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Elizabeth H Jeffery - One of the best experts on this subject based on the ideXlab platform.
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Influence of Seasonal Variation and Methyl Jasmonate Mediated Induction of Glucosinolate Biosynthesis on Quinone Reductase Activity in Broccoli Florets
2016Co-Authors: Elizabeth H Jeffery, John A JuvikAbstract:Methyl jasmonate spray treatments (250 μM) were utilized to alter glucosinolate composition in the florets of the commercial broccoli F1 hybrids ‘Pirate’, ‘Expo’, ‘Green Magic’, ‘Imperial’, and ‘Gypsy’ grown in replicated field plantings in 2009 and 2010. MeJA treatment significantly increased Glucoraphanin (11%), gluconasturtiin (59%), and neoglucobrassicin (248%) concentrations and their hydrolysis products including sulforaphane (152%), phenethyl isothiocyanate (318%), N-methoxyindole-3-carbinol (313%), and neoascorbigen (232%) extracted from florets of these genotypes over two seasons. Increased quinone reductase (QR) activity was significantly correlated with increased levels of sulforaphane, N-methoxyindole-3-carbinol, and neoascorbigen. Partitioning experiment-wide trait variances indicated that the variability in concentrations of sulforaphane (29%), neoascorbigen (48%), and QR activity (72%) was influenced by year-associated weather variables, whereas variation in neoglucobrassicin (63%) and N-methoxyindole-3-carbinol (46%) concentrations was primarily attributed to methyl jasmonate treatment. These results suggest that methyl jasmonate treatment can enhance QR inducing activity by increased hydrolysis of Glucoraphanin into sulforaphane and the hydrolysis products of neoglucobrassicin
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Total Myrosinase Activity Estimates in Brassica Vegetable Produce
2014Co-Authors: Edward B Dosz, John A Juvik, Elizabeth H JefferyAbstract:Isothiocyanates, generated from the hydrolysis of glucosinolates in plants of the Brassicaceae family, promote health, including anticancer bioactivity. Hydrolysis requires the plant enzyme myrosinase, giving myrosinase a key role in health promotion by brassica vegetables. Myrosinase measurement typically involves isolating crude protein, potentially underestimating activity in whole foods. Myrosinase activity was estimated using unextracted fresh tissues of five broccoli and three kale cultivars, measuring the formation of allyl isothiocyanate (AITC) and/or glucose from exogenous sinigrin. A correlation between AITC and glucose formation was found, although activity was substantially lower measured as glucose release. Using exogenous sinigrin or endogenous Glucoraphanin, concentrations of the hydrolysis products AITC and sulforaphane correlated (r = 0.859; p = 0.006), suggesting that broccoli shows no myrosinase selectivity among sinigrin and Glucoraphanin. Measurement of AITC formation provides a novel, reliable estimation of myrosinase-dependent isothiocyanate formation suitable for use with whole vegetable food samples
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Glucoraphanin hydrolysis by microbiota in the rat cecum results in sulforaphane absorption
Food & Function, 2010Co-Authors: Ren Hau Lai, Michael J Miller, Elizabeth H JefferyAbstract:In the absence of the plant enzyme myrosinase, such as in cooked broccoli, Glucoraphanin is considered to be hydrolyzed by bacteria in the lower gut to produce the bioactive isothiocyanate sulforaphane. Simulated digestion using US Pharmacopeia methods caused no loss of Glucoraphanin, confirming that Glucoraphanin is not destroyed by digestive enzymes during passage through the digestive tract and is able to reach the rat cecum intact. Introduction of Glucoraphanin (150 μmol/kg BW) directly into the cecum resulted in appearance of isothiocyanates in the mesenteric plasma by 120 min. In contrast, introduction of sulforaphane (150 μmol/kg BW) directly into the cecum resulted in the appearance of isothiocyanates in the mesenteric plasma within 15 min. Plasma levels remained constant for over an hour. Anaerobic incubation ex vivo of cecal microbiota from male F344 rats with Glucoraphanin resulted in very low levels of the hydrolytic metabolite erucin nitrile, showing that hydrolysis of glucosinolates is carried out by cecal microbiota, but metabolism ex vivo by microbiota did not reflect not reflect metabolism in situ. These data are the first to report direct evidence of hydrolysis of Glucoraphanin to sulforaphane in the cecum of rats and to show that sulforaphane is able to cross the cecal enterocyte for systemic absorption.
