Cellular Mechanisms Implicated in the Action of Neuroprotective Nutraceuticals

神经保护保健品作用中涉及的细胞机制

• 批准号: RGPIN-2015-04321
• 负责人: Martinoli, MariaGrazia
• 金额: $ 2.77万
• 依托单位: Université du Québec à Trois-Rivières
• 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=612897
• 关键词: Cellular; Mechanisms; Implicated; Action; Neuroprotective

My research program aims to elucidate the cellular mechanisms and pathways implicated in the action of neuroprotective nutraceuticals, specifically plant-derived molecules (phytochemicals). Nutraceuticals are products that range from isolated nutrients, dietary supplements and herbal molecules possessing beneficial physiological properties. An abundant amount of literature is currently proposing a positive effect for these natural molecules in human and animal health. However, in most cases, their alleged pleiotropic beneficial effects have not yet been accurately documented. In this context, my laboratory analyses the role of several phytochemicals in opposing neurodegeneration and neuroinflammation induced by neurotoxins or high glucose administration, in established cellular paradigms and animal models. We are specifically interested in defining the specific cellular mechanisms and pathways used by neuroprotective and anti-inflammatory phytochemicals. Recently, we demonstrated that plant derived molecules such as quercetin, cucurbitacins and sesamin possess multiple cellular properties that go beyond their anti-oxidation action generally known, but also extend to the reduction of both apoptosis and neuroinflammation. Based on our knowledge of natural compounds, for the next five years, I propose to elucidate the cellular mechanisms and pathways implicated in the action of neuroprotective phytochemicals. For this we will focus on three specific aims: 1. To define the cellular neuroprotective mechanisms of individual phytochemicals. 2. To define the cellular mechanisms by which mixtures of phytochemicals prevent neuroinflammation, in vitro. 3. To define the effects of phytochemical mixtures on neuroinflammation, in vivo. Our focus will shift from considering phytochemicals simply as antioxidants to describing them as potentially multi-targeting molecules with particular interest to their anti-inflammatory effects in a neuronal environment. In addition, we will investigate how mixtures of phytochemicals modulate multiple cellular pathways at different levels. Indeed, preliminary results in our laboratory show the use of combinations of phytochemicals to have a synergistic effect on parameters of neuroprotection. Thus my research program will test whether natural compounds, alone or in combination, reduce neurodegeneration and neuroinflammation thus promoting neuroprotection. We will use glia-neuron co-cultures, a reliable system which maintains two cell populations in separate compartments but at very close proximity, and an in vivo model of neuroinflammation, rodents fed with a high-fat diet. This novel research program is expected to yield long-awaited data describing the cellular impact of key phytochemicals in cell nerve homeostasis.

我的研究项目旨在阐明神经保护性营养品，特别是植物源性分子（植物化学物质）的作用所涉及的细胞机制和途径。营养保健品是具有有益生理特性的产品，包括分离的营养素、膳食补充剂和草药分子。大量的文献目前提出了这些天然分子对人类和动物健康的积极影响。然而，在大多数情况下，其所谓的多效性有益作用尚未得到准确的记录。在这种情况下，我的实验室分析了几种植物化学物质在对抗神经毒素或高葡萄糖管理诱导的神经变性和神经炎症中的作用，在建立的细胞范例和动物模型中。我们特别感兴趣的是确定神经保护和抗炎植物化学物质所使用的特定细胞机制和途径。最近，我们证明了植物衍生的分子，如槲皮素，葫芦素和芝麻素具有多种细胞特性，超出了他们的抗氧化作用一般已知的，但也扩展到减少细胞凋亡和神经炎症。基于我们对天然化合物的了解，在接下来的五年里，我建议阐明神经保护植物化学物质作用中所涉及的细胞机制和途径。为此，我们将重点关注三个具体目标： 1.明确植物化学物质的细胞神经保护机制。 2.确定植物化学物质混合物在体外预防神经炎症的细胞机制。 3.确定植物化学混合物在体内对神经炎症的影响。 我们的重点将从简单地将植物化学物质视为抗氧化剂转移到将它们描述为潜在的多靶向分子，特别关注它们在神经元环境中的抗炎作用。此外，我们将研究植物化学物质的混合物如何在不同水平上调节多种细胞途径。事实上，我们实验室的初步结果显示，使用植物化学物质的组合对神经保护的参数具有协同作用。因此，我的研究计划将测试天然化合物，单独或组合，是否减少神经变性和神经炎症，从而促进神经保护。我们将使用神经胶质-神经元共培养物，这是一种可靠的系统，它将两个细胞群保持在不同的隔室中，但非常接近，以及一种体内神经炎症模型，用高脂肪饮食喂养啮齿动物。这项新的研究计划有望产生期待已久的数据，描述关键植物化学物质对细胞神经稳态的影响。