Source: UNIVERSITY OF ILLINOIS submitted to NRP
PROTECTION FROM INFLAMMATION BY DIETARY BROCCOLI
Sponsoring Institution
National Institute of Food and Agriculture
Project Status
COMPLETE
Funding Source
Reporting Frequency
Annual
Accession No.
0220556
Grant No.
2010-65200-20398
Cumulative Award Amt.
$498,409.00
Proposal No.
2010-03553
Multistate No.
(N/A)
Project Start Date
Dec 15, 2009
Project End Date
Dec 14, 2014
Grant Year
2010
Program Code
[93130]- Bioactive Food Components for Optimal Health
Recipient Organization
UNIVERSITY OF ILLINOIS
2001 S. Lincoln Ave.
URBANA,IL 61801
Performing Department
Food Science & Human Nutrition
Non Technical Summary
We will evaluate the ability of a diet rich in the vegetable broccoli to decrease or prevent inflammation.
Animal Health Component
50%
Research Effort Categories
Basic
50%
Applied
50%
Developmental
(N/A)
Classification

Knowledge Area (KA)Subject of Investigation (SOI)Field of Science (FOS)Percent
70214401010100%
Goals / Objectives
To determine the impact of broccoli and broccoli components on the release of inflammatory biomarkers in response to an inflammatory agent .
Project Methods
Mice will be fed broccoli (or broccoli components) grown at the University of Illinois or in the selenium-contaminated soils of N. California and then given lippopolysaccharide, which triggers an inflammatory response, sickness behavior, and if prolonged can lead to cognitive deterioration. We will determine if broccoli is able to decrease the extent of response to lippopolysaccharide in all these areas.

Progress 12/15/09 to 12/14/14

Outputs
Target Audience: Members of the target audience include the vegetable industry, nutrition scientists, consumers of vegetables, and survivors of cancer. Changes/Problems: Nothing Reported What opportunities for training and professional development has the project provided? Students have carried out studies, learning techniques and the scientific method. They have attended science meetings, including Experimental Biology 2014 and AICR 2014. How have the results been disseminated to communities of interest? This year I have given press releases and answered phone and e-mail inquiries from industry and private members of the public. I have given talks at USDA (C street, Milner Memorial Symposium), Pet Food Forum (Chicago), American Horticulture Congress 2014 (Brisbane), Food Day at Bowie State College (Bowie, MD), American Institute for Cancer Research (Washington, DC), Sakata Broccoli Symposium (Warsaw, Poland), Carle Hospital Survivor’s Forum (Urbana, IL), and the University of Copenhagen (Copenhagen, Denmark). Travel was not paid by USDA funds for any of these, but my USDA-funded research was reported and USDA acknowledged. What do you plan to do during the next reporting period to accomplish the goals? Nothing Reported

Impacts
What was accomplished under these goals? We have shown that dietary broccoli inhibits Western diet-induced fatty liver and resulting inflammation. This work is being prepared for publication. We have also shown that sulforaphane has a mild amelioratory impact on the inflammation of aging, but does not impact cognitive decline. This has been published. The bioavailability model developed last year was refined and arrangements made to perform a study together with USDA Beltsville using this model. We found synergy between sulforaphane and quercetin at physiological levels, showing that whole broccoli food is more effective than purified sulforaphane.

Publications

  • Type: Journal Articles Status: Submitted Year Published: 2015 Citation: Ku, K.M., Jeffery, E.H., Juvik, J.A. and Kushad, M.M. Correlation of quinone reductase activity and allyl isothiocyanate content in different genotypes and grades of horseradish roots.
  • Type: Journal Articles Status: Accepted Year Published: 2014 Citation: Liu, A.G., Juvik, J.A., Jeffery, E.H., Berman-Booty, L.D., Clinton, S.K. and Erdman, JW. Enhancement of broccoli indole glucosinolates by methyl jasmonate treatment and effects on prostate carcinogenesis. J. Medicinal Food.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Dosz, E.B., Ku, K.M., Juvik, J.A. and Jeffery, E.H. Total myrosinase activity estimates in brassica vegetable produce. Journal of Agricultural and Food Chemistry 62: 8094 - 8100.
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Dosz, E.B. and Jeffery, E.H. Commercially produced frozen broccoli lacks the ability to form sulforaphane. Journal of Functional Foods, 5 (2), pp. 987-990.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Erdman, J.W., Jeffery, E.H., Hendrickx, M., Cross, A. and Lampe, J. Can food processing enhance cancer protection? Nutrition Today. 49(5):230-234, September/October 2014.
  • Type: Journal Articles Status: Published Year Published: 2014 Citation: Townsend, B.E., Chen, Y.J., Jeffery, .E.H. and Johnson, R.W. Dietary broccoli mildly improves neuroinflammation in aged mice but does not reduce lipopolyusaccharide-indcued sickness behavior. ScienceDirect 34: 990  999.