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epithiospecifier protein from broccoli brassica oleracea l ssp italica inhibits formation of the anticancer agent sulforaphane
Journal of Agricultural and Food Chemistry, 2006Co-Authors: Nathan V Matusheski, Richard Mithen, John A Juvik, Ranjan Swarup, Malcolm J Bennett, Elizabeth H JefferyAbstract:In some cruciferous plants, epithiospecifier protein (ESP) directs myrosinase (EC 3.2.3.1)-catalyzed hydrolysis of alkenyl glucosinolates toward epithionitrile formation. Here, for the first time, we show that ESP activity is negatively correlated with the extent of formation of the health-promoting phytochemical sulforaphane in broccoli (Brassica oleracea L. ssp. italica). A 43 kDa protein with ESP activity and sequence homology to the ESP of Arabidopsis thaliana was cloned from the broccoli cv. Packman and expressed in Escherichia coli. In a model system, the recombinant protein not only directed myrosinase-dependent metabolism of the alkenyl glucosinolate epi-progoitrin [(2S)-2-hydroxy-3-butenyl glucosinolate] toward formation of an epithionitrile but also directed myrosinase-dependent hydrolysis of the glucosinolate Glucoraphanin [4-(methylsulfinyl)butyl glucosinolate] to form sulforaphane nitrile, in place of the isothiocyanate sulforaphane. The importance of this finding is that, whereas sulforaphane has been shown to have anticarcinogenic properties, sulforaphane nitrile has not. Genetic manipulation designed to attenuate or eliminate expression of ESP in broccoli could increase the fractional conversion of Glucoraphanin to sulforaphane, enhancing potential health benefits.
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heating decreases epithiospecifier protein activity and increases sulforaphane formation in broccoli
Phytochemistry, 2004Co-Authors: Nathan V Matusheski, John A Juvik, Elizabeth H JefferyAbstract:Sulforaphane, an isothiocyanate from broccoli, is one of the most potent food-derived anticarcinogens. This compound is not present in the intact vegetable, rather it is formed from its glucosinolate precursor, Glucoraphanin, by the action of myrosinase, a thioglucosidase enzyme, when broccoli tissue is crushed or chewed. However, a number of studies have demonstrated that sulforaphane yield from Glucoraphanin is low, and that a non-bioactive nitrile analog, sulforaphane nitrile, is the primary hydrolysis product when plant tissue is crushed at room temperature. Recent evidence suggests that in Arabidopsis, nitrile formation from glucosinolates is controlled by a heat-sensitive protein, epithiospecifier protein (ESP), a non-catalytic cofactor of myrosinase. Our objectives were to examine the effects of heating broccoli florets and sprouts on sulforaphane and sulforaphane nitrile formation, to determine if broccoli contains ESP activity, then to correlate heat-dependent changes in ESP activity, sulforaphane content and bioactivity, as measured by induction of the phase II detoxification enzyme quinone reductase (QR) in cell culture. Heating fresh broccoli florets or broccoli sprouts to 60 °C prior to homogenization simultaneously increased sulforaphane formation and decreased sulforaphane nitrile formation. A significant loss of ESP activity paralleled the decrease in sulforaphane nitrile formation. Heating to 70 °C and above decreased the formation of both products in broccoli florets, but not in broccoli sprouts. The induction of QR in cultured mouse hepatoma Hepa lclc7 cells paralleled increases in sulforaphane formation.
John A Juvik - One of the best experts on this subject based on the ideXlab platform.
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Proposed gene regulation of Glucoraphanin biosynthesis in various tissues of broccoli and quinone reductase inducing activity.
2017Co-Authors: Young-sang Lee, Talon M. Becker, John A JuvikAbstract:Upper part indicates glucosinolate biosynthesis in broccoli florets and leaves. Bottom part indicates glucosinolate biosynthesis in broccoli roots. Each reservoir indicates pool of glucosinolate concentration. Size of each pipeline attached to reservoir indicates expression level of each gene. Accumulated Glucoraphanin concentration is associated with limited expression of the AOP2 gene (narrow pipeline) and elevated expression of FMOGS-OX2, 5 (thick pipeline). High concentrations of Glucoraphanin in broccoli florets contribute to quinone reductase (QR) inducing anticancer activity. However, roots have shown high expression of ESM1 and low expression of ESP homologs, resulting in a high percentage of isothiocyanate over nitrile form, which contributes to QR inducing activity in root tissues. Elevated concentrations of gluconasturtiin and glucoerucin likely did not contribute to quinone reductase inducing anticancer activity because of high hydrolysis product volatility.
