Herbal Biochemistry

[Guest guest]

Natural compound used in India reduces cholesterol by blocking

metabolism-controlling receptor

Contact: Susan Morrison

(214)648-3404

or e-mail: Susan.Morrison

 

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 today's 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 FXR's role in the body's

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 aren't getting rid of

enough cholesterol before the process shuts down.

 

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

medicine, a traditional Hindu medicine practiced in India for nearly

3,000 years, to treat a wide variety of ailments, including obesity

and lipid disorders. An ethyl acetate extract of this resin has been

found to lower low-density lipoprotein cholesterol and triglycerides

in humans. Since receiving regulatory approval in India in 1987,

this extract, called guglipid, has been widely and effectively used

to treat hyperlipidemia, according to the study researchers.

 

Amy Liverman, a student research assistant in Mangelsdorf's lab, led

UT Southwestern's contributions to the research. X-Ceptor

Therapeutics Inc. of San Diego also contributed to the research.

 

The study was supported by the National Institute of Diabetes and

Digestive and Kidney Diseases, the U.S. Department of Agriculture,

the National Institute of General Medical Sciences, HHMI, and the

Robert A. Welch Foundation.

 

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© 2002 The University of Texas Southwestern Medical Center at Dallas

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Last update: May 2, 2002