Bile acids are essential for solubilization and transport of dietary lipids, are the major products of cholesterol catabolism, and are physiological ligands for farnesoid X receptor (FXR), a nuclear receptor that regulates genes involved in lipid metabolism.1 They are also inherently cytotoxic, as physiological imbalance contributes to increased oxidative stress.2,3 Bile acid-
1 Makishima, M., Okamoto, A.Y., Repa, J.J., et al. Identification of a nuclear receptor for bile acids. Science 284 1362-1365 (1999).
2 Barbier, O., Torra, I.P., Sirvent, A., et al. FXR induces the UGT2B4 enzyme in hepatocytes: A potential mechanism of negative feedback control of FXR activity. Gastroenterology 124 1926-1940 (2003).
Tan, K.P., Yang, M., and Ito, S. Activation of nuclear factor (erythroid-
4 Urizar, N.L., Liverman, A.B., Dodds, D.T., et al. A natural product that lowers cholesterol as an anatagonist ligand for FXR.. Science 296 1703-1706 (2002).
5 Cui, J., Huang, L., Zhao, A., et al. Guggulsterone is a farnesoid X receptor antagonist in coactivator association assays but acts to enhance transcription of bile salt export pump. J Biol Chem 278(12) 10214-10220 (2003).
6 Wu, J., Xia, C., Meier, J., et al. The hypolipidemic natural product guggulsterone acts as an antagonist of the bile acid receptor. Mol Endocrinol 16(7) 1590-1597 (2002).
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