DALLAS--Research involving an extract from the guggul tree (Commiphora mukul) has demonstrated that the resin compound guggulsterone may be effective for reducing total cholesterol and triglyceride levels. The study, which was published online on May 2 in Science Express (www.sciencemag.org), was picked up by the national media, including a story that appeared on the Associated Press (AP) newswire.

Researchers, led by David Moore at the Baylor College of Medicine in Houston, discovered that guggulsterone acts as an antagonist, binding to and inhibiting the farnesoid X receptor (FXR), a protein that binds to bile acids and halts their production. Moore hypothesized that the binding property of guggulsterone would inhibit FXR, thereby lowering cholesterol.

To test this theory in vivo, Moore passed his work on to David J. Mangelsdorf, Ph.D., and his colleagues at the University of Texas Southwestern Medical Center, whose research is funded by the Howard Hughes Medical Institute, a nonprofit research institute based in Chevy Chase, Md., that funds scientists throughout universities in the United States. They administered guggulsterone to two types of mice--wild-type mice with normal FXR function and FXR-knockout mice with no FXR protein--to determine whether FXR was involved in the cholesterol-lowering effect of guggulsterone.

"When you give guggulsterone to the wild-type animal, it should lower its cholesterol. If this compound is working through FXR, when you give it to the FXR-knockout, it should have no effect," Mangelsdorf said. "And that was exactly what we saw. We demonstrated definitively in our laboratory that FXR was involved in the process, which is a key point to the paper, because it showed, in vivo, that the mechanism of action was as Dr. Moore's laboratory had suggested." In addition, researchers found that the compound lowered triglyceride levels, although this occurrence was unexplained.

"[Guggulsterone] is basically an antagonist--it interrupts what a normal protein in the body is doing by blocking its normal action," Mangelsdorf said. "Normally, that action would be good, but blocking [FXR] in this way with people who are hypercholesterolimic or hyperlipidemic may be beneficial because it lowers triglycerides and cholesterol."

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