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Garlic: Molecular Regulation of Hepatic Function.

大蒜：肝功能的分子调节。

基本信息

批准号：
7473778
负责人：
CRAIG D FISHER
金额：
$ 0.73万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-29 至 2008-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7473778
关键词：
Antioxidants Bilirubin Binding Biological Assay Blood CYP2B6 gene Carrier Proteins Cell Nucleus Chemicals Cytochrome P450 DNA Digestive System Disorders Electrophoretic Mobility Shift Assay Elements Enzyme Activation Enzyme Gene Enzyme Induction Enzymes Epoxide hydrolase Excretory function Family Fellowship Female Garlic Genes Genetic Transcription Glutathione S-Transferase Goals Hepatic Herb-Drug Interactions Human Hydrolysis Icterus Inbred WKY Rats Individual Liver Messenger RNA Metabolic Molecular Multi-Drug Resistance NAD(P)H dehydrogenase (quinone) 1, human NQO1 gene Names Nuclear Nuclear Hormone Receptors Nuclear Receptors Numbers Organic Anion Transporters Patients Personal Satisfaction Pharmaceutical Preparations Phase Proteins Quinones Rattus Reaction Receptor Activation Regulation Reporting Response Elements Role Signal Transduction Time Transcriptional Activation Transcriptional Regulation UDP-Glucuronosyltransferase 1A1 UGT1A1 gene Up-Regulation Western Blotting Xenobiotics allyl sulfide benzoquinone constitutive androstane receptor cytochrome P-450 CYP2B10 (murine)design diallyl disulfide drug mechanism gene induction heme oxygenase-1 human CYP2B6 protein hydrophilicity in vivo male promoter response uptake

项目摘要

DESCRIPTION (provided by applicant): Garlic and two constituents of garlic, diallyl sulfide (DAS) and diallyl disulfide (DADS), show an ability to regulate transcriptional activity of a number of hepatic enzymes and have the potential to induce herb-drug interactions. Garlic and DAS both cause increased cytochrome P450 (CYP) gene transcription. Garlic and DADS have been shown to increase transcriptional activity of antioxidant enzymes, such as NAD(P)H quinone oxidorecutase (NQO-1), and glutathione S-transferase (GST). While garlic induction of enzymes is well documented, the molecular mechanism(s) that cause these important reactions is not known. Aim 1 is designed to show that garlic and DAS induce transcriptional regulation of Phase I enzymes by activation of the Constitutive Androstane Receptor (CAR). Aim 2 is designed to show that garlic and DADS regulate transcription of antioxidant enzymes via activation of the nuclear factor-E2 related factor 2 (Nrf2). CAR activation results in an increase in the quantity of transporters and enzymes responsible for hepatic bilirubin clearance. Aim 3 is designed to determine whether garlic treatment can increase bilirubin clearance in vivo, and provide an alternative treatment for patients suffering from jaundice and other digestive diseases.

性状（由申请人提供）：大蒜和大蒜的两种成分二烯丙基硫化物（DAS）和二烯丙基二硫化物（DADS）显示出调节许多肝酶转录活性的能力，并有可能诱导草药-药物相互作用。大蒜和DAS均引起细胞色素P450（CYP 450）基因转录增加。大蒜和DADS已被证明可以增加抗氧化酶的转录活性，如NAD（P）H醌氧化还原酶（NQO-1）和谷胱甘肽S-转移酶（GST）。虽然大蒜对酶的诱导是有据可查的，但引起这些重要反应的分子机制尚不清楚。目的1旨在表明大蒜和DAS通过激活组成型雄甾烷受体（CAR）诱导I相酶的转录调节。目的2表明大蒜和DADS通过激活核因子E2相关因子2（Nrf 2）调节抗氧化酶的转录。CAR激活导致负责肝脏胆红素清除的转运蛋白和酶的数量增加。目的3是确定大蒜治疗是否可以增加体内胆红素清除率，并为患有黄疸和其他消化系统疾病的患者提供替代治疗。