Citrus polyphenol hesperidin stimulates production of nitric oxide in endothelial cells while improving endothelial function and reducing inflammatory markers in patients with metabolic syndrome

Journal of Clinical Endocrinology and Metabolism

Volumn 96, Issue 5, 2011, Pages

  Rizza, Stefano ^b   Muniyappa, Ranganath ^a   Iantorno, Micaela ^a   Kim, Jeong A ^d   Chen, Hui ^a   Pullikotil, Philomena ^a   Senese, Nicoletta ^b   Tesauro, Manfredi ^b   Lauro, Davide ^b   Cardillo, Carmine ^c   Quon, Michael J ^a  

^a NATIONAL INSTITUTES OF HEALTH   (United States)

^b UNIVERSITY OF ROME TOR VERGATA   (Italy)

^c CATHOLIC UNIVERSITY   (Italy)

^d University of Alabama at Birmingham   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADENYLATE KINASE; BIOLOGICAL MARKER; C REACTIVE PROTEIN; CELL ADHESION MOLECULE; ENDOTHELIAL LEUKOCYTE ADHESION MOLECULE 1; ENDOTHELIAL NITRIC OXIDE SYNTHASE; FIBRINOGEN; HESPERIDIN; HOMOCYSTEINE; HYDROGEN PEROXIDE; NITRIC OXIDE; PLACEBO; PROTEIN KINASE B; PROTEIN TYROSINE KINASE; SERUM AMYLOID A; TUMOR NECROSIS FACTOR ALPHA; VASCULAR CELL ADHESION MOLECULE 1;

ADULT; AGED; ANIMAL CELL; ANTIINFLAMMATORY ACTIVITY; ARTERY BLOOD FLOW; ARTERY DILATATION; ARTERY ENDOTHELIUM; ARTICLE; BRACHIAL ARTERY; CELL ADHESION; CELL STIMULATION; CELL STRAIN U937; CLINICAL ARTICLE; CONTROLLED STUDY; COW; CROSSOVER PROCEDURE; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG MECHANISM; ENDOTHELIAL DYSFUNCTION; ENDOTHELIUM CELL; ENZYME PHOSPHORYLATION; EXPLORATORY RESEARCH; FEMALE; HUMAN; INFLAMMATION; MALE; METABOLIC SYNDROME X; MONOCYTE; NONHUMAN; PRIORITY JOURNAL; PROTECTION; PROTEIN BLOOD LEVEL; PROTEIN EXPRESSION; RANDOMIZED CONTROLLED TRIAL; TREATMENT DURATION;

ADENYLATE KINASE; ANIMALS; CATTLE; CELL ADHESION; CELLS, CULTURED; CROSS-OVER STUDIES; DOUBLE-BLIND METHOD; ENDOTHELIAL CELLS; ENDOTHELIUM, VASCULAR; FEMALE; HESPERIDIN; HUMANS; INFLAMMATION; MALE; METABOLIC SYNDROME X; MIDDLE AGED; MONOCYTES; NITRIC OXIDE; NITRIC OXIDE SYNTHASE TYPE III; ONCOGENE PROTEIN V-AKT; SIGNAL TRANSDUCTION; STIMULATION, CHEMICAL; TUMOR NECROSIS FACTOR-ALPHA; VASODILATION;

BOVINAE; CITRUS;

EID: 79955655412     PISSN: 0021972X     EISSN: 0021972X     Source Type: Journal    
DOI: 10.1210/jc.2010-2879     Document Type: Article

References (54)

