RESUMO
Methyl jasmonate (MeJA) spray treatments were applied to the kale varieties 'Dwarf Blue Curled Vates' and 'Red Winter' in replicated field plantings in 2010 and 2011 to investigate alteration of glucosinolate (GS) composition in harvested leaf tissue. Aqueous solutions of 250 µM MeJA were sprayed to saturation on aerial plant tissues four days prior to harvest at commercial maturity. The MeJA treatment significantly increased gluconasturtiin (56%), glucobrassicin (98%), and neoglucobrassicin (150%) concentrations in the apical leaf tissue of these genotypes over two seasons. Induction of quinone reductase (QR) activity, a biomarker for anti-carcinogenesis, was significantly increased by the extracts from the leaf tissue of these two cultivars. Extracts of apical leaf tissues had greater MeJA mediated increases in phenolics, glucosinolate concentrations, GS hydrolysis products, and QR activity than extracts from basal leaf tissue samples. The concentration of the hydrolysis product of glucoraphanin, sulforphane was significantly increased in apical leaf tissue of the cultivar 'Red Winter' in both 2010 and 2011. There was interaction between exogenous MeJA treatment and environmental conditions to induce endogenous JA. Correlation analysis revealed that indole-3-carbanol (I3C) generated from the hydrolysis of glucobrassicin significantly correlated with QR activity (r = 0.800, P<0.001). Concentrations required to double the specific QR activity (CD values) of I3C was calculated at 230 µM, which is considerably weaker at induction than other isothiocyanates like sulforphane. To confirm relationships between GS hydrolysis products and QR activity, a range of concentrations of MeJA sprays were applied to kale leaf tissues of both cultivars in 2011. Correlation analysis of these results indicated that sulforaphane, NI3C, neoascorbigen, I3C, and diindolylmethane were all significantly correlated with QR activity. Thus, increased QR activity may be due to combined increases in phenolics (quercetin and kaempferol) and GS hydrolysis product concentrations rather than by individual products alone.
Assuntos
Acetatos/farmacologia , Brassica/efeitos dos fármacos , Brassica/metabolismo , Ciclopentanos/farmacologia , Glucosinolatos/biossíntese , NAD(P)H Desidrogenase (Quinona)/metabolismo , Oxilipinas/farmacologia , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Vias Biossintéticas/efeitos dos fármacos , Brassica/química , Ativação Enzimática/efeitos dos fármacos , Glicosídeo Hidrolases/metabolismo , Hidrólise , Oxirredução/efeitos dos fármacos , Fenóis/química , Extratos Vegetais/química , Reguladores de Crescimento de Plantas/farmacologia , Folhas de Planta/químicaRESUMO
Broccoli is rich in bioactive components, such as sulforaphane and indole-3-carbinol, which may impact cancer risk. The glucosinolate profile of broccoli can be manipulated through treatment with the plant stress hormone methyl jasmonate (MeJA). Our objective was to produce broccoli with enhanced levels of indole glucosinolates and determine its impact on prostate carcinogenesis. Brassica oleracea var. Green Magic was treated with a 250 µM MeJA solution 4 days prior to harvest. MeJA-treated broccoli had significantly increased levels of glucobrassicin, neoglucobrassicin, and gluconasturtiin (P < .05). Male transgenic adenocarcinoma of mouse prostate (TRAMP) mice (n = 99) were randomized into three diet groups at 5-7 weeks of age: AIN-93G control, 10% standard broccoli powder, or 10% MeJA broccoli powder. Diets were fed throughout the study until termination at 20 weeks of age. Hepatic CYP1A was induced with MeJA broccoli powder feeding, indicating biological activity of the indole glucosinolates. Following â¼ 15 weeks on diets, neither of the broccoli treatments significantly altered genitourinary tract weight, pathologic score, or metastasis incidence, indicating that broccoli powder at 10% of the diet was ineffective at reducing prostate carcinogenesis in the TRAMP model. Whereas broccoli powder feeding had no effect in this model of prostate cancer, our work demonstrates the feasibility of employing plant stress hormones exogenously to stimulate changes in phytochemical profiles, an approach that may be useful for optimizing bioactive component patterns in foods for chronic-disease-prevention studies.
