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Resveratrol: A Miracle Drug for Vascular Pathologies

  • Shishir Upadhyay
  • Kunj Bihari Gupta
  • Sukhchain Kaur
  • Rubal
  • Sandeep Kumar
  • Anil K. Mantha
  • Monisha Dhiman
Chapter

Abstract

Cardiovascular diseases (CVDs) are multifactorial noncommunicable diseases that are responsible for most prominent health problems worldwide in the twenty-first century. The genetic factors, environmental factors, change in diet, lifestyle, lack of physical activities, stress, and high blood pressure are the key risk factors for CVDs, and diseases like diabetes also contribute to the progression of CVDs. Platelet aggregation, vascular endothelial dysfunction, and imbalance in nitric oxide (NO) levels are the key events in cardiovascular pathologies that results in inflammation and oxidative stress that ultimately leads to death. To counteract the pathogenicity of CVDs, the use of phytochemicals is advancing as the conventional drugs have multiple side effects. Experimental demonstrations have showed that phytochemicals exhibit numerous cardioprotective properties with limited side effects. This chapter is focused on the use of resveratrol (3,5,4′-trihydroxystilbene), a phytochemical well known for its cardioprotective, antioxidant, anti-inflammatory, anti-atherosclerotic properties in vitro and in vivo. Existing systemic studies revealed that resveratrol could target various signaling pathways associated with cell growth and proliferation, inflammation, and mitochondrial functioning by modulating PGC-1α and SIRT-1 activity and also improves remodeling in the heart by activating adenosine monophosphate kinase (AMPK). Resveratrol can act as an inhibitor of migration and proliferation of aortic vascular smooth muscle cell by decreasing the cross talk between an inducer of matrix metalloproteinases (MMPs) and IL-18. Resveratrol improves the systolic performance of heart by regulating diastolic function and thus prevents heart failure risk. Scientific literature shows that the use of resveratrol as miracle drug for vascular pathogenesis can revamp cardiac health which will shed light on the path to make treatment strategies for medication of vascular-related disorders.

Keywords

CVDs Inflammation Oxidative stress Phytochemicals Resveratrol 

Notes

Acknowledgment

S.U., K.B.G. acknowledges the financial support from ICMR (New Delhi). Rubal and S. Kaur acknowledges UGC (New Delhi) for RGNF-JRF. S. Kumar is supported by the CUPB institutional fellowship for PhD. AKM acknowledges the Alzheimer’s Association, USA (NIRG-11-203527), and M.D. acknowledges the DST (Fast-Track: (SB/YS/LS-107/2013). Because of the limited focus of the manuscript, many appropriate references could not be included, for which the authors apologize.

References

  1. 1.
    Laslett LJ et al (2012) The worldwide environment of cardiovascular disease: prevalence, diagnosis, therapy, and policy issues: a report from the American College of Cardiology. J Am Coll Cardiol 60(25):S1–S49PubMedCrossRefGoogle Scholar
  2. 2.
    World Health Organization (2014) Global status report on alcohol and health 2014. World Health Organization, GenevaGoogle Scholar
  3. 3.
    Pearson TA et al (2003) Markers of inflammation and cardiovascular disease. Circulation 107(3):499–511PubMedCrossRefGoogle Scholar
  4. 4.
    Lippi G et al (2010) Moderate red wine consumption and cardiovascular disease risk: beyond the “French paradox”. In: Seminars in thrombosis and hemostasis. Thieme Medical Publishers, New YorkGoogle Scholar
  5. 5.
    Ramesh Vidavalur M et al (2006) Significance of wine and resveratrol in cardiovascular disease: French paradox revisited. Exp Clin Cardiol 11(3):217–225PubMedPubMedCentralGoogle Scholar
  6. 6.
    Ballini A et al (2017) Resveratrol in vascular diseases and therapeutics. Vasc Dis Ther 2:1–2Google Scholar
  7. 7.
    Zhu L, Luo X, Jin Z (2008) Effect of resveratrol on serum and liver lipid profile and antioxidant activity in hyperlipidemia rats. Asian Aust J Animal Sci 21(6):890CrossRefGoogle Scholar
  8. 8.