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Influence of Seasonal Variation and Methyl Jasmonate Mediated Induction of Glucosinolate Biosynthesis on Quinone Reductase Activity in Broccoli Florets
2016Co-Authors: Elizabeth H Jeffery, John A JuvikAbstract:Methyl jasmonate spray treatments (250 μM) were utilized to alter glucosinolate composition in the florets of the commercial broccoli F1 hybrids ‘Pirate’, ‘Expo’, ‘Green Magic’, ‘Imperial’, and ‘Gypsy’ grown in replicated field plantings in 2009 and 2010. MeJA treatment significantly increased Glucoraphanin (11%), gluconasturtiin (59%), and neoglucobrassicin (248%) concentrations and their hydrolysis products including sulforaphane (152%), phenethyl isothiocyanate (318%), N-methoxyindole-3-carbinol (313%), and neoascorbigen (232%) extracted from florets of these genotypes over two seasons. Increased quinone reductase (QR) activity was significantly correlated with increased levels of sulforaphane, N-methoxyindole-3-carbinol, and neoascorbigen. Partitioning experiment-wide trait variances indicated that the variability in concentrations of sulforaphane (29%), neoascorbigen (48%), and QR activity (72%) was influenced by year-associated weather variables, whereas variation in neoglucobrassicin (63%) and N-methoxyindole-3-carbinol (46%) concentrations was primarily attributed to methyl jasmonate treatment. These results suggest that methyl jasmonate treatment can enhance QR inducing activity by increased hydrolysis of Glucoraphanin into sulforaphane and the hydrolysis products of neoglucobrassicin
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total myrosinase activity estimates in brassica vegetable produce
Journal of Agricultural and Food Chemistry, 2014Co-Authors: Edward B Dosz, John A JuvikAbstract:Isothiocyanates, generated from the hydrolysis of glucosinolates in plants of the Brassicaceae family, promote health, including anticancer bioactivity. Hydrolysis requires the plant enzyme myrosinase, giving myrosinase a key role in health promotion by brassica vegetables. Myrosinase measurement typically involves isolating crude protein, potentially underestimating activity in whole foods. Myrosinase activity was estimated using unextracted fresh tissues of five broccoli and three kale cultivars, measuring the formation of allyl isothiocyanate (AITC) and/or glucose from exogenous sinigrin. A correlation between AITC and glucose formation was found, although activity was substantially lower measured as glucose release. Using exogenous sinigrin or endogenous Glucoraphanin, concentrations of the hydrolysis products AITC and sulforaphane correlated (r = 0.859; p = 0.006), suggesting that broccoli shows no myrosinase selectivity among sinigrin and Glucoraphanin. Measurement of AITC formation provides a novel, reliable estimation of myrosinase-dependent isothiocyanate formation suitable for use with whole vegetable food samples.
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Principal components biplot of phytochemicals (vectors) and 23 cultivars (circles) grown in four seasons in Oregon and Maine.
2014Co-Authors: Erica N. C. Renaud, Edith Lammerts T. Van Bueren, James R. Myers, Maria João Paulo, Fred A. Van Eeuwijk, Ning Zhu, John A JuvikAbstract:A. Biplot for conventional production, B. Biplot for organic production. See Table 1 for cultivar name abbreviations. Trait abbreviations: GLR: Glucoraphanin; GLB: Glucobrassicin; NGB: Neoglucobrassicin; DTO: δ-tocopherol; GTO: γ-tocopherol; ATO: α-tocopherol; LUT: Lutein; ZEA: Zeaxanthin; BCA: β-Carotene.
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Total Myrosinase Activity Estimates in Brassica Vegetable Produce
2014Co-Authors: Edward B Dosz, John A Juvik, Elizabeth H JefferyAbstract:Isothiocyanates, generated from the hydrolysis of glucosinolates in plants of the Brassicaceae family, promote health, including anticancer bioactivity. Hydrolysis requires the plant enzyme myrosinase, giving myrosinase a key role in health promotion by brassica vegetables. Myrosinase measurement typically involves isolating crude protein, potentially underestimating activity in whole foods. Myrosinase activity was estimated using unextracted fresh tissues of five broccoli and three kale cultivars, measuring the formation of allyl isothiocyanate (AITC) and/or glucose from exogenous sinigrin. A correlation between AITC and glucose formation was found, although activity was substantially lower measured as glucose release. Using exogenous sinigrin or endogenous Glucoraphanin, concentrations of the hydrolysis products AITC and sulforaphane correlated (r = 0.859; p = 0.006), suggesting that broccoli shows no myrosinase selectivity among sinigrin and Glucoraphanin. Measurement of AITC formation provides a novel, reliable estimation of myrosinase-dependent isothiocyanate formation suitable for use with whole vegetable food samples
Paul Talalay - One of the best experts on this subject based on the ideXlab platform.
