Isolation & Evaluation of Anticarcinogenic Glucosinolate

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• 批准号: 6895837
• 负责人: PAUL TALALAY
• 金额: $ 36.38万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6895837
• 关键词: NAD(H) phosphate; antineoplastics; cancer prevention; carcinogenesis; clinical research; dietary supplements; enzyme induction /repression; food; genetically modified animals; glucuronosyltransferase; glutathione transferase; high performance liquid chromatography; human subject; isothiocyanates; laboratory mouse; laboratory rat; medicinal plants; metabolism; neoplasm /cancer nutrition therapy; nutrition aspect of cancer; nutrition related tag; pharmacokinetics; phenols; plant extracts; quinones

DESCRIPTION (provided by applicant): Induction of cellular Phase 2 enzymes (e.g.,glutathione transferases, glucuronosyltransferases, NAD(P)H:quinone oxidoreductase) and elevation of glutathione levels are now recognized as effective strategies for reducing the risk of developing neoplasms caused by electrophilic carcinogens and reactive forms of oxygen. Transcriptional activation of the genes of Phase 2 enzymes is evoked by nine classes of chemical agents, many of which are present in edible plants and already widely consumed in our diets (isothiocyanates, phenols, quinones, phenylpropenoids, Michael reaction acceptors). The ultimate goals are to identify dietary Phase 2 enzyme inducers with low toxicity and consequently suitable for rapid evaluation of efficacy and long-term use in humans. This project focuses on a detailed evaluation of novel glucosinolates (the stable biological precursors of isothiocyanates) which are widely consumed and recognized as potentially valuable protectors against carcinogenesis. Aim 1 is designed to identify edible plants that contain substantial quantities of glucosinolates with structural features that have been previously shown to result in high inducer potency; and to isolate, crystallize, and characterize these glucosinolates in adequate quantities for biological evaluation in cells and animals. Aim 2 proposes the isolation and detailed characterization of an unusual rhamnosyloxybenzyl glucosinolate (whose corresponding isothiocyanate is an exceedingly potent Phase 2 inducer) that is abundant in all parts of the pantropical, totally edible, and widely consumed drumstick tree (Moringa oleifera). Related multiply glycosylated glucosinolates will also be isolated from various Moringa species, examined for inducer activity, and assessed for inhibition of carcinogenesis in appropriate cell and animal models. Aim 3 will establish in healthy volunteers the absorption, pharmacokinetics, metabolism and excretion of carefully characterized plant extracts containing glucosinolates of special interest, beginning with the rhamnosyloxybenzyl glucosinolate and its cognate isothiocyanate. These pharmacokinetic studies will set the stage for the development of safe and effective dietary chemoprotectors for human use.

描述（由申请人提供）：细胞相2酶的诱导（例如，谷胱甘肽转移酶，葡萄糖醛酸糖基转移酶，NAD（P）H：喹酮氧化还原酶）和谷胱甘肽水平的升高被认为是减少由电卵形产生的纳波氏菌的风险和反应性carcc carcc carcc carcricenogensgemenogensogensge and carcc carcricenogensge and Reative carcc carc的有效策略。九类化学剂唤起了2期酶基因的转录激活，其中许多是可食用植物中存在的，并且已经在我们的饮食中广泛消耗（异硫氰酸酯，苯酚，奎因酮，苯基丙烯类动物，迈克尔反应受体）。最终目标是确定饮食中2期诱导剂低毒性，因此适合快速评估人类的疗效和长期使用。该项目着重于对新型葡萄糖醇（异硫氰酸盐的稳定生物学前体）的详细评估，该评估被广泛消耗并被认为是潜在的有价值的保护者，以防止致癌作用。 AIM 1旨在识别含有大量葡萄糖醇的可食用植物，其结构特征先前已显示出高诱导剂的效力。并分离，结晶和表征这些葡萄糖醇的足够量，以用于细胞和动物的生物学评估。 AIM 2提出了不寻常的鼠李糖氧苯甲酰糖苷（其相应的异硫氰酸盐是一种极有效的2期诱导剂）的隔离和详细表征，在泛型的所有部分，完全可食用，完全可食用，且广泛消耗的drumstick Tree（Moringa oleifera）。相关的多糖基化葡萄糖醇也将从各种辣木物种中分离出来，检查是否有诱导者活性，并评估适当的细胞和动物模型中癌变的抑制。 AIM 3将在健康志愿者中建立，以鼠注羟苯甲酰氧基葡萄糖苷及其同源性异硫代异硫代盐的含量开始，在含有特殊兴趣的葡萄糖醇的精心表征的植物提取物中的吸收，药代动力学，代谢和排泄。这些药代动力学研究将为开发安全有效的饮食化学保护剂奠定阶段。