Molecular structures of citrus flavonoids determine their effects on lipid metabolism in HepG2 cells by primarily suppressing apoB secretion

Journal of Agricultural and Food Chemistry

Volumn 59, Issue 9, 2011, Pages 4496-4503

  Lin, Yuguang ^a   Vermeer, Mario A ^a   Bos, Wil ^a   Van Buren, Leo ^a   Schuurbiers, Eric ^a   Miret Catalan, Silvia ^a   Trautwein, Elke A ^a  

^a UNILEVER RESEARCH VLAARDINGEN   (Netherlands)

Author keywords

Cholesterol; HepG2 cells; Nobiletin; Polymethoxylated flavonoids (PMFs); Tangeretin; Triglycerides

Indexed keywords

HEPG2 CELLS; NOBILETIN; POLYMETHOXYLATED FLAVONOIDS (PMFS); TANGERETIN; TRIGLYCERIDES;

BLOOD; CHOLESTEROL; GLYCEROL; PHYSIOLOGY;

FLAVONOIDS;

APOLIPOPROTEIN B; FLAVONOID; PLANT EXTRACT;

ARTICLE; CELL STRAIN HEPG2; CHEMICAL STRUCTURE; CHEMISTRY; CITRUS FRUIT; DOWN REGULATION; DRUG EFFECT; GENETICS; HUMAN; LIPID METABOLISM; LIVER; METABOLISM; STRUCTURE ACTIVITY RELATION;

APOLIPOPROTEINS B; CITRUS; DOWN-REGULATION; FLAVONOIDS; HEP G2 CELLS; HUMANS; LIPID METABOLISM; LIVER; MOLECULAR STRUCTURE; PLANT EXTRACTS; STRUCTURE-ACTIVITY RELATIONSHIP;

CITRUS;

EID: 79955681996     PISSN: 00218561     EISSN: 15205118     Source Type: Journal    
DOI: 10.1021/jf1044475     Document Type: Article

References (39)