    Borriello A et al (2010) Dietary polyphenols: focus on resveratrol, a promising agent in the prevention of cardiovascular diseases and control of glucose homeostasis. Nutr Metab Cardiovasc Dis 20(8):618–625PubMedCrossRefGoogle Scholar
  9. 9.
    Bonnefont-Rousselot D (2016) Resveratrol and cardiovascular diseases. Nutrients 8(5):250PubMedCentralCrossRefPubMedGoogle Scholar
  10. 10.
    Tomé-Carneiro J et al (2013) One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease. Pharmacol Res 72:69–82PubMedCrossRefGoogle Scholar
  11. 11.
    Szkudelski T, Szkudelska K (2011) Anti-diabetic effects of resveratrol. Ann NY Acad Sci 1215(1):34–39PubMedCrossRefGoogle Scholar
  12. 12.
    Vallianou NG et al (2015) Resveratrol and cancer. Hosp Chron 10(3):137Google Scholar
  13. 13.
    Collaboration, P.S. (2002) Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 360(9349):1903–1913CrossRefGoogle Scholar
  14. 14.
    Gareth B, Lip GY, O’Brien E (2001) The ABC of hypertension: the pathophysiology of hypertension. BMJ 322:912–916CrossRefGoogle Scholar
  15. 15.
    Tzourio C (2007) Hypertension, cognitive decline, and dementia: an epidemiological perspective. Dialogues Clin Neurosci 9(1):61–70PubMedPubMedCentralGoogle Scholar
  16. 16.
    Franklin SS (2005) Arterial stiffness and hypertension. Hypertension 45(3):349–351PubMedCrossRefGoogle Scholar
  17. 17.
    Park S, Lakatta EG (2012) Role of inflammation in the pathogenesis of arterial stiffness. Yonsei Med J 53(2):258–261PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Rudijanto A (2007) The role of vascular smooth muscle cells on the pathogenesis of atherosclerosis. Acta Med Indones 39(2):86–93PubMedGoogle Scholar
  19. 19.
    Kitulwatte ID, Pollanen MS (2015) A comparative study of coronary atherosclerosis in young and old. Am J Forensic Med Pathol 36(4):323–326PubMedCrossRefGoogle Scholar
  20. 20.
    van Oijen M et al (2007) Atherosclerosis and risk for dementia. Ann Neurol 61(5):403–410PubMedCrossRefGoogle Scholar
  21. 21.
    Heeringa J et al (2007) Subclinical atherosclerosis and risk of atrial fibrillation: the Rotterdam study. Arch Intern Med 167(4):382–387PubMedCrossRefGoogle Scholar
  22. 22.
    Yasaka M, Yamaguchi T, Shichiri M (1993) Distribution of atherosclerosis and risk factors in atherothrombotic occlusion. Stroke 24(2):206–211PubMedCrossRefGoogle Scholar
  23. 23.
    Klein R et al (2002) The association of atherosclerosis, vascular risk factors, and retinopathy in adults with diabetes: the atherosclerosis risk in communities study. Ophthalmology 109(7):1225–1234PubMedCrossRefGoogle Scholar
  24. 24.
    Casserly I, Topol EJ (2004) Convergence of atherosclerosis and Alzheimer’s disease: inflammation, cholesterol, and misfolded proteins. Lancet 363(9415):1139–1146PubMedCrossRefGoogle Scholar
  25. 25.
    Befeler B et al (1977) Coronary artery aneurysms: study of their etiology, clinical course and effect on left ventricular function and prognosis. Am J Med 62(4):597–607PubMedCrossRefGoogle Scholar
  26. 26.
    Kaneko H et al (2011) Resveratrol prevents the development of abdominal aortic aneurysm through attenuation of inflammation, oxidative stress, and neovascularization. Atherosclerosis 217(2):350–357PubMedCrossRefGoogle Scholar
  27. 27.
    Rijbroek A et al (1994) Inflammation of the abdominal aortic aneurysm wall. Eur J Vasc Surg 8(1):41–46PubMedCrossRefGoogle Scholar
  28. 28.
    Cohen P, O’Gara PT (2008) Coronary artery aneurysms: a review of the natural history, pathophysiology, and management. Cardiol Rev 16(6):301–304PubMedCrossRefGoogle Scholar
  29. 29.
