Variable Influence of Kaempferol and Myricetin on in vitro Hepatocellular Cholesterol Biosynthesis

Abstract

Flavonoids, e. g., quercetin, luteolin, and taxifolin, are known to inhibit hepatocellular cholesterol biosynthesis. Surprisingly, we found that some flavonoids, namely kaempferol and myricetin, are able to considerably stimulate cholesterol biosynthesis, particularly within a low concentration range (between 0.1 and 10 μM), while they show a variable degree of inhibition at higher concentrations. Kaempferol 3-glucoside even stimulated cholesterol synthesis up to 100 μM. In contrast, kaempferol 7-neohesperidoside was ineffective. These effects were more pronounced in rat hepatocytes than in HepG2 cells except for myricetin which acted stimulatory even at high concentrations in HepG2 cells. These opposing effects on cholesterol biosynthesis are exerted in an indirect manner and seem possible though differential modulation of the complex regulation of HMGCoA reductase.

References

• 1 Ross J A, Kasum C M. Dietary flavonoids: bioavailability, metabolic effects, and safety.  Annual Reviews Nutrition. 2002;  22 19-34
• 2 Rice-Evans C A. Flavonoid antioxidants.  Current Medical Chemistry. 2001;  8 797-807
• 3 Hagiwara M, Inoue S, Tanaka T, Nunoki K, Ito M, Hidaka H. Differential effects of flavonoids as inhibitors of tyrosine protein kinases and serine/threonine protein kinases.  Biochemical Pharmacology. 1988;  37 2987-92
• 4 Miranda C L, Stevens J F, Ivanov V, CaCall M, Frei B, Deinzer M L, Buhler D R. Antioxidant and prooxidant actions of prenylated and nonprenylated chalcones and flavanones in vitro .  Journal of Agricultural Food Chemistry. 2000;  48 3876-84
• 5 Choi J S, Yokozawa T, Oura H. Antihyperlipidemic effects of flavonoids from Prunus davidiana .  Journal Natural Products. 1991;  54 218-24
• 6 Nassuato G, Iemmolo R M, Strazzabosco M, Lirussi F, Deana R, Francesconi M A, Muraca M, Passera D, Fragasso A, Orlando R, Csomos G, Okolocsanyi L. Effect of silibinin on biliary lipid composition: experimental and clinical study.  Journal Hepatology. 1991;  12 290-5
• 7 Krecman V, Skottova N, Walterova D, Ulrichova J, Simanek V. Silymarin inhibits the development of diet-induced hypercholesterolemia in rats.  Planta Medica. 1998;  64 138-42
• 8 Gebhardt R. Inhibition of cholesterol biosynthesis in primary cultured rat hepatocytes by artichoke (Cynara scolymus L.) extracts.  Journal of Pharmacology and Experimental Therapeutics. 1998;  286 1122-8
• 9 Theriault A, Wang Q, Van Iderstine S C, Chen B, Franke AA; Adeli K. Modulation of hepatic lipoprotein synthesis and secretion by taxifolin, a plant flavonoid.  Journal Lipid Research. 2000;  41 1969-79
• 10 Gebhardt R. Inhibition of cholesterol biosynthesis in HepG2 cells by artichoke extracts is reinforced by glucosidase pretreatment.  Phytotherapy Research. 2002;  16 368-72
• 11 Gläßer G, Graefe E U, Struck F, Veit M, Gebhardt R. Comparison of antioxidant capacities and inhibitory effects on cholesterol biosynthesis of quercetin and potential metabolites.  Phytomedicine. 2002;  9 33-40
• 12 Kik C, Kahane R, Gebhardt R. Garlic and health.  Nutrition Metaboblism and Cardiovascular Disease. 2001;  11 57-65
• 13 Gebhardt R. Inhibition of cholesterol-biosythesis by a water-soluble garlic extract in primary cultures of rat hepatocytes.  Arzneimittel-Forschung/Drug Research. 1991;  41 800-4
• 14 Sendl A, Schilack M, Loser R, Stanislaus F, Wagner H. Inhibition of cholesterol synthesis in vitro by extracts and isolated compounds prepared from garlic and wild garlic.  Atherosclerosis. 1992;  94 79-85
• 15 Carotenuto A, De Feo V, Fattorusso E, Lanzotti V, Magno S, Cicala C. The flavonoids of Allium ursinum .  Phytochemistry. 1996;  41 531-6
• 16 Mien K H, Mohamed S. Flavonoid (myricetin, quercetin, kaempferol, luteolin, and apigenin) content of edible tropical plants.  Journal Agricultural Food Chemistry. 2001;  49 3106-12
• 17 Koch P, Lawson L D. Garlic. The science and therapeutic application of Allium sativum L. and related species, 2^nd edition. Baltimore; Williams & Wilkins 1996
• 18 Gebhardt R, Beck H, Wagner K G. Inhibition of cholesterol biosynthesis by allicin and ajoene in rat hepatocytes and HepG2 cells.  Biochimica Biophysica Acta. 1994;  1213 57-62
• 19 Gebhardt R. Multiple inhibitory effects of garlic extracts on cholesterol biosynthesis in hepatocytes.  Lipids. 1993;  28 613-19