Oat Avenanthramides: A Novel Antioxidant

Authors: JI, LI LI - UNIV OF WISCONSIN; KOENIG, RYAN - UNIV OF WISCONSIN; Wise, Mitchell

Submitted to: Book Chapter
Publication Type: Book / Chapter
Publication Acceptance Date: 9/23/2009
Publication Date: 1/22/2009
Citation: Ji, L., Koenig, R., Wise, M.L. 2008. Oat Avenanthramides: A Novel Antioxidant. In: Mine, Y., Miyashita, K., Shahidi, F., editors. Nutrigenomics and proteomics in Health and Disease. Ames, IA: Wiley-Blackwell. p. 239-249.

Interpretive Summary: Avenanthramides are a group of anti-oxidants produced, among the food crops, exclusively in oat. There is increasing awareness that these metabolites might account, at least partially, for some of the beneficial health properties associated with oat consumption. This paper briefly describes some of the chemical characteristics of these interesting metabolites. In addition, a detailed review of the current research on the physiological effects of avenanthramides is provided. The evidence for the bioavailablity of three major forms of avenanthramides in different animals systems is presented. There appear to be differences in the rate at which the various avenanthramides are metabolized as well as differences in the bioavailability of the different avenanthramides in different animals. A variety of cellular model systems and whole animal experiments have been employed to evaluate the effect of avenanthramides on atherosclerosis development and the reduction of exercise and age related muscle inflammation. From these studies a role of avenanthramide regulation of certain transcription factors and other intercellular signaling mechanisms, which in turn, regulate cell proliferation and molecular mediators of inflammation is emerging. These results provide promising evidence that avenanthramides, and hence oats, offer nutritional benefits not found in other foods.

Technical Abstract: Avenanthramides are antioxidant compounds found, among food crops, exclusively in oat. There is a growing body of evidence that avenanthramides may provide beneficial physiological effects on animals and humans. In the grain of oat the three most abundant forms of avenanthramides are termed A, B and C. These phytonutrients are bio-available in rats, hamsters and humans, though with differences in their pharmacokinetic behavior. Cellular model systems have been employed to demonstrate the effect of avenanthramides on atherosclerotic plaque formation. Treatment of vascular smooth muscle cell in vitro with avenanthramide C and its methyl ester inhibit cell proliferation (a hallmark of sclerotic plaque formation) in a dose dependent manner. An avenanthramide enriched extract from oat also shows inhibition of the interlukin -1' (IL-1') stimulated expression of intracellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1) and E-selectin by cultured human aortic endothelial cells (HAEC). Moreover, the avenanthramide enriched cocktail reduced the IL-1' stimulated expression of additional cytokines including IL-8, IL-6 and monocyte chemo-attractant protein-1 (MCP-1). Thus, the avenanthramides appear to inhibit the inflammatory response of certain vascular endothelial cells. The avenanthramide enriched oat extract, as well as synthetic avenanthramide C (and its methyl ester), were also shown to retard the degradation of the tumor suppressor protein p53. P53 is a transcription factor for p21cip1 expression. This protein is a cyclin-dependent kinase (CDK) inhibitor; one of the functions of CDK is to phosphorylate the restinoblastosis protein (Rp). Polyphosphorylated Rp (pRp) is a key mediator of cell cycle transition for the G1 to S phase, reduction of pRp formation, due to CDK inhibition, results in cell cycle arrest. Avenanthramide C treatment of HEAC and vascular smooth muscle cells also up-regulates endothelial NO synthase biosynthesis, thus increasing nitric oxide (NO) production. NO has a myriad of anti-atherosclerotic properties. Thus a molecular rationale for avenanthramide inhibition of atherosclerotic plaque formation is coming to light. Additional studies on rats fed a diet containing synthetic avenanthramide C and subject to exercise induced oxidative stress demonstrate interesting but somewhat conflicting results. Although reactive oxygen species (ROS) generation in most of the tissues examined was unaffected, there was an ROS decrease in soleus (lower leg) muscle tissue. Likewise, superoxide dismutase (an anti-oxidant enzyme) showed higher activity in certain tissues (liver, kidney, DVL and soleus) in the avenanthramide treated animals, but lower activity in heart tissue. Interestingly, glutathione peroxidase (another anti-oxidant enzyme) levels were elevated in the hearts of avenanthramide treated rats. In a follow-up study, rats fed an avenanthramide diet and subject to exercise stress, demonstrated a reduction in oxidant production via mitochondrial respiration and polymorphnuclear NADPH oxidase activity in some muscle tissues but not in others. It appears that, although relatively strong anti-oxidants in vitro, avenanthramides exert a more profound influence via signaling and biosynthetic pathways in mammalian systems. These effects manifest in reduction of inflammatory processes and cellular proliferation which are likely to result in health benefits in humans. Exposure of these experimental results will enhance the value of the oat crop.