Assuntos
Acetatos/farmacologia , Brassica/metabolismo , Carcinogênese/efeitos dos fármacos , Ciclopentanos/farmacologia , Glucosinolatos/farmacologia , Indóis/farmacologia , Oxilipinas/farmacologia , Extratos Vegetais/farmacologia , Neoplasias da Próstata , Animais , Brassica/efeitos dos fármacos , Glucosinolatos/metabolismo , Glucosinolatos/uso terapêutico , Indóis/metabolismo , Indóis/uso terapêutico , Masculino , Camundongos Endogâmicos C57BL , Extratos Vegetais/uso terapêutico , Reguladores de Crescimento de Plantas/farmacologia , Neoplasias da Próstata/tratamento farmacológicoRESUMO
Camelina sativa L. Crantz is under development as a novel oilseed crop, yet bioefficacy of camelina phytochemicals is unknown. Defatted camelina seed meal contains two major aliphatic glucosinolates (GSLs), glucoarabin (9-(methylsulfinyl)nonylglucosinolate; GSL 9) and glucocamelinin (10-(methylsulfinyl)decylglucosinolate; GSL 10), with traces of a third, 11(methylsulfinyl)undecylglucosinolate and several flavonoids, mostly quercetin glycosides. In Hepa1c1c7 cells, hydrolyzed GSLs (hGSLs) 9 and 10 upregulated the phase II detoxification enzyme quinone reductase (NQO1), with no effect on cytochrome P450 (CYP) 1A1 activity. Isobologram graphs revealed synergy of NQO1 induction for a combination of hGSL 9 and quercetin. These findings suggest that defatted camelina seed meal should be evaluated for anticancer activity, similar to broccoli and other Brassicaceae family members. Interestingly, synergy of NQO1 induction was also seen for physiologically relevant doses of sulforaphane (SF) and quercetin, two key bioactives present in broccoli. This suggests that SF within broccoli may be more potent than purified SF.
Assuntos
Brassicaceae/química , Glucosinolatos/farmacologia , Extratos Vegetais/farmacologia , Quercetina/farmacologia , Sementes/química , Antineoplásicos/análise , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Gorduras/análise , Glucosinolatos/análise , Humanos , Extratos Vegetais/análise , Quercetina/análiseRESUMO
The in vivo bioavailability of the flavone-C-glycosides has been little studied compared to their O-glycoside analogues, which are both more common in nature and considered more easily hydrolyzed than C-glycosides, by both enterocytes and gut microbiota. In this study, we used vitexin-2-O-xyloside (VOX), an apigenin-8-C-glucoside-2-O-xyloside, purified from seeds of Swiss chard (Beta vulgaris cicla), to investigate VOX absorption into portal blood compared to its aglycone, apigenin. We used a rat model in which we ligated the ileo- and colo-caecal junctions, then administered apigenin or VOX directly into the caecum. Blood samples were drawn from the portal vein at timed intervals over 40 min. The kinetic profile of appearance in portal blood of the compounds and their metabolites was evaluated by HPLC-ESI-MS. Apigenin was found in portal blood both as the aglycone and as an apigenin-glucuronide derivative. The VOX was found unchanged and as a reduced monoglycoside, which underwent glucuronidation. By collecting the bile, we confirmed that the liver received unchanged VOX, which was returned to the gut by enterohepatic recirculation for reabsorption from the ileum. The amount of apigenin and VOX remaining in the caecum accounted for â¼15% and â¼26%, respectively. These data show for the first time that the C-glycoside VOX is absorbed unchanged and undergoes enterohepatic recirculation in addition to hydrolysis to the monoglycoside, reduction and conjugation to form a bioavailable glucuronide.
