The collective bioactivity of dietary flavonoids: importance of specific structural characteristics for cardiovascular benefits

膳食黄酮类化合物的集体生物活性：特定结构特征对心血管益处的重要性

• 批准号: BB/I005943/1
• 负责人: Nigel Botting
• 金额: $ 12.18万
• 依托单位: University of St Andrews
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2011
• 资助国家: 英国
• 起止时间: 2011 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FI005943%2F1
• 关键词: collective; bioactivity; dietary; flavonoids; importance

A high intake of fruits and vegetables reduces heart disease risk, but the components of the fruits and vegetables that provide these protective effects remains unclear. Growing evidence supports a role of fruit and vegetable components called flavonoids and research shows that people who consume high intakes of flavonoid-rich foods have improved cardiovascular health. In particular, research shows that some flavonoids and flavonoid-rich foods exert direct protective effects on blood vessel walls, and since cardiovascular diseases (CVD) and specifically stiffness of the arteries results from accumulated damage to blood vessel walls, these data suggest that flavonoids can help restore and optimise vessel function; therefore reducing CVD risk. When researchers measure the amount of any one type of flavonoid in the blood after we eat flavonoid-rich foods, their levels are too low to explain the observed cardiovascular benefit. Therefore, it is likely that the health benefits of flavonoid consumption results from the collective effects of consuming multiple types of flavonoids at the same time. We therefore believe that the health benefits resulting from flavonoid consumption must be the result of many different types of flavonoids working together, as happens when we eat them in our normal diet. Complex combinations of flavonoids are found in our blood and vessels as a result of the consumption of a diversity of flavonoid-rich foods, such as fruits, vegetables, chocolate, juice, wine, and tea. However, although we know that flavonoids are consumed as mixtures of compounds, to date, researchers have studied their impacts in isolation and using levels of flavonoids that are well above that which could be obtained through eating a normal diet. These existing findings are therefore likely to be inaccurate, making it difficult to use these findings to provide dietary advice for the health benefits of flavonoid consumption. We plan to study the cardiovascular benefits of consuming multiple flavonoids as would be consumed in the normal UK diet to provide more accurate data which could be used in the future to provide advice on the true health benefits of flavonoid consumption. Aims and objectives: We aim to use an advanced cell culture model involving both vascular and immune cells to establish if the beneficial effects of flavonoids on cardiovascular health are the result of many types of flavonoid working together. We will also apply flavonoids and their metabolites in both isolation and in combination to provide a more biologically realistic model. These studies will explore the activities of the flavonoids found in the highest abundance in the present UK diet as established using survey data from the National Diet and Nutrition Survey. As this survey established the current UK consumption of fruits and vegetables to be around 3 portions per day on average (and 2 portions below recommended intake levels), we will test the effects of consuming doses relative to 3, 5 and 7 servings of fruits and vegetables per day. Implications: This proposal promotes a nutritional strategy to improve cardiovascular health using a 'natural' dietary approach, involving flavonoids from multiple food sources which hold strong industrial, agricultural and public relevance. This project will provide evidence of the health impact of our current dietary consumption of flavonoid-rich foods, in relation to reaching optimal levels of 5-a-day and above; and will aid in the design of future feeding interventions directed at addressing dietary change in the UK for health benefit. This project will also provide 'proof of concept' for the design of future flavonoid intervention trials by establishing optimal cardiovascular endpoints, flavonoids and doses. Lastly, establishing a shared and cumulative bioactivity of a number of flavonoids will aid in establishing future functional health claims for many products high in flavonoids.

