Resveratrol and the eye: Activity and molecular mechanisms

Graefe's Archive for Clinical and Experimental Ophthalmology

Volumn 252, Issue 5, 2014, Pages 699-713

  Bola, Christina ^a   Bartlett, Hannah ^a   Eperjesi, Frank ^a  

^a ASTON UNIVERSITY   (United Kingdom)

Author keywords

Age related macular degeneration; Alcohol; Diabetic retinopathy; Polyphenols; Red wine; Resveratrol; Retinopathy of prematurity

Indexed keywords

ALCOHOL; FLAVONOID; POLYPHENOL; RESVERATROL; SODIUM SELENITE;

ANTIANGIOGENIC ACTIVITY; ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; BLINDNESS; CATARACT; CHEMICAL STRUCTURE; DIABETIC RETINOPATHY; DIET SUPPLEMENTATION; EYE; EYE DISEASE; GLAUCOMA; HEALTH PROMOTION; HUMAN; NONHUMAN; NUTRIENT; OXIDATIVE STRESS; POLYGONUM CUSPIDATUM; PRIORITY JOURNAL; RED WINE; RETINA MACULA AGE RELATED DEGENERATION; RETROLENTAL FIBROPLASIA; REVIEW; SYSTEMATIC REVIEW; TRADITIONAL MEDICINE; VISUAL IMPAIRMENT;

ANIMALS; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; ANTINEOPLASTIC AGENTS, PHYTOGENIC; ANTIOXIDANTS; EYE DISEASES; HUMANS; STILBENES; VASODILATOR AGENTS; WINE;

EID: 84902291025     PISSN: 0721832X     EISSN: 1435702X     Source Type: Journal    
DOI: 10.1007/s00417-014-2604-8     Document Type: Review

References (110)

