(E)-Guggulsterone

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.{10943} They are also inherently cytotoxic, as physiological imbalance contributes to increased oxidative stress.{14024,16793} Bile acid-controlled signaling pathways are promising novel targets to treat such metabolic diseases as obesity, type II diabetes, hyperlipidemia, and atherosclerosis.Guggulsterone, derived from resin of the guggul tree, is a competitive antagonist of FXR both in vitro and in vivo.{9823} The cis stereoisomer of guggulsterone, (E)-guggulsterone, decreases chenodeoxycholic acid (CDCA)-induced FXR activation with an IC50 value of 15 µM. {17615, 17566} By inhibiting CDCA-induced transactivation of FXR, guggulsterone lowers low-density lipoprotein cholesterol and triglyceride levels in rodents fed a high cholesterol diet.{9823}