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1.
Nutrients ; 14(7)2022 Mar 30.
Article in English | MEDLINE | ID: mdl-35406047

ABSTRACT

The list of known health benefits from inclusion of brassica vegetables in the diet is long and growing. Once limited to cancer prevention, a role for brassica in prevention of oxidative stress and anti-inflammation has aided in our understanding that brassica provide far broader benefits. These include prevention and treatment of chronic diseases of aging such as diabetes, neurological deterioration, and heart disease. Although animal and cell culture studies are consistent, clinical studies often show too great a variation to confirm these benefits in humans. In this review, we discuss causes of variation in clinical studies, focusing on the impact of the wide variation across humans in commensal bacterial composition, which potentially result in variations in microbial metabolism of glucosinolates. In addition, as research into host-microbiome interactions develops, a role for bitter-tasting receptors, termed T2Rs, in the gastrointestinal tract and their role in entero-endocrine hormone regulation is developing. Here, we summarize the growing literature on mechanisms of health benefits by brassica-derived isothiocyanates and the potential for extra-oral T2Rs as a novel mechanism that may in part describe the variability in response to brassica among free-living humans, not seen in research animal and cell culture studies.


Subject(s)
Brassica , Taste , Animals , Brassica/metabolism , Diet , Glucosinolates/metabolism , Glucosinolates/pharmacology , Taste/physiology , Vegetables/metabolism
3.
Front Nutr ; 7: 575092, 2020.
Article in English | MEDLINE | ID: mdl-33072799

ABSTRACT

Introduction: Preclinical studies suggest that brassica vegetable diets decrease cancer risk, but epidemiological studies show varied effects, resulting in uncertainty about any health impact of brassicas. Factors controlling absorption of glucosinolate metabolites may relate to inconsistent results. We reported previously that subjects with BMI > 26 kg/m2 (HiBMI), given cooked broccoli plus raw daikon radish (as a source of plant myrosinase) daily for 17 days, had lower glucosinolate metabolite absorption than subjects given a single broccoli meal. This difference was not seen in subjects with BMI < 26 kg/m2 (LoBMI). Our objective in this current study was to determine whether a similar response occurred when cooked broccoli was consumed without a source of plant myrosinase. Methods: In a randomized crossover study (n = 18), subjects consumed no broccoli for 16 days or the same diet with 200 g of cooked broccoli daily for 15 days and 100 g of broccoli on day 16. On day 17, all subjects consumed 200 g of cooked broccoli. Plasma and urine were collected for 24 h and analyzed for glucosinolate metabolites by LC-MS. Results: There was no effect of diet alone or interaction of diet with BMI. However, absorption doubled in HiBMI subjects (AUC 219%, plasma mass of metabolites 202% compared to values for LoBMI subjects) and time to peak plasma metabolite values and 24-h urinary metabolites also increased, to 127 and 177% of LoBMI values, respectively. Conclusion: BMI impacts absorption and metabolism of glucosinolates from cooked broccoli, and this association must be further elucidated for more efficacious dietary recommendations. Clinical Trial Registration: This trial was registered at clinicaltrials.gov (NCT03013465).

4.
Nutrients ; 12(9)2020 Aug 20.
Article in English | MEDLINE | ID: mdl-32825248

ABSTRACT

Diet and lifestyle choices contribute to obesity and liver disease. Broccoli, a brassica vegetable, may mitigate negative effects of both diet and lifestyle. Currently, there are no clinically relevant, established molecular biomarkers that reflect variability in human absorption of brassica bioactives, which may be the cause of variability/inconsistencies in health benefits in the human population. Here, we focused on the plasma metabolite profile and composition of the gut microbiome in rats, a relatively homogenous population in terms of gut microbiota, genetics, sex and diet, to determine if changes in the plasma metabolite profiles caused by dietary broccoli relate to molecular changes in liver. Our aim was to identify plasma indicators that reflect how liver health is impacted by dietary broccoli. Rats were fed a 10% broccoli diet for 14 days. We examined the plasma metabolite composition by metabolomics analysis using GC-MS and gut microbiota using 16S sequencing after 0, 1, 2, 4, 7, 14 days of broccoli feeding. We identified 25 plasma metabolites that changed with broccoli consumption, including metabolites associated with hepatic glutathione synthesis, and with de novo fatty acid synthesis. Glutamine, stearic acid, and S-methyl-L-cysteine (SMC) relative abundance changes correlated with changes in gut bacteria previously implicated in metabolic disease and with validated increases in expression of hepatic NAD(P)H dehydrogenase [quinone] 1 (NQO1) and nuclear factor (erythroid-derived 2)-like 2 (Nrf2), associated with elevated hepatic glutathione synthesis. Circulating biomarkers following broccoli consumption reflect gut-liver axis health.