1. Heberden W (1786) Some account of a disorder of the breast. Med Trans R Coll Physicians (London) 2:59-67
2. Klatsky AL, Friedman GD, Armstrong MA, Kipp H (2003) Wine, liquor, beer and mortality. Am J Epidemiol 158:585-595
3. St Leger AS, Moore F, Cochrane AL (1979) Factors associated with cardiomortality in developed countries with particular reference to consumption of wine. Lancet 1:1017-1020 (Pubitemid 9183433)
4. Renaud S, de Lorgeril M (1992) Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 339:1523-1526
5. German JB, Walzem RL (2000) The health benefits of wine. Annu Rev Nutr 20:561-593
6. Vinson JA, Hontz BA (1995) Phenol antioxidant index: Comparative antioxidant effectiveness of red and white wines. J Agric Food Chem 43:401-403
7. Cordova AC, Jackson LS, Berk-Schlessel DW, Sumpio BE (2005) The cardiovascular protective effect of red wine. J Am Coll Surg 200:428-439 (Pubitemid 40298978)
8. Eng ET, Williams D, Mandava U, Kirma N, Tekmal RR, Chen S (2001) Suppression of aromatase (estrogen synthetase) by red wine phytochemicals. Breast Cancer Res Treat 67:133-146 (Pubitemid 32744494)
9. Ruano-Ravina A, Figueiras A, Barros-Dios JM (2004) Type of wine and risk of lung cancer: a case-control study in Spain. Thorax 59:981-985 (Pubitemid 39490785)
10. Sieman EH, Creasy LL (1992) Concentration of phytoalexin resveratrol in wine. Am J Enol Vitic 43:49-52
11. Marambaud P, Zhao H, Davies P (2005) Resveratrol promotes clearance of Alzheimer 's disease amyloid-beta peptides. J Biol Chem 280:37377-37382 (Pubitemid 41642343)
12. Vine RP, Harkness EM, Linton SJ (2002) Enology (winemaking). In: Winemaking, from grape growing to marketplace, 2nd edn. Kluwer Academic/Plenum, New York, pp 102-118
13. Waterhouse AL (2002)Wine phenolics. Ann NYAcad Sci 957:21-36
14. Cordova AC (2009) Sumpio BE. Polyphenols are medicine: Is it time to prescribe red wine for our patients? Int J Angiol 18:111-117
15. King RE, Bomser JA, Min DB (2006) Bioactivity of resveratrol. Comp Rev Food Sci Food Saf 5:65-70 (Pubitemid 44668741)
16. Lyons M, Yu C, Toma RB et al (2003) Resveratrol in raw and baked blueberries and bilberries. J Agric Food Chem 51:5867-5870
17. Wang Y, Catane F, Yang Y, Roderick R, Van Breemen RB (2002) An LC-MS method for analysing total resveratrol in grape juice, cranberry juice and in wine. J Agric Food Chem 50:431-435 (Pubitemid 34106659)
18. Langcake P, Pryce RJ (1976) The production of resveratrol by vitis vinifera and other members of the vitacea as a response to infection or injury. Physiol Plant Pathol 9:77-86
19. Jeandet P, Bessis R, Maume BF, Meunier P, Peyron D, Trollat P (1995) Effect of enological practices on the resveratrol isomer content of wine. J Agric Food Chem 43:316-319
20. Nonomura S, Kanagawa H, Makimoto A (1963) Chemical constituents of polygonaceous plants. Studies on the components of Ko-jokon (Polygonum cuspidatum SIEB et ZUCC). Yakugaku Zasshi 83:983-988
21. Jayatilake GS, Jayasuriya H, Lee ES et al (1993) Kinase inhibitors from Polygonum cuspidatum. J Nat Prod 56:1805-1810 (Pubitemid 23326302)
22. Creasy LL, Coffee M (1988) Phytoalexin production potential of grape berries. J Am Soc Hortic Sci 113:230-234
23. Frémont L (2000) Biological effects of resveratrol. Life Sci 66:663-673
24. Soleas GJ, Goldberg DM (1995) Influences of viticultural and oenological factors on changes in cis- and trans-resveratrol in commercial wines. J Wine Res 6:107-22
25. Lamikanra O, Grimm CC, Rodin JB, Inyang ID (1996) Hydroxylated stilbenes in selected American wines. J Agric Food Chem 44:1111-1115 (Pubitemid 126466964)
26. Alonso ÁM, Domínguez C, Guillén DA, Barroso CG (2002) Determination of antioxidant power of red and white wines by a new electrochemical method and its correlation with polyphenolic content. J Agric Food Chem 50:3112-3115 (Pubitemid 34533608)
27. Li G, Luna C, Liton PB, Navarro I, Epstein DL, Gonzalez P (2007) Sustained stress response after oxidative stress in trabecular meshwork cells. Mol Vis 13:2282-2288 (Pubitemid 350303122)
