Identification of bioactive compounds from tef (Eragrostis tef) seed extracts for antioxidant properties.

总结 细胞氧化应激是包括糖尿病在内的几种人类疾病的危险因素， 心血管疾病（CVD）和癌症。天然和食品产品具有很大的潜力， 在氧化应激条件下保护细胞画眉草（Eragrostis tef）是一种无麸质谷物， 矿物质营养素、必需氨基酸、水溶性维生素和几种生物活性物质 植物化学物质包括多酚、类黄酮和多不饱和脂肪酸（PUFA）。TEF 已被美国国家研究理事会认定为具有优良营养价值的作物。 提高粮食安全的潜力和适宜性。然而，tef植物化学物质的生物活性具有 从未使用生理学相关模型进行过研究。在这项研究中，我们建议确定 生物活性化合物，并测试其对抗氧化应激的能力，从而防止 与活性氧（ROS）诱导的损伤相关的致病条件。这 该倡议是基于我们最近的发现，表明：1）茶籽提取物增加谷胱甘肽 (GSH)THP-1单核细胞中GSH水平的增加，2）棕色细胞中GSH水平的增加比 象牙tef种子，这表明生物活性物质的含量存在基因型变异， TEF种子提取物增加抗氧化剂主调节因子的表达 途径核因子红细胞2相关因子2（Nrf 2）及其靶点，包括血红素 加氧酶1（HO-1）、NAD（P）H醌氧化还原酶1（NQO 1）、谷胱甘肽还原酶（GR） 和γ-谷氨酸半胱氨酸连接酶催化（GCLC）和调节（GCLM）亚基，其发挥作用。 在GSH生物合成中起关键作用，4）茶黄素提取物的生物活性级分含有亚油酸衍生物 酸（LA）9-羟基十八碳二烯酸（9-HODE），是膜脂质的标志物 过氧化作用这些发现促使我们假设tef具有生物活性化合物， 在氧化应激条件下有可能通过以下途径促进抗氧化途径： NRF 2信号。本研究的主要目的是：1）生物活性物质的鉴定和功能表征 2）研究茶黄素生物活性化合物是否诱导氧化还原， 应激反应基因，并保护细胞免受ROS，3）了解遗传机制 调节TEF的抗氧化性能。这项研究将有助于开发替代药物， 氧化应激引起的疾病。它还将产生新的信息，可用于 或转移到主要谷物中，以增加这些作物的价值。这笔资金将推动 Osena实验室有能力探索未充分利用的作物，如谷子，以获得理想的性状 包括健康福利。奥塞纳实验室和格林斯伯勒格林斯伯勒的环境是 非常适合这项研究，并培训来自代表性不足的少数群体的学生。

Summary Cellular oxidative stress is a risk factor for several human disease including diabetes, cardiovascular diseases (CVD) and cancer. Natural and food products have a great potential to protect cells under oxidative stress conditions. Tef (Eragrostis tef) is gluten-free grain that is rich in mineral nutrients, essential amino acids, and water-soluble vitamins and several bioactive phytochemicals including polyphenols, flavonoids and polyunsaturated fatty acids (PUFAs). Tef has been recognized by the U.S. National Research Council as a crop with excellent nutritional potential and suitability to boost food security. However, the bioactivity of tef phytochemicals have never been studied using physiologically relevant models. In this study, we propose to identify bioactive compounds in tef grains and test their ability to combat oxidative stress, thus preventing the pathogenic conditions associated with reactive oxygen species (ROS)-induced damages. This initiative is based on our recent finding indicating that: 1) tef seed extracts increase glutathione (GSH) levels in THP-1 monocytes, 2) an increase in GSH level is more prominent in brown than ivory tef seeds, suggesting the existence of genotypic variability in the content of bioactive compound, 3) Tef seed extracts increase the expression of the master regulator of antioxidant pathway nuclear factor erythroid 2-related factor 2 (Nrf2) and its targets including Heme Oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase1 (NQO1), glutathione reductase (GR) and the γ-glutamate cysteine ligase catalytic (GCLC) and regulatory (GCLM) subunit, which play a key role in GSH biosynthesis, 4) A bioactive fraction of tef extract contains a derivative of linoleic acid (LA) 9-Hydroxyoctadecadienoic acid (9-HODE), which is a marker for membrane lipid peroxidation. These findings prompted us to hypothesize that tef has bioactive compounds which have the potential to boost the antioxidant pathway under oxidative stress conditions likely via Nrf2 signaling. Our aims are: 1) Identification and functional characterization of bioactive phytochemicals from tef seeds, 2) Studying whether tef bioactive compounds induce oxidative stress-responsive genes, and protect cells from ROS, 3) Understanding the genetic mechanism regulating antioxidant properties of tef. This study will help in developing alternative medicines for oxidative stress-induced diseases. It will also generate new information that can be used to improve tef or transferred to major cereals to add value to these crops. This funding will boost the capacity of the Osena laboratory to explore underutilized crops such as millets for desirable traits including health benefits. The Osena laboratory and the environment at UNC Greensboro are ideal for this research, and training students from underrepresented minority group.