1. Jeon, S. M.; Park, Y. B.; Choi, M. S. Antihypercholesterolemic property of naringin alters plasma and tissue lipids, cholesterol-regulating enzymes, fecal sterol and tissue morphology in rabbits. Clin. Nutr. 2004, 23, 1025-1034. (Pubitemid 39243016)
2. Bok, S. H.; Lee, S. H.; Park, Y. B.; Bae, K. H.; Son, K. H.; Jeong, T. S.; Choi, M. S. Plasma and hepatic cholesterol and hepatic activities of 3-hydroxy-3-methyl-glutaryl-CoA reductase and acyl CoA:cholesterol transferase are lower in rats fed citrus peel extract or a mixture of citrus bioflavonoids. J. Nutr. 1999, 129, 1182-1185.
3. Mulvihill, E. E.; Assini, J. M.; Sutherland, B. G.; Dimattia, A. S.; Khami, M.; Koppes, J. B.; Sawyez, C. G.; Whitman, S. C.; Huff, M. W. Naringenin decreases progression of atherosclerosis by improving dyslipidemia in high-fat-fed low-density lipoprotein receptor-null mice. Arterioscler. Thromb. Vasc. Biol. 2010, 30, 742-748.
4. Kurowska, E. M.; Manthey, J. A. Hypolipidemic effects and absorption of citrus polymethoxylated flavones in hamsters with diet-induced hypercholesterolemia. J. Agric. Food Chem. 2004, 52, 2879-2886.
5. Gorinstein, S.; Caspi, A.; Libman, I.; Lerner, H. T.; Huang, D.; Leontowicz, H.; Leontowicz, M.; Tashma, Z.; Katrich, E.; Feng, S.; Trakhtenberg, S. Red grapefruit positively influences serum triglyceride level in patients suffering from coronary atherosclerosis: studies in vitro and in humans. J. Agric. Food Chem. 2006, 54, 1887-1892.
6. Roza, J. M.; Xian-Liu, Z.; Guthrie, N. Effect of citrus flavonoids and tocotrienols on serum cholesterol levels in hypercholesterolemic subjects. Altern. Ther. Health Med. 2007, 13, 44-48. (Pubitemid 351299592)
7. Demonty, I.; Lin, Y.; Zebregs, Y. E.; Vermeer, M. A.; van der Knaap, H. C.; Jakel, M.; Trautwein, E. A. The citrus flavonoids hesperidin and naringin do not affect serum cholesterol in moderately hypercholesterolemic men and women. J. Nutr. 2010, 140, 1615-1620.
8. Kurowska, E. M.; Spence, J. D.; Jordan, J.; Wetmore, S.; Freeman, D. J.; Piche, L. A.; Serratore, P. HDL-cholesterol-raising effect of orange juice in subjects with hypercholesterolemia. Am. J. Clin. Nutr. 2000, 72, 1095-1100.
9. Day, A. J.; DuPont, M. S.; Ridley, S.; Rhodes, M.; Rhodes, M. J.; Morgan, M. R.; Williamson, G. Deglycosylation of flavonoid and isoflavonoid glycosides by human small intestine and liver β-glucosidase activity. FEBS Lett. 1998, 436, 71-75. (Pubitemid 28454609)
10. Bokkenheuser, V. D.; Shackleton, C. H.; Winter, J. Hydrolysis of dietary flavonoid glycosides by strains of intestinal Bacteroides from humans. Biochem. J. 1987, 248, 953-956. (Pubitemid 18012735)
11. Nielsen, I. L.; Chee, W. S.; Poulsen, L.; Offord-Cavin, E.; Rasmussen, S. E.; Frederiksen, H.; Enslen, M.; Barron, D.; Horcajada, M. N.; Williamson, G. Bioavailability is improved by enzymatic modification of the citrus flavonoid hesperidin in humans: a randomized, double-blind, crossover trial. J. Nutr. 2006, 136, 404-408. (Pubitemid 43228293)
12. Nielsen, S. E.; Breinholt, V.; Cornett, C.; Dragsted, L. O. Biotransformation of the citrus flavone tangeretin in rats. Identification of metabolites with intact flavane nucleus. Food Chem. Toxicol. 2000, 38, 739-746. (Pubitemid 30628868)
13. Wilcox, L. J.; Borradaile, N. M.; de Dreu, L. E.; Huff, M. W. Secretion of hepatocyte apoB is inhibited by the flavonoids, naringenin and hesperetin, via reduced activity and expression of ACAT2 and MTP. J. Lipid Res. 2001, 42, 725-734. (Pubitemid 32507172)
14. Borradaile, N. M.; de Dreu, L. E.; Huff, M.W. Inhibition of net HepG2 cell apolipoprotein B secretion by the citrus flavonoid naringenin involves activation of phosphatidylinositol 3-kinase, independent of insulin receptor substrate-1 phosphorylation. Diabetes 2003, 52, 2554-2561. (Pubitemid 37210545)
15. Mulvihill, E. E.; Allister, E. M.; Sutherland, B. G.; Telford, D. E.; Sawyez, C. G.; Edwards, J. Y.; Markle, J. M.; Hegele, R. A.; Huff, M. W. Naringenin prevents dyslipidemia, apolipoprotein B overproduction, and hyperinsulinemia in LDL receptor-null mice with diet-induced insulin resistance. Diabetes 2009, 58, 2198-2210.
16. Morin, B.; Nichols, L. A.; Zalasky, K. M.; Davis, J. W.; Manthey, J. A.; Holland, L. J. The citrus flavonoids hesperetin and nobiletin differentially regulate low density lipoprotein receptor gene transcription in HepG2 liver cells. J. Nutr. 2008, 138, 1274-1281. (Pubitemid 351930989)
17. Allister, E. M.; Borradaile, N. M.; Edwards, J. Y.; Huff, M. W. Inhibition of microsomal triglyceride transfer protein expression and apolipoprotein B100 secretion by the citrus flavonoid naringenin and by insulin involves activation of the mitogen-activated protein kinase pathway in hepatocytes. Diabetes 2005, 54, 1676-1683. (Pubitemid 40770757)
18. Buisson, D.; Quintin, J.; Lewin, G. Biotransformation of polymethoxylated flavonoids: access to their 40-O-demethylated metabolites. J. Nat. Prod. 2007, 70, 1035-1038. (Pubitemid 47056123)