Assuntos
Apigenina/farmacocinética , Ceco/metabolismo , Flavonoides/farmacocinética , Glicosídeos/farmacocinética , Extratos Vegetais/farmacocinética , Absorção , Animais , Apigenina/administração & dosagem , Apigenina/sangue , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Flavonoides/administração & dosagem , Flavonoides/sangue , Glucuronidase/metabolismo , Glicosídeos/administração & dosagem , Glicosídeos/sangue , Masculino , Extratos Vegetais/administração & dosagem , Extratos Vegetais/sangue , Ratos , Ratos Endogâmicos F344RESUMO
Methyl jasmonate (MeJA) treatment can significantly increase glucosinolate (GS) concentrations in Brassica vegetables and potentially enhance anticancer bioactivity. Although MeJA treatment may promote ethylene biosynthesis, which can be detrimental to postharvest quality, there are no previous reports of its effect on cauliflower postharvest quality. To address this, cauliflower curds in field plots were sprayed with either 0.1 % Triton X-100 (control) or 500 µM MeJA solutions four days prior to harvest, then stored at 4 °C. Tissue subsamples were collected after 0, 10, 20, and 30 days of postharvest storage and assayed for visual color change, ethylene production, GS concentrations, and extract quinone reductase inductive activity. MeJA treatment increased curd GS concentrations of glucoraphanin, glucobrassicin, and neoglucobrassicin by 1.5, 2.4, and 4.6-fold over controls, respectively. MeJA treated cauliflower showed significantly higher quinone reductase activity, a biomarker for anticancer bioactivity, without reducing visual color and postharvest quality for 10 days at 4 °C storage.
Assuntos
Acetatos/farmacologia , Anticarcinógenos/análise , Brassica/efeitos dos fármacos , Brassica/metabolismo , Ciclopentanos/farmacologia , Glucosinolatos/metabolismo , Oxilipinas/farmacologia , Anticarcinógenos/farmacologia , Cor , Etilenos/biossíntese , Manipulação de Alimentos/métodos , Qualidade dos Alimentos , Glucosinolatos/análise , Imidoésteres/metabolismo , Indóis/metabolismo , NAD(P)H Desidrogenase (Quinona)/metabolismo , Octoxinol/farmacologia , Oximas , Extratos Vegetais/metabolismo , SulfóxidosRESUMO
Gymnaster koraiensis (GK) is a Korean herb used in folk medicine and recently found to positively impact liver health. Because GK contains polyacetylenes and because other polyacetylenes have been found to exhibit anti-inflammatory and anti-cancer activities, we hypothesized that the polyacetylene gymnasterkoreayne B (GKB), known to increase hepatic detoxification enzymes, may also exert anti-inflammatory and anti-cancer activities. We fed male C57BL/6 mice purified AIN93G diets containing no additions, GKB or the GKB-rich fraction of an ethanol extract (GE) from GK to determine if these diets would slow or prevent either inflammation or inflammation-enhanced colon cancer, using the dextran sulfate sodium/azoxymethane mouse model. The GKB (500 µmol/kg diet daily) showed some anti-inflammatory activity, but GE, containing an equal dose of GKB, protected strongly against both inflammation and colon cancer, decreasing adenocarcinomas by 90%. These data support further research into GK as a promising potential anti-cancer agent.
Assuntos
Anti-Inflamatórios/farmacologia , Asteraceae/química , Colite/prevenção & controle , Neoplasias do Colo/patologia , Extratos Vegetais/farmacologia , Poli-Inos/farmacologia , Animais , Antineoplásicos/farmacologia , Azoximetano , Proliferação de Células , Colite/complicações , Neoplasias do Colo/complicações , Sulfato de Dextrana/farmacologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Inflamação/complicações , Inflamação/prevenção & controle , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
In broccoli, sulforaphane forms when the glucosinolate glucoraphanin is hydrolyzed by the endogenous plant thiohydrolase myrosinase. A myrosinase cofactor directs hydrolysis away from the formation of bioactive sulforaphane and toward an inactive product, sulforaphane nitrile. The cofactor is more heat sensitive than myrosinase, presenting an opportunity to preferentially direct hydrolysis toward sulforaphane formation through regulation of thermal processing. Four broccoli cultivars were microwave heated, boiled, or steamed for various lengths of time. Production of nitrile during hydrolysis of unheated broccoli varied among cultivars from 91 to 52% of hydrolysis products (Pinnacle > Marathon > Patriot > Brigadier). Boiling and microwave heating caused an initial loss of nitrile, with a concomitant increase in sulforaphane, followed by loss of sulforaphane, all within 1 min. In contrast, steaming enhanced sulforaphane yield between 1.0 and 3.0 min in all but Brigadier. These data are proof of concept that steaming for 1.0-3.0 min provides less nitrile and more sulforaphane yield from a broccoli meal.
