2002-05-02

A tree resin used in India for 2,000 years as a folk remedy for a variety of ailments has been found by modern researchers to be effective in controlling high cholesterol.

The sap from a tree known in India as guggul contains a compound that blocks the action of a cell receptor, called FXR, that helps regulate the level of cholesterol in the body, said David D. Moore, a molecular biologist at the Baylor School of Medicine in Houston. He is co-author of a study appearing Friday in Science Express, the electronic version of the journal Science.

"Our results suggest that other compounds that could affect FXR could also control cholesterol," said Moore. "This mechanism is completely different from the action of statin drugs," which are taken by millions of Americans to control cholesterol.

In studies at his Baylor lab, Moore and Nancy L. Urizar showed the guggul resin compound, called guggulsterone, acted on the FXR receptor.

Dr. David Mangelsdorf and Amy B. Liverman, researchers at the University of Texas Southwestern Medical Center in Dallas, then tested the compound in two types of mice, one with a normal FXR receptor and one without FXR. The study found that cholesterol levels dropped in the livers of mice that had the FXR receptor, but not in the others, thus proving that guggulsterone worked by affecting the FXR receptor.

Dr. Mitchell A. Lazar, an endocrinologist at the University of Pennsylvania, said the study is important because it suggests a new drug pathway for controlling cholesterol.

"We need to have multiple ways to lower lipids (cholesterol)," said Lazar.

He said the work also advances the notion that some traditional medicinal compounds may have important uses in modern medicine and emphasizes that the value of such compounds needs to be researched.

Exactly how guggulsterone affects the FXR receptor is unknown, Moore said.

"FXR regulates a number of genes and we are not sure which are the primary targets for lipid (cholesterol) control," said Moore, "but we have shown that this is a new mechanism for controlling cholesterol."

He said finding a new way to reduce cholesterol could be very important for patients who cannot tolerate the side effects that some people experience with statin drugs.

Guggulsterone is commonly available in health food stores, but Moore said he could not recommend people take it for cholesterol control because there is some evidence the compound affects the action of other drugs. More studies are needed to investigate this issue, Moore said.

The guggul tree, known technically as Commiphora mukul, grows in dry areas of India, Pakistan and Afghanistan. For thousands of years, folk healers have tapped the trees to make medicines used to control weight and to treat other ailments.

About 40 years ago, an Indian researcher found that the guggul compound also was effective in combating heart disease, a condition linked to cholesterol. Later studies in India showed that guggulsterone lowered cholesterol, and Indian health authorities approved the sale of the resin for treatment of heart disease.

Moore said more than 300 tons of the resin is used annually for medical purposes in India.

The FXR receptor controls cholesterol by regulating the level of bile acids in the body. Blocking the action of FXR would help the body rid itself of more cholesterol.

Normally, cholesterol is synthesized in the liver or enters the body from the diet. Statin drugs work by blocking an enzyme that helps to make cholesterol in the liver.

Bile acids, containing cholesterol, are made in the liver and go through the gall bladder to the small intestine where they help metabolize fats. The bile acid is then reprocessed and returned to the liver. Changing the action of the FXR receptor would mean that more cholesterol is excreted, Moore said.

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