Hypocholesterolemic activity of synthetic and natural tocotrienols.
Tocotrienols are farnesylated benzopyran natural products that exhibit hypocholesterolemic activity in vitro and in vivo. The mechanism of their hypolipidemic action involves posttranscriptional suppression of HMG-CoA reductase by a process distinct from other known inhibitors of cholesterol biosynthesis. An efficient synthetic route to tocotrienols and their isolation from palm oil distillate using an improved procedure is presented. gamma-Tocotrienol exhibits a 30-fold greater activity toward cholesterol biosynthesis inhibition compared to alpha-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 as demonstrated in vitro and in vivo.
Pearce
B C
BC
Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492.
Parker
R A
RA
Deason
M E
ME
Qureshi
A A
AA
Wright
J J
JJ
D000818:Animals; D000924:Anticholesteremic Agents / Q000138:chemical synthesis* / Q000302:isolation & purification / Q000494:pharmacology; D002478:Cells, Cultured; D002645:Chickens; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism; D002839:Chromans; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D024508:Tocotrienols; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology
D000924:Anticholesteremic Agents; D002839:Chromans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D024508:Tocotrienols; D014810:Vitamin E; C013649:plastochromanol 8; D002784:Cholesterol; C082032:tocotrienol, alpha; D006903:Hydroxymethylglutaryl CoA Reductases