Assuntos
Brassica/química , Culinária/métodos , Isotiocianatos/química , Extratos Vegetais/química , Temperatura Alta , Micro-Ondas , SulfóxidosRESUMO
Sulforaphane (SF) is a chemopreventive isothiocyanate (ITC) derived from glucoraphanin (GRP) hydrolysis by myrosinase, a thioglucoside present in broccoli. The ability of broccoli powders sold as supplements to provide dietary SF is often of concern as many supplements contain GRP, but lack myrosinase. In a previous study, biomarkers of SF bioavailability from a powder rich in GRP, but lacking myrosinase, were enhanced by co-consumption of a myrosinase-containing air-dried broccoli sprout powder. Here, we studied the absorption of SF from the GRP-rich powder used in the previous study, but in combination with fresh broccoli sprouts, which are commercially available and more applicable to the human diet than air-dried sprout powder. A total of four participants each consumed four meals (separated by 1 week) consisting of dry cereal and yogurt with sprouts equivalent to 70 µmol SF, GRP powder equivalent to 120 µmol SF, both or neither. Metabolites of SF were analysed in blood and urine. The 24 h urinary SF-N-acetylcysteine recovery was 65, 60 and 24 % of the dose ingested from combination, broccoli sprout and GRP powder meals, respectively. In urine and plasma, ITC appearance was delayed following the GRP powder meal compared with the sprout and combination meals. Compared with the GRP powder or sprouts alone, combining broccoli sprouts with the GRP powder synergistically enhanced the early appearance of SF, offering insight into the combination of foods for improved health benefits of foods that reduce the risk for cancer.
Assuntos
Brassica/química , Suplementos Nutricionais , Glucosinolatos/química , Imidoésteres/química , Isotiocianatos/farmacocinética , Absorção , Acetilcisteína/urina , Adolescente , Adulto , Anticarcinógenos/farmacocinética , Biomarcadores/sangue , Biomarcadores/urina , Estudos Cross-Over , Dieta , Humanos , Hidrólise , Isotiocianatos/sangue , Isotiocianatos/urina , Masculino , Neoplasias/prevenção & controle , Ciências da Nutrição , Oximas , Pós , Sulfóxidos , Inquéritos e Questionários , Adulto JovemRESUMO
Antioxidant foods and ingredients are an important component of the food industry. In the past, antioxidants were used primarily to control oxidation and retard spoilage, but today many are used because of putative health benefits. However, the traditional message that oxidative stress, which involves the production of reactive oxygen species (ROS), is the basis for chronic diseases and aging is being reexamined. Accumulating evidence suggests that ROS exert essential metabolic functions and that removal of too many ROS can upset cell signaling pathways and actually increase the risk of chronic disease. It is imperative that the food industry be aware of progress in this field to present the science relative to foods in a forthright and clear manner. This may mean reexamining the health implications of adding large amounts of antioxidants to foods.
