Apple proanthocyanidins and their metabolites: mechanisms of action in biological systems

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Canada faces significant challenges from population chronic and metabolic disease epidemics, which are directly or indirectly linked to the human diet. The regular consumption of diets rich in fruits and vegetables has been consistently associated with the promotion of beneficial physiological functions leading to human health and wellness. These health benefts have been attributed to biologically active, plantbased polyphenolic compounds, especially flavonoids, commonly found in fruits and vegetables. A large body of epidemilogical studies has strongly suggested that habitual dietary flavonoid intake can reduce the risk of numerous diseases including some cancers. *** A specific class of polymerized flavonoids, proanthocyanidins, represent over 50% of dietary polyphenols consumed; however, these polyphenols are poorly absorbed in the small intestine and therefore their beneficial effects are dependent on the colonic microflora of individuals. In the proposed research, polymeric proanthocyanidins isolated from apple processing waste will be bioconverted into simple bioactive molecules using isolated probiotic bacteria. The resulting newly formed molecules will be characterized by their structure, safety, and beneficial physiological functions. Understanding the molecular mechanisms of pleiotropic beneficial effects on human health such as antioxidant, anti-inflammatory, and anti-carcinogenic activities of probiotic metabolites of apple proanthocyanidins will be significant to advance the future approach to managing chronic disorders. Highly qualified personnel (HQP) will be trained in interdisciplinary emerging areas of nutritional metabolomics of bioactive compounds present in fruits. *** The overall goal of the research program is to elucidate the mechanisms of action of fruit flavonoids and their metabolites in relation to the specific physiological functions. The new knowledge generated through this research program will contribute to the development of flavonoid-based functional foods and nutraceuticals that will reduce the risk of chronic disorders of humans. The research findings will immensely advance the fundamental knowledge needed to develop effective cancer chemoprotective strategies. For example, apple proanthocyanidins can be developed as a unique prebiotic along with probiotic bacteria to introduce novel cancer preventive functional foods. The newly formed efficacious metabolites of proanthocyanidins can be used as candidates for anti-cancer drugs. As a result, underutilized apple processing waste can be turned into a valuable source of food ingredients and nutraceuticals, and in turn, these may contribute to reducing economic burdens associated with cancer incidence and mortality in our society.