Chapter

Health Benefits of Glucosinolates

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Abstract

There is considerable evidence from observational population studies that diets rich in cruciferous vegetables are associated with improved health benefits, which include protection from cancer incidence and progression and from cardiovascular disease. These vegetables uniquely contain the sulphur-containing phytochemicals glucosinolates, which can be hydrolysed by plants or in the human gut to isothiocyanates. It is these isothiocyanates that have been linked to their bioactivity. By far the most commonly consumed and well-studied glucosinolates within our diets are those that derive from methionine, such as sulforaphane, erucin and allyl-glucosinolates, and aromatic glucosinolates, such as phenethyl- and benzyl-glucosinolate. A significant amount of cell and animal studies suggest a role for all these in interfering with key processes that drive carcinogenesis and metastasis, but also protect cells from redox imbalance that underlies the development of several chronic inflammatory diseases. In this review I will summarize the metabolic fate of the common aliphatic and aromatic glucosinolates in humans, present the latest epidemiological evidence from metaanalyses studies and describe the mechanisms for their biological activity from cell and animal models, but also from the recent interventional studies in humans.

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... Their functional properties are due to their phytochemical composition, mainly consisting of specialized glucosinolates (GLSs) and their hydrolysis products (Fusari et al., 2020). Various laboratory and epidemiological studies have associated these with biological activities, including significantly lower risk of myocardial infarction and cancer development at different sites, anti-inflammatory, immunomodulatory activities, antimicrobial, restoration of skin integrity, and protection of the central nervous system (Traka, 2016). Their bioactivity is mediated by the regulation of xenobiotic metabolism, reduction of inflammation, regulation of epigenetic events, apoptosis and cell cycle arrest, angiogenesis and metastasis, antibacterial effect, induction of glyoxalase 1 activity, and modulation of hormone receptor expression (Capuano et al., 2017). ...
... The concentration of sinigrin observed in this study was found to be higher than its effective concentration observed during in vivo studies (Chu et al., 2020;Jie et al., 2014). Further, the products of its hydrolysis (allyl isothiocyanate and 1-cyano-2,3-epithiopropane) upon the action of myrosinase have also shown a high amount of therapeutic potential (Conde-Rioll et al., 2018;Traka, 2016). Benzyl GLS, on the other hand, has been associated with properties such as enhanced reproductive health, antifatigue, antioxidation, neuroprotection, antimicrobial activity, anti-cancer, hepatoprotection, immunomodulation, and improving skin health and digestive system's function (Traka, 2016;Wang & Zhu, 2019). ...
... Further, the products of its hydrolysis (allyl isothiocyanate and 1-cyano-2,3-epithiopropane) upon the action of myrosinase have also shown a high amount of therapeutic potential (Conde-Rioll et al., 2018;Traka, 2016). Benzyl GLS, on the other hand, has been associated with properties such as enhanced reproductive health, antifatigue, antioxidation, neuroprotection, antimicrobial activity, anti-cancer, hepatoprotection, immunomodulation, and improving skin health and digestive system's function (Traka, 2016;Wang & Zhu, 2019). ...
Article
Lepidium latifolium L. from Ladakh Himalayas is a high source of 2-propenyl glucosinolate (GLS). To utilize it as a functional food, differently aged sprouts (1st-, 2nd-, 3rd-, 4th-, and 8th-week) were evaluated for phytochemical, nutritional, and antioxidant properties. A combination of 2-propenyl and benzyl GLS was found in significantly (p ≤ 0.05) higher quantity during the first four stages. Benzyl GLS decreased during the 8th-week stage, with a concomitant increase in 2-propenyl GLS. The content of GLSs was found under the transcriptional regulation of the MYB transcription factors. Despite the similar metabolic content of GLSs, higher myrosinase activity during the 3rd-week might increase their bioavailability. Lepidium sprouts also contain higher amounts of nutritionally important vitamin C, carotenoids, phenolic acids, and fatty acids than observed in other Brassica species. The antioxidant potential in sprouts corroborated with the content of phenols and flavonoids and was higher during the first three weeks. Our results suggest that sprouts during the 3rd-week stage showed a unique combination of GLSs and qualitative and quantitative phytochemical superiority, hence could be promoted as a functional food.
... Glucosinolates (GSLs) are specialized metabolites in the family Brassicaceae 2,3 that act as protectants against generalists 4,5 , and can mediate the coevolutionary association between herbivores and plants. The bioactive products of GSL hydrolysis, typically isothiocyanates and nitriles 6,7 , are associated with improved health benefits 7 . Well-known allyl-isothiocyanate or benzyl-isothiocyanate (ITC) is a characteristic determinant of the pungent flavor associated with wasabi. ...
... Glucosinolates (GSLs) are specialized metabolites in the family Brassicaceae 2,3 that act as protectants against generalists 4,5 , and can mediate the coevolutionary association between herbivores and plants. The bioactive products of GSL hydrolysis, typically isothiocyanates and nitriles 6,7 , are associated with improved health benefits 7 . Well-known allyl-isothiocyanate or benzyl-isothiocyanate (ITC) is a characteristic determinant of the pungent flavor associated with wasabi. ...
... The synthesis of GSLs is emerging as a unique model with which to investigate nonlinear selection and a blend of convergent, divergent, and parallel evolution that shapes natural variation 7,18 . However, we do not yet fully understand how the selectivity and evolution of GSL transport may underlie natural variation within and between species. ...
Article
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Wasabi, horseradish and mustard are popular pungent crops in which the characteristic bioactive hydrolysis of specialized glucosinolates (GSLs) occurs. Although the metabolic pathways of GSLs are well elucidated, how plants have evolved convergent mechanisms to accumulate identical GSL components remains largely unknown. In this study, we discovered that sinigrin is predominantly synthesized in wasabi, horseradish and mustard in Brassicaceae. We de novo assembled the transcriptomes of the three species, revealing the expression patterns of gene clusters associated with chain elongation, side chain modification and transport. Our analysis further revealed that several gene clusters were convergently selected during evolution, exhibiting convergent shifts in amino acid preferences in mustard, wasabi and horseradish. Collectively, our findings provide insights into how unrelated crop species evolve the capacity for sinigrin super-accumulation and thus promise a potent strategy for engineering metabolic pathways at multiple checkpoints to fortify bioactive compounds for condiment or pharmaceutical purposes.
... Glucosinolates ( Figure 1) are composed of a glucose structure which is combined with an O-sulfated thiohydroximate moiety and are variable in length-side chain is variable in derivatives of amino acids. The aliphatic chain is biosynthesized most often from methionine, aromatic moiety from phenylalanine or tyrosine, and the indole components from tryptophan [27,28]. Isothiocyanates are formed during the hydrolysis of glucosinolates. ...
... An understanding of the mechanisms of glucosinolates transformation is essential to determine their presence in plant extracts. methionine, aromatic moiety from phenylalanine or tyrosine, and the indole comp from tryptophan [27,28]. Isothiocyanates are formed during the hydrolysis of glu olates. ...
... Linear maps of samples ( Figure 2), combined by the cluster dendrogram resulting from HC ( Figure 3), have revealed that juices contained very similar amounts of glucosinolates, with BL_JU (No 7) slightly differentiating from the rest ( Figure 3). These observations are in line with previous findings on the formation of glucosinolates in the plant tissues that underline that the process of oxidation is necessary to trigger the conformational changes in their structures [27]. Juices that were squeezed out from fresh tubers and immediately analysed did not contain high quantity of glucosinolates yet. ...
Article
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The aim of the study was to present the fingerprint of different Lepidium peruvianum tuber extracts showing glucosinolates-containing substances possibly playing an important role in preventinting dementia and other memory disorders. Different phenotypes of Lepidium peruvianum (Brassicaceae) tubers were analysed for their glucosinolate profile using a liquid chromatograph coupled with mass spectrometer (HPLC-ESI-QTOF-MS/MS platform). Qualitative analysis in 50% ethanolic extracts confirmed the presence of ten compounds: aliphatic, indolyl, and aromatic glucosinolates, with glucotropaeolin being the leading one, detected at levels between 0–1.57% depending on phenotype, size, processing, and collection site. The PCA analysis showed important variations in glucosinolate content between the samples and different ratios of the detected compounds. Applied in vitro activity tests confirmed inhibitory properties of extracts and single glucosinolates against acetylcholinesterase (AChE) (15.3–28.9% for the extracts and 55.95–57.60% for individual compounds) and butyrylcholinesterase (BuChE) (71.3–77.2% for the extracts and 36.2–39.9% for individual compounds). The molecular basis for the activity of glucosinolates was explained through molecular docking studies showing that the tested metabolites interacted with tryptophan and histidine residues of the enzymes, most likely blocking their active catalytic side. Based on the obtained results and described mechanism of action, it could be concluded that glucosinolates exhibit inhibitory properties against two cholinesterases present in the synaptic cleft, which indicates that selected phenotypes of L. peruvianum tubers cultivated under well-defined environmental and ecological conditions may present a valuable plant material to be considered for the development of therapeutic products with memory-stimulating properties.
... Many epidemiologic studies do not differ among the types of cruciferous vegetables, but the most common studies in the entire world include the broccoli, cauliflower, cabbages, bok choy, kale, watercress, turnip, and rocket [21]. Besides human health aspects, these metabolites play a fundamental role in the plants' defense against microorganisms; thus, there is an increasing interest in raising the content of these secondary compounds as a strategy of increasing the protection to cultures and reducing the use of agrochemicals. ...
... Brassica vegetables are the major source of glucosinolates that has been associated to its bioactivity, and these compounds may be responsible for their observed protecting effects. The glucosinolates are found in 16 families of dicotyledonous plants and in at least 120 different chemical structures that have been identified until now [21]. Depending on the chemical structure of the precursor amino acid, they are now classified into three groups: aliphatic, indole, and aromatic glucosinolates. ...
... En el caso específico de la flora epifítica de los vegetales, especialmente las bacterias ácido lácticas (BAL), utilizan los hidratos de carbono presentes en el tejido de las plantas transformándolos en ácidos orgánicos, logrando de esta manera un marcado descenso del pH y, en consecuencia la inhibición del desarrollo de bacterias indeseadas 1 . Además de este fenómeno, se producen distintas reacciones metabólicas que influyen por ejemplo, en la capacidad antibiótica mediante la formación de peróxido de hidrógeno, diacetilo y bacteriocinas 2 ; aumento de la ca-pacidad antioxidantes como consecuencia de la hidrólisis de polifenoles y flavonoides 3,4 ; incremento de moléculas bioactivas como la producción de tioglicolatos a partir de glucosinolatos por la acción de mirosinasas 5,6 , entre otras. ...
... El ácido fítico es definido desde el punto de vista químico como ácido mioinositol (1,2,3,4,5,6) hexafosfórico. Su estructura le permite formar quelatos estables e insolubles con cationes divalentes como Ca ++ , Mg ++ , Zn ++ , Cu ++ y Fe ++ , fenómeno que trae como consecuencia una disminución en la absorción y digestión de estos minerales en el tracto intestinal 11 . ...
Article
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Introducción Las fermentaciones han sido utilizadas históricamen-te por el hombre con el propósito de aumentar la vida útil de los alimentos y eliminar o inhibir bacterias patógenas o deteriorantes. En el caso específico de la flora epifítica de los vegetales, especialmente las bacterias ácido lácti-cas (BAL), utilizan los hidratos de carbono presentes en el tejido de las plantas transformándolos en ácidos orgánicos, logrando de esta manera un marcado descenso del pH y, en consecuencia la inhibición del desarrollo de bacterias indeseadas 1. Además de este fenómeno, se producen dis-tintas reacciones metabólicas que influyen por ejemplo, en la capacidad antibiótica mediante la formación de peróxido de hidrógeno, diacetilo y bacteriocinas 2 ; aumento de la ca-pacidad antioxidantes como consecuencia de la hidrólisis de polifenoles y flavonoides 3,4 ; incremento de moléculas bioactivas como la producción de tioglicolatos a partir de glucosinolatos por la acción de mirosinasas 5,6 , entre otras. Un cambio importante que se produce durante la fer-mentación es la disminución o eliminación de factores an-tinutricionales dentro de los que tenemos que considerar a los inhibidores de enzimas degradativas del tracto gastroin-testinal, especialmente la tripsina, o moléculas que interfie-ren en la biodisponibilidad de nutrientes 7. En este grupo de moléculas uno de los más importantes lo constituye el ácido fítico y sus derivados. Aproximadamente el 80 % del total del fósforo contenido en las células vegetales está presente Citation: Parada, R.; Sosa, F.; Marguet, E: Vallejo, M. Cambios en la concentración de ácido fítico, fósforo libre y hierro soluble durante la fermentación de repollo blanco y repollo chino.. Revis Bionatura 2022;7(2) 3. http://dx.
