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Abstract

Grant Number:	5F31AT002842-03
Project Title:	Garlic: Molecular Regulation of Hepatic Function.

PI Information:	Name	Email	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
DNA, androstane compound, anion, antioxidant, bilirubin, blood, chemical, cytochrome P450, drug interaction, element, energy source, enzyme, enzyme activity, enzyme induction /repression, enzyme mechanism, epoxide hydrolase, excretion, family, female, gene, gene expression, gene induction /repression, glutathione, heme oxygenase, hormone receptor, human, hydropathy, jaundice, lead, liver, male, nuclear receptor, oil, oxidoreductase, pharmacokinetics, protein, quality of life, quinone, receptor, role, sulfide, transferase, western blotting

Institution:	UNIVERSITY OF ARIZONA
	PO BOX 3308
	TUCSON, AZ 857223308
Fiscal Year:	2008
Department:	PHARMACOLOGY AND TOXICOLOGY
Project Start:	29-SEP-2006
Project End:	28-SEP-2010
ICD:	NATIONAL CENTER FOR COMPLEMENTARY & ALTERNATIVE MEDICINE
IRG:	ZAT1

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