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

加拿大面临着人口慢性病和代谢性疾病流行的重大挑战，这些疾病与人类饮食直接或间接相关。经常食用富含水果和蔬菜的饮食一直与促进有益的生理功能有关，从而促进人类的健康和健康。这些健康益处都归因于生物活性的植物多酚化合物，特别是水果和蔬菜中常见的类黄酮类化合物。大量的流行病学研究有力地表明，习惯性的饮食摄入类黄酮可以降低患多种疾病的风险，包括一些癌症。 一类特定的聚合类黄酮，原花青素，占膳食多酚消费量的50%以上；然而，这些多酚在小肠中的吸收很差，因此它们的有益效果取决于个人的结肠微生物区系。在这项拟议的研究中，从苹果加工废弃物中分离出来的聚合物原花青素将使用分离的益生菌生物转化为简单的生物活性分子。由此产生的新形成的分子将以它们的结构、安全性和有益的生理功能为特征。了解苹果原花青素的益生菌代谢产物的抗氧化、抗炎、抗癌等多种有益人体健康作用的分子机制，对于推进未来防治慢性疾病的途径具有重要意义。高素质人员(HQP)将在水果中存在的生物活性化合物营养代谢组学的跨学科新兴领域接受培训。 该研究计划的总体目标是阐明水果类黄酮及其代谢产物与特定生理功能相关的作用机制。通过这项研究计划产生的新知识将有助于以类黄酮类为基础的功能食品和营养食品的开发，这些食品和营养食品将降低人类慢性疾病的风险。研究结果将极大地促进开发有效的癌症化学保护策略所需的基础知识。例如，苹果原花青素可以作为一种独特的益生菌与益生菌一起开发出来，以推出新型的防癌功能食品。新形成的原花青素高效代谢物可作为抗癌药物的候选药物。因此，未得到充分利用的苹果加工废物可以被转化为食物成分和营养食品的宝贵来源，反过来，这些可能有助于减少与我们社会癌症发病率和死亡率相关的经济负担。

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.