Subject(s)
Animal Nutritional Physiological Phenomena/physiology , Brassica , Eating/physiology , Gastrointestinal Microbiome , Glutathione/metabolism , Liver/metabolism , Animals , Fatty Acids/metabolism , Metabolic Diseases/metabolism , Metabolome , NAD(P)H Dehydrogenase (Quinone)/metabolism , NF-E2-Related Factor 2/metabolism , Rats, Inbred F344
5.
Food Chem ; 311: 125880, 2020 May 01.
Article in English | MEDLINE | ID: mdl-31771913

ABSTRACT

Although flavonoid sophorosides are common glycosides in brassica vegetables, red raspberries and other food plants, there is a lack of studies of absorption and metabolism of any sophoroside. The aim of this study was to characterize the absorption, phase II metabolism and microbial catabolism of quercetin-3-O-sophoroside, compared to that of quercetin aglycone. Quercetin-3-O-sophoroside was purified from Apocynum venetum and characterized by MS2, 1H and 13C NMR. Using an in situ rat gut model, we found intact, methylated, sulfated and both methylated and sulfated quercetin sophoroside in the plasma following jejunal introduction of the sophoroside; we found derivatives of benzoic acid, phenylacetic acid, and phenyl propionic acid in the cecal contents following cecal introduction. This novel finding, that quercetin sophoroside was absorbed intact, without deglycosylation, points to a possible role for the terminal sugar and/or the type of linkage among glycosidic moieties in the mechanism of absorption of flavonoid glycosides.


Subject(s)
Brassica/chemistry , Quercetin/analogs & derivatives , Quercetin/metabolism , Animals , Brassica/metabolism , Cecum/microbiology , Chromatography, High Pressure Liquid , Flavonoids/blood , Flavonoids/chemistry , Flavonoids/metabolism , Male , Mass Spectrometry , Microbiota , Quercetin/blood , Quercetin/chemistry , Rats , Rats, Inbred F344
6.
J Nutr Biochem ; 63: 27-34, 2019 01.
Article in English | MEDLINE | ID: mdl-30317146

ABSTRACT

The human gastrointestinal microbiota is increasingly linked to health outcomes; however, our understanding of how specific foods alter the microbiota is limited. Cruciferous vegetables such as broccoli are a good source of dietary fiber and phytonutrients, including glucosinolates, which can be metabolized by gastrointestinal microbes. This study aimed to determine the impact of broccoli consumption on the gastrointestinal microbiota of healthy adults. A controlled feeding, randomized, crossover study consisting of two 18-day treatment periods separated by a 24-day washout was conducted in healthy adults (n=18). Participants were fed at weight maintenance with the intervention period diet including 200 g of cooked broccoli and 20 g of raw daikon radish per day. Fecal samples were collected at baseline and at the end of each treatment period for microbial analysis. Beta diversity analysis indicated that bacterial communities were impacted by treatment (P=.03). Broccoli consumption decreased the relative abundance of Firmicutes by 9% compared to control (P=.05), increased the relative abundance of Bacteroidetes by 10% compared to control (P=.03) and increased Bacteroides by 8% relative to control (P=.02). Furthermore, the effects were strongest among participants with body mass index <26 kg/m2, and within this group, there were associations between bacterial relative abundance and glucosinolate metabolites. Functional prediction revealed that broccoli consumption increased the pathways involved in the functions of the endocrine system (P=.05), transport and catabolism (P=.04), and energy metabolism (P=.01). These results reveal that broccoli consumption affects the composition and function of the human gastrointestinal microbiota.


