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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Flavonoids and Reduction of Cardiovascular Disease (CVD) in Chronic Obstructive Pulmonary Disease (COPD)

Author(s): ">Patrizia Russo*, ">Giulia Prinzi, ">Palma Lamonaca, ">Vittorio Cardaci and ">Massimo Fini

Volume 26, Issue 39, 2019

Page: [7048 - 7058] Pages: 11

DOI: 10.2174/0929867325666180514100640

Price: $65


Background: Chronic Obstructive Pulmonary Disease (COPD) and Cardiovascular Diseases (CV) Often Coexist. COPD and CVD are complex diseases characterized by a strict interaction between environment and genetic. The mechanisms linking these two diseases are complex, multifactorial and not entirely understood, influencing the therapeutic approach. COPD is characterized by several comorbidities, it hypothesized the treatment of cardiovascular co-morbidities that may reduce morbidity and mortality. Flavonoids are an important class of plant low molecular weight Secondary Metabolites (SMs). Convincing data from laboratory, epidemiological, and human clinical studies point the important effects on CVD risk prevention.

Objective: This review aims to provide up-to-date information on the ability of Flavonoids to reduce the CVD risk.

Conclusion: Current studies support the potential of Flavonoids to prevent the risk of CVD. Well-designed clinical studies are suggested to evaluate advantages and limits of Flavonoids for managing CVD comorbidity in COPD.

Keywords: Cardiovascular Disease Reduction, COPD, flavonoids, pathophysiological mechanisms, rehabilomics, inflammatory disease, comorbidity.