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RESEARCH ARTICLE Sulforaphane Bioavailability from Glucoraphanin-Rich Broccoli: Control by
2016Co-Authors: Active Endogenous Myrosinase, Kristina L Wade, Jed W. Fahey, David W Holtzclaw, Scott L Wehage, K. Stephenson, Paul TalalayAbstract:Glucoraphanin from broccoli and its sprouts and seeds is a water soluble and relatively inert precursor of sulforaphane, the reactive isothiocyanate that potently inhibits neoplastic cellu-lar processes and prevents a number of disease states. Sulforaphane is difficult to deliver in an enriched and stable form for purposes of direct human consumption. We have focused upon evaluating the bioavailability of sulforaphane, either by direct administration of glucor-aphanin (a glucosinolate, or β-thioglucoside-N-hydroxysulfate), or by co-administering glu-coraphanin and the enzyme myrosinase to catalyze its conversion to sulforaphane at economic, reproducible and sustainable yields. We show that following administration of Glucoraphanin in a commercially prepared dietary supplement to a small number of human volunteers, the volunteers had equivalent output of sulforaphane metabolites in their urine to that which they produced when given an equimolar dose of Glucoraphanin in a simple boiled and lyophilized extract of broccoli sprouts. Furthermore, when either broccoli sprouts or seeds are administered directly to subjects without prior extraction and consequent inactivation of endogenous myrosinase, regardless of the delivery matrix or dose, the sulfo-raphane in those preparations is 3- to 4-fold more bioavailable than sulforaphane from glu-coraphanin delivered without active plant myrosinase. These data expand upon earlier reports of inter- and intra-individual variability, when Glucoraphanin was delivered in either teas, juices, or gelatin capsules, and they confirm that a variety of delivery matrices may be equally suitable for Glucoraphanin supplementation (e.g. fruit juices, water, or various types of capsules and tablets)
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sulforaphane bioavailability from Glucoraphanin rich broccoli control by active endogenous myrosinase
PLOS ONE, 2015Co-Authors: Kristina L Wade, Katherine K Stephenson, Jed W. Fahey, David W Holtzclaw, Paul Talalay, Scott L WehageAbstract:Glucoraphanin from broccoli and its sprouts and seeds is a water soluble and relatively inert precursor of sulforaphane, the reactive isothiocyanate that potently inhibits neoplastic cellular processes and prevents a number of disease states. Sulforaphane is difficult to deliver in an enriched and stable form for purposes of direct human consumption. We have focused upon evaluating the bioavailability of sulforaphane, either by direct administration of Glucoraphanin (a glucosinolate, or β-thioglucoside-N-hydroxysulfate), or by co-administering Glucoraphanin and the enzyme myrosinase to catalyze its conversion to sulforaphane at economic, reproducible and sustainable yields. We show that following administration of Glucoraphanin in a commercially prepared dietary supplement to a small number of human volunteers, the volunteers had equivalent output of sulforaphane metabolites in their urine to that which they produced when given an equimolar dose of Glucoraphanin in a simple boiled and lyophilized extract of broccoli sprouts. Furthermore, when either broccoli sprouts or seeds are administered directly to subjects without prior extraction and consequent inactivation of endogenous myrosinase, regardless of the delivery matrix or dose, the sulforaphane in those preparations is 3- to 4-fold more bioavailable than sulforaphane from Glucoraphanin delivered without active plant myrosinase. These data expand upon earlier reports of inter- and intra-individual variability, when Glucoraphanin was delivered in either teas, juices, or gelatin capsules, and they confirm that a variety of delivery matrices may be equally suitable for Glucoraphanin supplementation (e.g. fruit juices, water, or various types of capsules and tablets).