1. Kim JA, Montagnani M, Koh KK, Quon MJ 2006 Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms. Circulation 113: 1888-1904 (Pubitemid 43739401)
2. Muniyappa R, Montagnani M, Koh KK, Quon MJ 2007 Cardiovascular actions of insulin. Endocr Rev 28:463-491 (Pubitemid 47236334)
3. Potenza MA, Marasciulo FL, Tarquinio M, Quon MJ, Montagnani M2006 Treatment of spontaneously hypertensive rats with rosiglitazone and/or enalapril restores balance between vasodilator and vasoconstrictor actions of insulin with simultaneous improvement in hypertension and insulin resistance. Diabetes 55:3594-3603
4. Harnly JM, Doherty RF, Beecher GR, Holden JM, Haytowitz DB, Bhagwat S, Gebhardt S 2006 Flavonoid content of U.S. fruits, vegetables, and nuts. J Agric Food Chem 54:9966-9977 (Pubitemid 46158998)
5. Hertog MG, Feskens EJ, Hollman PC, Katan MB, Kromhout D 1993 Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Lancet 342:1007-1011 (Pubitemid 23314801)
6. Hertog MG, Kromhout D, Aravanis C, Blackburn H, Buzina R, Fidanza F, Giampaoli S, Jansen A, Menotti A, Nedeljkovic S, Pekkarinen M, Simic BS, Toshima H, Feskens EJM, Hollman PCH, Katan MB 1995 Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study. Arch Intern Med 155:381-386
7. Mink PJ, Scrafford CG, Barraj LM, Harnack L, Hong CP, Nettleton JA, Jacobs Jr DR 2007 Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women. AmJ Clin Nutr 85:895-909 (Pubitemid 46393524)
8. Williamson G, Manach C 2005 Bioavailability and bioefficacy of polyphenols in humans. II. Review of 93 intervention studies. Am J Clin Nutr 81:243S-255S
9. Nielsen IL, Chee WS, Poulsen L, Offord-Cavin E, Rasmussen SE, Frederiksen H, Enslen M, Barron D, Horcajada MN, Williamson G 2006 Bioavailability is improved by enzymatic modification of the citrus flavonoid hesperidin in humans: a randomized, double-blind, crossover trial. J Nutr 136:404-408 (Pubitemid 43228293)
10. Choe SC, Kim HS, Jeong TS, Bok SH, Park YB 2001 Naringin has an antiatherogenic effect with the inhibition of intercellular adhesion molecule-1 in hypercholesterolemic rabbits. J Cardiovasc Pharmacol 38:947-955
11. Kim JY, Jung KJ, Choi JS, Chung HY 2006 Modulation of the age-related nuclear factor-κB(NF-κB) pathway by hesperetin. Aging Cell 5:401-411 (Pubitemid 44322536)
12. Miwa Y, Yamada M, Sunayama T, Mitsuzumi H, Tsuzaki Y, Chaen H, Mishima Y, Kibata M 2004 Effects of glucosyl hesperidin on serum lipids in hyperlipidemic subjects: preferential reduction in elevated serum triglyceride level. J Nutr Sci Vitaminol (Tokyo) 50: 211-218 (Pubitemid 39045124)
13. Jung UJ, Kim HJ, Lee JS, Lee MK, Kim HO, Park EJ, Kim HK, Jeong TS, Choi MS 2003 Naringin supplementation lowers plasma lipids and enhances erythrocyte antioxidant enzyme activities in hypercholesterolemic subjects. Clin Nutr 22:561-568 (Pubitemid 37455724)
14. Ohtsuki K, Abe A, Mitsuzuwi H, Kondo M, Uemura K, Iwasaki Y, KondoY2002 Effects of long-term administration of hesperidin and glucosyl hesperidin to spontaneously hypertensive rats. J Nutr Sci Vitaminol (Tokyo) 48:420-422
15. Allister EM, Borradaile NM, Edwards JY, Huff MW 2005 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 54:1676-1683 (Pubitemid 40770757)
16. Borradaile NM, de Dreu LE, Huff MW 2003 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 52:2554-2561 (Pubitemid 37210545)
17. Borradaile NM, Carroll KK, Kurowska EM 1999 Regulation of HepG2 cell apolipoprotein B metabolism by the citrus flavanones hesperetin and naringenin. Lipids 34:591-598 (Pubitemid 29314429)
18. Davignon J, Ganz P 2004 Role of endothelial dysfunction in atherosclerosis. Circulation 109:III27-III32
19. Kim JA, Formoso G, Li Y, Potenza MA, Marasciulo FL, Montagnani M, Quon MJ 2007 Epigallocatechin gallate, a green tea polyphenol, mediates NO-dependent vasodilation using signaling pathways in vascular endothelium requiring reactive oxygen species and Fyn. J Biol Chem 282:13736-13745 (Pubitemid 47100559)