Assuntos
Antioxidantes , Indústria Alimentícia/tendências , Alimentos , Envelhecimento , Animais , Antioxidantes/administração & dosagem , Antioxidantes/toxicidade , Doença Crônica , Suplementos Nutricionais/toxicidade , Expressão Gênica , Promoção da Saúde , Humanos , Modelos Biológicos , Oxidantes , Oxirredução , Estresse Oxidativo , Espécies Reativas de Oxigênio , Transdução de Sinais , Compostos de SulfidrilaRESUMO
Sulforaphane (SF) is a chemopreventive isothiocyanate (ITC) derived from the myrosinase-catalyzed hydrolysis of glucoraphanin, a thioglucoside present in broccoli. Broccoli supplements often contain glucoraphanin but lack myrosinase, putting in question their ability to provide dietary SF. This study compared the relative absorption of SF from air-dried broccoli sprouts rich in myrosinase and a glucoraphanin-rich broccoli powder lacking myrosinase, individually and in combination. Subjects (n=4) each consumed 4 meals consisting of dry cereal and yogurt with 2 g sprouts, 2 g powder, both, or neither. Blood and urine were analyzed for SF metabolites. The 24 h urinary SF recovery was 74%, 49%, and 19% of the dose ingested from broccoli sprouts, combination, and broccoli powder meals, respectively. Urinary and plasma ITC appearance was delayed from the broccoli powder compared to the sprouts and combination. A liver function panel indicated no toxicity from any treatment at 24 h. These data indicate a delayed appearance in plasma and urine of SF from the broccoli powder relative to SF from myrosinase-rich sprouts. Combining broccoli sprouts with the broccoli powder enhanced SF absorption from broccoli powder, offering the potential for development of foods that modify the health impact of broccoli products.
Assuntos
Brassica/química , Dieta , Glucosinolatos/farmacologia , Imidoésteres/farmacologia , Tiocianatos/farmacocinética , Adolescente , Adulto , Transporte Biológico , Estudos Cross-Over , Ingestão de Alimentos , Glicosídeo Hidrolases/metabolismo , Humanos , Hidrólise , Isotiocianatos/sangue , Masculino , Fenômenos Fisiológicos da Nutrição , Oximas , Sulfóxidos , Inquéritos e Questionários , Tiocianatos/urina , Adulto JovemRESUMO
Penstemon gentianoides (HBK) (Kunth) Poir (Plantaginaceae) is an evergreen shrub that grows the throughout high mountains from Guatemala, Mexico and Southern states of US. Its leaves and roots have been used therapeutically for inflammation-related conditions from Aztec times, but systematic studies of its anti-inflammatory activity are lacking and no specific active components have been identified. In this study, methanol, n-hexane, CH2Cl2, ethyl acetate and methanol/water (6:4) extracts, luteolin, diosmetin, verbascoside, martynoside, pensteminoside, globularisicin and plantarenaloside isolated from this plant were evaluated by determining their inhibitory effects on the production of proinflammatory mediators in lipopolysaccharide (LPS)-activated RAW 264.7 murine macrophage cells. Ethyl acetate extract, luteolin, and diosmetin exhibited potent anti-inflammatory and antioxidant activities. The results indicated that luteolin and diosmetin suppressed the LPS induced production of nitric oxide (NO), through the down-regulation of inducible nitric oxide synthases (iNOS) and cyclo-oxygenase 2 (COX-2) protein expressions and showed a potent antioxidant activity against DPPH, TBARS and DCFH. The inhibition of enzymes and NO production by selected extracts and compounds was dose-dependent with significant effects seen at concentration as low as 50 ìM. Thus, luteolin and diosmetin may provide a potential therapeutic approach for inflammation associated disorders.
Penstemon gentianoides (HBK) (Kunth) Poir (Plantaginaceae) es un arbusto perenne que crece a lo largo de las montañas altas de Guatemala, México y los estados del sur de los EE.UU.. Sus hojas y raíces se han utilizado terapéuticamente para afecciones relacionadas con inflamación desde la época de los aztecas, pero no existen estudios sistemáticos de su actividad anti-inflamatoria y ninguno de los metabolitos activos específicos han sido identificados. En este estudio, los extractos de metanol, n-hexano, CH2Cl2, acetato de etilo y metanol/agua (6:4), junto con, luteolina, diosmetina, verbascósido, martynoside, pensteminoside, globularisicin y plantarenaloside, aislados desde esta planta se evaluaron mediante la determinación de sus efectos inhibitorios sobre la producción de mediadores proinflamatorios en macrófagos murinos activados con lipopolisacárido (LPS)-RAW 264,7. El extracto de acetato de etilo, luteolina y diosmetina exhibieron una potente actividad anti-inflamatoria y antioxidante. Los resultados indican que luteolina y diosmetina suprimen la producción de óxido nítrico (NO), a través de la regulación de óxido nítrico sintasa-inducible (iNOS) y la ciclooxigenasa-2 (COX-2) ambas expresiones de proteínas. Ademas mostró una potente actividad antioxidante contra DPPH, TBARS y DCFH. La inhibición de las enzimas y la producción de NO por los extractos seleccionados y compuestos es dependiente de la dosis con efectos significativos visto en una concentración tan baja como 50 mM. Por lo tanto, luteolina y diosmetina puede proporcionar un enfoque terapéutico potencial para transtornos asociados a los procesos de inflamación.