... The decomposition products of glucosinolates usually contribute to their unique taste (Vig et al. 2009). Glucosinolates are reported to possess beneficial roles for human health, since they show protective effects against cancer and cardiovascular diseases (Traka 2016). ...
... In planta, GLSs constitute a line of defence, which becomes activated upon attack from pathogens or herbivores (Jeschke and Burow, 2018). For humans, the intake of brassicaceous vegetables has been associated with reduced risks of cardiovascular diseases and several types of cancer (reviewed in (Traka, 2016)), and with better insulin resistance for type 2 diabetes (Bahadoran et al., 2012). These health beneficial effects have made GLSs interesting as dietary supplements and primed a desire to engineer microbial production as rich source of GLSs. ...
Article
Microbial production of plant specialised metabolites is challenging as the biosynthetic pathways are often complex and can contain enzymes, which function is not supported in traditional production hosts. Glucosinolates are specialised metabolites of strong commercial interest due to their health-promoting effects. In this work, we engineered the production of benzyl glucosinolate in Escherichia coli. We systematically optimised the production levels by first screening different expression strains and by modification of growth conditions and media compositions. This resulted in production from undetectable to approximately 4.1 μM benzyl glucosinolate, but also approximately 3.7 μM of desulfo-benzyl glucosinolate, the final intermediate of this pathway. Additional optimisation of pathway flux through entry point cytochrome P450 enzymes and PAPS-dependent sulfotransferase increased the production additionally 5-fold to 20.3 μM (equivalent to 8.3 mg/L) benzyl glucosinolate.
... Conjugation with glutathione occurs spontaneously and is further promoted by glutathione-S-transferases (GSTs), which include Mu (GSTM1), considered the major determinant of ITC metabolism, Pi (GSTP1), and Theta (GSTT1) (Hayes et al., 2005). The glutathione conjugate is then rapidly exported from the cell with the help of multidrug resistanceassociated protein-1 (MRP1), MRP2, and P-glycoprotein-1 (Pgp-1) (Traka, 2016;Zhang and Callaway, 2002). ...
Chapter
Kale is a vegetable that belongs to the Brassicaceae family (Brassica oleracea). The importance of kale stems from the fact that it contains health-promoting phytochemicals. Among them, glucosinolates (GLSs) and its derivatives, isothyocianates (ITCs), are the most powerful components. GLSs are secondary metabolites that could come into contact with the enzyme myrosinase in the presence of water, leading to the formation of ITCs. Both components have received great attention due to the beneficial properties that they present in relation to human health. The epidemiological studies carried out suggest that consumption of kale is associated with reduced risk of developing cancer or cardiovascular diseases. Phenolic compounds are essential molecules due to their antioxidant properties. Flavonoids, flavanols, anthocyanins, and hydroxycinnamic acid are the most common in kale vegetables. Phytic acid can act as metal chelator (calcium, iron, and nickel) to inhibit the generation of highly reactive oxygen species such as OH hydroxyl free radicals, and finally brassinosteroids are compounds whose main function is protection against viruses.
... Moreover, their involvement in the plant response to abiotic stresses has also been evidenced (Martinez-Ballesta et al., 2015;Salehin et al., 2019). Further to this, GSLs have also been associated with human health, in particular sulforaphane breakdown products, which possess anticancer activity (Traka, 2016). ...
Article
• Although ammonium (NH4+) is a key intermediate of plant nitrogen metabolism, high concentrations of NH4+ in the soil provoke physiological disorders that lead to the development of stress symptoms. • Ammonium nutrition was shown to induce the accumulation of glucosinolates (GSLs) in leaves of different Brassicaceae species. To further understand the link between ammonium nutrition and GSLs, we analyzed the ammonium stress response of Arabidopsis mutants impaired in GSL metabolic pathway. • We show that MYB28 and MYB29 double mutant (myb28myb29), which is almost deprived of aliphatic GSLs, is highly hypersensitive to ammonium nutrition. Moreover, we evidence that the stress symptoms developed are not a consequence of the lack of aliphatic GSLs. Transcriptomic analysis highlighted the induction of iron (Fe) deficiency response in myb28myb29 under ammonium nutrition. Consistently, ammonium‐grown myb28myb29 plants showed altered Fe accumulation and homeostasis. Interestingly, we overall show that growing Arabidopsis with increased Fe availability relieved ammonium stress symptoms and that this was associated with MYB28 and MYB29 expression. • Taken together, our data indicate that the control of Fe homeostasis is crucial for Arabidopsis response to ammonium nutrition and evidence that MYB28 and MYB29 play a role in this control.
... Postharvest processing of many cruciferous crop plants involves damage to tissues through maceration, fermentation or drying (Rabie et al., 2011;Palani et al., 2016). Glucosinolate breakdown metabolites are relevant to the properties and final use given by humans to these products (Traka, 2016). Glucosinolate metabolism has received considerable attention in recent years as a plant defense response against herbivores, for its impact on the human digestive tract and in the study of glucosinolate recycling in plant cells (Fechner et al., 2018;Gimsing and Kirkegaard, 2009;Wittstock et al., 2016;Platz et al., 2015). ...
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Postharvest processing of maca (Lepidium meyenii Walp., Brassicaceae), a traditional high-altitude Andean root crop, involves slow field drying prior to milling into flour. The progressive tissue dehydration and release of hydrolytic enzymes and substrates from cellular compartments results in the slow accumulation of free monosaccharides, fatty acids and amino acids. A more complex, and faster, kinetic profile is that of glucosinolate breakdown. A number of reactive transient and stable accumulation products are generated during drying, some of which have noteworthy bioactive properties. Among these are macamides, inhibitors of endocannabinoid neurotransmitter degradation in mammalian nervous systems. They result from the condensation of benzyl amine, a glucosinolate hydrolysis product, with free fatty acids released from lipid hydrolysis. Recent research has focused on developing drying processes under controlled conditions that can modulate the biochemistry of glucosinolate hydrolysis to optimize the content of bioactive compounds in the root flour. Low temperature (35 °C) oven-drying of shredded maca roots under controlled air flow generates benzyl amine as primary accumulation product, accounting for up to 94% of hydrolyzed glucosinolate in the flour. Kinetic evidence suggests that both deaminated benzenoids and macamides are allocated from the benzylamine pool through amine oxidase activity or condensation with free fatty acids, accounting for the remaining hydrolyzed glucosinolate (<5%). These activities determine the allocation to either one of these pathways. Later stages of dehydration result in shifts in the molar ratios of deaminated benzenoids, the accumulation of benzoic acid esters and benzyl alcohol. We propose that these are the result of changes in the rates of the reductive and oxidative half-reactions of endogenous aldehyde dehydrogenases. It is the ratio of benzylamine deamination to amide formation that determines the eventual yields of macamides in relation to benzenoids and their esters in maca flour.
... When digested, it produces several biologically active I3C oligomers such as DIM. Earlier studies of dietary indole derivatives have focused on their anti-cancer effect, given that they have been shown to reduce the risk of cancer (45)(46)(47). Indoles have been shown to induce antioxidant activity and apoptosis of cancer cells, and to regulate hormone metabolism (48)(49)(50)(51). Recently, several studies have reported that indoles also have immunoregulatory properties, especially on T cells. ...
Article
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Indoles, as the ligands of aryl hydrocarbon receptor (AhR), have been shown to possess immune-modulating property in terms of the balancing between regulatory T cells (Treg) and T helper 17 cells (Th17) activities. In the present study, we examined the effects of dietary indoles, 3,3′-diindolylmethane (DIM) and indole-3-carbinol (I3C), on CD4+T cell population and functions in chickens. Furthermore, the effects of dietary DIM treatment on chicken coccidiosis caused by an apicomplexan parasite were investigated. Dietary treatment of healthy chickens with DIM and I3C induced increased CD4+CD25+ (Treg) cells and the mRNA expression of IL-10, while decreasing number of CD4+IL-17A+ (Th17) cells and Th17-related cytokines transcripts expression in the intestine. In addition, we explored the role of AhR in indole-treated splenic lymphocytes by using AhR antagonist and our results suggested that DIM is a ligand for chicken AhR. In chicken coccidiosis, treatment of DIM increased the ratio of Treg/Th17 cells and significantly reduced intestinal lesion although no significant changes in body weight and fecal oocyst production were noted compared to non-treated control group. These results indicate that DIM is likely to affect the ratios of Treg/Th17 reducing the level of local inflammatory response induced by Eimeria or facilitate repairing process of inflamed gut following Eimeria infection. The results described herein are thus consistent with the concept that AhR ligand modulates the T cell immunity through the alteration of Treg/Th17 cells with Treg dominance. To our knowledge, present study is the first scientific report showing the effects of dietary indole on T cell immunity in poultry species.
... Since the early 1990s, a large body of epidemiological evidence and experimental data have linked the consumption of Brassica vegetables with chemoprotective effects against various types of cancers, including lung (Lam et al. 2009), gastric (Wu et al. 2013), colorectal (Tse & Eslick 2014), breast (Liu & Lv 2013), bladder (Al-Zalabani et al. 2016), and prostate (Liu et al. 2012) cancer. In addition, consumption of Brassica vegetables has also been shown to decrease oxidative stress and protect against cardiovascular disease, neurodegeneration, diabetes, and several inflammatory disorders (Dinkova-Kostova & Kostov 2012, Possenti et al. 2016, Traka 2016. The biological activities of Brassica vegetables have been largely attributed to the hydrolytic products of GSLs, of which the isothiocyanates (ITCs) are prominent compounds. ...
Article
Glucosinolates (GSLs) are a class of sulfur-containing compounds found predominantly in the genus Brassica of the Brassicaceae family. Certain edible plants in Brassica, known as Brassica vegetables, are among the most commonly consumed vegetables in the world. Over the last three decades, mounting evidence has suggested an inverse association between consumption of Brassica vegetables and the risk of various types of cancer. The biological activities of Brassica vegetables have been largely attributed to the hydrolytic products of GSLs. GSLs can be hydrolyzed by enzymes; thermal or chemical degradation also breaks down GSLs. There is considerable variation of GSLs in Brassica spp., which are caused by genetic and environmental factors. Most Brassica vegetables are consumed after cooking; common cooking methods have a complex influence on the levels of GSLs. The variation of GSLs in Brassica vegetables and the influence of cooking and processing methods ultimately affect their intake and health-promoting properties. Expected final online publication date for the Annual Review of Food Science and Technology, Volume 12 is March 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
... GSLs are flavor and odor donors for Brassica vegetables (Bell et al. 2018). Some GSLs and their breakdown products have cancer-and cardiovascular diseasepreventive effects in humans (Talalay and Fahey 2001, Traka and Mithen 2009, Ishida et al. 2014, Traka 2016. For plants, induction of GSL catabolism to produce toxic compounds or signaling molecules is an effective defense strategy against herbivory and pathogen attack (Grubb and Abel 2006, Halkier and Gershenzon 2006, Bednarek et al. 2009, Clay et al. 2009, Wittstock and Burow 2010. ...