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keap1 nrf2 signaling a target for cancer prevention by sulforaphane
Topics in Current Chemistry, 2012Co-Authors: Jed W. Fahey, Thomas W Kensler, Patricia Egner, Abena S Agyeman, Kala Visvanathan, John Davis Groopman, Jian Guo Chen, Tao Yang Chen, Paul TalalayAbstract:Sulforaphane is a promising agent under preclinical evaluation in many models of disease prevention. This bioactive phytochemical affects many molecular targets in cellular and animal models; however, amongst the most sensitive is Keap1, a key sensor for the adaptive stress response system regulated through the transcription factor Nrf2. Keap1 is a sulfhydryl-rich protein that represses Nrf2 signaling by facilitating the polyubiquitination of Nrf2, thereby enabling its subsequent proteasomal degradation. Interaction of sulforaphane with Keap1 disrupts this function and allows for nuclear accumulation of Nrf2 and activation of its transcriptional program. Enhanced transcription of Nrf2 target genes provokes a strong cytoprotective response that enhances resistance to carcinogenesis and other diseases mediated by exposures to electrophiles and oxidants. Clinical evaluation of sulforaphane has been largely conducted by utilizing preparations of broccoli or broccoli sprouts rich in either sulforaphane or its precursor form in plants, a stable β-thioglucose conjugate termed Glucoraphanin. We have conducted a series of clinical trials in Qidong, China, a region where exposures to food- and air-borne carcinogens has been considerable, to evaluate the suitability of broccoli sprout beverages, rich in either Glucoraphanin or sulforaphane or both, for their bioavailability, tolerability, and pharmacodynamic action in population-based interventions. Results from these clinical trials indicate that interventions with well characterized preparations of broccoli sprouts may enhance the detoxication of aflatoxins and air-borne toxins, which may in turn attenuate their associated health risks, including cancer, in exposed individuals.
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dietary Glucoraphanin rich broccoli sprout extracts protect against uv radiation induced skin carcinogenesis in skh 1 hairless mice
Photochemical and Photobiological Sciences, 2010Co-Authors: Jed W. Fahey, Albena T Dinkovakostova, Andrea L Benedict, Stephanie N Jenkins, Scott L Wehage, Paul TalalayAbstract:Feeding broccoli sprout extracts providing daily doses of 10 μmol of Glucoraphanin to SKH-1 hairless mice with prior chronic exposure to UV radiation (30 mJ cm−2 of UVB, twice a week, for 17 weeks) inhibited the development of skin tumors during the subsequent 13 weeks; compared to the controls, tumor incidence, multiplicity, and volume were reduced by 25, 47, and 70%, respectively, in the animals that received the protective agent.
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safety tolerance and metabolism of broccoli sprout glucosinolates and isothiocyanates a clinical phase i study
Nutrition and Cancer, 2006Co-Authors: Theresa A Shapiro, Kristina L Wade, Katherine K Stephenson, Jed W. Fahey, Albena T Dinkovakostova, David W Holtzclaw, Lingxiang Ye, Paul TalalayAbstract:Abstract: Broccoli sprouts are widely consumed in many parts of the world. There have been no reported concerns with respect to their tolerance and safety in humans. A formal phase I study of safety, tolerance, and pharmacokinetics appeared justified because these sprouts are being used as vehicles for the delivery of the glucosinolate Glucoraphanin and its cognate isothiocyanate sulforaphane [1-isothiocyanato-(4R)-(methylsulfinyl)butane] in clinical trials. Such trials have been designed to evaluate protective efficacy against development of neoplastic and other diseases. A placebo-controlled, double-blind, randomized clinical study of sprout extracts containing either glucosinolates (principally Glucoraphanin, the precursor of sulforaphane) or isothiocyanates (principally sulforaphane) was conducted on healthy volunteers who were in-patients on our clinical research unit. The subjects were studied in three cohorts, each comprising three treated individuals and one placebo recipient. Following a 5-day ac...
Renato Iori - One of the best experts on this subject based on the ideXlab platform.
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Structure of the natural isothiocyanates sulforaphane (SFN) and moringin (GMG-ITC).
2016Co-Authors: Carina Michl, Gina Rosalinda De Nicola, Renato Iori, Fabio Vivarelli, Julia Weigl, Donatella Canistro, Moreno Paolini, Anne RascleAbstract:Sulforaphane (SFN; 1-isothiocyanato-4-(methylsulfinyl)-butane, also called Glucoraphanin isothiocyanate or GRA-ITC) and moringin (4-(α-L-rhamnopyranosyloxy)-benzyl isothiocyanate, also referred to as glucomoringin isothiocyanate or GMG-ITC) are produced by myrosinase-catalyzed hydrolysis of their glucosinolate precursors, Glucoraphanin (GRA) and glucomoringin (GMG) respectively [59].