Assuntos
Animais , Ratos , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Flavonoides/farmacologia , Penstemon/química , Anti-Inflamatórios , Flavonoides/isolamento & purificação , Macrófagos , Óxido Nítrico SintaseRESUMO
In vitro, animal, and epidemiological studies all show that broccoli products containing sulforaphane, the bioactive hydrolysis product of glucoraphanin (GRP), lower risk for cancer. As a result, GRP-rich extracts are appearing on the market as dietary supplements. However, these products typically have no hydrolyzing enzyme for sulforaphane (SF) formation. We evaluated safety and compared efficacy to other broccoli preparations. Four daily doses of 0.5 mmol GRP/kg BW, given by gavage to adult male F344 rats, caused temporary cecal inflammation that was essentially resolved four days later. A similar dose dispersed in the diet caused no inflammation. To compare efficacy, we fed rats 20% freeze-dried broccoli (heated or unheated), 3.5% broccoli seed meal, or 4.3% semipurified GRP, each balanced within an AIN93G semipurified diet, for 4 days. Diets lacking myrosinase (semipurified GRP and heated broccoli florets) caused upregulation of NAD(P)H-quinone oxidoreductase 1 (NQO1) in colon but not liver. Surprisingly, broccoli seed, rich in myrosinase and GRP, also caused NQO1 upregulation in colon but not liver. In contrast, unheated broccoli florets caused upregulation in both colon and liver. These data suggest that GRP supplements may not exert systemic effects. We hypothesize that within whole broccoli additional components enhanced sulforaphane-dependent upregulation of NQO1 in liver.
Assuntos
Brassica/química , Manipulação de Alimentos/métodos , Glucosinolatos/farmacocinética , Glicosídeo Hidrolases/metabolismo , Imidoésteres/farmacocinética , Extratos Vegetais/farmacocinética , Animais , Disponibilidade Biológica , Colo/efeitos dos fármacos , Colo/enzimologia , Colo/metabolismo , Expressão Gênica/efeitos dos fármacos , Glucosinolatos/administração & dosagem , Hidrólise , Imidoésteres/administração & dosagem , Isotiocianatos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Masculino , NAD(P)H Desidrogenase (Quinona)/genética , NAD(P)H Desidrogenase (Quinona)/metabolismo , Oximas , Extratos Vegetais/administração & dosagem , Ratos , Ratos Endogâmicos F344 , Sementes/química , Sulfóxidos , Tiocianatos/metabolismoRESUMO
Many studies have evaluated the cancer -preventive potential of individual bioactives from tomatoes and broccoli, but few have examined them within the context of a whole food. Male Copenhagen rats were fed diets containing 10% standard tomato powder, tomato enriched with lycopene or total carotenoids, standard broccoli floret, broccoli sprouts, or broccoli enriched with indole glucosinolates or selenium for 7 days. All broccoli diets increased the activity of colon quinone reductase (NQO1). Indole glucosinolate-enriched broccoli and selenium-enriched broccoli increased hepatic NQO1 and cytochrome P450 1A activity (P < 0.05). Standard broccoli and lycopene-enriched tomato diets down-regulated prostatic glutathione S-transferase P1 mRNA expression. Different tomato diets resulted in altered hepatic accumulation of lycopene, phytofluene, and phytoene. These results demonstrate that the bioactive content of vegetables affects both tissue content of bioactives and activity of detoxification enzymes. Enhancing bioactive content of tomatoes and broccoli may enhance efficacy in the prevention of prostate cancer.