Martinez, F.D. Early-life origins of chronic obstructive pulmonary disease. N. Engl. J. Med., 2016, 375(9), 871-878.
[] [PMID: 27579637]
Woodruff, P.G.; Agusti, A.; Roche, N.; Singh, D.; Martinez, F.J. Current concepts in targeting chronic obstructive pulmonary disease pharmacotherapy: making progress towards personalised management. Lancet, 2015, 385(9979), 1789-1798.
[] [PMID: 25943943]
Vanfleteren, L.E.G.W.; Spruit, M.A.; Wouters, E.F.M.; Franssen, F.M.E. Management of chronic obstructive pulmonary disease beyond the lungs. Lancet Respir. Med., 2016, 4(11), 911-924.
[] [PMID: 27264777]
Perret, J.L.; Walters, E.H.; Abramson, M.J.; McDonald, C.F.; Dharmage, S.C. The independent and combined effects of lifetime smoke exposures and asthma as they relate to COPD. Expert Rev. Respir. Med., 2014, 8(4), 503-514.
[] [PMID: 24834459]
Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Report 2017.Available at. (Accessed Date: 21 August, 2017)
Brown, J.P.; Martinez, C.H. Chronic obstructive pulmonary disease comorbidities. Curr. Opin. Pulm. Med., 2016, 22(2), 113-118.
[] [PMID: 26814720]
Lundbäck, B.; Lindberg, A.; Lindström, M.; Rönmark, E.; Jonsson, A.C.; Jönsson, E.; Larsson, L.G.; Andersson, S.; Sandström, T.; Larsson, K. Obstructive Lung disease in Northern Sweden studies. not 15 but 50% of smokers develop COPD?--report from the obstructive lung disease in Northern Sweden studies. Respir. Med., 2003, 97(2), 115-122.
[] [PMID: 12587960]
Vestbo, J.; Hurd, S.S.; Agustí, A.G.; Jones, P.W.; Vogelmeier, C.; Anzueto, A.; Barnes, P.J.; Fabbri, L.M.; Martinez, F.J.; Nishimura, M.; Stockley, R.A.; Sin, D.D.; Rodriguez-Roisin, R. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am. J. Respir. Crit. Care Med., 2013, 187(4), 347-365.
[] [PMID: 22878278]
Postma, D.S.; Bush, A.; van den Berge, M. Risk factors and early origins of chronic obstructive pulmonary disease. Lancet, 2015, 385(9971), 899-909.
[] [PMID: 25123778]
Schamberger, A.C.; Mise, N.; Meiners, S.; Eickelberg, O. Epigenetic mechanisms in COPD: implications for pathogenesis and drug discovery. Expert Opin. Drug Discov., 2014, 9(6), 609-628.
[] [PMID: 24850530]
Onishi, K. Total management of chronic obstructive pulmonary disease (COPD) as an independent risk factor for cardiovascular disease. J. Cardiol., 2017, 70(2), 128-134.
[] [PMID: 28325523]
Cazzola, M.; Calzetta, L.; Rinaldi, B.; Page, C.; Rosano, G.; Rogliani, P.; Matera, M.G. Management of chronic obstructive pulmonary disease in patients with cardiovascular diseases. Drugs, 2017, 77(7), 721-732.
[] [PMID: 28349353]
Roversi, S.; Fabbri, L.M.; Sin, D-D.; Hawkins, N.M.; Agustí, A. Chronic obstructive pulmonary disease and cardiac diseases. An urgent need for integrated care. Am. J. Respir. Crit. Care Med., 2016, 194(11), 1319-1336.
[] [PMID: 27589227]
Chen, W.; Thomas, J.; Sadatsafavi, M.; FitzGerald, J.M. Risk of cardiovascular comorbidity in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis. Lancet Respir. Med., 2015, 3(8), 631-639.
[] [PMID: 26208998]
Yin, H.L.; Yin, S.Q.; Lin, Q.Y.; Xu, Y.; Xu, H.W.; Liu, T. Prevalence of comorbidities in chronic obstructive pulmonary disease patients: A meta-analysis. Medicine (Baltimore), 2017, 96(19) e6836
[] [PMID: 28489768]
Kisialiou, A.; Prinzi, G.; Lamonaca, P.; Fini, M.; Bonassi, S.; Russo, P. Pharmacological Management of Chronic Obstructive Pulmonary Disease (COPD). Evidence from a Real-World Perspective. Curr. Med. Chem., 2017.
Divo, M.; Cote, C.; de Torres, J.P.; Casanova, C.; Marin, J.M.; Pinto-Plata, V.; Zulueta, J.; Cabrera, C.; Zagaceta, J.; Hunninghake, G.; Celli, B. BODE Collaborative Group. Comorbidities and risk of mortality in patients with chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med., 2012, 186(2), 155-161.
[] [PMID: 22561964]
Thomson, N.C. Asthma and smoking-induced airway disease without spirometric COPD. Eur. Respir. J., 2017, 49(5) 1602061
[] [PMID: 28461294]
