Garlic: Molecular Regulation of Hepatic Function.

描述（由申请人提供）：大蒜和大蒜的两种成分，二烯丙基硫醚（DAS）和二烯丙基二硫醚（DADS），显示出调节许多肝酶转录活性的能力，并有可能诱导草药相互作用。大蒜和DAS均可引起细胞色素P450 （CYP）基因转录升高。大蒜和DADS已被证明可以提高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有很好的文献记载，但引起这些重要反应的分子机制尚不清楚。Aim 1旨在表明大蒜和DAS通过激活组成型雄甾受体（CAR）诱导I期酶的转录调节。Aim 2旨在表明大蒜和DADS通过激活核因子e2相关因子2 （Nrf2）来调节抗氧化酶的转录。CAR激活导致负责肝胆红素清除的转运蛋白和酶的数量增加。Aim 3旨在确定大蒜治疗是否可以提高体内胆红素清除率，为患有黄疸等消化系统疾病的患者提供另一种治疗方法。

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.