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Abstract
Grant Number: 1F31AT002842-01A1 Project Title: Garlic: Molecular Regulation of Hepatic Function.
PI Information: Name Title FISHER, CRAIG D. cfisher@pharmacy.arizona.edu Abstract: 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.
Public Health Relevance:
This Public Health Relevance is not available.Thesaurus Terms:
angiosperm
bilirubin, enzyme
Institution: UNIVERSITY OF ARIZONA PO BOX 3308 TUCSON, AZ 857223308 Fiscal Year: 2006 Department: PHARMACOLOGY AND TOXICOLOGY Project Start: 29-SEP-2006 Project End: 28-SEP-2010 ICD: NATIONAL CENTER FOR COMPLEMENTARY & ALTERNATIVE MEDICINE IRG: ZAT1