Article
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Sulfur (S) is an essential element for plants, and S deficiency causes severe growth retardation. Although the catabolic process of glucosinolates (GSLs), the major S-containing metabolites specific to Brassicales including Arabidopsis, has been recognized as one of the S deficiency (-S) responses in plants, the physiological function of this metabolic process is not clear. Two β-glucosidases (BGLUs), BGLU28 and BGLU30, are assumed to be responsible for this catabolic process as their transcript levels were highly upregulated by -S. To clarify the physiological function of BGLU28 and BGLU30 and their roles in GSL catabolism, we analyzed the accumulation of GSLs and other S-containing compounds in the single and double mutant lines of BGLU28 and BGLU30 and in wild-type plants under different S conditions. GSL levels were highly increased, while the levels of sulfate, cysteine, glutathione and protein were decreased in the double mutant line of BGLU28 and BGLU30 (bglu28/30) under -S. Furthermore, transcript level of Sulfate Transporter1;2, the main contributor of sulfate uptake from the environment, was increased in bglu28/30 mutants under -S. With these metabolic and transcriptional changes, bglu28/30 mutants displayed obvious growth retardation under -S. Overall, our results indicate that BGLU28 and BGLU30 are required for -S-induced GSL catabolism and contribute to sustained plant growth under -S by recycling sulfate to primary S metabolism.
... Glucosinolates are chemically diverse amino acid-derived, sulfur-and nitrogencontaining thioglucosides almost solely found in plants of the order Brassicales with more than 130 identified structures to date (Blažević et al., 2019). The activation of glucosinolates has been intensively studied, both for their defensive roles against pathogens and herbivores and for their health beneficial roles for humans ( Burow et al., 2010;Pastorczyk and Bednarek, 2016;Traka, 2016;Wittstock et al., 2016a). In recent years, more and more studies uncovering additional roles of glucosinolates and glucosinolate-derived metabolites in feedback regulation of plant metabolism, growth and defense emerged ( Zhao et al., 2008;Kerwin et al., 2011;Burow et al., 2015;Jensen et al., 2015;Katz et al., 2015;Francisco et al., 2016a;Malinovsky et al., 2017;Urbancsok et al., 2017;Urbancsok et al., 2018). ...
Article
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Dynamically changing environmental conditions promote a complex regulation of plant metabolism and balanced resource investments to development and defense. Plants of the Brassicales order constitutively allocate carbon, nitrogen, and sulfur to synthesize glucosinolates as their primary defense metabolites. Previous findings support a model in which steady-state levels of glucosinolates in intact tissues are determined by biosynthesis and turnover through a yet uncharacterized turnover pathway. To investigate glucosinolate turnover in the absence of tissue damage, we quantified exogenously applied allyl glucosinolate and endogenous glucosinolates under different nutrient conditions. Our data shows that, in seedlings of Arabidopsis thaliana accession Columbia-0, glucosinolate biosynthesis and turnover are coordinated according to nutrient availability. Whereas exogenous carbon sources had general quantitative effects on glucosinolate accumulation, sulfur or nitrogen limitation resulted in distinct changes in glucosinolate profiles, indicating that these macronutrients provide different regulatory inputs. Raphanusamic acid, a breakdown product that can potentially be formed from all glucosinolate structures appears not to reflect in planta turnover rates, but instead correlates with increased accumulation of endogenous glucosinolates. Thus, raphanusamic acid could represent a metabolic checkpoint that allows glucosinolate-producing plants to measure the flux through the biosynthetic and/or turnover pathways and thereby to dynamically adjust glucosinolate accumulation in response to internal and external signals.
... 5 It has also been reported that these compounds may protect cells from the redox imbalance that underlies the development of several chronic inflammatory diseases. 6 The hydrolysis of glucoraphanin generates sulforaphane, which is a strong inducer of phase II enzymes capable of carrying out carcinogen detoxification. 7 Similarly, PHs are well-known health-promoting phytochemicals present in many plants. ...
Article
Background: Brassica oleracea var. alboglabra (Chinese kale) is an important vegetable grown in southern China. This study was aimed at searching for environmental-friendly and affordable approaches to increase the production of medicinally relevant glucosinolates and phenolic compounds in Chinese kale plants. For this purpose, the foliar application of liquiritin at 0 (control), 250, 500, and 750 ppm was tested starting from the four-leaf stage and repeated every two weeks until plants were two-month-old. Results: Foliar application of liquiritin in Chinese kale plants significantly increased glucosinolates and total phenolic content, in a dose-dependent manner. Compared with control plants, 2.3- and 1.9-fold increases in yields of glucosinolates and total phenolic content, respectively, were corroborated in Chinese kale plants treated with 750 ppm of liquiritin. Along with rises in the content of eight different glucosinolates, liquiritin elicitation effectively increased the concentration of glycosilated and acylated flavonoids and hydroxycinnamic acids. The expression of genes involved in glucosinolates and phenolics biosynthesis was significantly higher in liquiritin-treated plants as compared to controls. Conclusion: Liquiritin elicitation is a feasible and environmental-friendly practice to increase the production of medicinally important glucosinolates and phenolic compounds in Chinese kale plants, which may improve this plant's value as a nutraceutical food. This study also contributes to understanding the molecular mechanisms underlying liquiritin elicitation. This is the first report documenting the use of liquiritin for an elicitation purpose in plants. This article is protected by copyright. All rights reserved.
... Sulforaphane is absorbed readily into the enterocyte and conjugated with glutathione via the GSTM1 enzyme. Sulforaphane is then either metabolised and excreted in the urine via the mercapturic acid pathway or cleaved from glutathione into free sulforaphane [25]. SFN has been shown to have multi-modal influences on a wide variety of metabolic and cell-signalling pathways involved in cancer including the induction of antioxidant pathways, induction of apoptosis in cancer cells, inhibition of inflammation and angiogenesis and detoxification of carcinogens [27]. ...
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Prostate cancer has become the most common form of non-cutaneous (internal) malignancy in men, accounting for 26% of all new male visceral cancer cases in the UK. The aetiology and pathogenesis of prostate cancer are not understood, but given the age-adjusted geographical variations in prostate cancer incidence quoted in epidemiological studies, there is increasing interest in nutrition as a relevant factor. In particular, foods rich in phytochemicals have been proposed to reduce the risk of prostate cancer. Epidemiological studies have reported evidence that plant-based foods including cruciferous vegetables, garlic, tomatoes, pomegranate and green tea are associated with a significant reduction in the progression of prostate cancer. However, while there is well-documented mechanistic evidence at a cellular level of the manner by which individual dietary components may reduce the risk of prostate cancer or its progression, evidence from intervention studies is limited. Moreover, clinical trials investigating the link between the dietary bioactives found in these foods and prostate cancer have reported varied conclusions. Herein, we review the plant bioactives for which there is substantial evidence from epidemiological and human intervention studies. The aim of this review is to provide important insights into how particular plant bioactives (e.g., sulphur-containing compounds, carotenoids and polyphenols) present in commonly consumed food groups may influence the development and progression of prostate cancer.
... SFN-mediated cell-cycle arrest has been reported in several other cell lines (Lenzi et al., 2014). In vitro studies on glucosinolates and cell cycle arrest are summarized in Traka (2016). ...
Article
Although extensive resources are dedicated to the development and study of cancer drugs, the cancer burden is expected to rise by about 70% over the next 2 decade. This highlights a critical need to develop effective, evidence-based strategies for countering the global rise in cancer incidence. Except in high-risk populations, cancer drugs are not generally suitable for use in cancer prevention owing to potential side effects and substantial monetary costs (Sporn, 2011). There is overwhelming epidemiological and experimental evidence that the dietary bioactive compounds found in whole plant-based foods have significant anticancer and chemopreventative properties. These bioactive compounds often exert pleiotropic effects and act synergistically to simultaneously target multiple pathways of cancer. Common bioactive compounds in fruits and vegetables include carotenoids, glucosinolates, and polyphenols. These compounds have been shown to target multiple hallmarks of cancer in vitro and in vivo and potentially to address the diversity and heterogeneity of certain cancers. Although many studies have been conducted over the past 30 y, the scientific community has still not reached a consensus on exactly how the benefit of bioactive compounds in fruits and vegetables can be best harnessed to help reduce the risk for cancer. Different stages of the food processing system, from "farm-to-fork," can affect the retention of bioactive compounds and thus the chemopreventative properties of whole foods, and there are opportunities to improve handling of foods throughout the stages in order to best retain their chemopreventative properties. Potential target stages include, but are not limited to, pre- and postharvest management, storage, processing, and consumer practices. Therefore, there is a need for a comprehensive food-system-based approach that not only taking into account the effects of the food system on anticancer activity of whole foods, but also exploring solutions for consumers, policymakers, processors, and producers. Improved knowledge about this area of the food system can help us adjust farm-to-fork operations in order to consistently and predictably deliver desired bioactive compounds, thus better utilizing them as invaluable chemopreventative tools in the fight to reduce the growing burden of cancer worldwide.
... They are well-known for their involvement in plant defense response against insects and pathogens [158][159][160]. Moreover, several GLSs hydrolysis products may play a prominent role in chronic diseases prevention, including certain types of cancer, diabetes, cardiovascular disease, neurodegeneration, and several inflammatory disorders due to the oxidative stress [161][162][163][164]. The antioxidant properties of GLSs hydrolysis products were largely investigated. ...
Article
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Plant antioxidants are important compounds involved in plant defense, signaling, growth, and development. The quantity and quality of such compounds is genetically driven; nonetheless, light is one of the factors that strongly influence their synthesis and accumulation in plant tissues. Indeed, light quality affects the fitness of the plant, modulating its antioxidative profile, a key element to counteract the biotic and abiotic stresses. With this regard, light-emitting diodes (LEDs) are emerging as a powerful technology which allows the selection of specific wavelengths and intensities, and therefore the targeted accumulation of plant antioxidant compounds. Despite the unique advantages of such technology, LED application in the horticultural field is still at its early days and several aspects still need to be investigated. This review focused on the most recent outcomes of LED application to modulate the antioxidant compounds of plants, with particular regard to vitamin C, phenols, chlorophyll, carotenoids, and glucosinolates. Additionally, future challenges and opportunities in the use of LED technology in the growth and postharvest storage of fruits and vegetables were also addressed to give a comprehensive overview of the future applications and trends of research.
... Cutting, chewing and/or grinding raw cruciferous vegetables in the presence of water will release the enzyme myrosinase, which results in the hydrolysis of the parental glucosinolate compounds, forming bioactive glucosinolate hydrolysis products, such as isothiocyanates (ITCs). While cooking destroys myrosinase, the digestion of cooked vegetables by colonic bacteria also results in the formation of these metabolites [7] . Isothiocyanates are absorbed from the small bowel and colon; hence glucosinolate metabolites are detectable in human urine approximately 2-3 h after the consumption of Brassica vegetables [ 8 , 9 ]. ...
Article
Numerous epidemiological studies have indicated the potential effects of glucosinolates and their metabolites against cancer as well as other non-communicable diseases, such as cardiovascular disease and neurodegenerative disorders. However, information on the presence and quantity of glucosinolates in commonly consumed vegetables and in human fluids is sparse, largely because well-standardised methods for glucosinolate determination are not available, resulting in published data being inconsistent and conflicting. Thus, studies published since 2002 on the most recent developments of glucosinolate extraction and identification have been collected and reviewed with emphasis on determination of the intact glucosinolates by LC-MS and LC-MS/MS. This overview highlights the glucosinolate extraction methods used, the stability of glucosinolates during extraction, the availability of stable isotope labelled internal standards and the use of NMR for purity analysis, as well as the current analytical techniques that have been applied for glucosinolate analysis, e.g. liquid chromatography with mass spectrometric detection (LC-MS). It aims to interpret the findings with a focus on the development of a validated method, which will help to determine the glucosinolate content of vegetative plants and human tissues, and the identification and determination of selected glucosinolate metabolites.