    Brown TJ et al (2001) CD8 T lymphocytes and macrophages infiltrate coronary artery aneurysms in acute Kawasaki disease. J Infect Dis 184(7):940–943PubMedCrossRefGoogle Scholar
  30. 30.
    He R et al (2006) Characterization of the inflammatory and apoptotic cells in the aortas of patients with ascending thoracic aortic aneurysms and dissections. J Thorac Cardiovasc Surg 131(3):671–678 e2PubMedCrossRefGoogle Scholar
  31. 31.
    Szekanecz Z et al (1994) Human atherosclerotic abdominal aortic aneurysms produce interleukin (IL)-6 and interferon-gamma but not IL-2 and IL-4: the possible role for IL-6 and interferon-gamma in vascular inflammation. Inflamm Res 42(3):159–162Google Scholar
  32. 32.
    Koch A et al (1993) Enhanced production of the chemotactic cytokines interleukin-8 and monocyte chemoattractant protein-1 in human abdominal aortic aneurysms. Am J Pathol 142(5):1423PubMedPubMedCentralGoogle Scholar
  33. 33.
    Shimizu K et al (2004) Th2-predominant inflammation and blockade of IFN-γ signaling induce aneurysms in allografted aortas. J Clin Invest 114(2):300–308PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Parry DJ et al (2010) Markers of inflammation in men with small abdominal aortic aneurysm. J Vasc Surg 52(1):145–151PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Radonic T et al (2012) Inflammation aggravates disease severity in Marfan syndrome patients. PLoS One 7(3):e32963PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Nataatmadja M et al (2003) Abnormal extracellular matrix protein transport associated with increased apoptosis of vascular smooth muscle cells in Marfan syndrome and bicuspid aortic valve thoracic aortic aneurysm. Circulation 108(10 suppl 1):II-329–II-334Google Scholar
  37. 37.
    Wang Y et al (2010) TGF-β activity protects against inflammatory aortic aneurysm progression and complications in angiotensin II–infused mice. J Clin Invest 120(2):422–432PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Anahita Dua M et al (2013) A review of the role of platelets in vascular trauma patients compared to patients with chronic vascular disease. Vasc Dis Manag 10(11):E240–E243Google Scholar
  39. 39.
    Reinhart W (2013) Platelets in vascular disease. Clin Hemorheol Microcirc 53(1–2):71–79PubMedPubMedCentralGoogle Scholar
  40. 40.
    van der Loo B, Martin JF (1997) 6 megakaryocytes and platelets in vascular disease. Baillieres Clin Haematol 10(1):109–123PubMedCrossRefGoogle Scholar
  41. 41.
    Schmidt-Ott KM, Kagiyama S, Phillips MI (2000) The multiple actions of angiotensin II in atherosclerosis. Regul Pept 93(1):65–77PubMedCrossRefGoogle Scholar
  42. 42.
    Pacurari M et al (2014) The renin-angiotensin-aldosterone system in vascular inflammation and remodeling. Int J Inflamm 2014:1CrossRefGoogle Scholar
  43. 43.
    Arehart E et al (2007) Prostacyclin, atherothrombosis, and cardiovascular disease. Curr Med Chem 14(20):2161–2169PubMedCrossRefGoogle Scholar
  44. 44.
    Nagaya N (2010) Orally active prostacyclin analogue for cardiovascular disease. Int Angiol: J Int Union Angiol 29(2 Suppl):14–18Google Scholar
  45. 45.
    Böhm F, Pernow J (2007) The importance of endothelin-1 for vascular dysfunction in cardiovascular disease. Cardiovasc Res 76(1):8–18PubMedCrossRefGoogle Scholar
  46. 46.
    Agapitov AV, Haynes WG (2002) Role of endothelin in cardiovascular disease. J Renin-Angiotensin-Aldosterone Syst 3(1):1–15PubMedCrossRefGoogle Scholar
  47. 47.
    Qing P et al (2015) Association of big endothelin-1 with coronary artery calcification. PLoS One 10(11):e0142458PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Chester AH, Yacoub MH (2014) The role of endothelin-1 in pulmonary arterial hypertension. Glob Cardiol Sci Pract 2014:29CrossRefGoogle Scholar
  49. 49.