Assuntos
Brassica/química , Extratos Vegetais/administração & dosagem , Solanum lycopersicum/química , Animais , Biomarcadores/análise , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Expressão Gênica/efeitos dos fármacos , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , NAD(P)H Desidrogenase (Quinona)/genética , NAD(P)H Desidrogenase (Quinona)/metabolismo , Distribuição Aleatória , RatosRESUMO
Epidemiological studies have identified an inverse relationship between ingestion of plant foods and cancer risk. However, only approximately 2/3 of such studies show this association. Clinical trials based on epidemiological findings require preclinical studies to provide insight into reproducibility. The beta carotene story is an example of clinical trials based on epidemiological data, before mechanism, dose or the bioactive component had been clearly identified. Results showed rather than prevention, an increase in lung cancer in smokers. Epidemiological studies are used successfully to generate hypotheses for in vitro mechanistic studies of isolated components from plant foods, such as sulforaphane from broccoli. Yet even these studies are insufficient to plan clinical trials of whole foods, since bioavailability, disposition, dose, and effects of the food matrix remain unknown. Evidence-based information, from animal and small clinical studies carried out prior to clinical trials can assure an optimal design. Research into effects of broccoli and sulforaphane make an excellent example of how data gaps have closed between epidemiology and clinical trials. Data on efficacy of broccoli in animal cancer prevention studies are strong, and small clinical studies are emerging. The time is right for clinical trials of purified and semipurified sulforaphane, as well as whole broccoli.
Assuntos
Dieta/normas , Conhecimento , Neoplasias/epidemiologia , Brassicaceae , Ensaios Clínicos como Assunto , Humanos , Neoplasias/prevenção & controle , Fitoterapia , Projetos de Pesquisa/normasAssuntos
Desenvolvimento Fetal/efeitos dos fármacos , Genisteína/toxicidade , Fitoestrógenos/toxicidade , Reprodução/efeitos dos fármacos , Animais , Prova Pericial , Feminino , Genisteína/farmacocinética , Humanos , Técnicas In Vitro , Masculino , National Institutes of Health (U.S.) , Fitoestrógenos/farmacocinética , Gravidez , Estados UnidosRESUMO
Broccoli belongs to a group of vegetables termed cruciferous vegetables and characterized by their glucosinolate content. These glucosinolates are secondary metabolites that, upon hydrolysis, release bioactive isothiocyanates (ITCs). Bioactive ITCs are considered to protect the body from cancer by inducing detoxification enzymes such as quinone reductase (QR). This has the potential to make dietary choice a powerful strategy for achieving protection against carcinogenesis, mutagenesis, and other forms of toxicity from xenobiotic electrophiles and reactive forms of oxygen. The bioactive ITC sulforaphane (SF) is the hydrolysis product of glucoraphanin, the predominant aliphatic glucosinolate in broccoli. Because SF appears more potent than many other ITCs in induction of detoxification enzymes, it may have potential as a dietary cancer-preventative agent. One potential concern is that SF is highly reactive and has a very short half-life in the body, forming a glutathione conjugate that is further metabolized to the N-acetyl-L-cysteine conjugate (SF-NAC), the major excretory product found in the urine. However, the conjugate is a reversible complex, able to release free SF. The objective of this study was to compare QR-inducing activity by SF and its major metabolite SF-NAC, in murine hepatoma cells. Both SF and SF-NAC caused dose-related cell growth inhibition and QR induction. SF, 1 and 2 microM, resulted in a 3.0- and 3.5-fold induction of QR, respectively, and the same concentrations of SF-NAC caused a similar, although somewhat greater, induction of QR, 3.8- and 4.5-fold, respectively. These results strengthen the basis for considering that an effective therapeutic form of SF may be the ITC conjugate, formed in situ or given in place of purified ITC as prophylactic treatment to individuals at high risk for cancer.