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novel gram scale production of enantiopure r sulforaphane from tuscan black kale seeds
Molecules, 2014Co-Authors: Gina Rosalinda De Nicola, Patrick Rollin, Emanuela Mazzon, Renato IoriAbstract:Dietary R-sulforaphane is a highly potent inducer of the Keap1/Nrf2/ARE pathway. Furthermore, sulforaphane is currently being used in clinical trials to assess its effects against different tumour processes. This study reports an efficient preparation of enantiopure R-sulforaphane based on the enzymatic hydrolysis of its natural precursor Glucoraphanin. As an alternative to broccoli seeds, we have exploited Tuscan black kale seeds as a suitable source for gram-scale production of Glucoraphanin. The defatted seed meal contained 5.1% (w/w) of Glucoraphanin that was first isolated through an anion exchange chromatographic process, and then purified by gel filtration. The availability of Glucoraphanin (purity ≈ 95%, weight basis) has allowed us to develop a novel simple hydrolytic process involving myrosinase (EC 3.2.1.147) in a biphasic system to directly produce R-sulforaphane. In a typical experiment, 1.09 g of enantiopure R-sulforaphane was obtained from 150 g of defatted Tuscan black kale seed meal.
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sulfur containing metabolites in radishes further exploration of glucoraphenin desulfation
Journal of Sulfur Chemistry, 2013Co-Authors: Gina Rosalinda De Nicola, Arnaud Tatibouet, Renato Iori, Patrick RollinAbstract:Glucoraphenin (GRE), found in radishes, holds the unique structural specificity of a Michael acceptor vinyl sulfoxide site. For this reason, desulfo-GRE resulting from enzymatic desulfation is converted into thioimidate N-oxides. Under longer reaction times, a new sulfur-containing compound was isolated and characterized as a cyclic thiohydroximate.
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up regulation of cytochrome p450 and phase ii enzyme systems in rat precision cut rat lung slices by the intact glucosinolates Glucoraphanin and glucoerucin
Lung Cancer, 2011Co-Authors: Ahmad Faizal Abdull Razis, Gina Rosalinda De Nicola, Renato Iori, M Bagatta, Costas IoannidesAbstract:Abstract It is believed that the chemopreventive activity of cruciferous vegetables in the lung and other tissues is exclusively the result of exposure to degradation products of glucosinolates, such as the isothiocyanates, and that the parent glucosinolates make no contribution. In the present study, evidence is presented for the first time that, in rat lung, the intact glucosinolates, Glucoraphanin and glucoerucin, can modulate carcinogen-metabolising enzyme systems. The glucosinolates were isolated from cruciferous vegetables and incubated (1–25μM) with precision-cut rat lung slices for 24h. Both glucosinolates, at concentrations as low as 1μM, up-regulated the O -deethylation of ethoxyresorufin and the apoprotein levels of CYP1A1 and CYP1B1; supplementation of the incubation medium with myrosinase, the enzyme that converts glucosinolates to their corresponding isothiocyanates, abolished the rise in ethoxyresorufin O -deethylase activity. In contrast, neither glucosinolate, at the concentrations studied, influenced quinone reductase activity in the lung slices, but addition of myrosinase to the glucosinolate incubations led to a marked rise in activity. Glutathione S -transferase activity, monitored using 1-chloro-2,4-dinitrobenzene as the accepting substrate, was elevated in lung slices exposed to Glucoraphanin. GSTα protein levels were increased by Glucoraphanin and, to a much lesser extent, glucoerucin. It may be concluded that intact glucosinolates can modulate the activity of pulmonary carcinogen-metabolising enzyme systems, and can thus contribute to the documented chemopreventive activity of cruciferous vegetables in the lung.
