Agricultural outputs have resulted in food production continuously expanding. To satisfy the needs of a fast growing human population, higher yields, more efficient food processing, and food esthetic value, new crop varieties with higher caloric intake have and continue to be developed, but which lack many phytochemicals important for plant protection and adequate human nutrition. The increasing incidence of chronic diseases such as obesity, diabetes and cardiovascular diseases, combined with social disparity worldwide prompted the interest in developing enhanced crops that can simultaneously address the two sides of the current malnutrition sword, increasing yield while providing added nutritional value. Flavones, phytochemicals associated with the beneficial effects of the Mediterranean diet, have potent anti-inflammatory and anti-carcinogenic activities. However, many Mediterranean diet-associated vegetables are inaccessible, or lowly consumed, in many parts of the world. Maize is the most widely grown cereal crop, yet most lines used for hybrid maize production lack flavones. As a first step toward a sustainable strategy to increasing the nutritional value of maize-based diets, we investigated the accumulation and chemical properties of flavones in maize seeds of defined genotypes. We show that the pericarps of the P1-rr genotype accumulate flavones at levels comparable to those present in some flavone-rich vegetables, and are mostly present in their C- and O-glycosylated forms. Some of these glycosides can be readily converted into the corresponding more active health beneficial aglycones during food processing. Our results provide evidence that nutritionally beneficial flavones could be re-introduced into elite lines to increase the dietary benefits of maize.

The increasing prevalence of inflammatory diseases and the adverse effects associated with the long-term use of current anti-inflammatory therapies prompt the identification of alternative approaches to reestablish immune balance. Apigenin, an abundant dietary flavonoid, is emerging as a potential regulator of inflammation. Here, we show that apigenin has immune-regulatory activity in vivo. Apigenin conferred survival to mice treated with a lethal dose of Lipopolysaccharide (LPS) restoring normal cardiac function and heart mitochondrial Complex I activity. Despite the adverse effects associated with high levels of splenocyte apoptosis in septic models, apigenin had no effect on reducing cell death. However, we found that apigenin decreased LPS-induced apoptosis in lungs, infiltration of inflammatory cells and chemotactic factors’ accumulation, re-establishing normal lung architecture. Using NF-κB luciferase transgenic mice, we found that apigenin effectively modulated NF-κB activity in the lungs, suggesting the ability of dietary compounds to exert immune-regulatory activity in an organ-specific manner. Collectively, these findings provide novel insights into the underlying immune-regulatory mechanisms of dietary nutraceuticals in vivo.

Acute and chronic inflammation is characterized by increased reactive oxygen species (ROS) production, dysregulation of mitochondrial metabolism and abnormal immune function contributing to cardiovascular diseases and sepsis. Clinical and epidemiological studies suggest potential beneficial effects of dietary interventions in inflammatory diseases but understanding of how nutrients work remains insufficient. In the present study, we evaluated the effects of apigenin, an anti-inflammatory flavonoid abundantly found in our diet, in endothelial cells during inflammation. Here, we show that apigenin reduced lipopolysaccharide (LPS)-induced apoptosis by decreasing ROS production and the activity of caspase-3 in endothelial cells. Apigenin conferred protection against LPS-induced mitochondrial dysfunction and reestablished normal mitochondrial complex I activity, a major site of electron leakage and superoxide production, suggesting its ability to modulate endothelial cell metabolic function during inflammation. Collectively, these findings indicate that the dietary compound apigenin stabilizes mitochondrial function during inflammation preventing endothelial cell damage and thus provide new translational opportunities for the use of dietary components in the prevention and treatment of inflammatory diseases.