... Many cruciferous plants contain a number of nutrients and phytochemicals that are associated with health promoting effects, in particular glucosinolates, that are responsible for their typical pungent aromas and spicy taste [1,2]. Such compounds are considered health promoting constituents and have been examined as such in different in vitro, in vivo, clinical and epidemiological studies [3][4][5]. Eruca sativa (Brassicaceae) known as "rocket salad" is very well known vegetable that is widely consumed in many countries, being popular in mixed salads due to its distinctive taste and textural appearance [1,6]. Rocket contains a large number of bioactive constituents, and especially due to its content in glucosinolates, phenolics and unsaturated fatty acids, can be considered a good source of health promoting compounds [1,[6][7][8][9][10] Rocket salad is not only a healthy food, but could be useful as a valuable source for the preparation of extracts to be used in health-promoting products. ...
Article
Background: Eruca sativa Mill. is a good source of glucosinolates (GLS), phenolic compounds and unsaturated fatty acids, being a valuable material for the production of functional-foods or nutraceutical ingredients. Extraction by supercritical CO 2 (SCO 2) can be used and the limitations due to the apolar nature of CO 2 can be overcome using co-solvents. In this paper different cosolvents and conditions were used for SCO 2 extraction and the composition of the obtained extracts was studied by LC-MS. Results: Water resulted the ideal co-solvent, allowing the extraction of glucosinolates in comparable amounts to the classical procedure with boiling water, as it can be carried out at mild temperatures (45 • C vs. >100 • C). Increasing the pressure improved the GLS extraction. On the other hand polyphenol extraction under the studied conditions was not influenced by pressure and temperature variations. The in vitro antioxidant effect of the obtained extracts was also measured, showing significant activity in the DPPH and FC tests. Conclusions: The GLS, flavonoids and lipids composition of the obtained extracts was studied, showing the presence of numerous antioxidant constituents useful for nutraceutical applications. The extraction method using SCO 2 and water as co-solvent presents advantages in terms of safety because these solvents are generally recognised as safe. Water as cosolvent at 8% resulted useful for the extraction of both glucosinolates and phenolics in good amount and is environmentally acceptable as well as safe for food production.
... Mainly glucosinolates in cabbage have not been associated with direct antidiabetic mechanisms. However, these compounds may interfere with critical processes of carcinogenesis and metastasis by protecting cells from the redox imbalance that underlies the development of chronic metabolic diseases (Fuentes et al., 2015;Traka, 2016). Glucosinolates (in bioactive form) reduce glucose production in the liver and increases antioxidant resistance in human osteosarcoma cells (Guzmán-Pérez et al., 2016); they also decrease hepatic steatosis, improve glucose tolerance and insulin sensitivity (Nagata et al., 2017), and reduce fasting glucose and glycosylated hemoglobin (Axelsson et al., 2017). ...
Article
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Type 2 diabetes mellitus (T2DM) is increasing the prevalence worldwide at an alarming rate, becoming a serious public health problem that mainly affects developing countries. Functional food research is currently of great interest because it contributes to developing nutritional therapy strategies for T2DM prevention and treatment. Bioactive compounds identified in some plant foods contribute to human health by mechanisms of action that exert biological effects on metabolic pathways involved in the development of T2DM. Hence, vegetables with high bioactive compounds content may be a source of functional value for the control of T2DM. Cabbages varieties (Brassica oleracea var. capitata) such as green (GCB), white (WCB), and red (RCB) are foods consumed (raw or cooked) and cultivated in different regions of the world. Scientific evidence shows that cabbage has multi-target effects on glucose homeostatic regulation due to its high content of bioactive compounds. It has also been shown to decrease damage to organs affected by T2DM complications, such as the liver and kidney. Additionally, it could contribute as a preventive by attenuating problems underlying the development of T2DM as oxidative stress and obesity. This review highlights the functional properties of cabbage varieties involved in glucose regulation and the main mechanisms of the action exerted by their bioactive compounds. In conclusion, cabbage is a valuable food that can be employed as part of nutritional therapy or functional ingredient aimed at the prevention and treatment of T2DM.
... After absorption, ITCs are distributed through the hepatic portal vein to the liver where a high concentration of ITCs first occurs. The process is followed by first-pass metabolism before dissemination to other tissues [18], so lower concentrations of ITCs are detected in the systemic circulation. In the current study, the hepatocellular carcinoma cell line HepG2 was selected as a model of liver cancer where the high concentration of ITCs could be physiologically achieved. ...
Article
The structure of the isothiocyanates (ITCs)-erucin, sulforaphane, erysolin, sulforaphene, and phenethyl isothiocyanate-were assessed as well as their respective in vitro anticancer activity on the hepatocellular carcinoma cell line HepG2. All of these ITCs induced both apoptotic and necrotic cell death. FTIR analysis indicated that the ITCs caused changes in cellular components comparable to vinblastine. Despite no observable effect on DNA, the ITCs all induced generation of intracellular reactive oxygen species (ROS) and suppressed microtubule polymerization. The variation in sulfur oxidation states and the presence of an aromatic ring on the ITC side chain affected microtubule depolymerization and intracellular ROS generation, leading to apoptotic and necrotic cancer cell death. Knowing the influences of structural variations of the ITC side chain would be useful for selecting the more potent ITCs (i.e., erysolin) for the design and development of effective chemopreventive agents.
... Indole glucosinolates, which have side chains derived from tryptophan, are abundant in Brassica vegetables such as broccoli, cabbage, cauliflower, mustard greens, and rutabagas (13,14), and indole compounds have been reported to exhibit anti-inflammatory and anti-carcinogenic properties (15,16). In addition to indole compounds in plants, gut microbiota forms various indole derivatives from tryptophan catabolism, which have been shown to influence the modulation of immune responses through aryl hydrocarbon receptor (AhR) signaling and regulation of barrier function through the nutrient transporters and pregnane X receptor (PXR) (17,18). ...
Article
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Two studies were conducted to evaluate the effects of indole-3-carboxylate (ICOOH) as a postbiotic on maintaining intestinal homeostasis against avian coccidiosis. In the first study, an in vitro culture system was used to investigate the effects of ICOOH on the proinflammatory cytokine response of chicken macrophage cells (CMCs), gut integrity of chicken intestinal epithelial cells (IECs), differentiation of quail muscle cells (QMCs), and primary chicken embryonic muscle cells (PMCs) and anti-parasitic effect against Eimeria maxima. Cells to be tested were seeded in the 24-well plates and treated with ICOOH at concentrations of 0.1, 1.0, and 10.0 µg. CMCs were first stimulated by lipopolysaccharide (LPS) to induce an innate immune response, and QMCs and PMCs were treated with 0.5% and 2% fetal bovine serum, respectively, before they were treated with ICOOH. After 18 h of incubation, cells were harvested, and RT-PCR was performed to measure gene expression of proinflammatory cytokines of CMCs, tight junction (TJ) proteins of IECs, and muscle cell growth markers of QMCs and PMCs. In the second study, in vivo trials were carried out to study the effect of dietary ICOOH on disease parameters in broiler chickens infected with E. maxima. One hundred twenty male broiler chickens (0-day-old) were allocated into the following four treatment groups: 1) basal diet without infection (CON), 2) basal diet with E. maxima (NC), 3) ICOOH at 10.0 mg/kg feed with E. maxima (HI), and 4) ICOOH at 1.0 mg/kg feed with E. maxima (LO). Body weights (BWs) were measured on 0, 7, 14, 20, and 22 days. All groups except the CON chickens were orally infected with E. maxima on day 14. Jejunal samples were collected for lesion score and the transcriptomic analysis of cytokines and TJ proteins. In vitro, ICOOH increased the expression of TJ proteins in IECs and decreased IL-1β and IL-8 transcripts in the LPS-stimulated CMCs. In vivo, chickens on the HI diet showed reduced jejunal IL-1β, IFN-γ, and IL-10 expression and increased expression of genes activated by aryl hydrocarbon receptors and nutrient transporters in E. maxima-infected chickens. In conclusion, these results demonstrate the beneficial effects of dietary ICOOH on intestinal immune responses and barrier integrity in broiler chickens challenged with E. maxima. Furthermore, the present finding supports the notion to use microbial metabolites as novel feed additives to enhance resilience in animal agriculture.
... Some of these compounds are also associated with unpleasant taste (glucosinolates, sinapine, and kaempferols) (Chmielewska et al., 2020). Although some of these compounds having potential benefits to human health, for example reducing risks of cancers and cardiovascular diseases (glucosinolates) as well as exhibiting anti-oxidative, anti-microbial, anti-mutagenic, and anti-inflammatory activities (phenolics), their contents should be reduced to appropriate levels for application in human diet (Traka, 2016;Vuorela, 2005). ...
Article
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The study aimed to develop a biorefining process to recover proteins and dietary fibres from a food industry sidestream, canola (Brassica napus) oil pressing residues. The materials were treated with commercial protease, carbohydrase, and phytase to obtain protein-rich supernatants and fibre-rich precipitates. The compositions of these fractions were analyzed using LC-MS (glucosinolates and phenolics) and GC–MS (sugars, acids, and amino acids). Compared to raw material, the supernatants were richer in proteins, sugars, acids, amino acids, phenolic acids, and flavonols; the precipitates had higher levels of minerals and dietary fibres. The enzymatic treatment decreased the contents of phytic acid, glucosinolates, and phenolic alkaloids in all fractions. The applied enzymes effectively enhanced solubility of proteins, despite the lower yield of crude proteins compared to the alkaline extraction (40–82 vs 91 g/100 g dry matters). The impact of enzymes on other chemical components was also revealed by using principal component analysis.
... Among these, flavonoid glycosides induced in the ineffective partnership between Pbg and Arabidopsis are considered vital phytochemicals in diets and are of great interest due to their diverse bioactivities (Xiao et al., 2016). Similarly, glucosinolates in Brassica species (Traka 2016), hydroxycinnamic acid derivatives (Alam et al., 2016) and dihydroartemisinin in Artemisia (Tilley et al., 2016) are potential HPVC. In effective partnerships, the increase in these compounds is even more pronounced when we consider the increase in host biomass due to rhizobacteria inoculation. ...
Preprint
Various root-colonizing bacterial species can promote plant growth and trigger systemic resistance against aboveground leaf pathogens and herbivore insects. To date, the underlying metabolic signatures of these rhizobacteria-induced plant phenotypes are poorly understood. To identify core metabolic pathways that are targeted by growth-promoting rhizobacteria, we used combinations of three plant species and three rhizobacterial species and interrogated plant shoot chemistry by untargeted metabolomics. A substantial part (50-64%) of the metabolites detected in plant shoot tissue was differentially affected by the rhizobacteria. Among others, the phenylpropanoid pathway was targeted by the rhizobacteria in each of the three plant species. Differential regulation of the various branches of the phenylpropanoid pathways showed an association with either plant growth promotion or growth reduction. Overall, suppression of flavonoid biosynthesis was associated with growth promotion, while growth reduction showed elevated levels of flavonoids. Subsequent assays with twelve Arabidopsis flavonoid biosynthetic mutants revealed that the proanthocyanidin branch plays an essential role in rhizobacteria-mediated growth promotion. Our study also showed that a number of pharmaceutically and nutritionally relevant metabolites in the plant shoot were significantly increased by rhizobacterial treatment, providing new avenues to use rhizobacteria to tilt plant metabolism towards the biosynthesis of valuable natural plant products.
... Moreover, aspartic and glutamic acid are responsible for the umami taste of Brassica vegetables and polyphenols along with other components are likely to contribute to their bitterness. Sulforaphane was one of the well-studied glucosinolates (79). Brussels sprouts also contain high amounts of protein (one-third of dry matter), unsaturated fatty acids, and minerals, as well as low amount of nitrates and heavy metals (80). ...
Chapter
The genus Brassica comprises a large group of herbaceous plants, including many vegetables that originated in the Mediterranean region. These vegetables contain various phytochemicals such as phenolic acids, flavonoids, glucosinolates, and their hydrolyzed products. Among the Brassica vegetables, Brussels sprouts (Brassica oleracea var. gemmifera) are rich in vitamin A, ascorbic acid, glucosinolates, and certain phenolic compounds. This chapter gives an overview on extraction of health-promoting phytochemicals from Brussels sprouts, using green solvents with different extraction techniques from health perspective to reduce the detrimental issues associated with usage of organic solvents for the isolation in large quantities. In addition, we discuss the significance of accelerated solvent extraction and hyphenated chromatographic techniques used for rapid isolation and identification of phytochemicals. The functional properties of Brussels sprouts, along with the compounds identified, and assays used for determining their bioactivity are also presented in this chapter.