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intact glucosinolates modulate hepatic cytochrome p450 and phase ii conjugation activities and may contribute directly to the chemopreventive activity of cruciferous vegetables
Toxicology, 2010Co-Authors: Ahmad Faizal Abdull Razis, Gina Rosalinda De Nicola, Renato Iori, M Bagatta, Costas IoannidesAbstract:The currently accepted view is that the chemopreventive activity of glucosinolates is exclusively mediated by their degradation products, such as isothiocyanates. In the present study, evidence is presented for the first time that intact glucosinolates can modulate carcinogen-metabolising enzyme systems. The glucosinolates Glucoraphanin and glucoerucin were isolated from cruciferous vegetables and incubated with precision-cut rat liver slices. Both glucosinolates elevated the O-dealkylations of methoxy- and ethoxyresorufin, markers for CYP1 activity; supplementation of the incubation medium with myrosinase, the enzyme that converts glucosinolates to their corresponding isothiocyanates, abolished these effects. Moreover, both glucoerucin and Glucoraphanin increased the apoprotein levels of microsomal CYP1A1, CYP1A2 and CYP1B1. At higher concentrations, both glucosinolates enhanced quinone reductase activity, whereas Glucoraphanin also elevated glutathione S-transferase; in this instance, however, supplementation of the incubation medium with myrosinase exacerbated the inductive effect. Finally, both glucosinolates increased modestly cytosolic quinone reductase, GSTα and GSTμ protein levels, which became more pronounced when myrosinase was added to the incubations with the glucosinolate. It may be inferred that intact glucosinolates can modulate the activity of hepatic carcinogen-metabolising enzyme systems and this is likely to impact on the chemopreventive activity linked to cruciferous vegetable consumption.
Jed W. Fahey - One of the best experts on this subject based on the ideXlab platform.
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RESEARCH ARTICLE Sulforaphane Bioavailability from Glucoraphanin-Rich Broccoli: Control by
2016Co-Authors: Active Endogenous Myrosinase, Kristina L Wade, Jed W. Fahey, David W Holtzclaw, Scott L Wehage, K. Stephenson, Paul TalalayAbstract:Glucoraphanin from broccoli and its sprouts and seeds is a water soluble and relatively inert precursor of sulforaphane, the reactive isothiocyanate that potently inhibits neoplastic cellu-lar processes and prevents a number of disease states. Sulforaphane is difficult to deliver in an enriched and stable form for purposes of direct human consumption. We have focused upon evaluating the bioavailability of sulforaphane, either by direct administration of glucor-aphanin (a glucosinolate, or β-thioglucoside-N-hydroxysulfate), or by co-administering glu-coraphanin and the enzyme myrosinase to catalyze its conversion to sulforaphane at economic, reproducible and sustainable yields. We show that following administration of Glucoraphanin in a commercially prepared dietary supplement to a small number of human volunteers, the volunteers had equivalent output of sulforaphane metabolites in their urine to that which they produced when given an equimolar dose of Glucoraphanin in a simple boiled and lyophilized extract of broccoli sprouts. Furthermore, when either broccoli sprouts or seeds are administered directly to subjects without prior extraction and consequent inactivation of endogenous myrosinase, regardless of the delivery matrix or dose, the sulfo-raphane in those preparations is 3- to 4-fold more bioavailable than sulforaphane from glu-coraphanin delivered without active plant myrosinase. These data expand upon earlier reports of inter- and intra-individual variability, when Glucoraphanin was delivered in either teas, juices, or gelatin capsules, and they confirm that a variety of delivery matrices may be equally suitable for Glucoraphanin supplementation (e.g. fruit juices, water, or various types of capsules and tablets)
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sulforaphane bioavailability from Glucoraphanin rich broccoli control by active endogenous myrosinase
PLOS ONE, 2015Co-Authors: Kristina L Wade, Katherine K Stephenson, Jed W. Fahey, David W Holtzclaw, Paul Talalay, Scott L WehageAbstract:Glucoraphanin from broccoli and its sprouts and seeds is a water soluble and relatively inert precursor of sulforaphane, the reactive isothiocyanate that potently inhibits neoplastic cellular processes and prevents a number of disease states. Sulforaphane is difficult to deliver in an enriched and stable form for purposes of direct human consumption. We have focused upon evaluating the bioavailability of sulforaphane, either by direct administration of Glucoraphanin (a glucosinolate, or β-thioglucoside-N-hydroxysulfate), or by co-administering Glucoraphanin and the enzyme myrosinase to catalyze its conversion to sulforaphane at economic, reproducible and sustainable yields. We show that following administration of Glucoraphanin in a commercially prepared dietary supplement to a small number of human volunteers, the volunteers had equivalent output of sulforaphane metabolites in their urine to that which they produced when given an equimolar dose of Glucoraphanin in a simple boiled and lyophilized extract of broccoli sprouts. Furthermore, when either broccoli sprouts or seeds are administered directly to subjects without prior extraction and consequent inactivation of endogenous myrosinase, regardless of the delivery matrix or dose, the sulforaphane in those preparations is 3- to 4-fold more bioavailable than sulforaphane from Glucoraphanin delivered without active plant myrosinase. These data expand upon earlier reports of inter- and intra-individual variability, when Glucoraphanin was delivered in either teas, juices, or gelatin capsules, and they confirm that a variety of delivery matrices may be equally suitable for Glucoraphanin supplementation (e.g. fruit juices, water, or various types of capsules and tablets).
