Resveratrol role in cardiovascular and metabolic health and potential mechanisms of action

Nutrition Research

Volumn 32, Issue 9, 2012, Pages 648-658

  Xu, Qiang ^a   Si, Liang Yi ^a  

^a THIRD MILITARY MEDICAL UNIVERSITY   (China)

Author keywords

AMPK; Cardiovascular disease; Flavonoid; Metabolic disease; Resveratrol; SIRT1

Indexed keywords

ADENOSINE KINASE; APOLIPOPROTEIN E; CHOLESTEROL; CYCLOSPORIN A; FATTY ACID; LINOLEIC ACID; MITOGEN ACTIVATED PROTEIN KINASE; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; RESVERATROL; SIRTUIN; TRIACYLGLYCEROL;

ADIPOCYTE; ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; APOPTOSIS; ATHEROSCLEROSIS; AUTOPHAGY; BODY WEIGHT; BRAIN ISCHEMIA; BRAIN PROTECTION; CARDIOVASCULAR FUNCTION; CELL DIFFERENTIATION; CELL PROLIFERATION; CELL PROTECTION; CELL REGENERATION; CONCENTRATION RESPONSE; CYTOLOGY; DIABETES MELLITUS; DRUG EFFECT; DRUG MECHANISM; HEART INFARCTION; HEART PROTECTION; HUMAN; HYPERTENSION; INSULIN RESISTANCE; INSULIN SENSITIVITY; LIPID DIET; METABOLIC RATE; METABOLISM; NONHUMAN; OBESITY; OCCLUSIVE CEREBROVASCULAR DISEASE; OSTEOPOROSIS; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; PROTEIN TARGETING; REPERFUSION INJURY; REVIEW; SIGNAL TRANSDUCTION; STEM CELL; STEM CELL MOBILIZATION; TREATMENT DURATION; VASODILATATION;

AMP-ACTIVATED PROTEIN KINASES; ANIMALS; ANTI-INFLAMMATORY AGENTS; ANTIOXIDANTS; APOPTOSIS; AUTOPHAGY; CARDIOVASCULAR DISEASES; DISEASE MODELS, ANIMAL; HUMANS; METABOLIC DISEASES; SIGNAL TRANSDUCTION; SIRTUIN 1; STILBENES;

EID: 84867865164     PISSN: 02715317     EISSN: 18790739     Source Type: Journal    
DOI: 10.1016/j.nutres.2012.07.002     Document Type: Review

References (121)