20. Potenza MA, Marasciulo FL, Tarquinio M, Tiravanti E, Colantuono G, Federici A, Kim JA, Quon MJ, Montagnani M 2007 EGCG, a green tea polyphenol, improves endothelial function and insulin sensitivity, reduces blood pressure, and protects against myocardial I/R injury in SHR. Am J Physiol Endocrinol Metab 292: E1378-E1387 (Pubitemid 46684607)
21. Hooper L, Kroon PA, Rimm EB, Cohn JS, Harvey I, Le Cornu KA, Ryder JJ, Hall WL, Cassidy A 2008 Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of randomized controlled trials. Am J Clin Nutr 88:38-50
22. Muniyappa R, Hall G, Kolodziej TL, Karne RJ, Crandon SK, Quon MJ 2008 Cocoa consumption for 2 wk enhances insulin-mediated vasodilatation without improving blood pressure or insulin resistance in essential hypertension. Am J Clin Nutr 88:1685-1696
23. Widlansky ME, Hamburg NM, Anter E, Holbrook M, Kahn DF, Elliott JG, Keaney Jr JF, Vita JA 2007 Acute EGCG supplementation reverses endothelial dysfunction in patients with coronary artery disease. J Am Coll Nutr 26:95-102 (Pubitemid 46911252)
24. Formoso G, Chen H, Kim JA, Montagnani M, Consoli A, Quon MJ 2006 Dehydroepiandrosterone mimics acute actions of insulin to stimulate production of both nitric oxide and endothelin 1 via distinct phosphatidylinositol 3-kinase- and mitogen-activated protein kinase-dependent pathways in vascular endothelium. Mol Endocrinol 20:1153-1163
25. Grundy SM, Brewer Jr HB, Cleeman JI, Smith Jr SC, Lenfant C 2004 Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Arterioscler Thromb Vasc Biol 24:e13-e18
26. Miwa Y, Mitsuzumi H, Sunayama T, Yamada M, Okada K, Kubota M, Chaen H, Mishima Y, Kibata M 2005 Glucosyl hesperidin lowers serum triglyceride level in hypertriglyceridemic subjects through the improvement of very low-density lipoprotein metabolic abnormality. J Nutr Sci Vitaminol (Tokyo) 51:460-470 (Pubitemid 43151736)
27. Rizza S, Tesauro M, Cardillo C, Galli A, Iantorno M, Gigli F, Sbraccia P, Federici M, Quon MJ, LauroD2009 Fish oil supplementation improves endothelial function in normoglycemic offspring of patients with type 2 diabetes. Atherosclerosis 206:569-574
28. Tesauro M, Rizza S, Iantorno M, Campia U, Cardillo C, Lauro D, Leo R, Turriziani M, Cocciolillo GC, Fusco A, Panza JA, Scuteri A, Federici M, Lauro R, Quon MJ 2007 Vascular, metabolic, and inflammatory abnormalities in normoglycemic offspring of patients with type 2 diabetes mellitus. Metabolism 56:413-419 (Pubitemid 46209232)
29. Armitage P, Berry G, Matthews J 1994 Statistical methods in medical research. 4th ed. Oxford, UK: Blackwell Science
30. Dimmeler S, Fleming I, Fisslthaler B, Hermann C, Busse R, Zeiher AM 1999 Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature 399:601-605
31. Chen ZP, Mitchelhill KI, Michell BJ, Stapleton D, Rodriguez-Crespo I, Witters LA, Power DA, Ortiz de Montellano PR, Kemp BE 1999 AMP-activated protein kinase phosphorylation of endothelial NO synthase. FEBS Lett 443:285-289
32. Zeng G, Nystrom FH, Ravichandran LV, Cong LN, Kirby M, Mostowski H,Quon MJ 2000 Roles for insulin receptor, PI3-kinase, and Akt in insulin-signaling pathways related to production of nitric oxide in human vascular endothelial cells. Circulation 101:1539-1545
33. Montagnani M, Chen H, Barr VA, Quon MJ 2001 Insulin-stimulated activation of eNOS is independent of Ca2but requires phosphorylation by Akt at Ser(1179). J Biol Chem 276:30392-30398
34. Napoli C, de Nigris F, Williams-Ignarro S, Pignalosa O, Sica V, Ignarro LJ 2006 Nitric oxide and atherosclerosis: an update. Nitric Oxide 15:265-279 (Pubitemid 44649284)
35. Irani K, Xia Y, Zweier JL, Sollott SJ, Der CJ, Fearon ER, Sundaresan M, Finkel T, Goldschmidt-Clermont PJ 1997 Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts. Science 275: 1649-1652
36. Sundaresan M, Yu ZX, Ferrans VJ, Irani K, Finkel T 1995 Requirement for generation of H2O2 for platelet-derived growth factor signal transduction. Science 270:296-299
37. Rubanyi GM, Vanhoutte PM 1986 Oxygen-derived free radicals, endothelium, and responsiveness of vascular smooth muscle. Am J Physiol 250:H815-H821
38. Auger C, Kim JH, Chabert P, Chaabi M, Anselm E, Lanciaux X, Lobstein A, Schini-Kerth VB 2010 The EGCG-induced redox-sensitive activation of endothelial nitric oxide synthase and relaxation are critically dependent on hydroxyl moieties. Biochem Biophys Res Commun 393:162-167
39. Thomas SR, Chen K, Keaney Jr JF 2002 Hydrogen peroxide activates endothelial nitric-oxide synthase through coordinated phosphorylation and dephosphorylation via a phosphoinositide 3-kinase- dependent signaling pathway. J Biol Chem 277:6017-6024 (Pubitemid 34968385)
40. Orallo F, Alvarez E, Basaran H, Lugnier C 2004 Comparative study of the vasorelaxant activity, superoxide-scavenging ability and cyclic nucleotide phosphodiesterase-inhibitory effects of hesperetin and hesperidin. Naunyn Schmiedebergs Arch Pharmacol 370:452-463 (Pubitemid 40104758)
41. Orallo F, Camiña M, Alvarez E, Basaran H, Lugnier C 2005 Implication of cyclic nucleotide phosphodiesterase inhibition in the vasorelaxant activity of the citrus-fruits flavonoid (+/-)-naringenin. Planta Med 71:99-107
42. Liu L, Xu DM, Cheng YY 2008 Distinct effects of naringenin and hesperetin on nitric oxide production from endothelial cells. J Agric Food Chem 56:824-829 (Pubitemid 351300251)
43. Ghanim H, Mohanty P, Pathak R, Chaudhuri A, Sia CL, Dandona P 2007 Orange juice or fructose intake does not induce oxidative and inflammatory response. Diabetes Care 30:1406-1411 (Pubitemid 46871146)
44. Lambert JD, Elias RJ 2010 The antioxidant and pro-oxidant activities of green tea polyphenols: a role in cancer prevention. Arch Biochem Biophys 501:65-72
45. Ghanim H, Sia CL, Upadhyay M, Korzeniewski K, Viswanathan P, Abuaysheh S, Mohanty P, Dandona P 2010 Orange juice neutralizes the proinflammatory effect of a high-fat, high-carbohydrate meal and prevents endotoxin increase and Toll-like receptor expression. Am J Clin Nutr 91:940-949
46. Price DT, Loscalzo J 1999 Cellular adhesion molecules and atherogenesis. Am J Med 107:85-97 (Pubitemid 29328286)
47. Lee CH, Jeong TS, Choi YK, Hyun BH, Oh GT, Kim EH, Kim JR, Han JI, Bok SH 2001 Anti-atherogenic effect of citrus flavonoids, naringin and naringenin, associated with hepatic ACAT and aortic VCAM-1 and MCP-1 in high cholesterol-fed rabbits. Biochem Biophys Res Commun 284:681-688
48. Manach C, Williamson G, Morand C, Scalbert A, Rémésy C 2005 Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am J Clin Nutr 81:230S-242S
49. Yamamoto M, Suzuki A, HaseT2008 Short-term effects of glucosyl hesperidin and hesperetin on blood pressure and vascular endothelial function in spontaneously hypertensive rats. J Nutr Sci Vitaminol (Tokyo) 54:95-98
50. Witte DR, Westerink J, de Koning EJ, van der Graaf Y, Grobbee DE, Bots ML 2005 Is the association between flow-mediated dilation and cardiovascular risk limited to low-risk populations? J Am Coll Cardiol 45:1987-1993
51. Fernández-Real JM, Ricart W 2003 Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr Rev 24:278-301 (Pubitemid 36724371)
52. Tanigaki K, Mineo C, Yuhanna IS, Chambliss KL, Quon MJ, Bonvini E, Shaul PW 2009 C-Reactive protein inhibits insulin activation of endothelial nitric oxide synthase via the immunoreceptor tyrosine- based inhibition motif of FcγRIIB and SHIP-1. Circ Res 104: 1275-1282
53. Kurowska EM, Spence JD, Jordan J, Wetmore S, Freeman DJ, Piché LA, Serratore P 2000 HDL-cholesterol-raising effect of orange juice in subjects with hypercholesterolemia. Am J Clin Nutr 72:1095-1100
54. Demonty I, Lin Y, Zebregs YE, Vermeer MA, van der Knaap HC, Jäkel M, Trautwein EA 2010 The citrus flavonoids hesperidin and naringin do not affect serum cholesterol in moderately hypercholesterolemic men and women. J Nutr 140:1615-1620