28. Luna C, Li G, Liton PB, Qiu J, Epstein DL, Challa P, Gonzalez P (2009) Resveratrol prevents the expression of glaucoma markers induced by chronic oxidative stress in trabecular meshwork cells. Food Chem Toxicol 47:198-204
29. Doganay S, Borazan M, Iraz M, Cigremis Y (2006) The effect of resveratrol in experimental cataract model formed by sodium selenite. Curr Eye Res 31:147-153
30. Hightower KR, McCready JP (1991) Effect of selenite on epithelium of cultured rabbit lens. Invest Ophthalmol Vis Sci 32:406- 409
31. Soufi FG, Mohammad-Nejad D, Ahmadieh H (2012) Resveratrol improves diabetic retinopathy possibly through oxidative stress - nuclear factor kappaB - apoptosis pathway. Pharmacol Rep 64:1505-1514
32. Yar AS, Menevse S, Dogan I, Alp E, Ergin V, Cumaoglu A, Menevse A (2012) Investigation of ocular neovascularization-related genes and oxidative stress in diabetic rat eye tissues after resveratrol treatment. J Med Food 15:391-398
33. Kim YH, Kim YS, Roh GS, Choi WS, Cho GJ (2012) Resveratrol blocks diabetes-induced early vascular lesions and vascular endothelial growth factor induction in mouse retinas. Acta Ophthalmol (Copenh) 90:e31-e37
34. Li C, Wang L, Huang K, Zheng L (2012) Endoplasmic reticulum stress in retinal vascular degeneration: protective role of resveratrol. Invest Ophthalmol Vis Sci 53:3241-3249
35. Sheu SJ, Liu NC, Ou CC, Bee YS, Chen SC, Lin HC, Chan JYH (2013) Resveratrol stimulates mitochondrial bioenergetics to protect retinal pigment epithelial cells from oxidative damage. Invest Ophthalmol Vis Sci 54:6426-6438
36. Lopez PF, Grossniklaus HE, Aaberg TM, Sternburg P, Capone A, Lambert HM (1992) Pathogenetic mechanisms in anterior proliferative vitreoretinopathy. Am J Ophthalmol 114:257-270
37. Cai J, Nelson KC, Wu M, Sternberg P, Jones DP (2000) Oxidative damage and protection of the RPE. Prog Retin Eye Res 19:205-221
38. Kanski JJ, Bowling B (2001) Ophthalmology: A systematic approach, 7th edn. Elsevier Saunders, Edinburgh
39. Beatty S, Koh HH, Henson D, Boulton M (2000) The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol 45:115-134
40. King RE, Kent KD, Bomser JA (2005) Resveratrol reduces oxidation and proliferation of human retinal pigment epithelial cells via extracellular signal-regulated kinase inhibition. Chem Biol Interact 151:143-149 (Pubitemid 40208564)
41. Hecquet C, Lefevre G, Valtink M, Engelmann K, Mascarelli F (2002) Activation and role of MAP kinase-dependent pathways in retinal pigment epithelial cells: ERK and RPE proliferation. Invest Ophthalmol Vis Sci 43:3091-3098 (Pubitemid 34977064)
42. Szende B, Tyihák H, Király-Véghely (2000) Dose-dependent effect of resveratrol on proliferation and apoptosis in endothelial and tumor cell cultures. Exp Mol Med 32:88-92 (Pubitemid 30450087)
43. Zoberi I, Bradbury CM, Curry HA, Bisht KS, Goswami PC, Roti Roti JL, Gius D (2002) Radiosensitising and anti-proliferative effects of resveratrol in two human cervical tumor cell lines. Cancer Lett 175:165-173 (Pubitemid 34001714)
44. Qin S, Lu Y, Rodrigues G (2014) Resveratrol protects RPE cells from sodium iodate by modulating PPARα and PPARδ. Expl Eye Res 118:100-108
45. Anekonda TS, Adamus G (2008) Resveratrol prevents antibody-induced apoptotic death of retinal cells through upregulation of Sirt1 and Ku70. BMC Res Notes 1:122
46. Magrys A, Anekonda T, Ren G, Adamus G (2007) The role of anti-alpha-enolase autoantibodies in pathogenicity of autoimmunemediated retinopathy. J Clin Immunol 27:181-192 (Pubitemid 46348722)
47. Adamus G,Webb S, Shiraga S, Duvoisin RM (2006) Anti-recoverin antibodies induce an increase in intracellular calcium, leading to apoptosis in retinal cells. J Autoimmun 26:146-153 (Pubitemid 43138885)
48. Kubota S, Kurihara T, Ebinuma M, Kubota M, Yuki K, Sasaki M, Noda K, Ozawa Y, Oike Y, Ishida S, Tsubota K (2010) Resveratrol prevents light-induced retinal degeneration via suppressing activator protein-1 activation. Am J Pathol 177:1725-1731
49. van Ginkel PR, Darjatmoko SR, Sareen D, Subramanian L, Bhattacharya S, Lindstrom MJ, Albert DM, Polans AS (2008) Resveratrol inhibits uveal melanoma tumor growth via early mitochondrial dysfunction. Invest Ophthalmol Vis Sci 49:1299-1306
