Hypocholesterolemic activity of synthetic and natural tocotrienols

• Published in: Journal of medicinal chemistry Vol. 35; no. 20; pp. 3595 - 3606
• Main Authors: Pearce, Bradley C, Parker, Rex A, Deason, Michael E, Qureshi, Asaf A, Wright, J. J. Kim
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.10.1992; Amer Chemical Soc
• Subjects: Animals; Anticholesteremic Agents - chemical synthesis; Anticholesteremic Agents - isolation & purification; Anticholesteremic Agents - pharmacology; Biological and medical sciences; Cells, Cultured; Chemistry, Medicinal; Chickens; Cholesterol - biosynthesis; Cholesterol - metabolism; Chromans; General and cellular metabolism. Vitamins; Humans; Hydroxymethylglutaryl CoA Reductases - metabolism; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Life Sciences & Biomedicine; Liver - drug effects; Liver - enzymology; Male; Medical sciences; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Rats; Rats, Wistar; Science & Technology; Tocotrienols; Vitamin E - analogs & derivatives; Vitamin E - chemical synthesis; Vitamin E - isolation & purification; Vitamin E - pharmacology; PLASMA; INHIBITION; ENZYME; STEROL SYNTHESIS; PALM OIL; HMG-COA REDUCTASE; LOW-DENSITY LIPOPROTEIN; 3-HYDROXY-3-METHYLGLUTARYL COENZYME; CHOLESTEROL-BIOSYNTHESIS; 24(S),25-EPOXYCHOLESTEROL; Rat; Enzyme; Liver; Suppression; Rodentia; Natural product; Biosynthesis; In vitro; Cholesterol; Vertebrata; Palm oil; Mammalia; Synthetic product; Animal; Plant origin; Hydroxymethylglutaryl-CoA reductase; Isolation; Chicken; Inhibition; Aves; Mechanism of action; Chemical synthesis; Antilipemic agent
• DOI: 10.1021/jm00098a002
• ISSN: 0022-2623

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.