Centers for Disease Control and Prevention (US); National Center for Chronic Disease Prevention and Health Promotion (US); Office on Smoking and Health (US). How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease. A Report of the Surgeon General. Atlanta (GA): Centers for Disease Control and Pre-vention (US) 2010.Available at. (Accessed Date: 31 August, 2017)
The health consequences of smoking-50 years of progress: A report of the surgeon general. National center for chronic disease prevention and health promotion (us) of-fice on smoking and health. Atlanta (GA): Centers for disease control and prevention (US) 2014.Available at. (Accessed Date: 31 August, 2017)
West, R. Tobacco smoking: Health impact, prevalence, correlates and interventions. Psychol. Health, 2017, 32(8), 1018-1036.
[] [PMID: 28553727]
Argacha, J.F.; Bourdrel, T.; van de Borne, P. Ecology of the cardiovascular system: A focus on air-related environmental factors. Trends Cardiovasc. Med., 2018, 28(2), 112-126.
[] [PMID: 28826667]
Fragoso, C.A.; Liu, X.; Fragoso, C.A. Epidemiology of Chronic Obstructive Pulmonary Disease (COPD) in aging populations. COPD, 2016, 13(2), 125-129.
[] [PMID: 26629987]
Chronic Obstructive Pulmonary Disease among Adults Aged 18 and Over in the United States, 1998-2009. NCHS Data Brief No 63; National Center for Health Statistics: Hyattsville, MD, 2011.
Assaggaf, H.; Felty, Q. Gender, estrogen, and obliterative lesions in the lung. Int. J. Endocrinol., 2017, 2017 8475701
[] [PMID: 28469671]
Barnes, P.J. Mechanisms of development of multimorbidity in the elderly. Eur. Respir. J., 2015, 45(3), 790-806.
[] [PMID: 25614163]
Divo, M.J.; Celli, B.R.; Poblador-Plou, B.; Calderón-Larrañaga, A.; de-Torres, J.P.; Gimeno-Feliu, L.A.; Bertó, J.; Zulueta, J.J.; Casanova, C.; Pinto-Plata, V.M.; Cabrera-Lopez, C.; Polverino, F.; Carmona Píréz, J.; Prados-Torres, A.; Marin, J.M. EpiChron—BODE Collaborative Group. Chronic Obstructive Pulmonary Disease (COPD) as a disease of early aging: Evidence from the EpiChron Cohort. PLoS One, 2018, 13(2) e0193143
[] [PMID: 29470502]
Panche, A.N.; Diwan, A.D.; Chandra, S.R. Flavonoids: an overview. J. Nutr. Sci., 2016, 5 e47
[] [PMID: 28620474]
Kumar, S.; Pandey, A.K. Chemistry and biological activities of flavonoids: an overview. ScientificWorldJournal, 2013, 2013 162750
[] [PMID: 24470791]
Russo, P.; Del Bufalo, A.; Cesario, A. Flavonoids acting on DNA topoisomerases: recent advances and future perspectives in cancer therapy. Curr. Med. Chem., 2012, 19(31), 5287-5293.
[] [PMID: 22998568]
Menezes, R.; Rodriguez-Mateos, A.; Kaltsatou, A.; González-Sarrías, A.; Greyling, A.; Giannaki, C.; Andres-Lacueva, C.; Milenkovic, D.; Gibney, E.R.; Dumont, J.; Schär, M.; Garcia-Aloy, M.; Palma-Duran, S.A.; Ruskovska, T.; Maksimova, V.; Combet, E.; Pinto, P. Impact of flavonols on cardiometabolic biomarkers: A meta-analysis of randomized controlled human trials to explore the role of inter-individual variability. Nutrients, 2017, 9(2) E117
[] [PMID: 28208791]
Lin, X.; Zhang, I.; Li, A.; Manson, J.E.; Sesso, H.D.; Wang, L.; Liu, S. Cocoa flavanol intake and biomarkers for cardiometabolic health: A systematic review and meta-analysis of randomized controlled trials. J. Nutr., 2016, 146(11), 2325-2333.
[] [PMID: 27683874]
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(1), 38-50.
[] [PMID: 18614722]
Tokede, O.A.; Gaziano, J.M.; Djoussé, L. Effects of cocoa products/dark chocolate on serum lipids: a meta-analysis. Eur. J. Clin. Nutr., 2011, 65(8), 879-886.
[] [PMID: 21559039]
Ried, K.; Fakler, P.; Stocks, N.P. Effect of cocoa on blood pressure. Cochrane Database Syst. Rev., 2017, 4 CD008893
[] [PMID: 28439881]
Desch, S.; Schmidt, J.; Kobler, D.; Sonnabend, M.; Eitel, I.; Sareban, M.; Rahimi, K.; Schuler, G.; Thiele, H. Effect of cocoa products on blood pressure: systematic review and meta-analysis. Am. J. Hypertens., 2010, 23(1), 97-103.
[] [PMID: 19910929]
Ried, K.; Sullivan, T.; Fakler, P.; Frank, O.R.; Stocks, N.P. Does chocolate reduce blood pressure? A meta-analysis. BMC Med., 2010, 8, 39.
[] [PMID: 20584271]
