Stigmastanol (SG)

Stigmastanol is a phytosterol found in a variety of plant sources. Similar to sterol esters and stanol esters, stigmasterol inhibits the absorption of cholesterol from the diet. Animal studies suggest that it also inhibits biosynthesis of cholesterol in the liver. Stigmasterol, a soy lipid-derived phytosterol, is an antagonist of the bile acid nuclear receptor FXR. FXR (farnesoid X receptor, NR1H4). In HepG2 cells, stigmasterol acetate (StigAc), a water-soluble Stig derivative, suppressed ligand-activated expression of FXR target genes involved in adaptation to cholestasis (i.e. BSEP, FGF-19, OSTalpha/beta). Furthermore, StigAc antagonized BA-activated, FXR target genes SHP and BSEP in FXR+/+, but not in FXR-/- mouse hepatocytes. Both Stig and StigAc inhibited BA-activated, FXR-dependent reporter gene expression in transfected HepG2 cells, whereas the most prevalent phytosterol in lipids, beta-sitosterol, had no inhibitory effect.