... Glucosinolates are active compounds that are found mainly in cruciferous vegetables. Lots of studies have confirmed that eating cruciferous vegetables could greatly prevent cancer, due to the presence of glucosinolates that have demonstrated to have anti-cancer properties [237][238][239][240][241][242][243]. Glucosinolates are only harmful when they are processed for animal feed, because toxic products that are catalyzed by an enzyme called myrosinase could be released during the treatment [244]. ...
Article
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Brassica napus is a vegetable oil crop, which is commonly known as rapeseed (or canola). Rapeseed is widely used as a source of oil and protein for food and industrial applications, but also as a remedy, and in a field of attraction or as an ornament due to its diverse flower colors. Every part of rapeseed is useful, even the waste, which could be used to feed animals, or recycled. In this review, the usage of rapeseed in these applications is presented, starting with the preparation of oil and protein from the seeds, before their release in the market, to the utilization of natural unprocessed rapeseed. Progress in rapeseed exploitation for food, remedy, energy source, and industrial applications are analyzed to show variability in diverse findings, to provide insights and progressive descriptions of rapeseed usage to other scholars. Moreover, advancements in breeding for rapeseed improvement were described. In the future, strategies could be developed or improved to avoid or to decrease crop losses, but also to grow the interest in seeking enhancements for valuable traits of rapeseed.
... GLSs impart specific pungency and flavors to Brassicaceae vegetables such as mustard and cabbage (Fahey et al., 2001;Halkier, 2016;Possenti et al., 2017). Moreover, a few GLS compounds such as glucoraphanin (4-methylsulfinyl-n-butyl glucosinolate) are known to produce health-promoting chemicals with diverse bioactivities (Traka, 2016;Banerjee and Paruthy, 2017). Very recently, the enormous body of research activities on GLS has been compiled as two books entitled Glucosinolates with few overlaps (Kopriva, 2016;Mérillon and Ramawat, 2017). ...
Article
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Glucosinolates (GLSs) are a well-known class of specialized plant metabolites, distributed mostly in the order Brassicales. A vast research field in basic and applied sciences has grown up around GLSs owing to their presence in important agricultural crops and the model plant Arabidopsis thaliana, and their broad range of bioactivities beneficial to human health. The major purpose of GLSs in plants has been considered their function as a chemical defense against predators. GLSs are physically separated from a specialized class of beta-thioglucosidases called myrosinases, at the tissue level or at the single-cell level. They are brought together as a consequence of tissue damage, primarily triggered by herbivores, and their interaction results in the release of toxic volatile chemicals including isothiocyanates. In addition, recent studies have suggested that plants may adopt other strategies independent of tissue disruption for initiating GLS breakdown to cope with certain biotic/abiotic stresses. This hypothesis has been further supported by the discovery of an atypical class of GLS-hydrolyzing enzymes possessing features that are distinct from those of the classical myrosinases. Nevertheless, there is only little information on the physiological importance of atypical myrosinases. In this review, we focus on the broad diversity of the beta-glucosidase subclasses containing known atypical myrosinases in A. thaliana to discuss the hypothesis that numerous members of these subclasses can hydrolyze GLSs to regulate their diverse functions in plants. Also, the increasingly broadening functional repertoires of known atypical/classical myrosinases are described with reference to recent findings. Assessment of independent insights gained from A. thaliana with respect to (1) the phenotype of mutants lacking genes in the GLS metabolic/breakdown pathways, (2) fluctuation in GLS contents/metabolism under specific conditions, and (3) the response of plants to exogenous GLSs or their hydrolytic products, will enable us to reconsider the physiological importance of GLS breakdown in particular situations, which is likely to be regulated by specific beta-glucosidases.
... As a food-borne metabolite, SF is one of the strongest anti-cancer natural active ingredients known to date in vegetables (Klaus et al., 2011). It has been shown SF play a key role in preventing cardiovascular disease (Traka et al., 2016), antibacterial and anti-in ammatory (Choi et al., 2014), and antioxidant (Kang et al., 2017). At present, SF is mainly obtained from broccoli seeds or seedlings, which have the problems of low yield and high cost. ...
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Hairy roots obtained by infecting broccoli ( Brassica oleracea L. var . Italic Planch) leaves with Agrobacterium rhizogenes (ATCC15834) had the characteristics of phytohormone autonomy, genetic stability and can produce a large amount of anti-cancer substance Sulforaphane (SF) and SF biosynthetic precursors substance Glucoraphanin (GRA). The production of SF in hairy roots of broccoli increased significantly under the induction of exogenous signal molecule Methyl jasmonate (MeJA). However, the molecular mechanism of MeJA treatment hairy roots of broccoli have not been reported. In this study, the optimal concentration of MeJA for having treatment broccoli hairy roots were selected based on the yield of GRA and SF. After grew 18 days, broccoli hairy roots were treated with 10 mmol/L MeJA for 0, 3, 6, 9 and 12 h respectively. Compared with 0 h, the yields of GRA and SF increased under other treatments. The highest yield of GRA and SF was noted at 9 h, which were 2.22-fold and 1.74-fold of 0 h, respectively. Broccoli ( Brassica oleracea L. var. botrytis L) as reference genome, and 1195 co-differentially expressed genes (DEGs) at 0, 3, 6, 9 and 12 h was observed under treatment 10 mmol/L MeJA, which there were 3,826 down-regulated and 574 up-regulated genes. The six key genes that regulated Glucosinolates (GLS) synthesis, MAM1 , CYP79B1 , CYP83B1 , UGT74B1 , and FMOGS-OX5 , were up-regulated at 0 and 3 h, and down-regulated at the rest of the time; BCAT2 was up-regulated at 6, 9, 12 h, and at 0, 3 h expression was down-regulated, transcription factors MYB34 and MYB122 were up-regulated at 3 h, and down-regulated at other time points, MYB51 was up-regulated at 0, 3 h and down-regulated at 6, 9, 12 h. The pathway diagram of GRA biosynthesis and transformation pathway in broccoli hairy roots treatment by MeJA simulated, and the molecular mechanis0m of GRA biosynthesis and SF accumulation in broccoli hairy roots under MeJA treatment were revealed.
... Despite the fact that they have long been considered as antinutritional factors due to their effect on diet quality, especially due to their impact on protein digestibility and on the bioavailability of amino acids, [43] there is now evidence that these compounds may also have beneficial health effects. [44,45] In addition, the contents are low and they can be easily removed during processing. [46] Today, camelina is not only used in animal and human nutrition, but also for biofuel production and for biomaterials. ...
Article
Camelina sativa (C. sativa) seeds are rich in oil (30% – 49%) and protein (24% – 31%). They contain ω-3 acids, ω-6 acids, tocopherols, phytosterols and phenolic compounds, among others. From an agricultural perspective, growing of this crop is of interest due to its short growth cycle and low fertilizer and water input requirements. Camelina is also tolerant to cold and drought and is consequently well adapted to grow in semiarid regions. Camelina is mainly cultivated for its oil in Europe and North America. In this review, the processes applied for camelina oil extraction, composition and attributes, as well as the food and non-food applications of camelina oil are reviewed. Applications include animal feed, functional foods, materials, biofuels, and agrochemicals. Valorisation of the camelina protein found in the meal after the oil extraction is also discussed in this paper. Finally, some research avenues for future work are presented. Practical Applications: In this review, the need to develop an integrated process for the valorization of camelina seeds is highlighted. The integrated process would consist of a degumming step to extract the mucilage from the whole camelina seeds, followed by an oil extraction step, and finally by a protein extraction step. There is also a need to develop food applications of camelina oil. Despite the fact that camelina oil is approved for human consumption in many countries, the market is under-developed. This can be due to the low oxidative stability of camelina oil. In this context, the development of advanced delivery systems that will minimize oil oxidation and prolong shelf life could further expand the utilization of camelina oil in the food industry. More research works should also focus on the utilization of camelina oil in specialty applications such as functional foods, nutraceuticals, cosmetics, and pharmaceutical applications. This article is protected by copyright. All rights reserved
... It is commonly used as food for its pungent or bitter flavor and abundant nutrients (potassium, sulfur, iron, and vitamins A and C) in their edible leaves [5]. Arugula has also been used for many medicinal purposes [2] as its leaves contain large quantities of health-promoting compounds, mainly contributed from glucosinolates and antioxidants with proven pharmaceutical and anti-cancer properties [6,7]. Despite the numerous studies on utilization of arugula, scientific studies on cultural practices affecting its commercial production are still lacking, only information available is from anecdotal experience of producers [8]. ...
Article
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Arugula (Eruca sativa) is cultivated using hydroponic techniques in greenhouses to fulfill high year-round demand, but its nutrient management in hydroponic production has not yet been standardized, potentially leading to limited quality and productivity. Aiming to address this issue, we investigated the effect of electrical conductivity (EC) on yield, nutritional and phytochemical properties of arugula. The model cultivar arugula ‘Standard’ was grown at four different EC levels (1.2, 1.5, 1.8, and 2.1 dS·m−1). Our results indicated photosynthetic properties, SPAD, leaf area, yield and dry weight increased with increasing EC from 1.2 to 1.8 dS·m−1. Foliar nutrient content increased with higher EC, but nutrient solution with 2.1 dS·m−1 showed a significant decline in N, Ca and most of the micronutrients including Fe, Zn, Mo, Cu, B and Mn. Total glucosinolates, total chlorophyll and total carotenoids concentrations increased with increasing EC. In addition, total anthocyanin content was highest in plants grown in EC 1.2 and 2.1 dS·m−1, demonstrating a stress response when grown in extreme EC levels. Our results further indicated a rapid accumulation of nitrate with higher EC, potentially detrimental to human health. This research demonstrated the optimal EC range would be 1.5 to 1.8 dS·m−1 for arugula in hydroponic production systems based on yield, quality criteria and human health considerations.
... Previous studies have shown that glucosinolates are prominent groups of compounds exerting beneficial health effects in brassica vegetables [41]. Glucosinolates are key metabolites involved in controlling obesity, diabetes, and many other cardiovascular diseases [38]. ...
Article
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The antioxidant and antidiabetic properties and metabolite profiling of ethanol extracts of red cabbage (RC) and broccoli (BR) seeds and sprouts were investigated in this study. The total phenolic, flavonoid, and saponin contents were in the ranges of 385.4–480.4 mg FAE/100 g, 206.9–215.6 mg CE/100 g, and 17.8–27.0 mg soysaponin BE/100 g, respectively. BR seed had the highest total phenolic (480.4 mg FAE/100 g) and flavonoid (216.9 mg CE/100 g) contents, whereas BR sprout had the highest saponin content (27.0 soysaponin BE/100g). RC sprout demonstrated the highest antioxidant capacity, with DPPH and ABTS radical scavenging activity levels of 71.5% and 88.5%, respectively. Furthermore, BR and RC sprouts showed the most potent inhibition against α-glucosidase (91.32% and 93.11%, respectively) and pancreatic lipase (60.19% and 61.66%, respectively). BR seed (60.37%) demonstrated the lowest AGE inhibition. A total of 24 metabolites, predominantly amino acids and phenolic compounds, were characterized using UHPLC-QTOF-MS/MS. Germination not only improved the levels of metabolites but also resulted in the synthesis of new compounds. Therefore, these findings show that germination effectively enhanced the functional properties and metabolite profiles of broccoli and red cabbage seeds, making their sprouts more applicable as functional ingredients.
