Natural compound used in India reduces cholesterol by blocking metabolism-controlling receptor

DALLAS May 3, 2002 - UT Southwestern Medical Center at Dallas researchers have helped prove that a naturally occurring compound used for centuries as a dietary supplement in India can help lower cholesterol levels.

The research, published in todays issue of Science and done in collaboration with Baylor College of Medicine in Houston, shows that guggulsterone blocks the FXR receptor, which regulates cholesterol metabolism.

Dr. David Mangelsdorf, professor of pharmacology and an investigator in the Howard Hughes Medical Institute (HHMI) at UT Southwestern, and his colleagues previously had revealed FXRs role in the bodys conversion of cholesterol to bile acids. When the bile acids reach a certain level in the body, FXR is activated to interrupt the cholesterol-to-bile-acid process.

The receptor keeps bile acids in check, Mangelsdorf said. If you disturb it, it changes how cholesterol is metabolized.

Researchers at Baylor discovered that guggulsterone made from the sap of Commiphora mukul, a tree commonly known in India as guggul blocked FXR activity in a gene assay. Assays are flat panels used to study genetic activity outside living bodies. Mangelsdorf and his colleagues had used mouse models created for their earlier FXR studies. Those FXR-positive and FXR-negative mouse models allowed the researchers to test whether guggulsterone and FXR reacted the same way in living bodies as they did in the assays.

The mouse model tests confirmed the assay results and showed that cholesterol levels fell in FXR-positive mice that were given guggulsterone.

Mangelsdorf believes the work could lead to new drugs to control cholesterol by creating compounds based on the chemical structure of guggulsterone. Those drugs would prevent FXR from interrupting cholesterol metabolism in people whose bodies arent getting rid of enough cholesterol before the process shuts down.

The gum resin of the guggul tree has been used in Ayurved

Contact: Susan Morrison
UT Southwestern Medical Center

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