Progress 12/15/12 to 12/14/13

Outputs
Target Audience: Registered dietitians, physicians, scientisits at the American Institute for Cancer Research meetings (keynote + 3 posters and a blog interview), the international functional foods community (Experimental Biology 2013; FAV 2012 meetings presentations), USDA/ Beltsville (seminar to interested scientists and support of USDA work on glucosinolates), pet food manufacturers (Alltech keynote speech), the localcommunity (articles in local newspaper; interview on local television), the broader community (Men's Health magazine, SELF magazine, Reader's Digest articles), and students at the University of Illinois (seminars within the Department; group meetings with my own students). Changes/Problems: We had two major problems with broccoli harvest, due to unusual Fall weather. We are planning to have our last harvest Spring/Summer which has less trouble than the fall harvest. Furthermore, I have assurances from both Mark Farnham (USDA) and Allan Brown (Kannapolis) that they can provide me with broccoli as needed. We had personnel disruptions, as new students changed their career plans and mature students left after graduating. However, we are now safely on course to be completed by December 2014. What opportunities for training and professional development has the project provided? I have trained 5 graduate students and 3 post docs: one student remains with me, four graduates are employed; one as a technician, one as a registered dietition, one at Abbott Nutrition and one at General Mills. One of the post-docs has a faculty position (University of Maine), one has a scientist position at the University of Parma, Italy and one remains with me. How have the results been disseminated to communities of interest? I have given press releases and answered phone inquiries, and given talks and posters at meetings. I have consulted with scientists atUSDA Beltsville to help them measure glucosinolates and generate a database. What do you plan to do during the next reporting period to accomplish the goals? We expect to complete animal studies on systemic and CNS inflammation and complete studies on impact of multiple days' broccoli feeding on term length of efficacy. Present our findings at Kannapolis research campus North Carolina, the FAV 2014 meetings and at the Pet Food forum. We expect to submit a further 4 or 5 manuscripts during this year, as our studies become complete.

Impacts
What was accomplished under these goals? We have found a difference in anti-inflammatory responses between mouse and human cell lines, both liver and macrophage. Namely, different broccoli bioactives (sulforaphane, hydroyzed neoglucobrassicin and quercetin) all synergise in their anti-inflammatory action in mouse, whereas hydrolyzed neoglucobrassicin inhibits the anti-inflammatory effect of sulforaphane in human cell lines. The importance of these findings is that the mouse may not be a suitable model for the impact of dietary bioactives on inflammation. This work is very close to publication. In addition, we find that camelina isothiocyanates upregulate the detoxification enzyme quinone reductase similarly to sulforaphane, but have no effect on inflammation, in mouse macrophages. The importance of this finding is mechanistic - it means that quinone reductase and anti-inflammatory action are not regulated in exactly the same manner. We expct to submit this for publication in April.

Publications

  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Angelino, D. and Jeffery, E. Glucosinolate hydrolysis and bioavailability of resulting isothiocyanates: Focus on glucoraphanin. Journal of Functional Foods.
  • Type: Journal Articles Status: Submitted Year Published: 2014 Citation: Jeffery, E. Camelina sativa seed meal contains both alkyl sulfinyl glucosinolates and quercetin that synergize bioactivity. Journal of Nutritional Biochemistry.
  • Type: Journal Articles Status: Published Year Published: 2013 Citation: Angelino, D., Berhow, M., Ninfali, P. and Jeffery, E.H. Caecal absorption of vitexin-2-O-xyloside and its aglycone apigenin, in the rat. Food and Function, 4 (9), pp. 1339-1345.


