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Guggul: A natural product that lowers cholesterol

Guggul, an extract from the resin of the mukul myrrh tree (Commiphora mukul), has been used since 600 B.C. in Ayurvedic medicine to treat obesity and lipid disorders. Guggulipid, an ethyl acetate extract of this resin, is used to treat hyperlipidemia in India and is also available in the US. A 2002 study evaluated the mechanisms by which two compounds present in guggulipid, E- and Z-gugglusterone, decrease hepatic cholesterol levels.

Several tests were carried out in cell cultures and in mice. The resin extracts were evaluated for their effects on the activity of the bile acid receptor FXR because this receptor plays and important role in bile acid and cholesterol metabolism. Guggulsterone decreased the expression of the FXR receptor, indicating that it was an effective antagonist of this receptor. Guggulsterone did not directly affect DNA binding to FXR but did interact with and inhibit the FXR ligand-binding domain.

To determine whether the FXR antagonist property of guggulsterone is required for its cholesterol- lowering effects, normal and FXR-deficient mice were fed a normal diet or a high- cholesterol diet supplemented with guggulsterone for 1 week. The cholesterol diet increased liver cholesterol levels in both the normal and FXR-deficient mice. Guggulsterone deceased liver cholesterol levels in normal mice fed a high-cholesterol diet but had no effect in normal mice fed a normal diet or in FXR-deficient mice. These findings suggest that guggulsterone lowers cholesterol levels by acting as an antagonist of the FXR bile acid receptor important in the metabolism of cholesterol.

Source: NL Urizar, AB Liverman, DT Dodds, FV Silva, P Ordentlich, Y Yan, FJ Gonzalez, RA Heyman, DJ Mangelsdorf, and DD Moore. Science 2002 296:1703-1706


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