10.1021/jm00098a002
The study investigates the hypocholesterolemic activity of synthetic and natural tocotrienols, which are farnesylated benzopyran natural products that exhibit cholesterol-lowering effects both in vitro and in vivo. The research explores the mechanism of their hypolipidemic action, which involves posttranscriptional suppression of HMG-CoA reductase, a key enzyme in cholesterol biosynthesis. The study presents an efficient synthetic route to tocotrienols and their isolation from palm oil distillate. It was found that γ-tocotrienol has a 30-fold greater activity toward cholesterol biosynthesis inhibition compared to α-tocotrienol in HepG2 cells in vitro. The synthetic (racemic) and natural (chiral) tocotrienols exhibit nearly identical cholesterol biosynthesis inhibition and HMG-CoA reductase suppression properties. The study also examines the role of various tocotrienols, including α-, γ-, and δ-tocotrienols, in inhibiting cholesterol synthesis. The findings suggest that tocotrienols lacking the 5-methyl substitution, such as γ- and δ-tocotrienols, possess significantly greater cholesterol synthesis suppressive activity compared to α-tocotrienol.