    Kuhn H et al (2013) The role of endothelin in stroke. Issues 7(1)Google Scholar
  50. 50.
    Schaller BJ (2006) The role of endothelin in stroke: experimental data and underlying pathophysiology. Arch Med Sci 2(3):146Google Scholar
  51. 51.
    Li H, Förstermann U (2013) Uncoupling of endothelial NO synthase in atherosclerosis and vascular disease. Curr Opin Pharmacol 13(2):161–167PubMedCrossRefGoogle Scholar
  52. 52.
    Scheuner MT (2001) Genetic predisposition to coronary artery disease. Curr Opin Cardiol 16(4):251–260PubMedCrossRefGoogle Scholar
  53. 53.
    Wilde AA, Behr ER (2013) Genetic testing for inherited cardiac disease. Nat Rev Cardiol 10(10):571–583PubMedCrossRefGoogle Scholar
  54. 54.
    Enstrom JE, Kabat GC (2006) Environmental tobacco smoke and coronary heart disease mortality in the United States—a meta-analysis and critique. Inhal Toxicol 18(3):199–210PubMedCrossRefGoogle Scholar
  55. 55.
    Sauvant M-P, Pepin D (2002) Drinking water and cardiovascular disease. Food Chem Toxicol 40(10):1311–1325PubMedCrossRefGoogle Scholar
  56. 56.
    Lee B-J, Kim B, Lee K (2014) Air pollution exposure and cardiovascular disease. Cardiovasc Dis 3:24Google Scholar
  57. 57.
    Eriksson C et al (2007) Aircraft noise and incidence of hypertension. Epidemiology 18(6):716–721PubMedCrossRefGoogle Scholar
  58. 58.
    Momeni M et al (2014) Does water hardness have preventive effect on cardiovascular disease? Int J Prev Med 5(2):159PubMedPubMedCentralGoogle Scholar
  59. 59.
    Tsuji JS et al (2014) Association of low-level arsenic exposure in drinking water with cardiovascular disease: a systematic review and risk assessment. Toxicology 323:78–94PubMedCrossRefGoogle Scholar
  60. 60.
    James KA et al (2015) Association between lifetime exposure to inorganic arsenic in drinking water and coronary heart disease in Colorado residents. Environ Health Perspect (Online) 123(2):128CrossRefGoogle Scholar
  61. 61.
    Maria AG, Graziano R, Nicolantonio DO (2015) Carotenoids: potential allies of cardiovascular health? Food Nutr Res 59(1):26762cCrossRefGoogle Scholar
  62. 62.
    Dhiman M et al (2015) Oxidative stress and inflammation in cardiovascular diseases: two sides of the same coin. In: Free radicals in human health and disease. Springer, New Delhi, pp 259–278Google Scholar
  63. 63.
    Si H, Liu D (2009) Isoflavone genistein protects human vascular endothelial cells against tumor necrosis factor-α-induced apoptosis through the p38β mitogen-activated protein kinase. Apoptosis 14(1):66PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Babu PVA et al (2012) Genistein prevents hyperglycemia-induced monocyte adhesion to human aortic endothelial cells through preservation of the cAMP signaling pathway and ameliorates vascular inflammation in obese diabetic mice. J Nutr 142(4):724–730PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Shen Y et al (2013) Dietary quercetin attenuates oxidant-induced endothelial dysfunction and atherosclerosis in apolipoprotein E knockout mice fed a high-fat diet: a critical role for heme oxygenase-1. Free Radic Biol Med 65:908–915PubMedCrossRefGoogle Scholar
  66. 66.
    Tangney CC, Rasmussen HE (2013) Polyphenols, inflammation, and cardiovascular disease. Curr Atheroscler Rep 15(5):324PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Evans PC (2011) The influence of sulforaphane on vascular health and its relevance to nutritional approaches to prevent cardiovascular disease. EPMA J 2(1):9PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Si H, Liu D (2007) Phytochemical genistein in the regulation of vascular function: new insights. Curr Med Chem 14(24):2581–2589PubMedCrossRefGoogle Scholar
  69. 69.
