Summary
Cellular oxidative stress is a risk factor for several human disease including diabetes,
cardiovascular diseases (CVD) and cancer. Natural and food products have a great potential to
protect cells under oxidative stress conditions. Tef (Eragrostis tef) is gluten-free grain that is rich
in mineral nutrients, essential amino acids, and water-soluble vitamins and several bioactive
phytochemicals including polyphenols, flavonoids and polyunsaturated fatty acids (PUFAs). Tef
has been recognized by the U.S. National Research Council as a crop with excellent nutritional
potential and suitability to boost food security. However, the bioactivity of tef phytochemicals have
never been studied using physiologically relevant models. In this study, we propose to identify
bioactive compounds in tef grains and test their ability to combat oxidative stress, thus preventing
the pathogenic conditions associated with reactive oxygen species (ROS)-induced damages. This
initiative is based on our recent finding indicating that: 1) tef seed extracts increase glutathione
(GSH) levels in THP-1 monocytes, 2) an increase in GSH level is more prominent in brown than
ivory tef seeds, suggesting the existence of genotypic variability in the content of bioactive
compound, 3) Tef seed extracts increase the expression of the master regulator of antioxidant
pathway nuclear factor erythroid 2-related factor 2 (Nrf2) and its targets including Heme
Oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase1 (NQO1), glutathione reductase (GR)
and the ¿-glutamate cysteine ligase catalytic (GCLC) and regulatory (GCLM) subunit, which play
a key role in GSH biosynthesis, 4) A bioactive fraction of tef extract contains a derivative of linoleic
acid (LA) 9-Hydroxyoctadecadienoic acid (9-HODE), which is a marker for membrane lipid
peroxidation. These findings prompted us to hypothesize that tef has bioactive compounds which
have the potential to boost the antioxidant pathway under oxidative stress conditions likely via
Nrf2 signaling. Our aims are: 1) Identification and functional characterization of bioactive
phytochemicals from tef seeds, 2) Studying whether tef bioactive compounds induce oxidative
stress-responsive genes, and protect cells from ROS, 3) Understanding the genetic mechanism
regulating antioxidant properties of tef. This study will help in developing alternative medicines for
oxidative stress-induced diseases. It will also generate new information that can be used to
improve tef or transferred to major cereals to add value to these crops. This funding will boost the
capacity of the Osena laboratory to explore underutilized crops such as millets for desirable traits
including health benefits. The Osena laboratory and the environment at UNC Greensboro are
ideal for this research, and training students from underrepresented minority group.