Assuntos
Acetilcisteína/farmacologia , Anticarcinógenos/farmacologia , Brassica/química , NAD(P)H Desidrogenase (Quinona)/efeitos dos fármacos , Fitoterapia , Tiocianatos/farmacologia , Animais , Carcinoma Hepatocelular/prevenção & controle , Relação Dose-Resposta a Droga , Indução Enzimática/efeitos dos fármacos , Glucosinolatos/metabolismo , Isotiocianatos/metabolismo , Neoplasias Hepáticas/prevenção & controle , NAD(P)H Desidrogenase (Quinona)/biossíntese , Sulfóxidos , Células Tumorais CultivadasRESUMO
OBJECTIVE: The present study was conducted to determine the effects of dietary soy protein and isoflavones on bone and the reproductive tract in the absence of the ovary. DESIGN: Three-month-old Sprague-Dawley rats (n = 56) were either sham-operated or ovariectomized and then fed diets containing casein or soy protein +/- isoflavone extract for 12 weeks. The amounts of casein, soy protein, and extract (per kg diet) in each group were as follows: (1) Ovariectomy, 200 g of casein; (2) Ovariectomy+low soy, 100 g of casein + 100 g of soy protein; (3) Ovariectomy+high soy, 200 g of soy protein; (4) Ovariectomy+low extract, 200 g of casein + 17.2 g of extract; (5) Ovariectomy+high extract, 200 g of casein + 34.4 g of extract; (6) Ovary intact, 200 g of casein; (7) Ovariectomy+estradiol-17beta, 200 g of casein. Diet consumption, body weight, uterine weight, urine deoxypyridinoline, and bone mineral density of the femur and lumbar vertebrae were measured. The femur rigidity was evaluated by histomorphometry. The reproductive tract (uterus, vagina, and cervix) was studied histologically. RESULTS: The Ovariectomy group showed significant increases in body weight, diet consumption, and deoxypyridinoline, decreases in uterine weight and bone mineral density, and negative changes in histomorphometry compared with the Ovary intact group. Neither soy protein nor extract diets abrogated these alterations, except for the Ovariectomy+high extract group that showed statistically significant positive changes in histomorphometric parameters. There were no histological differences in the reproductive tract among Ovariectomy, Ovariectomy+soy, and Ovariectomy+extract groups. The estradiol-17beta replacement abrogated ovariectomy-induced alterations. CONCLUSION: Dietary intake of isoflavones by sexually mature ovariectomized rats has a minimal beneficial effect on bone with no effect on the reproductive tract.
Assuntos
Dieta , Isoflavonas/administração & dosagem , Osteoporose Pós-Menopausa/prevenção & controle , Fitoterapia , Proteínas de Soja/administração & dosagem , Animais , Densidade Óssea , Osso e Ossos/efeitos dos fármacos , Modelos Animais de Doenças , Estradiol/administração & dosagem , Feminino , Cabeça do Fêmur , Humanos , Vértebras Lombares , Ovariectomia , Extratos Vegetais/administração & dosagem , Ratos , Ratos Sprague-Dawley , Útero/efeitos dos fármacosRESUMO
Broccoli belongs to a group of cruciferous vegetables characterized by its content of glucosinolates, secondary metabolites that, upon hydrolysis, release bioactive isothiocyanates (ITCs). Sulforaphane, the major ITC from broccoli, is believed to protect the body from cancer by induction of detoxification enzymes such as quinone reductase (QR). Sulforaphane provides powerful protection against carcinogenesis, mutagenesis, and other forms of toxicity by electrophiles and reactive forms of oxygen. The purpose of this study was to investigate the effects of processing methods on the ability of broccoli to induce QR in various rat tissues. Male F344 rats (four per group) received an AIN 76B-40 diet containing either 0% or 20% broccoli processed by different methods (dehydrated, freeze-dried, or freeze-dried and hydrolyzed) for 5 days. Colon tissues of rats receiving dehydrated, freeze-dried, and hydrolyzed broccoli diets showed QR induction of 9.1-, 10.5-, and 6.4-fold, respectively. Induction of QR by dehydrated broccoli in the liver and kidney was significantly less robust than in colon, being 2.3- and 1.6-fold over control, respectively. These results suggest that freeze-drying and dehydration are promising approaches for providing the public with the functional benefits of broccoli consumption.