    Agarwal M et al (2012) Dynamic action of carotenoids in cardioprotection and maintenance of cardiac health. Molecules 17(4):4755–4769PubMedCrossRefGoogle Scholar
  70. 70.
    Thimmulappa RK et al (2002) Identification of Nrf2-regulated genes induced by the chemopreventive agent sulforaphane by oligonucleotide microarray. Cancer Res 62(18):5196–5203PubMedGoogle Scholar
  71. 71.
    Khurana S et al (2013) Polyphenols: benefits to the cardiovascular system in health and in aging. Nutrients 5(10):3779–3827PubMedPubMedCentralCrossRefGoogle Scholar
  72. 72.
    Alwi I et al (2008) The effect of curcumin on lipid level in patients with acute coronary syndrome. Acta Med Indones 40(4):201–210PubMedGoogle Scholar
  73. 73.
    Li Y (2011) Protective effects of curcumin on brain vascular dementia by chronic cerebral ischemia in rats and study of the molecular mechanism. Alzheimers Dement 7((4):e47–e48CrossRefGoogle Scholar
  74. 74.
    Zhirongwang YH et al (2002) Effects of red wine and wine polyphenol resveratrol on platelet aggregation in vivo and in vitro. Int J Mol Med 9:77–79Google Scholar
  75. 75.
    Shenouda SM, Vita JA (2007) Effects of flavonoid-containing beverages and EGCG on endothelial function. J Am Coll Nutr 26(4):366S–372SPubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Loke WM et al (2008) Pure dietary flavonoids quercetin and (−)-epicatechin augment nitric oxide products and reduce endothelin-1 acutely in healthy men. Am J Clin Nutr 88(4):1018–1025PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Gómez-Guzmán M et al (2012) Epicatechin lowers blood pressure, restores endothelial function, and decreases oxidative stress and endothelin-1 and NADPH oxidase activity in DOCA-salt hypertension. Free Radic Biol Med 52(1):70–79PubMedCrossRefPubMedCentralGoogle Scholar
  78. 78.
    Zou J et al (2000) Effects of resveratrol on oxidative modification of human low density lipoprotein. Chin Med J 113(2):99–102PubMedGoogle Scholar
  79. 79.
    Csiszar A et al (2006) Resveratrol attenuates TNF-α-induced activation of coronary arterial endothelial cells: role of NF-κB inhibition. Am J Phys Heart Circ Phys 291(4):H1694–H1699Google Scholar
  80. 80.
    Li Y, Cao Z, Zhu H (2006) Upregulation of endogenous antioxidants and phase 2 enzymes by the red wine polyphenol, resveratrol in cultured aortic smooth muscle cells leads to cytoprotection against oxidative and electrophilic stress. Pharmacol Res 53(1):6–15PubMedCrossRefGoogle Scholar
  81. 81.
    Ungvari Z et al (2010) Resveratrol confers endothelial protection via activation of the antioxidant transcription factor Nrf2. Am J Phys Heart Circ Phys 299(1):H18–H24Google Scholar
  82. 82.
    Ungvari Z et al (2007) Resveratrol increases vascular oxidative stress resistance. Am J Phys Heart Circ Phys 292(5):H2417–H2424Google Scholar
  83. 83.
    Renaud Sd, de Lorgeril M (1992) Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 339(8808):1523–1526PubMedCrossRefGoogle Scholar
  84. 84.
    Gambini J et al (2015) Properties of resveratrol: in vitro and in vivo studies about metabolism, bioavailability, and biological effects in animal models and humans. Oxidative Med Cell Longev 2015:1CrossRefGoogle Scholar
  85. 85.
    Bernard E, Britz-McKibbin P, Gernigon N (2007) Resveratrol photoisomerization: an integrative guided-inquiry experiment. J Chem Educ 84(7):1159CrossRefGoogle Scholar
  86. 86.
    Giovinazzo G et al (2012) Resveratrol biosynthesis: plant metabolic engineering for nutritional improvement of food. Plant Foods Hum Nutr 67(3):191–199PubMedCrossRefGoogle Scholar
  87. 87.
    Keylor MH, Matsuura BS, Stephenson CR (2015) Chemistry and biology of resveratrol-derived natural products. Chem Rev 115(17):8976–9027PubMedPubMedCentralCrossRefGoogle Scholar
  88. 88.