19. Li, S.; Lo, C. Y.; Ho, C. T. Hydroxylated polymethoxyflavones and methylated flavonoids in sweet orange (Citrus sinensis) peel. J. Agric. Food Chem. 2006, 54, 4176-4185. (Pubitemid 44013319)
20. Teupser, D.; Thiery, J.; Walli, A. K.; Seidel, D. Determination of LDL- and scavenger-receptor activity in adherent and non-adherent cultured cells with a new single-step fluorometric assay. Biochim. Biophys. Acta 1996, 1303, 193-198. (Pubitemid 26349038)
21. Beisiegel, U.; Schneider, W. J.; Brown, M. S.; Goldstein, J. L. Immunoblot analysis of low density lipoprotein receptors in fibroblasts from subjects with familial hypercholesterolemia. J. Biol. Chem. 1982, 257, 13150-13156. (Pubitemid 13219486)
22. Bilheimer, D. W.; Grundy, S. M.; Brown, M. S.; Goldstein, J. L. Mevinolin stimulates receptor-mediated clearance of low density lipoprotein from plasma in familial hypercholesterolemia heterozygotes. Trans. Assoc. Am. Physicians 1983, 96, 1-9.
23. Arbeeny, C. M.; Meyers, D. S.; Bergquist, K. E.; Gregg, R. E. Inhibition of fatty acid synthesis decreases very low density lipoprotein secretion in the hamster. J. Lipid Res. 1992, 33, 843-851.
24. DeBose-Boyd, R. A. Feedback regulation of cholesterol synthesis: sterol-accelerated ubiquitination and degradation of HMG CoA reductase. Cell Res. 2008, 18, 609-621.
25. Redman, C. M.; Avellino, G.; Yu, S. Secretion of proalbumin by canavanine-treated Hep-G2 cells. J. Biol. Chem. 1983, 258, 3446-3452. (Pubitemid 13055757)
26. Dixon, J. L.; Ginsberg, H. N. Regulation of hepatic secretion of apolipoprotein B-containing lipoproteins: information obtained from cultured liver cells. J. Lipid Res. 1993, 34, 167-179. (Pubitemid 23067522)
27. Chandler, C. E.; Wilder, D. E.; Pettini, J. L.; Savoy, Y. E.; Petras, S. F.; Chang, G.; Vincent, J.; Harwood, H. J., Jr. CP-346086: an MTP inhibitor that lowers plasma cholesterol and triglycerides in experimental animals and in humans. J. Lipid Res. 2003, 44, 1887-1901. (Pubitemid 37356661)
28. Kurowska, E. M.; Manthey, J. A. Regulation of lipoprotein metabolism in HepG2 cells by citrus flavonoids. Adv. Exp. Med. Biol. 2002, 505, 173-179. (Pubitemid 34526434)
29. Erlund, I.; Meririnne, E.; Alfthan, G.; Aro, A. Plasma kinetics and urinary excretion of the flavanones naringenin and hesperetin in humans after ingestion of orange juice and grapefruit juice. J. Nutr. 2001, 131, 235-241. (Pubitemid 32115362)
30. Miwa, Y.; Yamada, M.; Sunayama, T.; Mitsuzumi, H.; Tsuzaki, Y.; Chaen, H.; Mishima, Y.; Kibata, M. Effects of glucosyl hesperidin on serum lipids in hyperlipidemic subjects: preferential reduction in elevated serum triglyceride level. J. Nutr. Sci. Vitaminol. (Tokyo) 2004, 50, 211-218. (Pubitemid 39045124)
31. Manthey, J. A.; Cesar, T. B.; Jackson, E.; Mertens-Talcott, S. Pharmacokinetic study of nobiletin and tangeretin in rat serum by highperformance liquid chromatographyélectrospray ionization-mass spectrometry. J. Agric. Food Chem. 2011, 59, 145-151.
32. Borradaile, N. M.; de Dreu, L. E.; Barrett, P. H.; Huff, M. W. Inhibition of hepatocyte apoB secretion by naringenin: enhanced rapid intracellular degradation independent of reduced microsomal cholesteryl esters. J. Lipid Res. 2002, 43, 1544-1554.
33. Sato, R.; Imanaka, T.; Takano, T. The effect of HMG-CoA reductase inhibitor (CS-514) on the synthesis and secretion of apolipoproteins B and A-1 in the human hepatoblastoma Hep G2. Biochim. Biophys. Acta 1990, 1042, 36-41. (Pubitemid 20021611)
34. Haghpassand, M.; Wilder, D.; Moberly, J. B. Inhibition of apolipoprotein B and triglyceride secretion in human hepatoma cells (HepG2). J. Lipid Res. 1996, 37, 1468-1480. (Pubitemid 26249978)
35. Casaschi, A.; Rubio, B. K.; Maiyoh, G. K.; Theriault, A. G. Inhibitory activity of diacylglycerol acyltransferase (DGAT) and microsomal triglyceride transfer protein (MTP) by the flavonoid, taxifolin, in HepG2 cells: potential role in the regulation of apolipoprotein B secretion. Atherosclerosis 2004, 176, 247-253. (Pubitemid 39369513)
36. Casaschi, A.; Wang, Q.; Dang, K.; Richards, A.; Theriault, A. Intestinal apolipoprotein B secretion is inhibited by the flavonoid quercetin: potential role of microsomal triglyceride transfer protein and diacylglycerol acyltransferase. Lipids 2002, 37, 647-652.
37. Kurowska, E. M.; Manthey, J. A.; Casaschi, A.; Theriault, A. G. Modulation of HepG2 cell net apolipoprotein B secretion by the citrus polymethoxyflavone, tangeretin. Lipids 2004, 39, 143-151. (Pubitemid 38480944)
38. Borradaile, N. M.; de Dreu, L. E.; Wilcox, L. J.; Edwards, J. Y.; Huff, M. W. Soya phytoestrogens, genistein and daidzein, decrease apolipoprotein B secretion from HepG2 cells through multiple mechanisms. Biochem. J. 2002, 366, 531-539. (Pubitemid 35001697)
39. Li, S.; Wang, Z.; Sang, S.; Huang, M. T.; Ho, C. T. Identification of nobiletin metabolites in mouse urine. Mol. Nutr. Food Res. 2006, 50, 291-299.