Subject(s)
Brassica , Gastrointestinal Microbiome , Adult , Aged , Bacteroidetes , Body Mass Index , Feces/microbiology , Female , Gastrointestinal Microbiome/genetics , Humans , Male , Middle Aged
7.
Br J Nutr ; 120(12): 1370-1379, 2018 12.
Article in English | MEDLINE | ID: mdl-30499426

ABSTRACT

Sulphoraphane originates from glucoraphanin in broccoli and is associated with anti-cancer effects. A preclinical study suggested that daily consumption of broccoli may increase the production of sulphoraphane and sulphoraphane metabolites available for absorption. The objective of this study was to determine whether daily broccoli consumption alters the absorption and metabolism of isothiocyanates derived from broccoli glucosinolates. We conducted a randomised cross-over human study (n 18) balanced for BMI and glutathione S-transferase µ 1 (GSTM1) genotype in which subjects consumed a control diet with no broccoli (NB) for 16 d or the same diet with 200 g of cooked broccoli and 20 g of raw daikon radish daily for 15 d (daily broccoli, DB) and 100 g of broccoli and 10 g of daikon radish on day 16. On day 17, all subjects consumed a meal of 200 g of broccoli and 20 g of daikon radish. Plasma and urine were collected for 24 h and analysed for sulphoraphane and metabolites of sulphoraphane and erucin by triple quadrupole tandem MS. For subjects with BMI >26 kg/m2 (median), plasma AUC and urinary excretion rates of total metabolites were higher on the NB diet than on the DB diet, whereas for subjects with BMI <26 kg/m2, plasma AUC and urinary excretion rates were higher on the DB diet than on the NB diet. Daily consumption of broccoli interacted with BMI but not GSTM1 genotype to affect plasma concentrations and urinary excretion of glucosinolate-derived compounds believed to confer protection against cancer. This trial was registered as NCT02346812.


Subject(s)
Body Mass Index , Brassica/chemistry , Diet , Glucosinolates/chemistry , Isothiocyanates/metabolism , Acetylcysteine/chemistry , Adult , Aged , Anticarcinogenic Agents , Area Under Curve , Cooking , Cross-Over Studies , Female , Genotype , Glucose/analogs & derivatives , Glucose/chemistry , Glutathione Transferase/metabolism , Glycoside Hydrolases/metabolism , Humans , Imidoesters/chemistry , Isothiocyanates/blood , Isothiocyanates/chemistry , Isothiocyanates/urine , Male , Mannitol/chemistry , Middle Aged , Oximes , Raphanus , Sulfides/blood , Sulfides/chemistry , Sulfides/urine , Sulfoxides , Tandem Mass Spectrometry , Thiocyanates/blood , Thiocyanates/chemistry , Thiocyanates/urine
8.
Nutrients ; 10(6)2018 Jun 08.
Article in English | MEDLINE | ID: mdl-29890681

ABSTRACT

Dietary broccoli is anti-inflammatory. Past studies have typically investigated raw broccoli, even though most consumers prefer cooked broccoli, where the plant myrosinase is inactivated by heat, resulting in failure of formation of the anti-inflammatory bioactive compound sulforaphane (SF). This study compareed efficacy of lightly cooked broccoli (CB) containing greatly diminished myrosinase activity, with raw broccoli (RB), in mitigating colitis in dextran sulfate sodium (DSS)-treated mice. Male C57BL/6 mice were fed for two weeks on a 10% RB, 10% CB or control diet, all based on the AIN-93M diet. Half (n = 9) of each group received drinking water, half received 2.5% DSS in water for one week, starting from Day 7 of the diet. Even with far less plant myrosinase activity, CB was essentially as effective as RB in lessening damage by DSS, evidenced by decreased disease activity index, attenuated colon length shrinkage, less endotoxin (lipopolysaccharide) leakage into blood, and less severe colon lesions as assessed by histopathology. mRNA expression of pro-inflammatory cytokines indicated that broccoli anti-inflammatory action may be through inhibition of the IL-6 trans-signaling pathway, as evidenced by reversal of the DSS-increased expression of IL-6, CCR2 and vascular cell adhesion molecule 1 (VCAM-1).