    He S, Yan X (2013) From resveratrol to its derivatives: new sources of natural antioxidant. Curr Med Chem 20(8):1005–1017PubMedGoogle Scholar
  89. 89.
    Urpí-Sardà M et al (2005) Uptake of diet resveratrol into the human low-density lipoprotein. Identification and quantification of resveratrol metabolites by liquid chromatography coupled with tandem mass spectrometry. Anal Chem 77(10):3149–3155PubMedCrossRefGoogle Scholar
  90. 90.
    Cottart CH et al (2010) Resveratrol bioavailability and toxicity in humans. Mol Nutr Food Res 54(1):7–16PubMedCrossRefGoogle Scholar
  91. 91.
    Boocock DJ et al (2007) Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Cancer Epidemiol Prev Biomark 16(6):1246–1252CrossRefGoogle Scholar
  92. 92.
    Walle T (2011) Bioavailability of resveratrol. Ann N Y Acad Sci 1215(1):9–15CrossRefGoogle Scholar
  93. 93.
    Walle T et al (2004) High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos 32(12):1377–1382PubMedCrossRefGoogle Scholar
  94. 94.
    Yu C et al (2002) Human, rat, and mouse metabolism of resveratrol. Pharm Res 19(12):1907–1914PubMedCrossRefGoogle Scholar
  95. 95.
    Johnson JJ et al (2011) Enhancing the bioavailability of resveratrol by combining it with piperine. Mol Nutr Food Res 55(8):1169–1176PubMedPubMedCentralCrossRefGoogle Scholar
  96. 96.
    De Santi C et al (2000) Glucuronidation of resveratrol, a natural product present in grape and wine, in the human liver. Xenobiotica 30(11):1047–1054PubMedCrossRefGoogle Scholar
  97. 97.
    De Santi C et al (2000) Sulphation of resveratrol, a natural compound present in wine, and its inhibition by natural flavonoids. Xenobiotica 30(9):857–866PubMedCrossRefGoogle Scholar
  98. 98.
    Biasutto L, Zoratti M (2014) Prodrugs of quercetin and resveratrol: a strategy under development. Curr Drug Metab 15(1):77–95PubMedCrossRefGoogle Scholar
  99. 99.
    Smoliga JM, Blanchard O (2014) Enhancing the delivery of resveratrol in humans: if low bioavailability is the problem, what is the solution? Molecules 19(11):17154–17172PubMedCrossRefGoogle Scholar
  100. 100.
    Wang S et al (2014) Application of nanotechnology in improving bioavailability and bioactivity of diet-derived phytochemicals. J Nutr Biochem 25(4):363–376PubMedCrossRefGoogle Scholar
  101. 101.
    Delmas D, Solary E, Latruffe N (2011) Resveratrol, a phytochemical inducer of multiple cell death pathways: apoptosis, autophagy and mitotic catastrophe. Curr Med Chem 18(8):1100–1121PubMedCrossRefGoogle Scholar
  102. 102.
    Casanova F et al (2012) Resveratrol chemosensitizes breast cancer cells to melphalan by cell cycle arrest. J Cell Biochem 113(8):2586–2596PubMedCrossRefGoogle Scholar
  103. 103.
    Varoni EM et al (2016) Anticancer molecular mechanisms of resveratrol. Front Nutr 3:8PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Gülçin İ (2010) Antioxidant properties of resveratrol: a structure–activity insight. Innovative Food Sci Emerg Technol 11(1):210–218CrossRefGoogle Scholar
  105. 105.
    Donnelly LE et al (2004) Anti-inflammatory effects of resveratrol in lung epithelial cells: molecular mechanisms. Am J Phys Lung Cell Mol Phys 287(4):L774–L783Google Scholar
  106. 106.
    Das S, Das DK (2007) Anti-inflammatory responses of resveratrol. Inflamm Allergy Drug Targets (Form Curr Drug Targets Inflamm Allergy) 6(3):168–173CrossRefGoogle Scholar
  107. 107.
    Ungvari Z et al (2011) Mitochondrial protection by resveratrol. Exerc Sport Sci Rev 39(3):128PubMedPubMedCentralCrossRefGoogle Scholar
  108. 108.