... After oral absorption, the ITCs go through the hepatic portal veins to liver where the first-pass metabolism occurs. The metabolic process yields metabolites and reduces ITC concentrations before distribution to other body tissues (Traka, 2016). In this study, the hepatocellular carcinoma cell line HepG2 was thus used as a liver cancer model because highconcentration of ITCs could be achieved after oral administration before first-pass metabolism. ...
Article
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To determine the chemopreventive potential of alyssin and iberin, the in vitro anticancer activities and molecular targets of isothiocyanates (ITCs) were measured and compared to sulforaphane in hepatocellular carcinoma cell HepG2. The SR-FTIR spectra observed a similar pattern vis-à-vis the biomolecular alteration amongst the ITCs-treated cells suggesting a similar mode of action. All of the ITCs in this study cause cancer cell death through both apoptosis and necrosis in concentration dependent manner (20-80 µM). We found no interactions of any of the ITCs studied with DNA. Notwithstanding, all of the ITCs studied increased intracellular reactive oxygen species (ROS) and suppressed tubulin polymerization, which led to cell-cycle arrest in the S and G2/M phase. Alyssin possessed the most potent anticancer ability; possibly due to its ability to increase intracellular ROS rather than tubulin depolymerization. Nevertheless, the structural influence of alkyl chain length on anticancer capabilities of ITCs remains inconclusive. The results of this study indicate an optional, potent ITC (viz., alyssin) because of its underlying mechanisms against hepatic cancer. As a consequence, further selection and development of effective chemotherapeutic ITCs is recommended.
Article
We compared the secondary metabolite composition in seeds of Camelina sativa and its wild relatives to identify potential germplasm with reduced levels of antinutritional compounds. Twenty Camelina accessions, from five different species, were analyzed by liquid chromatography mass spectrometry and subjected to principal component analysis, which revealed that Camelina spp. separated into distinct chemotaxonomic groups. Three major glucosinolates (GSs) were identified in our study, namely, 9-methylsulfinylnonyl GS (GS9), 10-methylsulfinyldecyl GS (GS10), and 11-methylsulfinylundecyl GS (GS11). While there were differences in total GS levels, species-specific patterns for GS9 and GS11 were noted. Sinapine content ranged between 1.4 and 5.6 mg/g FW, with the lowest levels observed in C. laxa and C. sativa. Lignin levels were also lowest in C. sativa, with most accessions containing less than 6 mg/g FW. Our results show that wild Camelina spp. have distinct metabolomes, and based on their levels of major antinutritionals, some could be incorporated into breeding programs with C. sativa.
Article
Hairy roots obtained by infecting broccoli (Brassica oleracea var. italica) leaves with Agrobacterium rhizogenes (ATCC15834) have the characteristics of phytohormone autonomy, genetic stability and can produce a large amount of the anti-cancer substance Sulforaphane (SF) and the biosynthetic precursor Glucoraphanin (GRA). Under the induction of the exogenous signaling molecule methyl jasmonate (MeJA), the production of SF in broccoli hairy roots was significantly increased. However, the molecular mechanism of GRA and SF synthesis in hairy roots of broccoli treated with MeJA has not been reported. In this study, according to the yield of GRA and SF, the best concentration of MeJA treatment for hairy roots of broccoli was selected. After 18 days of growth, broccoli hairy roots were treated with 10 mmol L–1 MeJA for 0, 3, 6, 9 and 12 h. Compared with 0 h, the yield of GRA and SF increased under other treatments. The highest yield of GRA and SF occurred at 9 h, which were 2.22-fold and 1.74-fold higher than those at 0 h. Brassica oleracea var. botrytis was used as reference genome, and 5,757 differentially expressed genes (DEG) were observed at 0, 3, 6, 9 and 12 h under 10 mmol L–1 MeJA treatment, of which 4,673 were down-regulated and 1084 were up-regulated. The key genes regulating GRA synthesis, CYP79F1, CYP83A1, UGT74B1, FMOGS-OX5 and GSL-OH, were up-regulated at 0 and 3 h, and down-regulated the rest of the time; BCAT2 was up-regulated at 6, 9, 12 h, and at 0, 3 h expression was down-regulated, transcription factors MYB28 and MYB29 were down-regulated by exogenous MeJA treatment. A pathway of GRA biosynthesis and transformation pathways in MeJA-treated broccoli hairy roots was simulated and the molecular mechanism of GRA biosynthesis and SF accumulation in broccoli hairy roots under MeJA treatment was revealed.
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Background Sprouts and microgreens, which are tender, flavourful, rich in nutrients, have a short growth cycle, and have been recognized as functional foods in the human diet. Culturing under artificial light sources could regulate the growth, the phytochemical compound content and antioxidant capacity of sprouts and microgreens. Scope and approach In this review, the effects of light-emitting diode (LED) on growth, phytochemical compound content and antioxidant capacity, as well as the post-harvest quality of sprouts and microgreens were overviewed, and the underlying mechanisms were discussed. The future applications and research, which aim to improve the growth and nutritional quality of sprouts and microgreens, were also investigated. Key findings and conclusions LED light can promote the accumulation of different phytochemicals, such as phenolic compounds, vitamins, glucosinolates, chlorophyll and carotenoids. Meanwhile, the antioxidant capacity could also be significantly increased by growth under LED light, in particular UV-B light. The accumulation of mineral elements (Ca²⁺, Fe²⁺, K⁺) increased after light exposure. The effects of LED light on the growth was species dependent. Therefore, growth under LED light is an efficient and promising strategy for producing sprouts and microgreens with higher nutritional values.
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Insects have many ways of disabling plant chemical defenses during feeding. Plant phloem feeders use surplus ingested sugar to block the activation of glucosinolate toxins, providing a target for precise resistance breeding.
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Sulfur (S) is an essential macronutrient for plant growth and development. S is majorly absorbed as sulfate from soil, and is then translocated to plastids in leaves, where it is assimilated into organic products. Cysteine (Cys) is the first organic product generated from S, and it is used as a precursor to synthesize many S-containing metabolites with important biological functions, such as glutathione (GSH) and methionine (Met). The reduction of sulfate takes place in a two-step reaction involving a variety of enzymes. Sulfate transporters (SULTRs) are responsible for the absorption of SO42− from the soil and the transport of SO42− in plants. There are 12–16 members in the S transporter family, which is divided into five categories based on coding sequence homology and biochemical functions. When exposed to S deficiency, plants will alter a series of morphological and physiological processes. Adaptive strategies, including cis-acting elements, transcription factors, non-coding microRNAs, and phytohormones, have evolved in plants to respond to S deficiency. In addition, there is crosstalk between S and other nutrients in plants. In this review, we summarize the recent progress in understanding the mechanisms underlying S homeostasis in plants.
Chapter
Glucosinolates are an important group of plant secondary metabolites found in Brassicaceae. They are part of plant defense responses against insects, fungal and bacterial pathogens, are responsible for taste and flavor of cruciferous vegetables, and have beneficial health properties. Because of their importance, ABR Volume 80 was dedicated to these compounds, reviewing the metabolism, regulation, and function of glucosinolates. Here the content of the volume will be shortly recapitulated and the progress in various areas of glucosinolate research will be reviewed. Apart from further details on the genes and enzymes involved in glucosinolate synthesis and downstream metabolism, new emerging areas are discussed, such as the function of glucosinolates in shaping the plant microbiome and their further interactions with bacteria and other microorganisms. A number of ways for successful engineering of glucosinolate pathways toward improved yield, health, and nutritional properties of crops are discussed.
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The objective of the present study was to evaluate the periodical UV-B radiation hormesis during kale seeds germination in their main content of secondary metabolite compounds (phenols; glucosinolates; total antioxidant capacity – TAC–) and their changes during a refrigerated shelf-life. The total UV-B doses received were 0, 5, 10, and 15 kJ m⁻² (CTRL, UVB5, UVB10, and UVB15) in where the 25 % was applied on the 3rd, 5th, 7th, and 10th sprouting day. UV radiation did not affect the morphological development of the sprouts. UVB10 and UVB15 treatments increased their phenolic content (>30 %). Likewise, TAC was increased by UV-B lighting ∼10 % (DPPH) and ∼20 % (FRAP). The hydroxycinnamic acid content in UVB15-treated sprouts increased by 52 %, while UVB5 reported an increase of 34 % in the kaempferol-3,7-di-O-glucoside concentration, compared to CTRL. After 10 d at 4ºC of shelf-life, content of gallic acid hexoside I and gallic acid increased by 55 and 78 % compared to UV-untreated kale sprouts, respectively. Glucoraphanin was the main glucosinolate found in kale sprouts and seeds, followed by 4-hydroxy-glucobrassicin, whose biosynthesis was enhanced by UVB10 (∼24 and ∼27 %) and UVB15 (∼36 and ∼30 %), respectively, compared to CTRL. In conclusion, periodical low UV-B illumination represents a useful tool to stimulate phytochemicals biosynthesis in kale sprouts as an important source of bioactive compounds with potential health benefits.
Chapter
Glucosinolates are characteristic metabolites of Brassicaceae family which includes many edible species. Glucosinolate profile differs qualitatively as well as quantitatively among species, varieties, cultivars, and also within a plant. Glucosinolates (nitrogen and sulfur-containing compounds) are hydrolyzed by plant and/or gut myrosinase to different biologically active compounds including isothiocyanates, nitriles, and thiocyanates. These bioactive compounds, especially isothiocyanates, possess a variety of health-promoting properties like anticarcinogenic, antiinflammatory, antimicrobial, and antioxidant. There are few studies showing toxicity effects in livestock species like goiter, gastrointestinal irritation, and anemia. Bioavailability of isothiocyanate for health-promoting functions is greatly regulated by storage and culinary practices as well as the composition of gut microflora of the individual. This chapter summarizes hydrolysis, bioavailability, and mechanism of action of glucosinolates and their by-products.
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Ethnopharmacological relevance Lepidium virginicum L. (Brassicaceae) is a plant widely used in traditional Mexican medicine as an expectorant, diuretic, and as a remedy to treat diarrhea and dysentery, infection-derived gastroenteritis. However, there is no scientific study that validates its clinical use as an anti-inflammatory in the intestine. Aim of the study This study aimed to investigate the anti-inflammatory properties of the ethanolic extract of Lepidium virginicum L. (ELv) in an animal model of inflammatory bowel disease (IBD)-like colitis. Materials and methods The 2,4-dinitrobenzene sulfonic acid (DNBS) animal model of IBD was used. Colitis was induced by intrarectal instillation of 200 mg/kg of DNBS dissolved vehicle, 50% ethanol. Control rats only received the vehicle. Six hours posterior to DNBS administration, ELv (3, 30, or 100 mg/kg) was administered daily by gavage or intraperitoneal injection. The onset and course of the inflammatory response were monitored by assessing weight loss, stool consistency, and fecal blood. Colonic damage was evaluated by colon weight/length ratio, histopathology, colonic myeloperoxidase (MPO) activity, and gene expression of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), chemokine C-X-C motif ligand 1 (CXCL-1), and interleukin-6 (IL-6). Results Rats treated with DNBS displayed significant weight loss, diarrhea, fecal blood, colon shortening, a significant increase in immune cell infiltration and MPO activity, as well as increased proinflammatory cytokine expression. Intraperitoneal administration of ELv significantly reduced colon inflammation, whereas oral treatment proved to be ineffective. In fact, intraperitoneal ELv significantly attenuated the clinical manifestations of colitis, immune cell infiltration, MPO activity, and pro-inflammatory (CXCL-1, TNF-α, and IL-1β) gene expression in a dose-dependent manner. Conclusion Traditional medicine has employed ELv as a remedy for common infection-derived gastrointestinal symptoms; however, we hereby present the first published study validating its anti-inflammatory properties in the mitigation of DNBS-induced colitis.