大量摄入水果和蔬菜可降低心脏病风险，但提供这些保护作用的水果和蔬菜成分仍不清楚。越来越多的证据支持水果和蔬菜成分黄酮类化合物的作用，研究表明，摄入大量富含黄酮类化合物的食物的人可以改善心血管健康。特别是，研究表明，一些黄酮类化合物和富含黄酮类化合物的食物对血管壁产生直接的保护作用，由于心血管疾病（CVD），特别是动脉僵硬是血管壁累积损伤的结果，这些数据表明黄酮类化合物可以帮助恢复和优化血管功能;因此降低CVD风险。当研究人员测量我们吃富含类黄酮的食物后血液中任何一种类黄酮的含量时，它们的水平太低，无法解释观察到的心血管益处。因此，食用类黄酮的健康益处很可能是由于同时食用多种类型的类黄酮的集体效应。因此，我们认为，食用类黄酮对健康的益处必须是许多不同类型的类黄酮共同作用的结果，就像我们在正常饮食中食用它们一样。由于食用了各种富含类黄酮的食物，如水果、蔬菜、巧克力、果汁、葡萄酒和茶，在我们的血液和血管中发现了类黄酮的复杂组合。然而，尽管我们知道类黄酮是作为化合物的混合物被消耗的，但到目前为止，研究人员已经研究了它们的影响，并使用了远高于通过正常饮食获得的类黄酮水平。因此，这些现有的研究结果可能是不准确的，因此很难使用这些研究结果来提供关于类黄酮消费的健康益处的饮食建议。我们计划研究食用多种黄酮类化合物的心血管益处，就像在正常的英国饮食中食用的那样，以提供更准确的数据，这些数据可以在未来用于为黄酮类化合物消费的真正健康益处提供建议。目的和目标：我们的目标是使用涉及血管和免疫细胞的先进细胞培养模型来确定类黄酮对心血管健康的有益作用是否是多种类黄酮共同作用的结果。我们还将应用黄酮类化合物及其代谢产物的分离和组合，以提供一个更生物现实的模型。这些研究将探索目前英国饮食中含量最高的类黄酮的活动，这些活动是使用国家饮食和营养调查的调查数据建立的。由于这项调查确定了目前英国水果和蔬菜的消费量平均每天约为3份（低于推荐摄入量2份），我们将测试相对于每天3份，5份和7份水果和蔬菜的消费剂量的影响。含义：该提案促进了一种营养策略，使用“天然”饮食方法改善心血管健康，涉及来自多种食物来源的黄酮类化合物，这些食物来源具有很强的工业，农业和公共相关性。该项目将提供证据证明我们目前膳食中富含类黄酮的食物对健康的影响，达到每天5种及以上的最佳水平;并将有助于设计未来的喂养干预措施，旨在解决英国的饮食变化，以促进健康。该项目还将通过建立最佳心血管终点、黄酮类化合物和剂量，为未来黄酮类化合物干预试验的设计提供“概念验证”。最后，建立一个共享的和累积的生物活性的类黄酮类化合物的数量将有助于建立未来的功能性健康索赔的许多产品高类黄酮。

项目成果

Common Phenolic Metabolites of Flavonoids, but Not Their Unmetabolized Precursors, Reduce the Secretion of Vascular Cellular Adhesion Molecules by Human Endothelial Cells.

• DOI: 10.3945/jn.115.217943
• 发表时间: 2016-03
• 期刊: The Journal of nutrition
• 作者: Warner EF;Zhang Q;Raheem KS;O'Hagan D;O'Connell MA;Kay CD
• 通讯作者: Kay CD

Anthocyanins and their physiologically relevant metabolites alter the expression of IL-6 and VCAM-1 in CD40L and oxidized LDL challenged vascular endothelial cells.

花青素及其与生理相关的代谢产物改变了CD40L中IL-6和VCAM-1的表达，并氧化了LDL挑战血管内皮细胞。

• DOI: 10.1002/mnfr.201400803
• 发表时间: 2015-06
• 期刊: Molecular nutrition & food research
• 影响因子: 5.2
• 作者: Amin HP;Czank C;Raheem S;Zhang Q;Botting NP;Cassidy A;Kay CD
• 通讯作者: Kay CD