhanced HIF-1 inhibitory effects. The O-methylated derivatives were less active at inhibiting HIF-1 and suppressing cell proliferation/viability. Mechanistic studies indicate that these compounds act as anionic protonophores that potently uncouple mitochondrial electron transport and disrupt hypoxic signaling.


Assuntos
Antineoplásicos Fitogênicos , Respiração Celular/efeitos dos fármacos , Cumarínicos , Fator 1 Induzível por Hipóxia/efeitos dos fármacos , Mammea/química , Algoritmos , Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Cumarínicos/síntese química , Cumarínicos/química , Cumarínicos/isolamento & purificação , Cumarínicos/farmacologia , Dominica , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Masculino , Estrutura Molecular , Casca de Planta/química , Prenilação , Relação Estrutura-Atividade
16.
Chem Pharm Bull (Tokyo) ; 58(11): 1487-91, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21048341

RESUMO

A new geranylated coumarin, (E)-4-(1-hydroxypropyl)-5,7-dihydroxy-6-(3,7-dimethyl-2,6-octadienyl)-8-(3-methyl-1-oxobutyl)coumarin (named surangin D), was isolated from the bark of Mammea siamensis collected in Vietnam, along with four known coumarins, surangins B and C, and theraphins B and C, and seven xanthones, 1,7-dihydroxyxanthone, 7-hydroxy-1-methoxyxanthone, 1,7-dimethoxyxanthone, 1,7-dimethoxy-6-hydroxyxanthone, 1,6,7-trihydroxyxanthone, 1,3,7-trihydroxyxanthone, and 1,7-dihydroxy-3-methoxyxanthone. Their structures were determined by spectroscopic methods (mainly 1D- and 2D-NMR) and preparation of methylated derivatives. The four coumarins, surangins C and D and theraphins B and C, were tested for inhibition of cell proliferation in DLD-1 (colon cancer), MCF-7 (breast adenocarcinoma), HeLa (human cervical cancer) and NCI-H460 (human lung cancer) cell lines using the sulforhodamine B (SRB) assay. In all four cell lines, theraphin C showed the strongest activity (IC50 in the range of 1.6-5.7 µM). Testing the anti-proliferative effect of the methylated derivatives showed reduced cellular effects of all derivatives, indicating that the number and position of free hydroxyl groups were very important for the anti-proliferative effect.


Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Cumarínicos/química , Cumarínicos/farmacologia , Mammea/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Cumarínicos/isolamento & purificação , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Neoplasias/tratamento farmacológico , Casca de Planta/química , Vietnã
17.
J Nat Prod ; 73(11): 1868-72, 2010 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-20929261

RESUMO

The mammea-type coumarin mammea E/BB (1) was found to inhibit both hypoxia-induced and iron chelator-induced hypoxia-inducible factor-1 (HIF-1) activation in human breast tumor T47D cells with IC(50) values of 0.96 and 0.89 µM, respectively. Compound 1 suppressed the hypoxic induction of secreted VEGF protein (T47D cells) and inhibited cell viability/proliferation in four human tumor cell lines. Compound 1 (at 5 and 20 µM) inhibited human breast tumor MDA-MB-231 cell migration. While the mechanisms that underlie their biological activities have remained unknown, prenylated mammea coumarins have been shown to be cytotoxic to human tumor cells, suppress tumor growth in animal models, and display a wide variety of antimicrobial effects. Mechanistic studies revealed that 1 appears to exert an assemblage of cellular effects by functioning as an anionic protonophore that potently uncouples mitochondrial electron transport and disrupts mitochondrial signaling in human tumor cell lines.


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Cumarínicos/isolamento & purificação , Cumarínicos/farmacologia , Fator 1 Induzível por Hipóxia/efeitos dos fármacos , Mammea/química , Mitocôndrias/efeitos dos fármacos , Casca de Planta , Animais , Antineoplásicos Fitogênicos/química , Cumarínicos/química , Modelos Animais de Doenças , Dominica , Transporte de Elétrons , Feminino , Humanos , Mitocôndrias/metabolismo , Estrutura Molecular , Casca de Planta/química , Prenilação , Fatores de Crescimento do Endotélio Vascular/efeitos dos fármacos
18.
Chem Pharm Bull (Tokyo) ; 58(9): 1221-3, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20823603

RESUMO

A new butenolide, aspernolide D (1), and furandione, asperterone (2), together with four known butenolides, butyrolactones I-IV and aspernolide B, were obtained from cultures of the endophytic fungus Aspergillus terreus, isolated from the flowering plant Mammea siamensis. The structures of these compounds were elucidated by analysis of NMR spectroscopic and mass spectrometric data.