Progress 12/15/11 to 12/14/12

Outputs
OUTPUTS: We have developed an obese mouse model in which C57 mice are fed an AIN93 prototype diet altered to contain high fat/high sugar, with or without added freeze-dried broccoli, 10%. The mice showed steatosis (NAFLD, non-alcoholic fatty liver disease) but not steatohepatitis (NASH, non-alcoholic steatohepatitis). We are developing an advanced diet to allow mice to develop NASH also. Preliminary results show that broccoli is able to control steatatosis. PARTICIPANTS: Ajie is a graduate student studying prevention of inflammation by sulforaphane in macrophages. Townsend is a graduate student studying the impact of sulforaphane on inflammation in microglia, the brain's equivalent to macrophages. Nilanjan Das is a post-doc, replacing post-doc Angela Myracle, in evaluating the effect of broccoli and broccoli components on systemic inflammation and determining the length of time that a dose of broccoli remains effective. Jefery, Johnson and Juvik are faculty at the University of Illinois, participating in training the students and post-docs. TARGET AUDIENCES: The audience is both research scientists from academia, USDA and industry, as well as the general public. We reach the latter through articles in magazines and news reports. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
This work was presented at EB2012, as well as Trouw annual pet food conference and the International Society of Functional Foods conference. This work supports the message to the public that 3 - 5 servings of brassica vegetables per week will decrease risk for many chronic diseases.

Publications

  • Wang, G.C., Farnham, M. and Jeffery, E.H. 2012. Impact of thermal processing on sulforaphane yield from broccoli (Brassica oleraceae L. var italica). J. Ag. Fd. Chem. 60:6743-6748.


Progress 12/15/10 to 12/14/11

Outputs
OUTPUTS: We have carried out studies in vitro and in mice initiating inflammation, using LPS in vitro and dextran sulfate sodium in vivo and determined the effects of sulforaphane in cell culture using macrophages and the effects of broccoli and broccoli sprouts using mice. We are presently developing a model of obesity-induced inflammation and will evaluate the effect of sulforaphane on cultured cells and dietary broccoli on obesity-induced inflammation in mice. Information has been disseminated at science meetings, including both Experimental Biology and American Chemical Society. PARTICIPANTS: Whitney Ajie and Sonja Volker are graduate students, performing the work and being trained in the scientific method. Angela Myracle is a post-doc who is performing research and learning to train students. Drs. Jeffery, Juvik and Johnson are all faculty at the University of Illinois, participating in training the students and post-doc. TARGET AUDIENCES: The scientific community, by presenting at scientific meetings. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
We find that sulforaphane slows NO production in mouse macrophages treated with LPS, and that quercetin enhances the sulforaphane effect. In hepatocytes, quercetin also enhances sulforaphane-induced increaes in quinone reductase. We also find that both broccoli and broccoli sprouts quench inflammation of the colon, whereas only broccoli at 10% in the diet, and not sprouts at 5% in the diet, was able to decreae azoxymethane-induced cancer, suggesting that quenching inflammation alone, as seen with broccoli sprouts, is not the sole impact of broccoli on colon cancer.

Publications

  • No publications reported this period


Progress 12/15/09 to 12/14/10

Outputs
OUTPUTS: We have grown broccoli, harvested and are in the process of freeze drying. We have evaluated the ability of sulforaphane to inhibit LPS-induced acute inflammation in microglia in vitro and are in the process of identifying which proteins are affected. We have provided mice with a high fat diet to generate chronic inflammation and are feeding them freeze-dried broccoli. Some of this work was presented as a poster at IFT 2010. PARTICIPANTS: Broccoli was grown and harvested by Dr. J. Juvik, a plant geneticist. Microglia work was carried out by Dr. R. Johnson and his student S. Jang, both immunologists. Animal feeding studies are ongoing, run by Dr. E. Jeffery and her post-doctoral student A. Myracle. This project allows collaboration, and thus understanding, across disciplines. It also trains students in both disciplinary and cross-disciplinary research. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.

Impacts
We find that sulforaphane, at concentrations found in blood after feed broccoli, was able to inhibit LPS-induced acute inflammation, including inhibition of cytokines IL-6 and IL-1B, although TNKa was not as greatly affected. If broccoli is found to curtail neuroinflammation in vivo, it may be able to help maintain a healthy mental attitude when the body is undergoing damage/wounding.

Publications

  • No publications reported this period