The Power of Rye congress, Mariehamn, June 7–8, 2017
The role of benzoxazinoids, new players for human health
Inge S Fomsgaard*, Stine Krogh Steffensen, Khem Bahadur Adhikari, Hans Albert Pedersen, Fariha Tanwir
& Per L Gregersen
In 2008 we discovered that mature grains of rye and wheat contain benzoxazinoids (BXs)1. Bread baked in
our lab from rye or hydrothermally processed wheat showed to contain substantial amounts of BXs 2. The
composition and quantity of BXs in food products depended much more on the food preparation process
than on the cultivar2, 3. BXs were taken up by pigs, rats and humans after consuming rye-based food 4-7.
BXs have a range of potential pharmacological properties, as reviewed by Adhikari et al8. When bacteria
induce the production of inflammatory cytokines in innate immune cells, a previous diet high in BXs
enhances this production, indicating an immune-modulating effect of the BXs9. With a highly sensitive
analytical method uptake of 6 BX compounds in human prostate tissue was documented after one week’s
high-BX diet.
Recent analytical papers revealed that profiles of methoxylated hydroxamic acids in young maize plants
varied depending on sample treatment10, and that chromatographic separation of glucosylated DIMBOA
and DIM2BOA required the use of uncommon chromatographic columns11. 25 commercial cereal food
products contained from nd to >500 µg/g dry weight total BXs. Most products high in rye content had high
concentrations of BXs12.
Our above-mentioned results do not stand alone. Knowledge about BX structures took a leap forward
when multiple glycosylated BXs13, 14, BXs with both glycosylation and acetylation15 and a 6-hydroxylated
MBOA (6-methoxy-benzoxazolin-2-one)16 were identified. Recent identification of a ScBX6-like enzyme in
rye, will aid in future understanding of BX biosynthesis in rye17.
Based on the above, benzoxazinoids are good candidates as future players in human and animal health.
Future research should cover: full characterization of BX structures; methods for easy isolation of pure
compounds; fate of benzoxazinoids in the body - occurrence in plasma and urine, and distribution to
tissues; effect studies - not only registration of effects but understanding of mechanisms behind effects.
References
1. Fomsgaard, I. S.; Mortensen, A. G.; Holm, P. B.; Gregersen, P. L. Use of benzoxazinoids-containing cereal grain products for health-improving purposes. Patent application. EP 2 265 133 A1,
2009.
2. Pedersen, H. A.; Laursen, B.; Mortensen, A.; Fomsgaard, I. S., Bread from common cereal cultivars contains an important array of neglected bioactive benzoxazinoids. Food Chemistry 2011,
127, 1814-1820.
3. Tanwir, F.; Fredholm, M.; Gregersen, P. L.; Fomsgaard, I. S., Comparison of the levels of bioactive benzoxazinoids in different wheat and rye fractions and the transformation of these compounds
in homemade foods. Food Chemistry 2013, 141, 444-450.
4. Adhikari, K. B.; Laursen, B. B.; Laerke, H. N.; Fomsgaard, I. S., Bioactive benzoxazinoids in rye bread are absorbed and metabolized in pigs. Journal of Agricultural and Food Chemistry 2012, 60,
2497-2506.
5. Adhikari, K. B.; Laerke, H. N.; Mortensen, A. G.; Fomsgaard, I. S., Plasma and urine concentrations of bioactive dietary benzoxazinoids and their glucuronidated conjugates in rats fed a rye
bread-based diet. Journal of Agricultural and Food Chemistry 2012, 60, 11518-11524.
6. Adhikari, K. B.; Laursen, B. B.; Gregersen, P. L.; Schnoor, H. J.; Witten, M.; Poulsen, L. K.; Jensen, B. M.; Fomsgaard, I. S., Absorption and metabolic fate of bioactive dietary benzoxazinoids in
humans. Molecular Nutrition & Food Research 2013, 57, 1847-1858.
7. Jensen, B. M.; Adhikari, K. B.; Schnoor, H. J.; Juel-Berg, N.; Fomsgaard, I. S.; Poulsen, L. K., Quantitative analysis of absorption, metabolism, and excretion of benzoxazinoids in humans after the
consumption of high- and low-benzoxazinoid diets with similar contents of cereal dietary fibres: a crossover study. Eur J Nutr 2017, 56, 387-397.
8. Adhikari, K. B.; Tanwir, F.; Gregersen, P. L.; Steffensen, S. K.; Jensen, B. M.; Poulsen, L. K.; Nielsen, C. H.; Hoyer, S.; Borre, M.; Fomsgaard, I. S., Benzoxazinoids: Cereal phytochemicals with
putative therapeutic and health-protecting properties. Molecular Nutrition & Food Research 2015, 59, 1324-1338.
9. Damgaard, D.; Jensen, B. M.; Palarasah, Y.; Nielsen, M. F. B.; Adhikari, K. B.; Schnoor, H. J.; Juel-Berg, N.; Poulsen, L. K.; Fomsgaard, I. S.; Nielsen, C. H., Dietary exposure to benzoxazinoids
enhances bacteria-induced monokine responses by peripheral blood mononuclear cells. Molecular Nutrition & Food Research 2015, 59, 2190-2198.
10. Pedersen, H. A.; Heinrichson, K.; Fomsgaard, I. S., Alterations of the benzoxazinoid profiles of uninjured maize seedlings during freezing, storage, and lyophilization. Journal of Agricultural
and Food Chemistry 2017, DOI: 10.1021/acs.jafc.7b01158.
11. Pedersen, H. A.; Steffensen, S. K.; Heinrichson, K.; Fomsgaard, I. S., How to achieve good separation of the glucosides of DIMBOA and DIM2BOA. Under revision 2017.
12. Steffensen, S. K.; Adhikari, K. B.; Borre, M.; Borre, M.; Høyer, S.; Laursen, B.; Jensen, C.; Fomsgaard, I. S., Bioactive small molecules in commercially available cereal products from Danish
supermarkets: Benzoxazinoids. Submitted 2017.
13. Hanhineva, K.; Rogachev, I.; Aura, A.-M.; Aharoni, A.; Poutanen, K.; Mykkänen, H., Qualitative characterization of benzoxazinoid derivatives in whole grain rye and wheat by LC-MS metabolite
profiling. Journal of Agricultural and Food Chemistry 2011, 59, 921-927.
14. Pihlava, J. M.; Kurtelius, T., Determination of benzoxazinoids in wheat and rye beers by HPLC-DAD and UPLC-QTOF MS. Food Chemistry 2016, 204, 400-408.
15. de Bruijn, W. J. C.; Vincken, J.-P.; Duran, K.; Gruppen, H., Mass Spectrometric Characterization of Benzoxazinoid Glycosides from Rhizopus-elicited Wheat (Triticum aestivum) Seedlings.
Journal of Agricultural and Food Chemistry 2016.
16. Wu, W. H.; Chen, T. Y.; Lu, R. W.; Chen, S.; Chang, C. C., Benzoxazinoids from Scoparia dulcis (sweet broomweed) with antiproliferative activity against the DU-145 human prostate cancer cell
line. Phytochemistry 2012, 83, 110-115.
17. Tanwir, F.; Dionisio, G.; Adhikari, K. B.; Fomsgaard, I. S.; Gregersen, P. L., Biosynthesis and chemical transformation of benzoxazinoids in rye during seed germination and the identification of
a rye Bx6-like gene. Phytochemistry 2017, 140, 95-107.