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Glucosinolates and camalexin are secondary metabolites that, as phytoanticipins and phytoalexins, play a crucial role in plant defence. The present work proposes an improved analytical method for routine analysis and quantification of glucosinolates and camalexin in brassicaceous small-sized samples by using the very specific desulfation process of glucosinolates analysis and the specificity of fluorescence detection for camalexin analysis. The approach is based on a simultaneous ultrasound-assisted extraction followed by a purification on an anion-exchange column. Final analyses are conducted by HPLC-UV-MS for desulfo-glucosinolates and HPLC coupled to a fluorescence detector (HPLC-FLD) for camalexin. The method is linear for glucosinolates (50-3500 µM) and camalexin (0.025-5 µg.mL⁻¹) with an LOD/LOQ of 3.8/12.6 µM and 0.014/0.046 µg.mL⁻¹ respectively. The method demonstrated adequate precision, accuracy and trueness on certified reference rapeseed. A practical application of our approach was conducted on different Brassicaceae genera (Barbarea vulgaris, Brassica nigra, Capsella bursa-pastoris, Cardamine hirsuta, Coincya monensis, Sinapis arvensis, and Sisymbrium officinale) and Arabidopsis thaliana genotypes (Columbia and Wassilewskija). Futhermore, different plant organs (seeds and leaves) were analysed, previously inoculated or not with the pathogenic fungus Alternaria brassicicola.
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The food waste generated by small and medium agro-industrial enterprises requires appropriate management and valorization in order to decrease environmental problems and recover high-value products, respectively. In this study, the Camelina sativa seed by-product was used as a source of glucosinolates. To begin, the chemical profile of the extract obtained using an international organization for standardization (ISO) procedure was determined by UPLC-HRMS/MS analysis. In addition, an extraction method based on ultrasound-assisted extraction was developed as an alternative and green method to recover glucosinolates. Main parameters that affect extraction efficiency were optimized using a response surface design. Under optimized conditions, the extract showed an improvement in extraction yield with a reduction in organic solvent amount compared to those obtained using the ISO procedure. Finally, the extract obtained with the ultrasound-assisted method was purified, tested on human colorectal cancer cell lines, and showed promising results.
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Cardiovascular disease (CVD) is the leading cause of death in the United States and hypercholesterolemia is a major risk factor. Population studies, as well as animal and intervention studies, support the consumption of a variety of vegetables as a means to reduce CVD risk through modulation of hypercholesterolemia. Microgreens of a variety of vegetables and herbs have been reported to be more nutrient dense compared to their mature counterparts. However, little is known about the effectiveness of microgreens to affect lipid and cholesterol levels. The present study used a rodent diet-induced obesity (DIO) model to address this question. C57BL/6NCr mice (n=60, male, five-week old) were randomly assigned to six feeding groups: 1) low fat diet; 2) high fat diet; 3) low fat diet+1.09% red cabbage microgreens; 4) low fat diet+1.66% mature red cabbage; 5) high fat diet+1.09% red cabbage microgreens; 6) high fat diet+1.66% mature red cabbage. The animals were on their respective diets for eight weeks. We found microgreen supplementation attenuated high fat diet induced weight gain. Moreover, supplementation with microgreens significantly lowered circulating LDL levels in animals fed the high fat diet, reduced hepatic cholesterol ester and triacylglycerol levels and expression of inflammatory cytokines in the liver. These data suggest that microgreens can modulate weight gain and cholesterol metabolism, and may protect against CVD by preventing hypercholesterolemia.
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Histone acetylation, regulated by histone deacetylases (HDACs) is a key epigenetic mechanism controlling gene expressions. Although dendritic cells (DCs) are playing pivotal roles in host immune responses, the effect of epigenetic modulation of DCs immune responses remains unknown. Sulforaphane (SFN) as a HDAC inhibitor has anti-inflammatory properties, which is used to investigate the epigenetic regulation of LPS-induced immune gene and HDAC family gene expressions in porcine monocyte-derived dendritic cells (moDCs). SFN was found to inhibit the lipopolysaccharide LPS induced HDAC6, HDAC10 and DNA methyltransferase (DNMT3a) gene expression, whereas up-regulated the expression of DNMT1 gene. Additionally, SFN was observed to inhibit the global HDAC activity, and suppressed moDCs differentiation from immature to mature DCs through down-regulating the CD40, CD80 and CD86 expression and led further to enhanced phagocytosis of moDCs. The SFN pre-treated of moDCs directly altered the LPS-induced TLR4 and MD2 gene expression and dynamically regulated the TLR4-induced activity of transcription factor NF-κB and TBP. SFN showed a protective role in LPS induced cell apoptosis through suppressing the IRF6 and TGF-ß1 production. SFN impaired the pro-inflammatory cytokine TNF-α and IL-1ß secretion into the cell culture supernatants that were induced in moDCs by LPS stimulation, whereas SFN increased the cellular-resident TNF-α accumulation. This study demonstrates that through the epigenetic mechanism the HDAC inhibitor SFN could modulate the LPS induced innate immune responses of porcine moDCs.
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Prostate cancer can transform from androgen-responsive to an androgen-independent phenotype. The mechanism responsible for the transformation remains unclear. We studied the effects of an epigenetic modulator, phenethyl isothiocyanate (PEITC), on the androgen-responsive LNCaP cells. After treatment with PEITC, floating spheres were formed with characteristics of prostate cancer stem cells (PCSC). These spheres were capable of self-renewal in media with and without androgen. They have been maintained in both types of media as long term cultures. Upon androgen deprivation, the adherent spheres differentiated to neuroendocrine cells (NEC) with decreased proliferation, expression of androgen receptor, and PSA. NEC reverse differentiated to spheres when androgen was replenished. The sphere cells expressed surface marker CD44 and had enhanced histone H3K4 acetylation, DNMT1 down-regulation and GSTP1 activation. We hypothesize that PEITC-mediated alteration in epigenomics of LNCaP cells may give rise to sphere cells, whereas reversible androgenomic alterations govern the shuttling between sphere PCSC and progeny NEC. Our findings identify unrecognized properties of prostate cancer sphere cells with multi-potential plasticity. This system will facilitate development of novel therapeutic agents and allow further exploration into epigenomics and androgenomics governing the transformation to hormone refractory prostate cancer.
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Background: The dietary agent sulforaphane (SFN) has been reported to induce nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2)-dependent pathways as well as inhibiting histone deacetylase (HDAC) activity. The current investigation sought to examine the relationships between Nrf2 status and HDAC expression in preclinical and translational studies. Results: Wild type (WT) and Nrf2-deficient (Nrf2(-/+)) mice were treated with the colon carcinogen 1,2-dimethylhydrazine (DMH) followed by 400 ppm SFN in the diet (n = 35 mice/group). WT mice were more susceptible than Nrf2(-/+) mice to tumor induction in the colon. Tumors from WT mice had higher HDAC levels globally and locally on genes such as cyclin-dependant kinase inhibitor 2a (Cdkn2a/p16) that were dysregulated during tumor development. The average tumor burden was reduced by SFN from 62.7 to 26.0 mm(3) in WT mice and from 14.6 to 11.7 mm(3) in Nrf2(-/+) mice. The decreased antitumor activity of SFN in Nrf2(-/+) mice coincided with attenuated Cdkn2a promoter interactions involving HDAC3. HDAC3 knockdown in human colon cancer cells recapitulated the effects of SFN on p16 induction. Human subjects given a broccoli sprout extract supplement (200 μmol SFN equivalents), or reporting more than five cruciferous vegetable servings per week, had increased p16 expression that was inversely associated with HDAC3 in circulating peripheral blood mononuclear cells (PBMCs) and in biopsies obtained during screening colonoscopy. Conclusions: Nrf2 expression varies widely in both normal human colon and human colon cancers and likely contributes to the overall rate of tumor growth in the large intestine. It remains to be determined whether this influences global HDAC protein expression levels, as well as local HDAC interactions on genes dysregulated during human colon tumor development. If corroborated in future studies, Nrf2 status might serve as a biomarker of HDAC inhibitor efficacy in clinical trials using single agent or combination modalities to slow, halt, or regress the progression to later stages of solid tumors and hematological malignancies.
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The myrosinase-glucosinolate system is involved in a range of biological activities affecting herbivorous insects, plants and fungi. The system characteristic of the order Capparales includes sulphur-containing substrates, the degradative enzymes myrosinases, and cofactors. The enzyme-catalyzed hydrolysis of glucosinolates initially involves cleavage of the thioglucoside linkage, yielding D-glucose and an unstable thiohydroximate-Ο-sulphonate that spontaneously rearranges, resulting in the production of sulphate and one of a wide range of possible reaction products. The products are generally a thiocyanate, isothiocyanate or nitrile, depending on factors such as substrate, pH or availability of ferrous ions. Glucosinolates in crucifers exemplify components that are often present in food and feed plants and are a major problem in the utilization of products from the plants. Toxic degradation products restrict the use of cultivated plants, e.g. those belonging to the Brassicaceae. The myrosinase-glucosinolate system may, however, have several functions in the plant. The glucosinolate degradation products are involved in defence against insects and phytopathogens, and potentially in sulphur and nitrogen metabolism and growth regulation. The compartmentalization of the components of the myrosinase-glucosinolate system and the cell-specific expression of the myrosinase represents a unique plant defence system. In this review, we summarize earlier results and discuss the organisation and biochemistry of the myrosinase-glucosinolate system.
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Cruciferous-rich diets have been associated with reduction in plasma LDL-cholesterol (LDL-C), which may be due to the action of isothiocyanates derived from glucosinolates that accumulate in these vegetables. This study tests the hypothesis that a diet rich in high glucoraphanin (HG) broccoli will reduce plasma LDL-C. One hundred and thirty volunteers were recruited to two independent double-blind, randomly allocated parallel dietary intervention studies, and were assigned to consume either 400 g standard broccoli or 400 g HG broccoli per week for 12 weeks. Plasma lipids were quantified before and after the intervention. In study 1 (37 volunteers), the HG broccoli diet reduced plasma LDL-C by 7.1% (95% CI: -1.8%, -12.3%, p = 0.011), whereas standard broccoli reduced LDL-C by 1.8% (95% CI +3.9%, -7.5%, ns). In study 2 (93 volunteers), the HG broccoli diet resulted in a reduction of 5.1% (95% CI: -2.1%, -8.1%, p = 0.001), whereas standard broccoli reduced LDL-C by 2.5% (95% CI: +0.8%, -5.7%, ns). When data from the two studies were combined the reduction in LDL-C by the HG broccoli was significantly greater than standard broccoli (p = 0.031). Evidence from two independent human studies indicates that consumption of high glucoraphanin broccoli significantly reduces plasma LDL-C. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Smoking is estimated to cause about half of all bladder cancer cases. Case-control studies have provided evidence of an inverse association between fruit and vegetable intake and bladder cancer risk. As part of the World Cancer Research/American Institute for Cancer Research Continuous Update Project, we conducted a systematic review and meta-analysis of prospective studies to assess the dose-response relationship between fruit and vegetables and incidence and mortality of bladder cancer. We searched PubMed up to December 2013 for relevant prospective studies. We conducted highest compared with lowest meta-analyses and dose-response meta-analyses using random effects models to estimate summary relative risks (RRs) and 95% confidence intervals (CIs), and used restricted cubic splines to examine possible nonlinear associations. Fifteen prospective studies were included in the review. The summary RR for an increase of 1 serving/day (80 g) were 0.97 (95% CI: 0.95-0.99) I(2) = 0%, eight studies for fruits and vegetables, 0.97 (95% CI: 0.94-1.00, I(2) = 10%, 10 studies) for vegetables and 0.98 (95% CI: 0.96-1.00, I(2) = 0%, 12 studies) for fruits. Results were similar in men and women and in current, former and nonsmokers. Amongst fruits and vegetables subgroups, for citrus fruits the summary RR for the highest compared with the lowest intake was 0.87 (95% CI: 0.76-0.99, I(2) = 0%, eight studies) and for cruciferous vegetables there was evidence of a nonlinear relationship (P = 0.001). The current evidence from cohort studies is not consistent with a role for fruits and vegetables in preventing bladder cancer. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
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Scope: Diets rich in cruciferous vegetables are associated with lower levels of pro-inflammatory cytokines, which may contribute to potential health-promoting properties of these vegetables. We investigate whether sulforaphane (SF), an isothiocyanate (ITC) obtained from broccoli, could suppress LPS-induced transcription and subsequent pro-inflammatory cytokine secretion at a physiologically relevant concentration using in vitro models of chronic inflammation. Methods and results: We find that exposure of the LPS receptor Toll-like receptor-4 (TLR4) to physiologically appropriate concentrations of SF under non-reducing conditions results in covalent modification of cysteine residues 246 and 609. We further demonstrate that the changes in expression of 1210 genes (p ≤ 0.01) in THP-1 monocytes and the secretion of pro-inflammatory cytokines in both human peripheral blood mononuclear cells (PBMCs) and THP-1 monocytes induced by LPS exposure can be completely suppressed through exposure with physiologically appropriate concentrations of SF. Finally, we show that in vivo exposure of human PBMCs to ITCs within human circulation reduces secretion of pro-inflammatory cytokines following subsequent ex vivo LPS challenge (p < 0.001). Conclusion: Covalent modification of TLR4 by ITCs and resultant suppression of LPS-induced cell signalling could lead to reductions in levels of pro-inflammatory cytokines in people with chronic diseases who consume diets rich in cruciferous vegetables.