50. Kanski JJ, Bowling B (2011) Clinical ophthalmology: a systematic approach, 7th edn. Elsevier Saunders, Edinburgh
51. Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CWW, Fong HHS, Farnsworth NR, Kinghorn AD, Mehta RG, Moon RC, Pezzuto JM (1997) Cancer chemopreventative activity of resveratrol, a natural product derived from grapes. Science 275:218-220 (Pubitemid 127696281)
52. Sareen D, van Ginkel PR, Takach JC, Mohiuddin A, Darjatmoko ADM, Polans AS (2006) Mitochondria as the primary target of resveratrol-induced apoptosis in human retinoblastoma cells. Invest Ophthalmol Vis Sci 47:3708-3716 (Pubitemid 46049513)
53. Subbaramaiah K, Chung WJ, Michaluart P, Telang N, Tanabe T, Inoue H, Jang M, Pezzuto JM, Dannedberg AJ (1998) Resveratrol inhibits cyclooxgenase-2 transcription and activity in phorbol estertreated human mammary epithelial cells. J Bio Chem 1273:21875-21882 (Pubitemid 28405365)
54. Pendurthi UR, Williams JT, Rao LVM (1999) Resveratrol, a polyphenolic compound found in wine, inhibits tissue factor expression in vascular cells: a possible mechanism for the cardiovascular benefits associated with moderate wine consumption. Arterioscler Thromb Vasc Biol 19:419-426 (Pubitemid 29072759)
55. Culpitt SV, Rogers DF, Fenwick PS, Shah P, de Matos C, Russell REK, Barnes PJ,Donnelly LE (2003) Inhibition by red wine extract, resveratrol, of cytokine release by alveolar macrophages in COPD. Thorax 58:942-946 (Pubitemid 37392803)
56. Manna SK, Mukhopadhyay A, Aggarwal BB (2000) Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-κB, Activator protein-1, and apoptosis: potential role of reactive oxygen intermediates and lipid peroxidation. J Immunol 164:6509-6519 (Pubitemid 30408836)
57. Ambati J, Anand A, Fernandez S, Sakurai E, Lynn BC, Kuziel WA, Rollins BJ, Ambati BK (2003) An animal model of age-related macular degeneration in senescent Ccl-2- or Ccr-2-deficient mice. Nat Med 9:1390-1397 (Pubitemid 37466188)
58. Joussen AM, Poulaki V, Le ML, Koizumi K, Esser C, Janicki H, Schraermeyer U, Kociok N, Fauser S, Kirchhof B, Kern TS, Adamis AP (2004) A central role for inflammation in the pathogenesis of diabetic retinopathy. FASEB J 18:1450-1452 (Pubitemid 39561611)
59. Satici A, Guzey M, Gurler B, Vural H, Gurkan T (2003) Malondialdehyde and antioxidant enzyme levels in the aqueous humor of rabbits in endotoxin-induced uveitis. Eur J Ophthalmol 13:779-783 (Pubitemid 38198703)
60. Kubota S, Kurihara T, Mochimaru H, Satofuka S, Noda K, Ozawa Y, Oike Y, Ishida S, Tsubota K (2009) Prevention of ocular inflammation in endotoxin-induced uveitis with resveratrol by inhibiting oxidative damage and nuclear factor-κB activation. Invest Ophthalmol Vis Sci 50:3512-3519
61. Baldwin AS Jr (1996) The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol 14:649-683
62. Fuentes ME, Durham SK, Swerdel MR, Lewin AC, Barton DS, Megill JR, Bravo R, Lira SA (1995) Controlled recruitment of monocytes and macrophages to specific organs through transgenic expression of monocyte chemoattractant protein-1. J Immunol 155:5769-5776
63. Becker MD, Garman K, Whitcup SM, Planck SR, Rosenbaum JT (2001) Inhibition of leukocyte sticking and infiltration, but not rolling, by antibodies to ICAM-1 and LFA-1 in murine endotoxin-induced uveitis. Invest Ophthalmol Vis Sci 42:2563-2566 (Pubitemid 32954863)
64. Bordone L, Guarente L (2005) Calorie restriction SIRT1 and metabolism: understanding longevity. Nat Rev Mol Cell Biol 6:298-305 (Pubitemid 40516896)
65. Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski ZLL, Scherer B, Sinclair DA (2003) Small molecule activators of sirtuins extends Saccharomyces cerevisiae lifespan. Nature 425:191-196 (Pubitemid 37150899)
66. Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, Sinclair D (2004) Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 430:686-689 (Pubitemid 39061685)
67. Valenzano DR, Terzibasi E, Genade T, Cattaneo A, Domenici L, Cellerino A (2006) Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Curr Biol 16:296-300 (Pubitemid 43190229)
