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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

基本信息

批准号：
8148074
负责人：
Shengmin Sang
金额：
$ 12.6万
依托单位：
NORTH CAROLINA AGRI & TECH ST UNIV
依托单位国家：
美国
项目类别：
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/8148074
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

项目摘要

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.

项目描述（申请人提供）：本项目旨在研究生姜提取物及其主要成分[6]-姜辣素和[6]-姜辣素的生物活性，开发一种具有高水平姜辣素（GEHS）的生姜提取物作为肺癌预防剂。姜是一种叫姜的植物的根茎，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、抗炎和抗肿瘤的作用而受到广泛关注。姜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。姜还含有姜酚同系物，这些同系物是在储存或热加工过程中由相应的姜酚脱水形成的。在新鲜姜中，很少能检测到shogaols。而在干姜中，在某些制剂中，shogaol的含量甚至可能高于姜辣素。大多数研究者认为姜辣素是一种活性成分，而对大屠杀的关注较少。我们最近的研究结果表明，[6]-姜辣素对肺癌和结肠癌细胞系的生长抑制活性比[6]-姜辣素高约10倍。我们的假设是，shogaols可能是姜制剂的主要活性成分，GEHS具有比其他姜提取物更强的防癌作用。具体目标是：1。制备GEHS制剂，研究小鼠给药后[6]-shogaol和[6]-姜辣素的生物利用度和生物转化，并确定GEHS在小鼠体内的最佳剂量。2. 测定GEHS、鲜姜提取物（EFG）以及[6]- shogaol和[6]-gingerol对4-（甲基亚硝胺）-1-（3-吡啶基）-1-丁酮（NNK）诱导的a /J小鼠肺癌模型的抑制作用。我们相信该项目的研究结果将为研究生姜提取物中关键的抗癌活性成分提供基础信息。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临床前和临床研究。