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Background: Observational studies suggest an association between fruit and vegetables intake and risk of bladder cancer, but the results are controversial. Methods: We therefore summarized the evidence from observational studies in categorical, linear, and nonlinear, dose-response meta-analysis. Pertinent studies were identified by searching EMBASE and PubMed from their inception to August 2013. Results: Thirty-one observational studies involving 12,610 cases and 1,121,649 participants were included. The combined rate ratio (RR, 95 % CI) of bladder cancer for the highest versus lowest intake was 0.83 (0.69-0.99) for total fruit and vegetables, 0.81 (0.70-0.93) for total vegetables, 0.77 (0.69-0.87) for total fruit, 0.84 (0.77-0.91) for cruciferous vegetables, 0.79 (0.68-0.91) for citrus fruits, and 0.74 (0.66-0.84) for yellow-orange vegetables. Subgroup analysis showed study design and gender as possible sources of heterogeneity. A nonlinear relationship was found of citrus fruits intake with risk of bladder cancer (P for nonlinearity = 0.018), and the RRs (95 % CI) of bladder cancer were 0.87 (0.78-0.96), 0.80 (0.67-0.94), 0.79 (0.66-0.94), 0.79 (0.65-0.96), and 0.79 (0.64-0.99) for 30, 60, 90, 120, and 150 g/day. A nonlinear relationship was also found of yellow-orange vegetable intake with risk of bladder cancer risk (P for nonlinearity = 0.033). Some evidence of publication bias was observed for fruit, citrus fruits, and yellow-orange vegetables. Conclusion: This meta-analysis supports the hypothesis that intakes of fruit and vegetables may reduce the risk of bladder cancer. Future well-designed studies are required to confirm this finding.
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Tumor metastasis is a prominent cause of treatment failure in cervical carcinoma. Phenethyl isothiocyanate (PEITC) is an active component extracted from cruciferous plants that has exhibited anticancer activity in various types of human cancer; however, its effect on the inhibition of metastasis remains unclear. The current study aimed to explore the effect of PEITC on the suppression of metastasis in HeLa cervical carcinoma cells. Multiple variables were assessed with different methods as follows: Cell viability, with a Vi‑CELL analyzer; cell adhesion, by MTS assay; cell invasion, by Transwell assay; cell cycle, by flow cytometry assay; cytokine concentration, by ELISA assay; metastasis‑related gene and protein expression, by quantitative polymerase chain reaction and western blotting; and transcription factor activity, by gene reporter assay. The results indicated that PEITC exhibited an inhibitory effect on the adhesion and invasion of HeLa cells by induction of G2/M phase arrest, it reduced the expression of CDK1, MMP‑2/9, CD44, ICAM‑1, increased the production of TGF‑β, IL‑6 and IL‑8, and increased the phosphorylation of Smad2. These results suggest that PEITC may be a potential antitumor compound, acting through the TGF‑β/Smad2 pathway; and it has the potential for future use as a therapy for cervical carcinoma subsequent to further studies.
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Broccoli sprouts are a convenient and rich source of the glucosinolate, glucoraphanin, which can generate the chemopreventive agent, sulforaphane, an inducer of glutathione S-transferases (GSTs) and other cytoprotective enzymes. A broccoli sprout-derived beverage providing daily doses of 600 µmol glucoraphanin and 40 µmol sulforaphane was evaluated for magnitude and duration of pharmacodynamic action in a 12-week randomized clinical trial. Two hundred and ninety-one study participants were recruited from the rural He-He Township, Qidong, in the Yangtze River delta region of China, an area characterized by exposures to substantial levels of airborne pollutants. Exposure to air pollution has been associated with lung cancer and cardiopulmonary diseases. Urinary excretion of the mercapturic acids of the pollutants, benzene, acrolein, and crotonaldehyde, were measured before and during the intervention using liquid chromatography tandem mass spectrometry. Rapid and sustained, statistically significant (p ≤ 0.01) increases in the levels of excretion of the glutathione-derived conjugates of benzene (61%), acrolein (23%), but not crotonaldehyde were found in those receiving broccoli sprout beverage compared with placebo. Excretion of the benzene-derived mercapturic acid was higher in participants who were GSTT1-positive compared to the null genotype, irrespective of study arm assignment. Measures of sulforaphane metabolites in urine indicated that bioavailability did not decline over the 12-week daily dosing period. Thus, intervention with broccoli sprouts enhances the detoxication of some airborne pollutants and may provide a frugal means to attenuate their associated long-term health risks.
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The objective of this study was to gain insights into the effect of the cooking method on the liking as well as the retention of glucosinolates in broccoli. With this knowledge it can be concluded whether the health aspects of broccoli be improved by the cooking method without deteriorating sensory perception. For this, broccoli was cooked by methods commonly applied by consumers: boiling with a cold (water) start; boiling with a hot (water) start; and steaming. Firmness, greenness and amount of total glucosinolates in cooked broccoli were instrumentally determined. Sensory evaluation by untrained consumers (n = 99) for liking and sensory attributes intensity rating were performed on broccoli cooked by steaming and boiling-cold start at three time points, which resulted in 'high', 'medium', 'low' firm broccoli samples. At the end of cooking, steaming showed an increase in the amount of total glucosinolates (+17 %). Boiling-hot start (-41 %) and boiling-cold start (-50 %) showed a decrease in amount of total glucosinolates. Sensory evaluation did not show statistically significant differences between steaming and boiling-cold start in liking at 'high' and 'medium' firmness; and in the attribute intensity ratings (except for juiciness at 'medium' firmness, and flavour at 'medium' and 'low' firmness). This study demonstrates that medium firm broccoli showed optimum liking and that steaming compared to boiled-cold start showed higher amount of glucosinolates. It is concluded that the health aspects of broccoli can be improved without reducing the sensory aspects by optimising the cooking method.
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The transcription factor NF-E2 p45-related factor 2 (Nrf2) and its negative regulator Kelch-like ECH associated protein 1 (Keap1) control the expression of nearly 500 genes with diverse cytoprotective functions. Keap1, a substrate adaptor protein for Cullin3/Rbx1 ubiquitin ligase, normally continuously targets Nrf2 for degradation, but loses this ability in response to electrophiles and oxidants (termed inducers). Consequently, Nrf2 accumulates and activates transcription of its downstream target genes. Many inducers are phytochemicals, and cruciferous vegetables represent one of the richest sources of inducer activity among the most commonly used edible plants. Here we summarize the discovery of the isothiocyanate sulforaphane as a potent inducer which reacts with cysteine sensors of Keap1, leading to activation of Nrf2. We then describe the development of a quantitative Förster Resonance Energy Transfer (FRET)-based methodology combined with multiphoton fluorescence lifetime imaging microscopy (FLIM) to investigate the interactions between Keap1 and Nrf2 in single live cells, and the effect of sulforaphane, and other cysteine-reactive inducers, on the dynamics of the Keap1-Nrf2 protein complex. We present the experimental evidence for the “cyclic sequential attachment and regeneration” or “conformation cycling” model of Keap1-mediated Nrf2 degradation. Finally, we discuss the implications of this mode of regulation of Nrf2 for achieving a fine balance under normal physiological conditions, and the consequences and mechanisms of disrupting this balance for tumor biology.
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Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2, also called Nfe2l2) is a transcription factor that regulates the cellular redox status. Nrf2 is controlled through a complex transcriptional/epigenetic and post-translational network that ensures its activity increases during redox perturbation, inflammation, growth factor stimulation and nutrient/energy fluxes, thereby enabling the factor to orchestrate adaptive responses to diverse forms of stress. Besides mediating stress-stimulated induction of antioxidant and detoxification genes, Nrf2 contributes to adaptation by upregulating the repair and degradation of damaged macromolecules, and by modulating intermediary metabolism. In the latter case, Nrf2 inhibits lipogenesis, supports β-oxidation of fatty acids, facilitates flux through the pentose phosphate pathway, and increases NADPH regeneration and purine biosynthesis; observations that suggest it directs metabolic reprogramming during stress.
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Metastasis and chemoresistance represent two detrimental events that greatly hinder the outcome for those suffering with head and neck squamous cell carcinoma (HNSCC). Herein, we investigated benzyl isothiocyanate's (BITC) ability to inhibit HNSCC migration and invasion and enhance chemotherapy. Our data suggests that treatment with BITC 1) induced significant reductions in the viability of multiple HNSCC cell lines tested (HN12, HN8, and HN30) after 24 and 48 h, 2) decreased migration and invasion of the HN12 cells in a dose dependent manner, and 3) inhibited expression and altered localization of the epithelial-mesenchymal transition (EMT) marker, vimentin. We also observed that a pretreatment of BITC followed by cisplatin treatment 1) induced a greater decrease in HN12, HN30, and HN8 cell viability and total cell count than either treatment alone and 2) significantly increased apoptosis when compared to either treatment alone. Taken together these data suggest that BITC has the capacity to inhibit processes involved in metastasis and enhance the effectiveness of chemotherapy. Consequently, the results indicate that further investigation, including in vivo studies, are warranted.
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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.
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ScopeSulforaphane (SFN), an isothiocyanate derived from crucifers, has numerous health benefits. SFN bioavailability from dietary sources is a critical determinant of its efficacy in humans. A key factor in SFN absorption is the release of SFN from its glucosinolate precursor, glucoraphanin, by myrosinase. Dietary supplements are used in clinical trials to deliver consistent SFN doses, but myrosinase is often inactivated in available supplements. We evaluated SFN absorption from a myrosinase-treated broccoli sprout extract (BSE) and are the first to report effects of twice daily, oral dosing on SFN exposure in healthy adults.Methods and resultsSubjects consumed fresh broccoli sprouts or the BSE, each providing 200 μmol SFN daily, as a single dose and as two 100-μmol doses taken 12 h apart. Using HPLC-MS/MS, we detected ∼3 x higher SFN metabolite levels in plasma and urine of sprout consumers, indicating enhanced SFN absorption from sprouts. Twelve-hour dosing retained higher plasma SFN metabolite levels at later time points than 24-hour dosing. No dose responses were observed for molecular targets of SFN (i.e. heme oxygenase-1, histone deacetylase activity, p21).Conclusion We conclude that the dietary form and dosing schedule of SFN may impact SFN absorption and efficacy in human trials.
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For each construction material used, there is certain theoretical limit in sizes. For tall building construction, the reduction in slab weight is the first step to take in order to break such size limits. In this paper, the feasibility of such objective is proven and given by numerical analysis result. For a typical building slab, both concrete and advanced composite sandwich panels are considered. The concrete slab is treated as a special orthotropic plate to obtain more accurate result. For each panel, the deflection under the dead and live loads is compared, since both tensile and compressive strengths of the composites are far more higher than those of concrete. All types of sandwich panels considered, except one case, have self-weights less than one tenth of that of the reinforced concrete slab, with deflections less than that of the reinforced concrete slab.