Toxicity and Biological Reactivity of Naturally Occurring Polyphenols

天然多酚的毒性和生物反应性

• 批准号: RGPIN-2015-03748
• 负责人: Krol, Edward
• 金额: $ 1.46万
• 依托单位: University of Saskatchewan
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=612541
• 关键词: Toxicity; Biological; Reactivity; Naturally; Occurring

The use of natural product-based remedies to maintain good health or treat disease has been known for centuries, and in recent years the use of natural health products has increased in Canada. Beneficial effects observed with natural health products are the result of the actions of the specific natural products present, unfortunately a great deal remains poorly understood regarding their safety and effectiveness. Our research is aimed at developing a better understanding of how some natural health products work. Specifically, we are investigating the fundamental chemical properties of these natural products, and how they may help us to learn about their health benefits. One research focus is on a group of compounds called lignans. A lignan in flaxseed, secoisolariciresinol (SECO), is associated with improved heart health and cancer treatment, whereas a lignan found in the creosote bush, nordihydroguaiaretic acid (NDGA), has both beneficial effects and also causes liver and kidney toxicity. We have determined that NDGA undergoes reactions to produce a toxic compound as well as a new compound, known as cNDGA, whose properties remain unknown. We are synthesizing new lignans that will allow us to determine what structural factors control the reactions of SECO, NDGA, and cNDGA and how this may influence their function as natural health products. A second research focus is how natural plant products called flavonols protect against damage caused by excess exposure to sunlight. Our goal is to determine whether flavonols possess properties that would make them candidates for topical sunscreens. We have determined the stability of several flavonols when exposed to ultraviolet (UV) radiation and observed these compounds undergo unexpected reactions under these conditions. We are continuing to determine those structural features that help maintain flavonol stability to UV and pH. We have developed a method to measure DNA damage by UV and are using this to assess how the flavonols may provide protection against UV. The information created through this research will be critical to better predict the properties of lignans, flavonols and other natural products and in evaluating the safety and efficacy of natural products.

使用天然产品为基础的补救措施，以保持良好的健康或治疗疾病已被称为几个世纪以来，近年来，使用天然保健产品在加拿大增加。天然保健产品所观察到的有益效果是目前特定天然产品作用的结果，不幸的是，关于其安全性和有效性仍然知之甚少。我们的研究旨在更好地了解一些天然健康产品的工作原理。 具体来说，我们正在研究这些天然产品的基本化学性质，以及它们如何帮助我们了解它们的健康益处。 一个研究重点是一组称为木脂素的化合物。亚麻籽中的木酚素，开环异落叶松树脂酚（SECO），与改善心脏健康和癌症治疗有关，而木酚素在杂酚油灌木中发现，去甲二氢愈创木酸（NDGA），既有有益的效果，也会导致肝脏和肾脏毒性。我们已经确定NDGA经历反应产生一种有毒化合物以及一种新化合物，称为cNDGA，其性质仍然未知。我们正在合成新的木脂素，这将使我们能够确定哪些结构因素控制SECO，NDGA和cNDGA的反应，以及这如何影响它们作为天然健康产品的功能。 第二个研究重点是被称为黄酮醇的天然植物产品如何防止过度暴露于阳光下造成的损害。我们的目标是确定黄酮醇是否具有使其成为局部防晒剂候选者的特性。我们已经确定了几种黄酮醇暴露于紫外线（UV）辐射时的稳定性，并观察到这些化合物在这些条件下发生意想不到的反应。我们正在继续确定那些有助于保持黄酮醇对紫外线和pH值稳定性的结构特征。我们已经开发出一种方法来测量紫外线对DNA的损伤，并利用这种方法来评估黄酮醇如何提供抗紫外线的保护。 通过这项研究创建的信息对于更好地预测木脂素，黄酮醇和其他天然产品的特性以及评估天然产品的安全性和有效性至关重要。