Discovery that theonellasterol a marine sponge sterol is a highly selective FXR antagonist that protects against liver injury in cholestasis.

ABSTRACT:

Background

The farnesoid-x-receptor (FXR) is a bile acid sensor expressed in the liver and gastrointestinal tract. Despite FXR ligands are under investigation for treatment of cholestasis, a biochemical condition occurring in a number of liver diseases for which available therapies are poorly effective, mice harboring a disrupted FXR are protected against liver injury caused by bile acid overload in rodent models of cholestasis. Theonellasterol is a 4-methylene-24-ethylsteroid isolated from the marine sponge Theonella swinhoei. Here, we have characterized the activity of this theonellasterol on FXR-regulated genes and biological functions.

Principal findings

Interrogation of HepG2 cells, a human hepatocyte cell line, by microarray analysis and transactivation assay shows tha

SUBMITTER: Renga B 

PROVIDER: S-EPMC3264597 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature