Quercetin: A treatment for hypertension? - A review of efficacy and mechanisms

Pharmaceuticals

Volumn 3, Issue 1, 2010, Pages 237-250

  Larson, Abigail J ^a   Symons, J David ^a   Jalili, Thunder ^a  

^a UNIVERSITY OF UTAH   (United States)

Author keywords

Angiotensin converting enzyme; Antioxidants; Endothelial function; Hypertension; Quercetin

Indexed keywords

AGLYCONE; ANTICOAGULANT AGENT; CAPTOPRIL; DIPEPTIDYL CARBOXYPEPTIDASE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; IMIDAPRIL; PLACEBO; QUERCETIN; RUTOSIDE;

ABSENCE OF SIDE EFFECTS; ALLERGY; ARTHRITIS; ASTHMA; BACTERIAL INFECTION; BLOOD PRESSURE MEASUREMENT; BLOOD VESSEL FUNCTION; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CHRONIC DRUG ADMINISTRATION; CLINICAL TRIAL; DEGENERATIVE DISEASE; DIET SUPPLEMENTATION; DISEASE SEVERITY; DOSE RESPONSE; DRUG ABSORPTION; DRUG ANTAGONISM; DRUG BINDING AND TRANSPORT; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CONJUGATION; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG MEGADOSE; DRUG SAFETY; DRUG STRUCTURE; ENZYME INHIBITION; EYE DISEASE; GENE EXPRESSION REGULATION; GOUT; HEADACHE; HEART PROTECTION; HUMAN; HUMAN VERSUS ANIMAL COMPARISON; HYPERTENSION; MODULATION; NAUSEA; NONHUMAN; OXIDATIVE STRESS; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; SIGNAL TRANSDUCTION; SINGLE DRUG DOSE; SKIN TINGLING; TREATMENT DURATION; VASCULAR SMOOTH MUSCLE; VASODILATATION;

EID: 77951949716     PISSN: None     EISSN: 14248247     Source Type: Journal    
DOI: 10.3390/ph3010237     Document Type: Review

References (52)

1. Chobanian, A.V.; Bakris, G.L.; Black, H.R.; Cushman, W.C.; Green, L.A.; Izzo, J.L.; Jones, D.W.; Materson, B.J.; Oparil, S.; Wright, J.T.; Roccella, E.J. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003, 42, 1206-1252.
2. Zago, A.S.; Zanesco, A. Nitric oxide, cardiovascular disease and physical exercise. Arq. Bras. Cardiol. 2006, 87, 264-270.
3. Perez-Vizcaino, F.; Duarte, J.; Andriantsitohaina, R. Endothelial function and cardiovascular disease: Effects of quercetin and wine polyphenols. Free Radic. Res. 2006, 40, 1054-1065.
4. Bohm, F.; Pernow, J. The importance of endothelin-1 for vascular dysfunction in cardiovascular disease. Cardiovasc. Res. 2007, 76, 8-18.
5. Carretero, O.A. Novel mechanism of action of ACE and its inhibitors. Am. J. Physiol. Heart Circ. Physiol. 2005, 289, 796-1797.
6. Parissis, J.T.; Korovesis, S.; Giazitzoglou, E.; Kalivas, P.; Katritsis, D. Plasma profiles of peripheral monocyte-related inflammatory markers in patients with arterial hypertension. Correlations with plasma endothelin-1. Int. J. Cardiol. 2002, 83, 13-21.
7. Unger, T.; Jakobsen, A.; Heroys, J.; Ralph, A.; Rees, T.; Shaw, M. Targeting cardiovascular protection: The concept of dual renin-angiotensin system control. Medscape J. Med. 2008, 10, 4.
8. Ziai, S.A.; Seyedhosseini, D.; Taiebi, L.; Salekmoghadam, E.; Mahmoudian, M. Correlation between ACE activity and mean blood pressure in Iranian normotensive subjects after oral administration of a single dose of enalapril. Acta Physiol. Hung 2000, 87, 153-159.
9. Vikrant, S.; Tiwari, S.C. Essential hypertension - Pathogenesis and pathophysiology. J. Indian Acad. Clin. Med. 2001, 2, 141-161.
10. Sica, D.A. Angiotensin-converting enzyme inhibitor use in the year 2005. J. Clin. Hypertens. (Greenwich) 2005, 7, 8-11.
11. Nijveldt, R.J.; van Nood, E.; van Hoorn, D.E.; Boelens, P.G.; van Norren, K.; van Leeuwen, P. A. Flavonoids: A review of probable mechanisms of action and potential applications. Am. J. Clin. Nutr. 2001, 74, 418-425.
12. Geleijnse, J.M.; Launer, L.J.; Van der Kuip, D.A.; Hofman, A.; Witteman, J.C. Inverse association of tea and flavonoid intakes with incident myocardial infarction: The Rotterdam Study. Am. J. Clin. Nutr. 2002, 75, 880-886.
13. Hertog, M.G.; Feskens, E.J.; Hollman, P.C.; Katan, M.B.; Kromhout, D. Dietary antioxidant flavonoids and risk of coronary heart disease: The Zutphen Elderly Study. Lancet 1993, 342, 1007-1011.
14. Knekt, P.; Kumpulainen, J.; Jarvinen, R.; Rissanen, H.; Heliovaara, M.; Reunanen, A.; Hakulinen, T.; Aromaa, A. Flavonoid intake and risk of chronic diseases. Am. J. Clin. Nutr. 2002, 76, 560-568.
15. Manach, C.; Williamson, G.; Morand, C.; Scalbert, A.; Remesy, C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am. J. Clin. Nutr. 2005, 81, 230-242.
16. Scalbert, A.; Williamson, G. Dietary intake and bioavailability of polyphenols. J. Nutr. 2000, 130, 2073-2085.
17. Agriculture, USDA. USDA database for the flavonoid content of selected foods. In USDA; Beltsville, 2003. http://www.nal.usda.gov/fnic/foodcomp/Data/Flav/flav.pdf/, accessed 15 October 2008.
18. Chen, X.; Yin, O.Q.; Zuo, Z.; Chow, M.S. Pharmacokinetics and modeling of quercetin and metabolites. Pharm. Res. 2005, 22, 892-901.
19. Egert, S.; Wolffram, S.; Bosy-Westphal, A.; Boesch-Saadatmandi, C.; Wagner, A.E.; Frank, J.; Rimbach, G.; Mueller, M.J. Daily quercetin supplementation dose-dependently increases plasma quercetin concentrations in healthy humans. J. Nutr. 2008, 138, 1615-1621.
