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: 7529090
• 负责人: Shengmin Sang
• 金额: $ 14.07万
• 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 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7529090
• 关键词: 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-Butanone; 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; End Point; 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; Numbers; Plants; Plasma; Preparation; Preventive; Process; Property; Public Health; Purpose; Research Personnel; Rhizome; Sampling; Series; Spices; Standardization; Structure of parenchyma of lung; Time; Tissues; Tobacco-Associated Carcinogen; Urine; adenoma; base; colon cancer cell line; gingerol; improved; liquid chromatography mass spectrometry; lung cancer prevention; lung carcinogenesis; oleoresins; pre-clinical; research study; response; shogaol; size; 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）：本项目的目的是研究生姜提取物及其关键成分[6]-姜辣素和[6]-姜烯酚的生物活性，并开发具有高水平姜烯酚的生姜提取物（GEHS）作为肺癌预防剂。姜，植物姜的根茎，自古以来就被用作中国，印度和阿拉伯国家的草药。近年来，生姜因其抗氧化、抗炎、抗肿瘤等活性而受到广泛关注。生姜中的主要成分是一系列辛辣的油树脂成分，称为姜辣素，其中[6]-姜辣素是主要成分。姜还含有姜烯酚同系物，其在储存或热加工期间通过相应姜辣素的脱水形成。在新鲜的生姜中，可以检测到很少的姜烯酚。而在干姜中，姜烯酚的含量甚至可以高于某些制剂中的姜辣素。大多数研究人员认为姜辣素是有效成分，而对姜烯酚的关注很少。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（约10倍）比[6]-姜辣素。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预防癌症作用。具体目标是：1.为了开发GEHS制剂，研究给予小鼠GEHS后[6]-姜烯酚和[6]-姜辣素的生物利用度和生物转化，并找到GEHS用于小鼠研究的最佳剂量。2.目的：研究生姜提取物（EFG）、姜烯酚（6- shogaol）和姜辣素（6-gingerol）对4-（甲基亚硝胺）-1-（3-吡啶基）-1-丁酮（NNK）诱发的A/J小鼠肺癌的抑制作用。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。标准化和更有效的生姜提取物制剂的开发将促进生姜提取物健康益处的未来临床前和临床研究。 公共卫生相关性：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，目前还不清楚生姜中主要的活性抗肿瘤成分是什么。生姜中的主要成分是一系列辛辣的油树脂成分，称为姜辣素，其中[6]-姜辣素是主要成分。而在干姜中，姜酚（姜辣素在热加工过程中的脱水产物）是主要成分。在某些制剂中，它们的含量甚至高于姜辣素。大多数研究人员认为姜辣素是有效成分，而对姜烯酚的关注很少。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]-姜辣素更强。在这个项目中，我们将开发和标准化生姜提取物与高水平的姜烯酚（GEHS），并研究生物利用度和生物转化的[6]-姜烯酚和[6]-姜辣素在GEHS相比，该化合物单独给药小鼠。此外，我们将确定GEHS和生姜提取物以及[6]-姜烯酚和[6]-姜辣素在A/J小鼠NNK诱导的肺癌发生模型中的抑制活性。NNK（4-（Methylnitrosamino）-1-（3-pyridyl）-1-butanone）是一种烟草致癌物，该模型与人类肺癌形成高度相关。这些研究的结果将有可能1）开发有效预防肺癌的生姜提取物的最佳制备工艺; 2）为旨在进行化学预防健康声明的生姜补充剂的标准化提供科学依据; 3）确定姜烯酚和姜辣素的血浆和组织水平，为理解化学预防效果提供基础;以及4）通过使用标准化提取物和开发食用生姜产品的暴露生物标志物来提高未来关于化学预防效果的临床试验的质量。