Assuntos
4-Butirolactona/análogos & derivados , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Aspergillus/química , Furanos/isolamento & purificação , Furanos/farmacologia , 4-Butirolactona/química , 4-Butirolactona/isolamento & purificação , 4-Butirolactona/farmacologia , Antibacterianos/química , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Furanos/química , Espectroscopia de Ressonância Magnética , Mammea/microbiologia , Espectrometria de Massas
19.
J Ethnopharmacol ; 127(2): 368-72, 2010 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-19879938

RESUMO

AIM OF THE STUDY: The stem bark of Mammea africana Sabine (Guttiferae) is used in African rain forest to treat various diseases, including diabetes mellitus. We investigated whether Mammea africana extract induced hypoglycaemic activity in rats. MATERIALS AND METHODS: We tested the effects of acute (5h) and sub-acute (21 days) oral administrations of the CH(2)Cl(2)-MeOH stem bark extract of Mammea africana (19-300 mg/kg body weight) on blood glucose levels of normal and streptozotocin (STZ)-induced type 1 diabetic rats. The effects were compared with those of glibenclamide. RESULTS: Acute administration reduced blood glucose in the diabetic rats only (33.87%, P<0.01). Sub-acute treatment for 21 days also reduced blood glucose level in diabetic rats (73.29%, P<0.01). A reduction or stabilization in total serum protein, triglyceride, cholesterol and alanine amino transferase levels was also observed. No effect was observed on body weight loss but food and water intakes were significantly reduced (P<0.01) in diabetic rats. The maximal anti-diabetic effect was obtained with the dose of 75 mg/kg and was more important than that of glibenclamide. CONCLUSION: It can be concluded that extracts of Mammea africana exhibited a significant anti-hyperglycaemic activity and improved the metabolic alterations in STZ-diabetic rats. These results provide a rationale for the use of Mammea africana to treat diabetes mellitus and hypercholesterolemia.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Mammea , Extratos Vegetais/uso terapêutico , Animais , Diabetes Mellitus Experimental/sangue , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/farmacologia , Masculino , Casca de Planta , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Caules de Planta , Ratos , Ratos Wistar
20.
Curr Microbiol ; 59(3): 233-9, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19504157

RESUMO

Four different food matrices (alfalfa, cilantro, mamey sapote, and mung bean) were contaminated with three different dilutions 10(6), 10(4), and 10(3) cfu/g of Yersinia enterocolitica. DNA was isolated from each food mix and used in chromosomal amplifications. The amplified DNA was used as templates in single PCR reactions of the four genes (virF, ail, yst, and blaA) followed by mixing the four reactions for one PCR primer extension reaction. The presence and the limit of detection of four genes in four food matrices were established by microarray hybridization. Data revealed the diversity of signal intensities. Neither the microarray chip hybridization nor the single PCR amplification could detect virF's presence located on a plasmid. Ail was detected in 10(3) cfu/g, whereas blaA and yst were detected from 10(5) to 10(6) cfu/g in all food matrices. Therefore, the ail gene could be the gene of choice in identifying Y. enterocolitica in alfalfa, cilantro, mamey, and mung bean. Other genes--blaA, yst, virF--exhibited wide variability in hybridization signals, highlighting the need of a better DNA purification step prior to DNA microarray hybridization.


Assuntos
Microbiologia de Alimentos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Reação em Cadeia da Polimerase/métodos , Yersinia enterocolitica/isolamento & purificação , Contagem de Colônia Microbiana , Coriandrum/microbiologia , Fabaceae/microbiologia , Genes Bacterianos , Mammea/microbiologia , Sensibilidade e Especificidade , Yersinia enterocolitica/genética
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