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: 8069090
• 负责人: Shengmin Sang
• 金额: $ 9.42万
• 依托单位: NORTH CAROLINA AGRI & TECH ST UNIV
• 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 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8069090
• 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（申请人提供）：本项目的目的是研究生姜提取物及其关键成分[6]-姜酚和[6]-姜烯酚的生物活性，并开发一种高含量姜烯酚的生姜提取物（GEHS） ）作为肺癌预防剂。生姜是植物姜（Zingiber officinale）的根茎，自古以来在中国、印度和阿拉伯国家就被用作草药。近年来，生姜因其抗氧化、抗炎和抗肿瘤活性而受到广泛关注。生姜的主要成分是一系列辛辣的油树脂成分，称为姜酚，其中[6]-姜酚是主要成分。生姜还含有姜烯酚同系物，其是由相应的姜辣素在储存或热处理过程中脱水形成的。在新鲜生姜中，可以检测到很少量的姜烯酚。而在干姜中，姜烯酚的含量甚至比某些制剂中的姜酚含量还要高。大多数研究人员认为姜辣素是有效成分，而很少关注姜烯酚。我们最近的研究结果表明，[6]-姜烯酚对肺癌和结肠癌细胞系的生长抑制活性比[6]-姜酚更强（约10倍）。我们的假设是姜烯酚可能是生姜制剂的主要活性成分，并且GEHS比其他生姜提取物具有更强的癌症预防作用。具体目标是： 1.开发GEHS制剂，研究小鼠给予GEHS后[6]-姜烯酚和[6]-姜酚的生物利用度和生物转化，寻找GEHS在小鼠研究中的最佳剂量。 2. 测定GEHS和鲜姜提取物(EFG)以及[6]-姜烯酚和[6]-姜酚在4-(甲基亚硝基氨基)-1-(3-吡啶基)-1-丁酮中的抑制活性(NNK) 诱导的 A/J 小鼠肺癌模型。我们相信，该项目的结果将提供生姜提取物中关键活性癌症预防成分的基本信息。标准化和更活性的生姜提取物制剂的开发将有助于未来关于生姜提取物的健康益处的临床前和临床研究。 公共健康相关性：生姜作为香料和药用目的已经种植了数千年。最近的研究表明生姜具有抗氧化、抗炎和抗肿瘤活性。然而，目前尚不清楚生姜中主要的抗肿瘤活性成分是什么。新鲜生姜的主要成分是一系列辛辣的油树脂成分，称为姜酚，其中[6]-姜酚是主要成分。而在干姜中，姜烯酚（姜辣素在热处理过程中的脱水产物）是主要成分。在某些制剂中，它们的含量甚至比姜辣素还要高。大多数研究人员认为姜辣素是有效成分，而很少关注姜烯酚。我们最近的结果表明，[6]-姜烯酚对肺癌和结肠癌细胞系比[6]-姜酚具有更强的生长抑制活性。在这个项目中，我们将开发和标准化高含量姜烯酚 (GEHS) 的生姜提取物，并研究 GEHS 中 [6]-姜烯酚和 [6]-姜酚的生物利用度和生物转化，并与单独施用的化合物进行比较。老鼠。此外，我们将在 A/J 小鼠 NNK 诱导的肺癌模型中测定 GEHS 和新鲜生姜提取物以及 [6]-姜烯酚和 [6]-姜酚的抑制活性。 NNK（4-（甲基亚硝基氨基）-1-（3-吡啶基）-1-丁酮）是一种烟草致癌物质，该模型与人类肺癌的形成高度相关。这些研究的结果将使以下成为可能：1）开发出有效预防肺癌的生姜提取物的最佳制备工艺； 2）为生姜补充剂的标准化提供科学依据，旨在做出化学预防健康主张； 3）测定血浆和组织中姜烯酚和姜辣素的水平，为了解化学预防作用提供基础； 4) 通过使用标准化提取物和开发生姜产品消费的暴露生物标志物，提高未来化学预防效果临床试验的质量。