Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Mol Endocrinol. 2002 Jul;16(7):1590-7.

The hypolipidemic natural product guggulsterone acts as an antagonist of the bile acid receptor.

Author information

  • 1Department of Biotechnology, Pharmacia Corp., St. Louis, Missouri 63198, USA.

Abstract

Ayurveda, the ancient Indian system of health care and medicine, has a well-organized materia medica in which plants form a dominant part. A key illustration of the exploitation of this knowledge toward the development of a modern drug is the isolation and characterization of two antihyperlipidemic compounds, Z-, and E-guggulsterone from the tree Commiphora mukul, the exudate of which has been traditionally used for mitigating lipid disorders. Here, we demonstrate that Z-guggulsterone and an analog, 80-574 currently in clinical trials, act as antagonists of the bile acid receptor (BAR), a member of the intracellular receptor superfamily. These compounds antagonize the activity of BAR in vitro, and in cell culture systems on promoters and endogenous target genes. In biochemical assays, they are able to displace coactivator peptides from the receptor in a dose-dependent manner. The mechanism by which they act as BAR antagonists is likely through their inability to recruit coactivator proteins, failure to release corepressor proteins from unliganded receptor, and ability to compete with BAR agonists to block coactivator recruitment. Our data suggest these compounds may mediate at least some of their effects via the BAR.

PMID:
12089353
[PubMed - indexed for MEDLINE]

MeSH Terms, Substances

MeSH Terms

Substances

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Atypon
    Loading ...
    Write to the Help Desk