title: Hypocholesterolemic activity of synthetic and natural tocotrienols.
abstract: 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.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492.
authors.forename: B C
authors.initials: BC
authors.lastname: Pearce
authors.forename: R A
authors.initials: RA
authors.lastname: Parker
authors.forename: M E
authors.initials: ME
authors.lastname: Deason
authors.forename: A A
authors.initials: AA
authors.lastname: Qureshi
authors.forename: J J
authors.initials: JJ
authors.lastname: Wright
mesh_terms: 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
chemical_list: 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