Ginger Extract: Bioavailability Study and Lung Cancer Preventive Effect

生姜提取物：生物利用度研究和肺癌预防作用

• 批准号: 7672542
• 负责人: Shengmin Sang
• 金额: $ 4.66万
• 依托单位: NORTH CAROLINA CENTRAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7672542
• 关键词: A/J Mouse; Abbreviations; Anti-Inflammatory Agents; Anti-inflammatory; Antioxidants; Apoptosis; Attention; Biological; Biological Availability; Biological Markers; Butanones; Cell Proliferation; Chemoprevention; Chemopreventive Agent; China; Chinese People; Clinical Research; Clinical Trials; Comparative Study; Consumption; Country; Dehydration; Development; Diet; Dose; Epigallocatechin Gallate; Future; Ginger; Ginger extract; Growth; Health; Health Benefit; Herbal Medicine; Homologous Gene; Human; India; Lung; Lung Neoplasms; Malignant Neoplasms; Malignant neoplasm of lung; Medicine; Metabolic Biotransformation; Metabolism; Modeling; Mus; Nitric Oxide; Plants; Plasma; Preparation; Preventive; Process; Property; Research Personnel; Rhizome; Sampling; Series; Spices; Standardization; Structure of parenchyma of lung; Time; Tissues; Tobacco-Associated Carcinogen; Urine; adenoma; base; colon cancer cell line; improved; liquid chromatography mass spectrometry; lung cancer prevention; lung carcinogenesis; oleoresins; pre-clinical; public health relevance; research study; response; shogaol; tumor

DESCRIPTION (provided by applicant): The objective of this project is to study the biological activities of ginger extract and its key constituents, [6]-gingerol and [6]-shogaol, and develop a ginger extract with high level of shogaols (GEHS) as a lung cancer preventive agent. Ginger, the rhizome of the plant Zingiber officinale, has been used as a herbal medicine in China, India, and Arabic countries since ancient times. Recently, ginger has received extensive attention due to its anti-oxidant, anti-inflammatory, and anti-tumor activities. The main principles in ginger are the series of pungent oleoresin constituents known as gingerols, with [6]-gingerol being the major component. Ginger also contains shogaol homologues that are formed by dehydration of corresponding gingerols during storage or thermal processing. In fresh ginger, very little shogaols can be detected. Whereas in dried ginger, the levels of shogaols can be even higher than gingerols in some preparations. Most researchers have considered gingerols as the active principles and have paid little attention to shogaols. Our recent results showed that [6]- shogaol has greater growth inhibitory activity (about 10 fold) on lung and colon cancer cell lines than [6]- gingerol. Our hypothesis is that shogaols can be the major active constituents of ginger preparations and GEHS has stronger cancer preventive effect than other ginger extracts. The specific aims are: 1. To develop a GEHS preparation, study the bioavailability and biotransformation of [6]-shogaol and [6]-gingerol after administration of GEHS to mice, and find the optimal doses of GEHS for studies in mice. 2. To determine the inhibitory activities of GEHS and extract from fresh ginger (EFG) as well as [6]- shogaol and [6]-gingerol in a 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung carcinogenesis model in A/J mice. We believe that results from this project will provide the basic information on key active cancer preventive constituents in ginger extracts. The development of a standardized and a more active ginger extract preparation will facilitate future pre-clinical and clinical studies on the health benefit of ginger extracts. PUBLIC HEALTH RELEVANCE: Ginger has been cultivated for thousands of years as a spice and for medicinal purposes. Recent studies have shown that ginger has antioxidant, anti-inflammatory, and anti-tumor activities. However, it is unclear what the major active anti-tumor components in ginger are. The main principles in fresh ginger are the series of pungent oleoresin constituents known as gingerols, with [6]-gingerol being the major component. Whereas in dried ginger, shogaols, the dehydration products of gingerols during thermal processing, are predominant components. Their levels can be even higher than gingerols in some preparations. Most researchers have considered gingerols as the active principles and have paid little attention to shogaols. Our recent results showed that [6]-shogaol has greater growth inhibitory activity on lung and colon cancer cell lines than [6]-gingerol. In this project, we will develop and standardize ginger extract with high levels of shogaols (GEHS), and study the bioavailability and biotransformation of [6]-shogaol and [6]-gingerol in GEHS in comparison to that of the compound administered alone in mice. Furthermore, we will determine the inhibitory activities of GEHS and extract from fresh ginger, as well as [6]-shogaol and [6]-gingerol in a NNK-induced lung carcinogenesis model in A/J mice. NNK (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone) is a tobacco carcinogen, and this model is highly relevant to human lung cancer formation. Results from these studies will make it possible to 1) develop an optimal preparation process of ginger extract that will be effective in the prevention of lung cancer; 2) provide a scientific basis for standardization of ginger supplements aim to make chemoprevention health claims; 3) determine the plasma and tissue levels of shogaols and gingerols which provide basis for understanding the chemopreventive effects; and 4) improve the quality of future clinical trials on chemopreventive effect through use of standardized extracts and the development of exposure biomarkers for the consumption of ginger products.

