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

加拿大面临着与人类饮食直接或间接相关的人口慢性和代谢性疾病流行病的重大挑战。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，从而促进人体健康和健康。这些健康益处归功于生物活性的植物性多酚化合物，尤其是水果和蔬菜中常见的类黄酮。大量的流行病学研究强烈表明，习惯性饮食中摄入类黄酮可以降低包括某些癌症在内的许多疾病的风险。***一种特殊的类黄酮聚合物，原花青素，占超过50%的膳食多酚消耗；然而，这些多酚在小肠中吸收不良，因此它们的有益作用取决于个体的结肠菌群。在拟议的研究中，从苹果加工废料中分离的聚合物原花青素将利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其结构、安全性和有益的生理功能为特征。了解苹果原花青素益生菌代谢产物的抗氧化、抗炎、抗癌等多效性对人体健康有益作用的分子机制，对促进未来慢性疾病的治疗具有重要意义。高素质人才（HQP）将在水果中存在的生物活性化合物的营养代谢组学的跨学科新兴领域进行培训。***本研究计划的总体目标是阐明水果黄酮类化合物及其代谢产物与特定生理功能的作用机制。通过这项研究项目产生的新知识将有助于开发以类黄酮为基础的功能性食品和营养保健品，从而降低人类慢性疾病的风险。研究结果将极大地推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元与益生菌一起开发，以引入新的癌症预防功能食品。新形成的原花青素有效代谢产物可作为抗癌药物的候选物。因此，未充分利用的苹果加工废料可以转化为食品成分和营养药品的宝贵来源，反过来，这些可能有助于减少与我们社会中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.