Subject(s)
Brassica , Colitis/prevention & control , Colon , Cooking , Dextran Sulfate , Animals , Brassica/enzymology , Colitis/chemically induced , Colitis/metabolism , Colitis/pathology , Colon/metabolism , Colon/pathology , Disease Models, Animal , Enzyme Stability , Glycoside Hydrolases/metabolism , Hot Temperature , Hydrolysis , Interleukin-6/metabolism , Isothiocyanates/metabolism , Male , Mice, Inbred C57BL , NF-E2-Related Factor 2/metabolism , Permeability , Protein Denaturation , Receptors, CCR2/metabolism , Signal Transduction , Sulfoxides , Vascular Cell Adhesion Molecule-1/metabolism
9.
Nutrients ; 9(3)2017 Mar 10.
Article in English | MEDLINE | ID: mdl-28287418

ABSTRACT

Broccoli consumption brings many health benefits, including reducing the risk of cancer and inflammatory diseases. The objectives of this study were to identify global alterations in the cecal microbiota composition using 16S rRNA sequencing analysis and glucoraphanin (GRP) hydrolysis to isothiocyanates ex vivo by the cecal microbiota, following different broccoli diets. Rats were randomized to consume AIN93G (control) or different broccoli diets; AIN93G plus cooked broccoli, a GRP-rich powder, raw broccoli, or myrosinase-treated cooked broccoli. Feeding raw or cooked broccoli for four days or longer both changed the cecal microbiota composition and caused a greater production of isothiocyanates ex vivo. A more than two-fold increase in NAD(P)H: quinone oxidoreductase 1 activity of the host colon mucosa after feeding cooked broccoli for seven days confirmed the positive health benefits. Further studies revealed that dietary GRP was specifically responsible for the increased microbial GRP hydrolysis ex vivo, whereas changes in the cecal microbial communities were attributed to other broccoli components. Interestingly, a three-day withdrawal from a raw broccoli diet reversed the increased microbial GRP hydrolysis ex vivo. Findings suggest that enhanced conversion of GRP to bioactive isothiocyanates by the cecal microbiota requires four or more days of broccoli consumption and is reversible.


Subject(s)
Brassica , Gastrointestinal Microbiome , Glucosinolates/metabolism , Imidoesters/metabolism , Isothiocyanates/metabolism , Animals , Base Sequence , Cecum/microbiology , Colon/microbiology , Cooking , Hydrolysis , Intestinal Mucosa/microbiology , NAD(P)H Dehydrogenase (Quinone)/genetics , NAD(P)H Dehydrogenase (Quinone)/metabolism , Oximes , RNA, Ribosomal, 16S/isolation & purification , Rats , Rats, Inbred F344 , Sulfoxides
10.
J Agric Food Chem ; 65(2): 301-308, 2017 Jan 18.
Article in English | MEDLINE | ID: mdl-27992213

ABSTRACT

Due to the importance of glucosinolates and their hydrolysis products in human nutrition and plant defense, optimizing the content of these compounds is a frequent breeding objective for Brassica crops. Toward this goal, we investigated the feasibility of using models built from relative transcript abundance data for the prediction of glucosinolate and hydrolysis product concentrations in broccoli. We report that predictive models explaining at least 50% of the variation for a number of glucosinolates and their hydrolysis products can be built for prediction within the same season, but prediction accuracy decreased when using models built from one season's data for prediction of an opposing season. This method of phytochemical profile prediction could potentially allow for lower phytochemical phenotyping costs and larger breeding populations. This, in turn, could improve selection efficiency for phase II induction potential, a type of chemopreventive bioactivity, by allowing for the quick and relatively cheap content estimation of phytochemicals known to influence the trait.


Subject(s)
Brassica/chemistry , Brassica/genetics , Glucosinolates/genetics , Glucosinolates/analysis , Hydrolysis , Models, Biological , NAD(P)H Dehydrogenase (Quinone)/genetics , NAD(P)H Dehydrogenase (Quinone)/metabolism
11.
J Funct Foods ; 24: 57-62, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27672403

ABSTRACT

Western-style high fat, high sugar diets are associated with non-alcoholic fatty liver disease (NAFLD) and increased liver cancer risk. Sulforaphane from broccoli may protect against these. Previously we initiated broccoli feeding to mice prior to exposure to the hepatocarcinogen diethylnitrosamine (DEN), and saw protection against NAFLD and liver cancer. Here we administered DEN to unweaned mice, initiating broccoli feeding two weeks later, to determine if broccoli protects against cancer progression. Specifically, male 15-day-old C57BL/6J mice were given DEN and placed on a Western or Western+10%Broccoli diet from the age of 4 weeks through 7 months. Dietary broccoli decreased hepatic triacylglycerols, NAFLD, liver damage and tumour necrosis factor by month 5 without changing body weight or relative liver weight, but did not slow carcinogenesis, seen in 100% of mice. We conclude that broccoli, a good source of sulforaphane, slows progression of hepatic lipidosis, but not tumourigenesis in this robust model.