68. Milne JC, Lambert PD, Schenk S (2007) Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature 450:712-716 (Pubitemid 350207685)
69. Araki T, Sasaki Y, Millbrandt J (2004) Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration. Science 305:1010-1013 (Pubitemid 39071777)
70. Schindler KS, Ventura E, Rex TS, Elliott P, Rostami A (2007) SIRT1 activation confers neuroprotection in experimental optic neuritis. Invest Ophthalmol Vis Sci 48:3602-3609 (Pubitemid 351261095)
71. Khan RS, Fonseca-Kelly Z, Callinan C, Zuo L, Sachdeva MM, Shindler KS (2012) SIRT1 activating compounds reduce oxidative stress and prevent cell death in neuronal cells. Front Cell Neurosci 6:63
72. Kim SH, Park JH, Kim YJ, Park KH (2013) The neuroprotective effect of resveratrol on retinal ganglion cells after optic nerve transection. Mol Vis 19:1667-1676
73. Fonseca-Kelly Z, Nassrallah M, Uribe J, Khan RS, Dine K, Dutt M, Shindler KS (2012) Resveratrol neuroprotection in a chronic mouse model of multiple sclerosis. Front Neurol 3:84
74. Zuo L, Khan RS, Lee V, Dine K, Wu W, Shindler KS (2013) SIRT1 Promotes RGC survival and delays loss of function following optic nerve crush. Invest Ophthalmol Vis Sci 54:5097-5102
75. Vin AP, Hu H, Zhai Y, Von Zee CL, Logeman A, Stubbs EB Jr, Bu P (2013) Neuroprotective effect of resveratrol prophylaxis on experimental retinal ischemic injury. Exp Eye Res 108:72-75
76. Huang W, Li G, Qiu J, Gonzalez P, Challa P (2013) Protective effects of resveratrol in experimental retinal detachment. Plos One 8:9
77. Villaroel M, Garcia-Ramirez M, Corraliza L, Hernandez C, Simo R (2009) Effects of high glucose concentration on the barrier function and the expression of tight junction proteins in human retinal pigment epithelial cells. Exp Eye Res 89:913-920
78. Losso JN, Truax RE, Richard G (2010) trans-Resveratrol inhibits hyperglycemia-induced inflammation and connexin downregulation in retinal pigment epithelial cells. J Agric Food Chem 58:8246-8252
79. Giebel SJ, Menicucci G, McGuire PG, Das A (2005)Matrix metalloproteinases in early diabetic retinopathy and their role in alteration of the blood-retinal barrier. Lab Invest 85:597-607 (Pubitemid 40675441)
80. Malfait M, Gomez P, van Veen TAB, Parys JB, de Smedt H, Vereecke J,Himpens B (2001) Effects of hyperglycemia and protein kinase C on connexin 43 expression in cultured rat retinal pigment epithelial cells. J Membr Biol 181:31-40 (Pubitemid 32411365)
81. Richer S, Stiles W, Ulanski L, Carroll D, Podella C (2013) Observation of human retinal remodeling in octogenarians with a resveratrol based nutritional supplement. Nutrients 5:6
82. Hua J, Guerin KI, Chen J, Michan S, Stahl A, Krah NM, Seaward MR, Dennison RJ, Juan AM, Hatton CJ, Sapieha P, Sinclair DA, Smith LEH (2011) Resveratrol inhibits pathologic retinal neovascularization in Vldlr-/- Mice. Invest Ophthalmol Vis Sci 52:2809-2816
83. Yannuzzi LA, Bardal AM, Freund KB, Chen KJ, Eandi CM, Blodi B (2006) Idiopathic macular telangiectasia. Arch Ophthalmol 124:450-460
84. Kovach JL, Rosenfeld PJ (2009) Bevacizumab (avastin) therapy for idiopathic macular telangiectasia type II. Retina 29:27-32
85. Khan AA, Dace DS, Ryazanov AG, Kelly J, Apte RS (2010) Resveratrol regulates pathologic angiogenesis by a eukaryotic elongation factor-2 kinase-regulated pathway. Am J Pathol 177:481-492
86. Horman S, Browne G, Krause U (2002) Activation of AMP-activated protein kinase leads to the phosphorylation of elongation factor 2 and an inhibition of protein synthesis. Curr Biol 12:1419-1423 (Pubitemid 34915545)
87. Doganay S, Firat PG, Cankaya C, Kirimlioglu H (2013) Evaluation of the effects of resveratrol and bevacizumab on experimental corneal alkali burn. Burns 39:326-330
88. Kim WT, Suh ES (2010) Retinal protective effects of resveratrol via modulation of nitric oxide synthase on oxygen-induced retinopathy. Korean J Ophthalmol 24:108-118
89. Miller EC, Capps BE, Sanghani RR, Clemmons DR, Maile LA (2007) Regulation of IGF-I signaling in retinal endothelial cells by hyperglycemia. Invest Ophthalmol Vis Sci 48:3878-3887 (Pubitemid 351261130)