描述（由申请人提供）：该项目的目的是研究生姜提取物及其关键成分的生物学活性[6] - 吉果和[6] -shogaol，并开发具有高水平的Shogaols（GEHS）的生姜提取物作为肺癌预防剂。 Ginger是植物Zingiber Officinale的根茎，自远古时代以来，在中国，印度和阿拉伯国家就被用作草药医学。最近，由于其抗氧化剂，抗炎和抗肿瘤活性，Ginger受到了广泛的关注。生姜中的主要原理是一系列刺激性油素成分，称为姜醇，[6] - 果胶是主要成分。生姜还包含shogaol同源物，这些同源物是在储存或热加工过程中相应的姜醇脱水而形成的。在新鲜的生姜中，几乎没有发现的shogaols。而在干燥的生姜中，在某些制剂中，shogaol的水平甚至比生姜高。大多数研究人员都将生姜视为活跃原则，几乎不关注Shogaols。我们最近的结果表明，[6] - shogaol在肺和结肠癌细胞系上的生长抑制活性（约10倍）比[6] -gingerol具有更大的生长抑制活性（约10倍）。我们的假设是，Shogaols可以是生姜制剂的主要活性成分，而GEHS比其他姜提取物具有更强的癌症预防作用。具体目的是：1。要开发GEHS制备，研究[6] -shogaol的生物利用度和生物转化，在给小鼠施用GEHS后[6] -shogaol和[6] - 吉果，并找到用于小鼠研究的GEHS的最佳剂量。 2。确定GEHS的抑制作用，并从新鲜生姜（EFG）以及[6] - Shogaol和[6] - 果仁酚中提取4-（甲基硝基氨基氨基）-1-（3-吡啶基）-1-丁烷（NNK）诱导的肺癌发生模型。我们认为，该项目的结果将提供有关姜提取物中关键活跃癌症预防成分的基本信息。标准化和更活跃的生姜提取物制备的发展将促进有关生姜提取物健康益处的未来临床和临床研究。 公共卫生相关性：生姜已经作为香料和药用目的种植了数千年。最近的研究表明，生姜具有抗氧化剂，抗炎和抗肿瘤活性。但是，目前尚不清楚生姜中主要的主要活性抗肿瘤成分是什么。新鲜生姜的主要原理是一系列刺激性油脂素成分，称为姜醇，[6] - 果胶是主要成分。在干燥的姜中，shogaols，在热加工过程中生姜的脱水产物是主要成分。在某些制剂中，它们的水平甚至可能高于生姜。大多数研究人员都将生姜视为活跃原则，几乎不关注Shogaols。我们最近的结果表明，与[6] - 果仁醇相比，[6] - 肖戈尔对肺和结肠癌细胞系具有更大的抑制活性。在这个项目中，我们将使用高水平的shogaols（GEHS）开发和标准化姜提取物，并研究[6] -shogaol和[6] gyerol的生物利用度和生物转化与与小鼠中单独使用的化合物相比。此外，我们将在A/J小鼠中NNK诱导的肺癌发生模型中确定GEHS的抑制作用，以及来自新鲜生姜的抑制作用，以及[6] -shogaol和[6] gyerol的抑制作用。 NNK（4-（甲基硝基氨基氨基）-1-（3-吡啶基）-1-丁酮）是烟草致癌物，该模型与人类肺癌形成高度相关。这些研究的结果将使1）开发出有效预防肺癌的生姜提取物的最佳制备过程； 2）为姜补充剂的标准化提供了科学基础，旨在提出化学预防健康主张； 3）确定Shogaols和Gingerols的血浆和组织水平，这些水平为理解化学预防作用提供了基础； 4）通过使用标准化提取物以及开发姜产品的曝光生物标志物来提高未来临床试验的临床试验质量。