    Bhat KP, Kosmeder JW, Pezzuto JM (2001) Biological effects of resveratrol. Antioxid Redox Signal 3(6):1041–1064PubMedCrossRefGoogle Scholar
  109. 109.
    Yang T et al (2015) Properties and molecular mechanisms of resveratrol: a review. Die Pharmazie-Int J Pharm Sci Res 70(8):501–506Google Scholar
  110. 110.
    De Lorgeril M et al (2002) Mediterranean diet and the French paradox. Cardiovasc Res 54(3):503–515PubMedCrossRefGoogle Scholar
  111. 111.
    Novakovic A et al (2006) The mechanism of endothelium-independent relaxation induced by the wine polyphenol resveratrol in human internal mammary artery. J Pharmacol Sci 101(1):85–90PubMedCrossRefGoogle Scholar
  112. 112.
    Jäger U, Nguyen-Duong H (1999) Relaxant effect of trans-resveratrol on isolated porcine coronary arteries. Arzneimittelforschung 49(03):207–211PubMedGoogle Scholar
  113. 113.
    Silan C (2008) The effects of chronic resveratrol treatment on vascular responsiveness of streptozotocin-induced diabetic rats. Biol Pharm Bull 31(5):897–902PubMedCrossRefPubMedCentralGoogle Scholar
  114. 114.
    Gojković-Bukarica L et al (2013) Cardiovascular effects of resveratrol. Vojnosanit Pregl 70(12):1145–1150CrossRefGoogle Scholar
  115. 115.
    Reuter S et al (2010) Oxidative stress, inflammation, and cancer: how are they linked? Free Radic Biol Med 49(11):1603–1616PubMedPubMedCentralCrossRefGoogle Scholar
  116. 116.
    Spanier G et al (2009) Resveratrol reduces endothelial oxidative stress by modulating the gene expression of superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPx1) and NADPH oxidase subunit (Nox4). J Physiol Pharmacol 60(Suppl 4):111–116PubMedPubMedCentralGoogle Scholar
  117. 117.
    Wong R et al (2011) Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure. Nutr Metab Cardiovasc Dis 21(11):851–856PubMedCrossRefGoogle Scholar
  118. 118.
    Shen MY et al (2007) Inhibitory mechanisms of resveratrol in platelet activation: pivotal roles of p38 MAPK and NO/cyclic GMP. Br J Haematol 139(3):475–485PubMedGoogle Scholar
  119. 119.
    Wang H et al (2012) Resveratrol in cardiovascular disease: what is known from current research? Heart Fail Rev 17(3):437–448PubMedCrossRefGoogle Scholar
  120. 120.
    Gresele P et al (2008) Resveratrol, at concentrations attainable with moderate wine consumption, stimulates human platelet nitric oxide production. J Nutr 138(9):1602–1608PubMedCrossRefGoogle Scholar
  121. 121.
    Mader I et al (2010) Identification of a novel proapoptotic function of resveratrol in fat cells: SIRT1-independent sensitization to TRAIL-induced apoptosis. FASEB J 24(6):1997–2009PubMedCrossRefGoogle Scholar
  122. 122.
    Weber O et al (2010) Cholesteryl ester transfer protein and its inhibition. Cell Mol Life Sci 67(18):3139–3149PubMedCrossRefGoogle Scholar
  123. 123.
    Grover-Páez F, Zavalza-Gómez AB (2009) Endothelial dysfunction and cardiovascular risk factors. Diabetes Res Clin Pract 84(1):1–10PubMedCrossRefGoogle Scholar
  124. 124.
    Dohadwala MM, Vita JA (2009) Grapes and cardiovascular disease. J Nutr 139(9):1788S–1793SPubMedPubMedCentralCrossRefGoogle Scholar
  125. 125.
    Das DK, Mukherjee S, Ray D (2010) Resveratrol and red wine, healthy heart and longevity. Heart Fail Rev 15(5):467–477PubMedCrossRefGoogle Scholar
  126. 126.
    Dolinsky VW et al (2009) Resveratrol prevents the prohypertrophic effects of oxidative stress on LKB1. Circulation 119(12):1643–1652PubMedCrossRefGoogle Scholar
  127. 127.