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keap1 nrf2 signaling a target for cancer prevention by sulforaphane
Topics in Current Chemistry, 2012Co-Authors: Jed W. Fahey, Thomas W Kensler, Patricia Egner, Abena S Agyeman, Kala Visvanathan, John Davis Groopman, Jian Guo Chen, Tao Yang Chen, Paul TalalayAbstract:Sulforaphane is a promising agent under preclinical evaluation in many models of disease prevention. This bioactive phytochemical affects many molecular targets in cellular and animal models; however, amongst the most sensitive is Keap1, a key sensor for the adaptive stress response system regulated through the transcription factor Nrf2. Keap1 is a sulfhydryl-rich protein that represses Nrf2 signaling by facilitating the polyubiquitination of Nrf2, thereby enabling its subsequent proteasomal degradation. Interaction of sulforaphane with Keap1 disrupts this function and allows for nuclear accumulation of Nrf2 and activation of its transcriptional program. Enhanced transcription of Nrf2 target genes provokes a strong cytoprotective response that enhances resistance to carcinogenesis and other diseases mediated by exposures to electrophiles and oxidants. Clinical evaluation of sulforaphane has been largely conducted by utilizing preparations of broccoli or broccoli sprouts rich in either sulforaphane or its precursor form in plants, a stable β-thioglucose conjugate termed Glucoraphanin. We have conducted a series of clinical trials in Qidong, China, a region where exposures to food- and air-borne carcinogens has been considerable, to evaluate the suitability of broccoli sprout beverages, rich in either Glucoraphanin or sulforaphane or both, for their bioavailability, tolerability, and pharmacodynamic action in population-based interventions. Results from these clinical trials indicate that interventions with well characterized preparations of broccoli sprouts may enhance the detoxication of aflatoxins and air-borne toxins, which may in turn attenuate their associated health risks, including cancer, in exposed individuals.
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dietary Glucoraphanin rich broccoli sprout extracts protect against uv radiation induced skin carcinogenesis in skh 1 hairless mice
Photochemical and Photobiological Sciences, 2010Co-Authors: Jed W. Fahey, Albena T Dinkovakostova, Andrea L Benedict, Stephanie N Jenkins, Scott L Wehage, Paul TalalayAbstract:Feeding broccoli sprout extracts providing daily doses of 10 μmol of Glucoraphanin to SKH-1 hairless mice with prior chronic exposure to UV radiation (30 mJ cm−2 of UVB, twice a week, for 17 weeks) inhibited the development of skin tumors during the subsequent 13 weeks; compared to the controls, tumor incidence, multiplicity, and volume were reduced by 25, 47, and 70%, respectively, in the animals that received the protective agent.
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safety tolerance and metabolism of broccoli sprout glucosinolates and isothiocyanates a clinical phase i study
Nutrition and Cancer, 2006Co-Authors: Theresa A Shapiro, Kristina L Wade, Katherine K Stephenson, Jed W. Fahey, Albena T Dinkovakostova, David W Holtzclaw, Lingxiang Ye, Paul TalalayAbstract:Abstract: Broccoli sprouts are widely consumed in many parts of the world. There have been no reported concerns with respect to their tolerance and safety in humans. A formal phase I study of safety, tolerance, and pharmacokinetics appeared justified because these sprouts are being used as vehicles for the delivery of the glucosinolate Glucoraphanin and its cognate isothiocyanate sulforaphane [1-isothiocyanato-(4R)-(methylsulfinyl)butane] in clinical trials. Such trials have been designed to evaluate protective efficacy against development of neoplastic and other diseases. A placebo-controlled, double-blind, randomized clinical study of sprout extracts containing either glucosinolates (principally Glucoraphanin, the precursor of sulforaphane) or isothiocyanates (principally sulforaphane) was conducted on healthy volunteers who were in-patients on our clinical research unit. The subjects were studied in three cohorts, each comprising three treated individuals and one placebo recipient. Following a 5-day ac...