20. Erlund, I.; Kosonen, T.; Alfthan, G.; Maenpaa, J.; Perttunen, K.; Kenraali, J.; Parantainen, J.; Aro, A. Pharmacokinetics of quercetin from quercetin aglycone and rutin in healthy volunteers. Eur. J. Clin. Pharmacol. 2000, 56, 545-553.
21. Hollman, P.C.; vd Gaag, M.; Mengelers, M.J.; van Trijp, J.M.; de Vries, J.H.; Katan, M.B., Absorption and disposition kinetics of the dietary antioxidant quercetin in man. Free Radic. Biol. Med. 1996, 21, 703-707.
22. Lesser, S.; Cermak, R.; Wolffram, S. Bioavailability of quercetin in pigs is influenced by the dietary fat content. J. Nutr. 2004, 134, 1508-1511.
23. Moon, Y.J.; Wang, L.; DiCenzo, R.; Morris, M.E. Quercetin pharmacokinetics in humans. Biopharm. Drug Dispos. 2008, 29, 205-217.
24. Wiczkowski, W.; Romaszko, J.; Bucinski, A.; Szawara-Nowak, D.; Honke, J.; Zielinski, H.; Piskula, M.K. Quercetin from shallots (Allium cepa L. var. aggregatum) is more bioavailable than its glucosides. J. Nutr. 2008, 138, 885-888.
25. Hooper, L.; Kroon, P.A.; Rimm, E.B.; Cohn, J.S.; Harvey, I.; Le Cornu, K.A.; Ryder, J.J.; Hall, W.L.; Cassidy, A. Flavonoids, flavonoid-rich foods, and cardiovascular risk: A meta-analysis of randomized controlled trials. Am. J. Clin. Nutr. 2008, 88, 38-50.
26. Loke, W.M.; Hodgson, J.M.; Proudfoot, J.M.; McKinley, A.J.; Puddey, I.B.; Croft, K.D. Pure dietary flavonoids quercetin and (-)-epicatechin augment nitric oxide products and reduce endothelin-1 acutely in healthy men. Am. J. Clin. Nutr. 2008, 88, 1018-1025.
27. Larson, A.; Bruno, R.; Guo, Y.; Gale, D.; Tanner, J.; Jalili, T.; Symons, J. Acute Quercetin Supplementation Does Not Lower Blood Pressure or Ace Activity in Normotensive Males. J. Am. Diet. Assoc. 2009, 109, 16.
28. Carlstrom, J.; Symons, J.D.; Wu, T.C.; Bruno, R.S.; Litwin, S.E.; Jalili, T. A quercetin supplemented diet does not prevent cardiovascular complications in spontaneously hypertensive rats. J. Nutr. 2007, 137, 628-633.
29. Duarte, J.; Perez-Palencia, R.; Vargas, F.; Ocete, M.A.; Perez-Vizcaino, F.; Zarzuelo, A.; Tamargo, J. Antihypertensive effects of the flavonoid quercetin in spontaneously hypertensive rats. Br. J. Pharmacol. 2001, 133, 117-124.
30. Yamamoto, Y.; Oue, E. Antihypertensive effect of quercetin in rats fed with a high-fat high- sucrose diet. Biosci. Biotechnol. Biochem. 2006, 70, 933-939.
31. Duarte, J.; Jimenez, R.; O'Valle, F.; Galisteo, M.; Perez-Palencia, R.; Vargas, F.; Perez-Vizcaino, F.; Zarzuelo, A.; Tamargo, J. Protective effects of the flavonoid quercetin in chronic nitric oxide deficient rats. J. Hypertens. 2002, 20, 1843-1854.
32. Hackl, L.P.; Cuttle, G.; Dovichi, S.S.; Lima-Landman, M.T.; Nicolau, M. Inhibition of angiotesin-converting enzyme by quercetin alters the vascular response to brandykinin and angiotensin I. Pharmacology 2002, 65, 182-186.
33. Jalili, T.; Carlstrom, J.; Kim, S.; Freeman, D.; Jin, H.; Wu, T.C.; Litwin, S.E.; David Symons, J. Quercetin-supplemented diets lower blood pressure and attenuate cardiac hypertrophy in rats with aortic constriction. J. Cardiovasc. Pharmacol. 2006, 47, 531-541.
34. Mackraj, I.; Govender, T.; Ramesar, S. The antihypertensive effects of quercetin in a salt-sensitive model of hypertension. J. Cardiovasc. Pharmacol. 2008, 51, 239-245.
35. Perez-Vizcaino, F.; Ibarra, M.; Cogolludo, A. L.; Duarte, J.; Zaragoza-Arnaez, F.; Moreno, L.; Lopez-Lopez, G.; Tamargo, J. Endothelium-independent vasodilator effects of the flavonoid quercetin and its methylated metabolites in rat conductance and resistance arteries. J. Pharmacol. Exp. Ther. 2002, 302, 66-72.
36. Chen, C.K.; Pace-Asciak, C.R. Vasorelaxing activity of resveratrol and quercetin in isolated rat aorta. Gen. Pharmacol. 1996, 27, 363-366.
37. Edwards, R.L.; Lyon, T.; Litwin, S.E.; Rabovsky, A.; Symons, J.D.; Jalili, T. Quercetin reduces blood pressure in hypertensive subjects. J. Nutr. 2007, 137, 2405-2411.
38. Conquer, J.A.; Maiani, G.; Azzini, E.; Raguzzini, A.; Holub, B.J. Supplementation with quercetin markedly increases plasma quercetin concentration without effect on selected risk factors for heart disease in healthy subjects. J. Nutr. 1998, 128, 593-597.
39. Appel, L.J.; Moore, T.J.; Obarzanek, E.; Vollmer, W.M.; Svetkey, L.P.; Sacks, F.M.; Bray, G.A.; Vogt, T.M.; Cutler, J.A.; Windhauser, M.M.; Lin, P.H.; Karanja, N. A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. N. Engl. J. Med. 1997, 336, 1117-1124.
40. Egert, S.; Bosy-Westphal, A.; Seiberl, J.; Kurbitz, C.; Settler, U.; Plachta-Danielzik, S.; Wagner, A.E.; Frank, J.; Schrezenmeir, J.; Rimbach, G.; Wolffram, S.; Muller, M.J. Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: A double-blinded, placebo-controlled cross-over study. Br. J. Nutr. 2009, 102, 1-10.
41. Wyld, P.J.; Grant, J.; Lippi, A.; Criscuoli, M.; Del Re, G.; Subissi, A. Pharmacokinetics and biochemical efficacy of idrapril calcium, a novel ACE inhibitor, after multiple oral administration in humans. Br. J. Clin. Pharmacol. 1994, 38, 421-425.
42. Loizzo, M.R.; Said, A.; Tundis, R.; Rashed, K.; Statti, G.A.; Hufner, A.; Menichini, F. Inhibition of angiotensin converting enzyme (ACE) by flavonoids isolated from Ailanthus excelsa (Roxb) (Simaroubaceae). Phytother. Res. 2007, 21, 32-36.
43. Sainani, G.S.; Maru, V.G. Role of endothelial cell dysfunction in essential hypertension. J. Assoc. Physicians India 2004, 52, 966-969.
44. Perticone, F.; Ceravolo, R.; Pujia, A.; Ventura, G.; Iacopino, S.; Scozzafava, A.; Ferraro, A.; Chello, M.; Mastroroberto, P.; Verdecchia, P.; Schillaci, G. Prognostic significance of endothelial dysfunction in hypertensive patients. Circulation 2001, 104, 191-196.
45. Endemann, D.H.; Schiffrin, E.L. Endothelial dysfunction. J. Am. Soc. Nephrol. 2004, 15, 1983-1992.
46. Moens, A.L.; Goovaerts, I.; Claeys, M.J.; Vrints, C.J. Flow-mediated vasodilation: A diagnostic instrument, or an experimental tool? Chest 2005, 127, 2254-2263.
47. Vita, J.A. Polyphenols and cardiovascular disease: Effects on endothelial and platelet function. Am. J. Clin. Nutr. 2005, 81, 292-297.
48. Nicholson, S.K.; Tucker, G.A.; Brameld, J.M. Effects of dietary polyphenols on gene expression in human vascular endothelial cells. Proc. Nutr. Soc. 2008, 67, 42-47.
49. Sanchez, M.; Galisteo, M.; Vera, R.; Villar, I.C.; Zarzuelo, A.; Tamargo, J.; Perez-Vizcaino, F.; Duarte, J. Quercetin downregulates NADPH oxidase, increases eNOS activity and prevents endothelial dysfunction in spontaneously hypertensive rats. J. Hypertens. 2006, 24, 75-84.
50. Zhao, X.Y.; Gu, Z.L. Effects of quercetin on production and release of endothelin and cGMP from cultured endothelial cells. Zhongguo Yao Li Xue Bao 1996, 17, 442-444.
51. Rendig, S.V.; Symons, J.D.; Longhurst, J.C.; Amsterdam, E.A. Effects of red wine, alcohol, and quercetin on coronary resistance and conductance arteries. J. Cardiovasc. Pharmacol. 2001, 38, 219-227.
52. Harwood M.; Danielewska-Nikiel B.; Borzellaca J.F.; Flamm G.W.; Williams G.M.; Lines T.C. A Critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties. Food Chem. Toxicol. 2007, 45, 2178-2205.