90. Nagaoka T, Hein TW, Yoshida A, Kuo L (2007) Resveratrol, a component of red wine, elicits dilation of isolated porcine retinal arterioles: role of nitric oxide and potassium channels. Invest Ophthalmol Vis Sci 48:4232-4239 (Pubitemid 351261054)
91. Walle T, Hsieh F, DeLegge MH, Oatis JE Jr, Walle UK (2004) High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos 32:1377-1382 (Pubitemid 39564557)
92. Change4Life (2012) http://www.nhs.uk/Change4Life/Pages/change-for-life. aspx. Accessed 20th February 2013
93. Paulo L, Oleastro M, Gallardo E, Queiroz JA, Domingues F (2001) Antimicrobial properties of resveratrol: a review. In: Mendez-Vilas A (ed) Science againstmicrobial pathogens: communicating current research and technological advances. Formatex Research Center, Spain, pp 1225-1235
94. Chan MMY (2002) Antimicrobial effect of resveratrol on dermatophytes and bacterial pathogens of the skin.Biochem Pharm 63:99-104
95. Frémont L, Belguendouz L, Delpal S (1999) Antioxidant activity of resveratrol and alcohol-free wine polyphenols related to LDL oxidation and polyunsaturated fatty acids. Life Sci 64:2511-2521 (Pubitemid 29268427)
96. Ray PS, Maulik G, Gerald GA, Bertelli AAE, Bertelli A, Das DK (1999) The red wine antioxidant resveratrol protects isolated rat hearts from ischemia reperfusion injury. Free Radical Biol Med 27:160-9 (Pubitemid 29353096)
97. Leonard SS, Xia C, Jiang BH, Stinefelt B, Klandorf H, Harris GK, Shi X (2003) Resveratrol scavenges reactive oxygen species and effects radical-induced cellular responses. Biochem and Biophys Res Comm 309:1017-1026 (Pubitemid 37122632)
98. Gehm BD, McAndrews JM, Chien PY, Jameson JL (1997) Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Proc Natl Acad Sci 94:14138-14143 (Pubitemid 28009723)
99. Bowers JL, Tyulmenkov VV, Jernigan SC, Klinge CM (2000) Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta. Endocrinology 141:3657-3667
100. Belguendouz L, Fremont L, Linard A (1997) Resveratrol inhibits metal ion-dependent and independent peroxidation of porcine lowdensity lipoproteins. Biochem Pharmacol 53:1347-1355 (Pubitemid 27305634)
101. Tadolini B, Juliano C, Piu L, Franconi F, Cabrini L (2000) Resveratrol inhibition of lipid peroxidation. Free Radic Res 33:105-114 (Pubitemid 30349988)
102. Aziz MH, Kumar R, Ahmad N (2003) Cancer chemoprevention by resveratrol: In vitro and in vivo studies and the underlying mechanisms (Review). Int J Oncol 23:17-28
103. Wang Z, Huang Y, Zou J, Cao K, Xu Y, Wu JM (2002) Effects of red wine and wine polyphenol resveratrol on platelet aggregation in vivo and in vitro. Int J Mol Med 9:77-79
104. Shen MY, Hsiao G, Liu CL, Fong TH, Lin KH, Chou DS, Sheu JR (2007) Inhibitory mechanisms of resveratrol in platelet activation: pivotal roles of p38 MAPK and NO/cyclic GMP. Br J Haematol 139:475-485 (Pubitemid 47512173)
105. Donnelly LE, Newton R, Kennedy GE, Fenwick PS, Leung RHF, Ito K, Russell REK, Barnes PJ (2004) Antiinflammatory effects of resveratrol in lung epithelial cells: molecular mechanisms. Am J Physiol Lung Cell Mol Physiol 287:774-783
106. Martin AR, Villegas I, Sánchez-Hidalgo M, de la Lastra CA (2006) The effects of resveratrol, a phytoalexin derived from red wines, on chronic inflammation induced in an experimentally induced colitis model. Br J Pharmacol 147:873-885
107. Novakovic A, Gojkovic-Bukarica L, Peric M, Nezic D, Djukanovic B, Markovic-Lipkovski HH (2006) The mechanism of endothelium independent relaxation induced by the wine polyphenol resveratrol in human internal mammary artery. J Pharmacol Sci 101:85-90 (Pubitemid 43765339)
108. Rush JW, Quadrilatero J, Levy AS, Ford RJ (2007) Chronic resveratrol enhances endothelium-dependent relaxation but does not alter eNOS levels in aorta of spontaneously hypertensive rats. Exp Biol Med 232:814-22 (Pubitemid 46827824)
109. Jang M, Pezzuto JM (1998) Resveratrol blocks eicosanoid production and chemically-induced cellular transformation: Implications for cancer chemoprevention. Pharm Biol 36:28-34
110. Ahn J, Cho I, Kim S, Kwon D, Ha T (2008) Dietary resveratrol alters lipid metabolism-related gene expression of mice on an atherogenic diet. J Hepatol 49:1019-1028