    Xin P et al (2010) Favorable effects of resveratrol on sympathetic neural remodeling in rats following myocardial infarction. Eur J Pharmacol 649(1):293–300PubMedCrossRefGoogle Scholar
  128. 128.
    Pagliaro B et al (2015) Phytochemical compounds and protection from cardiovascular diseases: a state of the art. Biomed Res Int 2015:1CrossRefGoogle Scholar
  129. 129.
    Noga AA et al (2007) Expression of an active LKB1 complex in cardiac myocytes results in decreased protein synthesis associated with phenylephrine-induced hypertrophy. Am J Phys Heart Circ Phys 292(3):H1460–H1469Google Scholar
  130. 130.
    Venkatesan B et al (2009) Resveratrol blocks interleukin-18-EMMPRIN cross-regulation and smooth muscle cell migration. Am J Physiol Heart Circ Physiol 297(2):H874–H886PubMedPubMedCentralCrossRefGoogle Scholar
  131. 131.
    Wang Z et al (2006) Regulation of proliferation and gene expression in cultured human aortic smooth muscle cells by resveratrol and standardized grape extracts. Biochem Biophys Res Commun 346(1):367–376PubMedCrossRefGoogle Scholar
  132. 132.
    Gurusamy N et al (2010) Red wine antioxidant resveratrol-modified cardiac stem cells regenerate infarcted myocardium. J Cell Mol Med 14(9):2235–2239PubMedPubMedCentralCrossRefGoogle Scholar
  133. 133.
    Raj P, Zieroth S, Netticadan T (2015) An overview of the efficacy of resveratrol in the management of ischemic heart disease. Ann N Y Acad Sci 1348(1):55–67PubMedCrossRefGoogle Scholar
  134. 134.
    Mukhopadhyay P et al (2010) Restoration of altered microRNA expression in the ischemic heart with resveratrol. PLoS One 5(12):e15705PubMedPubMedCentralCrossRefGoogle Scholar
  135. 135.
    Lancon A et al (2012) Control of MicroRNA expression as a new way for resveratrol to deliver its beneficial effects. J Agric Food Chem 60(36):8783–8789PubMedCrossRefGoogle Scholar
  136. 136.
    Ungvari Z et al (2013) Aging-induced dysregulation of dicer1-dependent microRNA expression impairs angiogenic capacity of rat cerebromicrovascular endothelial cells. J Gerontol Ser A Biol Med Sci 68(8):877–891CrossRefGoogle Scholar
  137. 137.
    Lopez MS, Dempsey RJ, Vemuganti R (2016) Resveratrol preconditioning induces cerebral ischemic tolerance but has minimal effect on cerebral microRNA profiles. J Cereb Blood Flow Metab 36(9):1644–1650PubMedPubMedCentralCrossRefGoogle Scholar
  138. 138.
    Tanko Y et al (2016) Resveratrol protects rabbits against cholesterol diet-induced hyperlipidaemia. Niger J Physiol Sci 31(1):71–75PubMedGoogle Scholar
  139. 139.
    Mendes KL et al (2016) Distinct metabolic effects of resveratrol on lipogenesis markers in mice adipose tissue treated with high-polyunsaturated fat and high-protein diets. Life Sci 153:66–73PubMedCrossRefGoogle Scholar
  140. 140.
    Lima LM, Carvalho MDG, Sousa MO (2007) Apo B/apo AI ratio and cardiovascular risk prediction. Arq Bras Cardiol 88(6):e187–e190PubMedCrossRefGoogle Scholar
  141. 141.
    Csiszar A et al (2009) Resveratrol prevents monocrotaline-induced pulmonary hypertension in rats. Hypertension 54(3):668–675PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Shishir Upadhyay
    • 1
  • Kunj Bihari Gupta
    • 2
  • Sukhchain Kaur
    • 2
  • Rubal
    • 2
  • Sandeep Kumar
    • 2
  • Anil K. Mantha
    • 1
  • Monisha Dhiman
    • 2
  1. 1.Department of Animal Sciences, School of Basic and Applied SciencesCentral University of PunjabBathindaIndia
  2. 2.Department of Biochemistry and Microbial Sciences, School of Basic and Applied SciencesCentral University of PunjabBathindaIndia

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