1. Constant J. Alcohol, ischemic heart disease, and the French paradox. Coron Artery Dis 1997, 8:645-649.
2. Siemann E., Creasy L. Concentration of the phytoalexin resveratrol in wine. Am J Enol Vitic 1992, 43:49-52.
3. Petrovski G., Gurusamy N., Das D.K. Resveratrol in cardiovascular health and disease. Ann N Y Acad Sci 2011, 1215:22-33.
4. Delmas D., Solary E., Latruffe N. Resveratrol, a phytochemical inducer of multiple cell death pathways: apoptosis, autophagy and mitotic catastrophe. Curr Med Chem 2011, 18:1100-1121.
5. Williamson G., Carughi A. Polyphenol content and health benefits of raisins. Nutr Res 2010, 30:511-519.
6. Pearson K.J., Baur J.A., Lewis K.N., Peshkin L., Price N.L., Labinskyy N., et al. Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab 2008, 8:157-168.
7. Soylemez S., Sepici A., Akar F. Resveratrol supplementation gender independently improves endothelial reactivity and suppresses superoxide production in healthy rats. Cardiovasc Drugs Ther 2009, 23:449-458.
8. Mizutani K., Ikeda K., Kawai Y., Yamori Y. Resveratrol attenuates ovariectomy-induced hypertension and bone loss in stroke-prone spontaneously hypertensive rats. J Nutr Sci Vitaminol (Tokyo) 2000, 46:78-83.
9. Thandapilly S.J., Wojciechowski P., Behbahani J., Louis X.L., Yu L., Juric D., et al. Resveratrol prevents the development of pathological cardiac hypertrophy and contractile dysfunction in the SHR without lowering blood pressure. Am J Hypertens 2010, 23:192-196.
10. Bhatt S.R., Lokhandwala M.F., Banday A.A. Resveratrol prevents endothelial nitric oxide synthase uncoupling and attenuates development of hypertension in spontaneously hypertensive rats. Eur J Pharmacol 2011, 667:258-264.
11. Juric D., Wojciechowski P., Das D.K., Netticadan T. Prevention of concentric hypertrophy and diastolic impairment in aortic-banded rats treated with resveratrol. Am J Physiol Heart Circ Physiol 2007, 292:H2138-H2143.
12. Toklu H.Z., Sehirli O., Ersahin M., Suleymanoglu S., Yiginer O., Emekli-Alturfan E., et al. Resveratrol improves cardiovascular function and reduces oxidative organ damage in the renal, cardiovascular and cerebral tissues of two-kidney, one-clip hypertensive rats. J Pharm Pharmacol 2010, 62:1784-1793.
13. Chan V., Fenning A., Iyer A., Hoey A., Brown L. Resveratrol improves cardiovascular function in DOCA-salt hypertensive rats. Curr Pharm Biotechnol 2011, 12:429-436.
14. Do G.M., Kwon E.Y., Kim H.J., Jeon S.M., Ha T.Y., Park T., et al. Long-term effects of resveratrol supplementation on suppression of atherogenic lesion formation and cholesterol synthesis in apo E-deficient mice. Biochem Biophys Res Commun 2008, 374:55-59.
15. Fukao H., Ijiri Y., Miura M., Hashimoto M., Yamashita T., Fukunaga C., et al. Effect of trans-resveratrol on the thrombogenicity and atherogenicity in apolipoprotein E-deficient and low-density lipoprotein receptor-deficient mice. Blood Coagul Fibrinolysis 2004, 15:441-446.
16. Xia N., Daiber A., Habermeier A., Closs E.I., Thum T., Spanier G., et al. Resveratrol reverses endothelial nitric-oxide synthase uncoupling in apolipoprotein E knockout mice. J Pharmacol Exp Ther 2010, 335:149-154.
17. Wang Z., Zou J., Cao K., Hsieh T.C., Huang Y., Wu J.M. Dealcoholized red wine containing known amounts of resveratrol suppresses atherosclerosis in hypercholesterolemic rabbits without affecting plasma lipid levels. Int J Mol Med 2005, 16:533-540.
18. Sato M., Ray P.S., Maulik G., Maulik N., Engelman R.M., Bertelli A.A., et al. Myocardial protection with red wine extract. J Cardiovasc Pharmacol 2000, 35:263-268.
19. Samuel S.M., Thirunavukkarasu M., Penumathsa S.V., Paul D., Maulik N. Akt/FOXO3a/SIRT1-mediated cardioprotection by n-tyrosol against ischemic stress in rat in vivo model of myocardial infarction: switching gears toward survival and longevity. J Agric Food Chem 2008, 56:9692-9698.
20. Kaga S., Zhan L., Matsumoto M., Maulik N. Resveratrol enhances neovascularization in the infarcted rat myocardium through the induction of thioredoxin-1, heme oxygenase-1 and vascular endothelial growth factor. J Mol Cell Cardiol 2005, 39:813-822.
21. Gorbunov N., Petrovski G., Gurusamy N., Ray D., Kim D.H., Das D.K. Regeneration of infarcted myocardium with resveratrol-modified cardiac stem cells. J Cell Mol Med 2011, 16:174-184.
22. Inoue H., Jiang X.F., Katayama T., Osada S., Umesono K., Namura S. Brain protection by resveratrol and fenofibrate against stroke requires peroxisome proliferator-activated receptor alpha in mice. Neurosci Lett 2003, 352:203-206.
23. Yousuf S., Atif F., Ahmad M., Hoda N., Ishrat T., Khan B., et al. Resveratrol exerts its neuroprotective effect by modulating mitochondrial dysfunctions and associated cell death during cerebral ischemia. Brain Res 2009, 1250:242-253.
24. Ban J.Y., Cho S.O., Choi S.H., Ju H.S., Kim J.Y., Bae K., et al. Neuroprotective effect of Smilacis chinae rhizome on NMDA-induced neurotoxicity in vitro and focal cerebral ischemia in vivo. J Pharmacol Sci 2008, 106:68-77.
25. Gao D., Zhang X., Jiang X., Peng Y., Huang W., Cheng G., et al. Resveratrol reduces the elevated level of MMP-9 induced by cerebral ischemia-reperfusion in mice. Life Sci 2006, 78:2564-2570.
26. Wallerath T., Deckert G., Ternes T., Anderson H., Li H., Witte K., et al. Resveratrol, a polyphenolic phytoalexin present in red wine, enhances expression and activity of endothelial nitric oxide synthase. Circulation 2002, 106:1652-1658.
27. Wang M.J., Huang H.M., Hsieh S.J., Jeng K.C., Kuo J.S. Resveratrol inhibits interleukin-6 production in cortical mixed glial cells under hypoxia/hypoglycemia followed by reoxygenation. J Neuroimmunol 2001, 112:28-34.
28. Belguendouz L., Fremont L., Gozzelino M.T. Interaction of transresveratrol with plasma lipoproteins. Biochem Pharmacol 1998, 55:811-816.
29. Fremont L., Belguendouz L., Delpal S. Antioxidant activity of resveratrol and alcohol-free wine polyphenols related to LDL oxidation and polyunsaturated fatty acids. Life Sci 1999, 64:2511-2521.
30. Bastianetto S., Zheng W.H., Quirion R. Neuroprotective abilities of resveratrol and other red wine constituents against nitric oxide-related toxicity in cultured hippocampal neurons. Br J Pharmacol 2000, 131:711-720.
31. Zhuang H., Kim Y.S., Koehler R.C., Dore S. Potential mechanism by which resveratrol, a red wine constituent, protects neurons. Ann N Y Acad Sci 2003, 993:276-286. [discussion 87-8].
32. Zhang H., Schools G.P., Lei T., Wang W., Kimelberg H.K., Zhou M. Resveratrol attenuates early pyramidal neuron excitability impairment and death in acute rat hippocampal slices caused by oxygen-glucose deprivation. Exp Neurol 2008, 212:44-52.
33. Lagouge M., Argmann C., Gerhart-Hines Z., Meziane H., Lerin C., Daussin F., et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1 [alpha]. Cell 2006, 127:1109-1122.
34. Baur J.A., Pearson K.J., Price N.L., Jamieson H.A., Lerin C., Kalra A., et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 2006, 444:337-342.
35. Um J.H., Park S.J., Kang H., Yang S., Foretz M., McBurney M.W., et al. AMP-activated protein kinase-deficient mice are resistant to the metabolic effects of resveratrol. Diabetes 2010, 59:554-563.
36. