Beneficial Effects of Citrus Flavonoids on Cardiovascular and Metabolic Health

Overview

Journal Oxid Med Cell Longev

Publisher Wiley

Specialties Cell Biology
Endocrinology

Date 2019 Apr 10

PMID 30962863

Citations 101

Authors

Ayman M Mahmoud

Rene J Hernandez Bautista

Mansur A Sandhu

Omnia E Hussein

Affiliations

Soon will be listed here.

Abstract

The prevalence of cardiovascular disease (CVD) is increasing over time. CVD is a comorbidity in diabetes and contributes to premature death. Citrus flavonoids possess several biological activities and have emerged as efficient therapeutics for the treatment of CVD. Citrus flavonoids scavenge free radicals, improve glucose tolerance and insulin sensitivity, modulate lipid metabolism and adipocyte differentiation, suppress inflammation and apoptosis, and improve endothelial dysfunction. The intake of citrus flavonoids has been associated with improved cardiovascular outcomes. Although citrus flavonoids exerted multiple beneficial effects, their mechanisms of action are not completely established. In this review, we summarized recent findings and advances in understanding the mechanisms underlying the protective effects of citrus flavonoids against oxidative stress, inflammation, diabetes, dyslipidemia, endothelial dysfunction, and atherosclerosis. Further studies and clinical trials to assess the efficacy and to explore the underlying mechanism(s) of action of citrus flavonoids are recommended.

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References

Merat S, Casanada F, Sutphin M, Palinski W, Reaven P . Western-type diets induce insulin resistance and hyperinsulinemia in LDL receptor-deficient mice but do not increase aortic atherosclerosis compared with normoinsulinemic mice in which similar plasma cholesterol levels are achieved by a.... Arterioscler Thromb Vasc Biol. 1999; 19(5):1223-30. DOI: 10.1161/01.atv.19.5.1223. View

Borradaile N, Carroll K, Kurowska E . Regulation of HepG2 cell apolipoprotein B metabolism by the citrus flavanones hesperetin and naringenin. Lipids. 1999; 34(6):591-8. DOI: 10.1007/s11745-999-0403-7. View

Desvergne B, Wahli W . Peroxisome proliferator-activated receptors: nuclear control of metabolism. Endocr Rev. 1999; 20(5):649-88. DOI: 10.1210/edrv.20.5.0380. View

Virmani R, Kolodgie F, Burke A, Farb A, Schwartz S . Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions. Arterioscler Thromb Vasc Biol. 2000; 20(5):1262-75. DOI: 10.1161/01.atv.20.5.1262. View

Russo A, Acquaviva R, Campisi A, Sorrenti V, Di Giacomo C, Virgata G . Bioflavonoids as antiradicals, antioxidants and DNA cleavage protectors. Cell Biol Toxicol. 2000; 16(2):91-8. DOI: 10.1023/a:1007685909018. View

Fuhrman B, Aviram M . Flavonoids protect LDL from oxidation and attenuate atherosclerosis. Curr Opin Lipidol. 2001; 12(1):41-8. DOI: 10.1097/00041433-200102000-00008. View

Wilcox L, Borradaile N, de Dreu L, Huff M . 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(5):725-34. View

Lee C, Jeong T, Choi Y, Hyun B, Oh G, Kim E . 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. 2001; 284(3):681-8. DOI: 10.1006/bbrc.2001.5001. View

Choe S, Kim H, Jeong T, Bok S, Park Y . Naringin has an antiatherogenic effect with the inhibition of intercellular adhesion molecule-1 in hypercholesterolemic rabbits. J Cardiovasc Pharmacol. 2001; 38(6):947-55. DOI: 10.1097/00005344-200112000-00017. View

10.

Chen H, Ward M, Graubard B, Heineman E, Markin R, Potischman N . Dietary patterns and adenocarcinoma of the esophagus and distal stomach. Am J Clin Nutr. 2002; 75(1):137-44. DOI: 10.1093/ajcn/75.1.137. View

11.

Jeon S, Bok S, Jang M, Kim Y, Nam K, Jeong T . Comparison of antioxidant effects of naringin and probucol in cholesterol-fed rabbits. Clin Chim Acta. 2002; 317(1-2):181-90. DOI: 10.1016/s0009-8981(01)00778-1. View

12.

Borradaile N, de Dreu L, Barrett P, Huff M . Inhibition of hepatocyte apoB secretion by naringenin: enhanced rapid intracellular degradation independent of reduced microsomal cholesteryl esters. J Lipid Res. 2002; 43(9):1544-54. DOI: 10.1194/jlr.m200115-jlr200. View

13.

Borradaile N, de Dreu L, Barrett P, Behrsin C, Huff M . Hepatocyte apoB-containing lipoprotein secretion is decreased by the grapefruit flavonoid, naringenin, via inhibition of MTP-mediated microsomal triglyceride accumulation. Biochemistry. 2003; 42(5):1283-91. DOI: 10.1021/bi026731o. View

14.

Huxley R, Neil H . The relation between dietary flavonol intake and coronary heart disease mortality: a meta-analysis of prospective cohort studies. Eur J Clin Nutr. 2003; 57(8):904-8. DOI: 10.1038/sj.ejcn.1601624. View

15.

Bucki R, Pastore J, Giraud F, Sulpice J, Janmey P . Flavonoid inhibition of platelet procoagulant activity and phosphoinositide synthesis. J Thromb Haemost. 2003; 1(8):1820-8. DOI: 10.1046/j.1538-7836.2003.00294.x. View

16.

Naghavi M, Libby P, Falk E, Casscells S, Litovsky S, Rumberger J . From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I. Circulation. 2003; 108(14):1664-72. DOI: 10.1161/01.CIR.0000087480.94275.97. View

17.

Jung U, Kim H, Lee J, Lee M, Kim H, Park E . Naringin supplementation lowers plasma lipids and enhances erythrocyte antioxidant enzyme activities in hypercholesterolemic subjects. Clin Nutr. 2003; 22(6):561-8. DOI: 10.1016/s0261-5614(03)00059-1. View

18.

Manach C, Scalbert A, Morand C, Remesy C, Jimenez L . Polyphenols: food sources and bioavailability. Am J Clin Nutr. 2004; 79(5):727-47. DOI: 10.1093/ajcn/79.5.727. View

19.

Miwa Y, Yamada M, Sunayama T, Mitsuzumi H, Tsuzaki Y, Chaen H . Effects of glucosyl hesperidin on serum lipids in hyperlipidemic subjects: preferential reduction in elevated serum triglyceride level. J Nutr Sci Vitaminol (Tokyo). 2004; 50(3):211-8. DOI: 10.3177/jnsv.50.211. View

20.

Spagnoli L, Mauriello A, Sangiorgi G, Fratoni S, Bonanno E, Schwartz R . Extracranial thrombotically active carotid plaque as a risk factor for ischemic stroke. JAMA. 2004; 292(15):1845-52. DOI: 10.1001/jama.292.15.1845. View