12.
J Agric Food Chem ; 64(34): 6524-32, 2016 Aug 31.
Article in English | MEDLINE | ID: mdl-27523193

ABSTRACT

Glucosinolates, their hydrolysis product concentrations, and the quinone reductase (QR) inducing activity of extracts of leaf tissue were assayed from 39 arugula (Eruca sativa Mill.) accessions. Arugula accessions from Mediterranean countries (n = 16; Egypt, Greece, Italy, Libya, Spain, and Turkey) and Northern Europe (n = 2; Poland and United Kingdom) were higher in glucosinolates and their hydrolysis products, especially glucoraphanin and sulforaphane, compared to those from Asia (n = 13; China, India, and Pakistan) and Middle East Asia (n = 8; Afghanistan, Iran, and Israel). The QR inducing activity was also the highest in Mediterranean and Northern European arugula accessions, possibly due to a significant positive correlation between sulforaphane and QR inducing activity (r = 0.54). No nitrile hydrolysis products were found, suggesting very low or no epithiospecifier protein activity from these arugula accessions. Broad sense heritability (H(2)) was estimated to be 0.91-0.98 for glucoinolates, 0.55-0.83 for their hydrolysis products, and 0.90 for QR inducing activity.


Subject(s)
Brassica/chemistry , Glucosinolates/chemistry , NAD(P)H Dehydrogenase (Quinone)/metabolism , Plant Proteins/metabolism , Asia , Brassica/classification , Brassica/metabolism , Europe , Glucosinolates/metabolism , Hydrolysis , Plant Leaves/chemistry , Plant Leaves/metabolism
13.
Toxicol Pathol ; 44(6): 913-6, 2016 08.
Article in English | MEDLINE | ID: mdl-27207684

ABSTRACT

Diethylnitrosamine (DEN) is a chemical broadly used in animal models as a hepatocarcinogen, reported to also cause pulmonary neoplasms in mice. The original objective was to evaluate the impact of a Western diet with or without 10% broccoli on DEN-induced on liver cancer. We administered DEN (45 mg/kg) intraperitoneally to young adult male B6C3F1 mice by 6 weekly injections and evaluated liver cancer 6 months after the DEN treatments. Here, we report unexpected primary tumorigenesis in nasal epithelium, independent of dietary treatment. More than 50% of DEN-treated B6C3F1 mice developed nasal neoplasm-related lesions, not reported previously in the literature. Only one of these neoplasms was visible externally prior to postmortem examination. Intraperitoneal DEN treatment used as a model for liver cancer can have a carcinogenic effect on the nasal epithelium in B6C3F1 mice, which should be carefully monitored in future liver cancer studies.


Subject(s)
Carcinogenesis/chemically induced , Carcinogens/toxicity , Diethylamines/toxicity , Nose Neoplasms/chemically induced , Animals , Liver Neoplasms/chemically induced , Male , Mice , Mice, Inbred Strains
14.
J Nutr ; 146(3): 542-50, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26865652

ABSTRACT

BACKGROUND: The high-fat and high-sugar Westernized diet that is popular worldwide is associated with increased body fat accumulation, which has been related to the development of nonalcoholic fatty liver disease (NAFLD). Without treatment, NAFLD may progress to hepatocellular carcinoma (HCC), a cancer with a high mortality rate. The consumption of broccoli in the United States has greatly increased in the last 2 decades. Epidemiologic studies show that incorporating brassica vegetables into the daily diet lowers the risk of several cancers, although, to our knowledge, this is the first study to evaluate HCC prevention through dietary broccoli. OBJECTIVE: We aimed to determine the impact of dietary broccoli on hepatic lipid metabolism and the progression of NAFLD to HCC. Our hypothesis was that broccoli decreases both hepatic lipidosis and the development of HCC in a mouse model of Western diet-enhanced liver cancer. METHODS: Adult 5-wk-old male B6C3F1 mice received a control diet (AIN-93M) or a Western diet (high in lard and sucrose, 19% and 31%, wt:wt, respectively), with or without freeze-dried broccoli (10%, wt:wt). Starting the following week, mice were treated once per week with diethylnitrosamine (DEN; 45 mg/kg body weight intraperitoneally at ages 6, 7, 8, 10, 11, and 12 wk). Hepatic gene expression, lipidosis, and tumor outcomes were analyzed 6 mo later, when mice were 9 mo old. RESULTS: Mice receiving broccoli exhibited lower hepatic triglycerides (P < 0.001) and NAFLD scores (P < 0.0001), decreased plasma alanine aminotransferase (P < 0.0001), suppressed activation of hepatic CD68(+) macrophages (P < 0.0001), and slowed initiation and progression of hepatic neoplasm. Hepatic Cd36 was downregulated by broccoli feeding (P = 0.006), whereas microsomal triglyceride transfer protein was upregulated (P = 0.045), supporting the finding that dietary broccoli decreased hepatic triglycerides. CONCLUSION: Long-term consumption of whole broccoli countered both NAFLD development enhanced by a Western diet and hepatic tumorigenesis induced by DEN in male B6C3F1 mice.