Zhu, Y.; Bo, Y.; Wang, X.; Lu, W.; Wang, X.; Han, Z.; Qiu, C. The effect of anthocyanins on blood pressure: A PRISMA-compliant meta-analysis of randomized clinical trials. Medicine (Baltimore), 2016, 95(15) e3380
[] [PMID: 27082604]
Sahebkar, A. Effects of quercetin supplementation on lipid profile: A systematic review and meta-analysis of randomized controlled trials. Crit. Rev. Food Sci. Nutr., 2017, 57(4), 666-676.
[] [PMID: 25897620]
Sahebkar, A.; Simental-Mendía, L.E.; Giorgini, P.; Ferri, C.; Grassi, D. Lipid profile changes after pomegranate consumption: A systematic review and meta-analysis of randomized controlled trials. Phytomedicine, 2016, 23(11), 1103-1112.
[] [PMID: 26857863]
Sahebkar, A. A systematic review and meta-analysis of the effects of pycnogenol on plasma lipids. J. Cardiovasc. Pharmacol. Ther., 2014, 19(3), 244-255.
[] [PMID: 24346156]
Qi, n Y.; Niu, K.; Zeng, Y.; Liu, P.; Yi, L.; Zhang, T.; Zhang, Q.Y.; Zhu, -JD.; Mi, YM-T. Isoflavones for hypercholesterolaemia in adults. Cochrane Database Syst. Rev., 2013, 6 CD009518
[] [PMID: 23744562]
Jia, L.; Liu, X.; Bai, Y.Y.; Li, S.H.; Sun, K.; He, C.; Hui, R. Short-term effect of cocoa product consumption on lipid profile: a meta-analysis of randomized controlled trials. Am. J. Clin. Nutr., 2010, 92(1), 218-225.
[] [PMID: 20504978]
Jiang, W.; Wei, H.; He, B. Dietary flavonoids intake and the risk of coronary heart disease: a dose-response meta-analysis of 15 prospective studies. Thromb. Res., 2015, 135(3), 459-463.
[] [PMID: 25555317]
Wang, Z.M.; Nie, Z.L.; Zhou, B.; Lian, X.Q.; Zhao, H.; Gao, W.; Wang, Y.S.; Jia, E.Z.; Wang, L.S.; Yang, Z.J. Flavonols intake and the risk of coronary heart disease: a meta-analysis of cohort studies. Atherosclerosis, 2012, 222(1), 270-273.
[] [PMID: 22429503]
Li, S.H.; Tian, H.B.; Zhao, H.J.; Chen, L.H.; Cui, L.Q. The acute effects of grape polyphenols supplementation on endothelial function in adults: meta-analyses of controlled trials. PLoS One, 2013, 8(7) e69818
[] [PMID: 23894543]
Li, S.H.; Liu, X.X.; Bai, Y.Y.; Wang, X.J.; Sun, K.; Chen, J.Z.; Hui, R.T. Effect of oral isoflavone supplementation on vascular endothelial function in postmenopausal women: a meta-analysis of randomized placebo-controlled trials. Am. J. Clin. Nutr., 2010, 91(2), 480-486.
[] [PMID: 19923372]
Beavers, D.P.; Beavers, K.M.; Miller, M.; Stamey, J.; Messina, M.J. Exposure to isoflavone-containing soy products and endothelial function: a Bayesian meta-analysis of randomized controlled trials. Nutr. Metab. Cardiovasc. Dis., 2012, 22(3), 182-191.
[] [PMID: 20709515]
McCullough, M.L.; Chevaux, K.; Jackson, L.; Preston, M.; Martinez, G.; Schmitz, H.H.; Coletti, C.; Campos, H.; Hollenberg, N.K. Hypertension, the Kuna, and the epidemiology of flavanols. J. Cardiovasc. Pharmacol., 2006, 47(Suppl. 2), S103-S109.
[] [PMID: 16794446]
Lawes, C.M.; Vander Hoorn, S.; Rodgers, A. International Society of Hypertension. Global burden of blood-pressure-related disease, 2001. Lancet, 2008, 371(9623), 1513-1518.
[] [PMID: 18456100]
Martiniuk, A.L.; Lee, C.M.; Lawes, C.M.; Ueshima, H.; Suh, I.; Lam, T.H.; Gu, D.; Feigin, V.; Jamrozik, K.; Ohkubo, T.; Woodward, M. Asia-pacific cohort studies collaboration. Hypertension: its prevalence and population-attributable fraction for mortality from cardiovascular disease in the Asia-Pacific region. J. Hypertens., 2007, 25(1), 73-79.
[] [PMID: 17143176]
Kim, S.H.; Park, J.H.; Lee, J.K.; Heo, E.Y.; Kim, D.K.; Chung, H.S. Chronic obstructive pulmonary disease is independently associated with hypertension in men: A survey design analysis using nationwide survey data. Medicine (Baltimore), 2017, 96(19) e6826
[] [PMID: 28489760]
Kaufman, T.; Justeson, J. History of the Word for ‘Cacao’ and Related Terms in Ancient Meso-America. In: McNeil, C. L. Chocolate in Mesoamerica: A Cultural History of Cacao; University Press of Florida, 2006; p. 121.
Magrone, T.; Russo, M.A.; Jirillo, E.E. Cocoa and dark chocolate polyphenols: From biology to clinical applications. Front. Immunol., 2017, 8, 677.
[] [PMID: 28649251]
Fraga, C.G.; Litterio, M.C.; Prince, P.D.; Calabró, V.; Piotrkowski, B.; Galleano, M. Cocoa flavanols: effects on vascular nitric oxide and blood pressure. J. Clin. Biochem. Nutr., 2011, 48(1), 63-67.
[] [PMID: 21297914]
Schnorr, O.; Brossette, T.; Momma, T.Y.; Kleinbongard, P.; Keen, C.L.; Schroeter, H.; Sies, H. Cocoa flavanols lower vascular arginase activity in human endothelial cells in vitro and in erythrocytes in vivo. Arch. Biochem. Biophys., 2008, 476(2), 211-215.
[] [PMID: 18348861]
Grassi, D.; Desideri, G.; Mai, F.; Martella, L.; De Feo, M.; Soddu, D.; Fellini, E.; Veneri, M.; Stamerra, C.A.; Ferri, C. Cocoa, glucose tolerance, and insulin signaling: cardiometabolic protection. J. Agric. Food Chem., 2015, 63(45), 9919-9926.
[] [PMID: 26126077]
Persson, I.A.; Persson, K.; Hägg, S.; Andersson, R.G. Effects of cocoa extract and dark chocolate on angiotensin-converting enzyme and nitric oxide in human endothelial cells and healthy volunteers--a nutrigenomics perspective. J. Cardiovasc. Pharmacol., 2011, 57(1), 44-50.
[] [PMID: 20966764]
Moreno-Ulloa, A.; Cid, A.; Rubio-Gayosso, I.; Ceballos, G.; Villarreal, F.; Ramirez-Sanchez, I. Effects of (-)-epicatechin and derivatives on nitric oxide mediated induction of mitochondrial proteins. Bioorg. Med. Chem. Lett., 2013, 23(15), 4441-4446.
[] [PMID: 23791569]
Martin, M.A.; Goya, L.; Ramos, S. Antidiabetic actions of cocoa flavanols. Mol. Nutr. Food Res., 2016, 60(8), 1756-1769.
[] [PMID: 26824673]
Lococo, F.; Cesario, A.; Del Bufalo, A.; Ciarrocchi, A.; Prinzi, G.; Mina, M.; Bonassi, S.; Russo, P. Novel therapeutic strategy in the management of COPD: a systems medicine approach. Curr. Med. Chem., 2015, 22(32), 3655-3675.
[] [PMID: 26337103]
Barnes, P.J. Cellular and molecular mechanisms of asthma and COPD. Clin. Sci. (Lond.), 2017, 131(13), 1541-1558.
[] [PMID: 28659395]
Kim, H.P.; Lim, H.; Kwon, Y.S. Therapeutic potential of medicinal plants and their constituents on lung inflammatory disorders. Biomol. Ther. (Seoul), 2017, 25(2), 91-104.
[] [PMID: 27956716]
Santana, F.P.; Pinheiro, N.M.; Mernak, M.I.; Righetti, R.F.; Martins, M.A.; Lago, J.H.; Lopes, F.D.; Tibério, I.F.; Prado, C.M. Evidences of herbal medicine-derived natural products effects in inflammatory lung diseases. Mediators Inflamm., 2016, 2016 2348968
[] [PMID: 27445433]
Weseler, A.R.; Geraets, L.; Moonen, H.J.; Manders, R.J.; van Loon, L.J.; Pennings, H.J.; Wouters, E.F.; Bast, A.; Hageman, G.J. Poly (ADP-ribose) polymerase-1-inhibiting flavonoids attenuate cytokine release in blood from male patients with chronic obstructive pulmonary disease or type 2 diabetes. J. Nutr., 2009, 139(5), 952-957.
[] [PMID: 19321592]
Liu, X.J.; Bao, H.R.; Zeng, X.L.; Wei, J.M. Effects of resveratrol and genistein on nuclear factorκB, tumor necrosis factorα and matrix metalloproteinase9 in patients with chronic obstructive pulmonary disease. Mol. Med. Rep., 2016, 13(5), 4266-4272.
[] [PMID: 27035424]
Hirayama, F.; Lee, A.H.; Binns, C.W.; Hiramatsu, N.; Mori, M.; Nishimura, K. Dietary intake of isoflavones and polyunsaturated fatty acids associated with lung function, breathlessness and the prevalence of chronic obstructive pulmonary disease: possible protective effect of traditional Japanese diet. Mol. Nutr. Food Res., 2010, 54(7), 909-917.
[] [PMID: 20112297]
Adesanoye, D.T.; Willey, C.J. Does cardiovascular comorbidity influence the prescribing of bronchodilators in chronic obstructive pulmonary disease? Ann. Pharmacother., 2017, 51(10), 855-861.
[] [PMID: 28573879]
Loscalzo, J.; Kohane, I.; Barabasi, A.L. Human disease classification in the postgenomic era: a complex systems approach to human pathobiology. Mol. Syst. Biol., 2007, 3, 124.
[] [PMID: 17625512]
Wagner, A.K. TBI rehabilomics research: an exemplar of a biomarker-based approach to precision care for populations with disability. Curr. Neurol. Neurosci. Rep., 2017, 17(11), 84-89.
[] [PMID: 28929311]

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