Subject(s)
Brassica , Diet, Western/adverse effects , Diethylnitrosamine/adverse effects , Liver Neoplasms/diet therapy , Alanine Transaminase/blood , Animals , Carcinoma, Hepatocellular/chemically induced , Carcinoma, Hepatocellular/diet therapy , Lipid Metabolism , Liver/metabolism , Liver Neoplasms/chemically induced , Male , Mice , Non-alcoholic Fatty Liver Disease/chemically induced , Non-alcoholic Fatty Liver Disease/diet therapy , Triglycerides/metabolism
15.
Front Plant Sci ; 6: 831, 2015.
Article in English | MEDLINE | ID: mdl-26500669

ABSTRACT

Brassicales contain a myrosinase enzyme that hydrolyzes glucosinolates to form toxic isothiocyanates (ITC), as a defense against bacteria, fungi, insects and herbivores including man. Low levels of ITC trigger a host defense system in mammals that protects them against chronic diseases. Because humans typically cook their brassica vegetables, destroying myrosinase, there is a great interest in determining how human microbiota can hydrolyze glucosinolates and release them, to provide the health benefits of ITC. ITC are highly reactive electrophiles, binding reversibly to thiols, but accumulating and causing damage when free thiols are not available. We found that addition of excess thiols released protein-thiol-bound ITC, but that the microbiome supports only poor hydrolysis unless exposed to dietary glucosinolates for a period of days. These findings explain why 3-5 servings a week of brassica vegetables may provide health effects, even if they are cooked.

16.
J Agric Food Chem ; 63(11): 2947-55, 2015 Mar 25.
Article in English | MEDLINE | ID: mdl-25684599

ABSTRACT

Horseradish (Armoracia rusticana) is a perennial crop and its ground root tissue is used in condiments because of the pungency of the glucosinolate (GS)-hydrolysis products allyl isothiocyanate (AITC) and phenethyl isothiocyanate (PEITC) derived from sinigrin and gluconasturtiin, respectively. Horseradish roots are sold in three grades: U.S. Fancy, U.S. No. 1, and U.S. No. 2 according to the USDA standards. These grading standards are primarily based on root diameter and length. There is little information on whether root grades vary in their phytochemical content or potential health promoting properties. This study measured GS, GS-hydrolysis products, potential anticancer activity (as quinone reductase inducing activity), total phenolic content, and antioxidant activities from different grades of horseradish accessions. U.S. Fancy showed significantly higher sinigrin and AITC concentrations than U.S. No. 1 ,whereas U.S. No. 1 showed significantly higher concentrations of 1-cyano 2,3-epithiopropane, the epithionitrile hydrolysis product of sinigrin, and significantly higher total phenolic concentrations than U.S. Fancy.


Subject(s)
Armoracia/enzymology , Isothiocyanates/analysis , Plant Proteins/metabolism , Quinone Reductases/metabolism , Armoracia/chemistry , Armoracia/classification , Armoracia/genetics , Genotype , Glucosinolates/analysis , Glucosinolates/metabolism , Isothiocyanates/metabolism , Plant Proteins/genetics , Plant Roots/chemistry , Plant Roots/enzymology , Plant Roots/genetics , Quinone Reductases/genetics
17.
Nutr Res ; 34(11): 990-9, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25439028

ABSTRACT

Aging is associated with oxidative stress and heightened inflammatory response to infection. Dietary interventions to reduce these changes are therefore desirable. Broccoli contains glucoraphanin, which is converted to sulforaphane (SFN) by plant myrosinase during cooking preparation or digestion. Sulforaphane increases antioxidant enzymes including NAD(P)H quinone oxidoreductase and heme oxygenase I and inhibits inflammatory cytokines. We hypothesized that dietary broccoli would support an antioxidant response in brain and periphery of aged mice and inhibit lipopolysaccharide (LPS)-induced inflammation and sickness. Young adult and aged mice were fed control or 10% broccoli diet for 28 days before an intraperitoneal LPS injection. Social interactions were assessed 2, 4, 8, and 24 hours after LPS, and mRNA was quantified in liver and brain at 24 hours. Dietary broccoli did not ameliorate LPS-induced decrease in social interactions in young or aged mice. Interleukin-1ß (IL-1ß) expression was unaffected by broccoli consumption but was induced by LPS in brain and liver of adult and aged mice. In addition, IL-1ß was elevated in brain of aged mice without LPS. Broccoli consumption decreased age-elevated cytochrome b-245 ß, an oxidative stress marker, and reduced glial activation markers in aged mice. Collectively, these data suggest that 10% broccoli diet provides a modest reduction in age-related oxidative stress and glial reactivity, but is insufficient to inhibit LPS-induced inflammation. Thus, it is likely that SFN would need to be provided in supplement form to control the inflammatory response to LPS.


Subject(s)
Aging , Brassica/chemistry , Illness Behavior , Lipopolysaccharides/administration & dosage , Lipopolysaccharides/adverse effects , Animals , Behavior, Animal , Brain/drug effects , Brain/metabolism , CX3C Chemokine Receptor 1 , Glial Fibrillary Acidic Protein/genetics , Glial Fibrillary Acidic Protein/metabolism , Interleukin-1beta/metabolism , Liver/metabolism , Mice , Mice, Inbred BALB C , Microglia/metabolism , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, Chemokine/genetics , Receptors, Chemokine/metabolism , Up-Regulation
18.
PLoS One ; 9(8): e103407, 2014.
Article in English | MEDLINE | ID: mdl-25084454

ABSTRACT

Methyl jasmonate (MeJA) spray treatments were applied to the kale varieties 'Dwarf Blue Curled Vates' and 'Red Winter' in replicated field plantings in 2010 and 2011 to investigate alteration of glucosinolate (GS) composition in harvested leaf tissue. Aqueous solutions of 250 µM MeJA were sprayed to saturation on aerial plant tissues four days prior to harvest at commercial maturity. The MeJA treatment significantly increased gluconasturtiin (56%), glucobrassicin (98%), and neoglucobrassicin (150%) concentrations in the apical leaf tissue of these genotypes over two seasons. Induction of quinone reductase (QR) activity, a biomarker for anti-carcinogenesis, was significantly increased by the extracts from the leaf tissue of these two cultivars. Extracts of apical leaf tissues had greater MeJA mediated increases in phenolics, glucosinolate concentrations, GS hydrolysis products, and QR activity than extracts from basal leaf tissue samples. The concentration of the hydrolysis product of glucoraphanin, sulforphane was significantly increased in apical leaf tissue of the cultivar 'Red Winter' in both 2010 and 2011. There was interaction between exogenous MeJA treatment and environmental conditions to induce endogenous JA. Correlation analysis revealed that indole-3-carbanol (I3C) generated from the hydrolysis of glucobrassicin significantly correlated with QR activity (r = 0.800, P<0.001). Concentrations required to double the specific QR activity (CD values) of I3C was calculated at 230 µM, which is considerably weaker at induction than other isothiocyanates like sulforphane. To confirm relationships between GS hydrolysis products and QR activity, a range of concentrations of MeJA sprays were applied to kale leaf tissues of both cultivars in 2011. Correlation analysis of these results indicated that sulforaphane, NI3C, neoascorbigen, I3C, and diindolylmethane were all significantly correlated with QR activity. Thus, increased QR activity may be due to combined increases in phenolics (quercetin and kaempferol) and GS hydrolysis product concentrations rather than by individual products alone.


Subject(s)
Acetates/pharmacology , Brassica/drug effects , Brassica/metabolism , Cyclopentanes/pharmacology , Glucosinolates/biosynthesis , NAD(P)H Dehydrogenase (Quinone)/metabolism , Oxylipins/pharmacology , Plant Leaves/drug effects , Plant Leaves/metabolism , Biosynthetic Pathways/drug effects , Brassica/chemistry , Enzyme Activation/drug effects , Glycoside Hydrolases/metabolism , Hydrolysis , Oxidation-Reduction/drug effects , Phenols/chemistry , Plant Extracts/chemistry , Plant Growth Regulators/pharmacology , Plant Leaves/chemistry
19.
J Agric Food Chem ; 62(33): 8385-91, 2014 Aug 20.
Article in English | MEDLINE | ID: mdl-25050614

ABSTRACT

Camelina sativa L. Crantz is under development as a novel oilseed crop, yet bioefficacy of camelina phytochemicals is unknown. Defatted camelina seed meal contains two major aliphatic glucosinolates (GSLs), glucoarabin (9-(methylsulfinyl)nonylglucosinolate; GSL 9) and glucocamelinin (10-(methylsulfinyl)decylglucosinolate; GSL 10), with traces of a third, 11(methylsulfinyl)undecylglucosinolate and several flavonoids, mostly quercetin glycosides. In Hepa1c1c7 cells, hydrolyzed GSLs (hGSLs) 9 and 10 upregulated the phase II detoxification enzyme quinone reductase (NQO1), with no effect on cytochrome P450 (CYP) 1A1 activity. Isobologram graphs revealed synergy of NQO1 induction for a combination of hGSL 9 and quercetin. These findings suggest that defatted camelina seed meal should be evaluated for anticancer activity, similar to broccoli and other Brassicaceae family members. Interestingly, synergy of NQO1 induction was also seen for physiologically relevant doses of sulforaphane (SF) and quercetin, two key bioactives present in broccoli. This suggests that SF within broccoli may be more potent than purified SF.


Subject(s)
Brassicaceae/chemistry , Glucosinolates/pharmacology , Plant Extracts/pharmacology , Quercetin/pharmacology , Seeds/chemistry , Antineoplastic Agents/analysis , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Synergism , Fats/analysis , Glucosinolates/analysis , Humans , Plant Extracts/analysis , Quercetin/analysis
20.
J Med Food ; 17(11): 1177-82, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24983303

ABSTRACT

Broccoli is rich in bioactive components, such as sulforaphane and indole-3-carbinol, which may impact cancer risk. The glucosinolate profile of broccoli can be manipulated through treatment with the plant stress hormone methyl jasmonate (MeJA). Our objective was to produce broccoli with enhanced levels of indole glucosinolates and determine its impact on prostate carcinogenesis. Brassica oleracea var. Green Magic was treated with a 250 µM MeJA solution 4 days prior to harvest. MeJA-treated broccoli had significantly increased levels of glucobrassicin, neoglucobrassicin, and gluconasturtiin (P < .05). Male transgenic adenocarcinoma of mouse prostate (TRAMP) mice (n = 99) were randomized into three diet groups at 5-7 weeks of age: AIN-93G control, 10% standard broccoli powder, or 10% MeJA broccoli powder. Diets were fed throughout the study until termination at 20 weeks of age. Hepatic CYP1A was induced with MeJA broccoli powder feeding, indicating biological activity of the indole glucosinolates. Following ∼ 15 weeks on diets, neither of the broccoli treatments significantly altered genitourinary tract weight, pathologic score, or metastasis incidence, indicating that broccoli powder at 10% of the diet was ineffective at reducing prostate carcinogenesis in the TRAMP model. Whereas broccoli powder feeding had no effect in this model of prostate cancer, our work demonstrates the feasibility of employing plant stress hormones exogenously to stimulate changes in phytochemical profiles, an approach that may be useful for optimizing bioactive component patterns in foods for chronic-disease-prevention studies.


Subject(s)
Acetates/pharmacology , Brassica/metabolism , Carcinogenesis/drug effects , Cyclopentanes/pharmacology , Glucosinolates/pharmacology , Indoles/pharmacology , Oxylipins/pharmacology , Plant Extracts/pharmacology , Prostatic Neoplasms , Animals , Brassica/drug effects , Glucosinolates/metabolism , Glucosinolates/therapeutic use , Indoles/metabolism , Indoles/therapeutic use , Male , Mice, Inbred C57BL , Plant Extracts/therapeutic use , Plant Growth Regulators/pharmacology , Prostatic Neoplasms/drug therapy
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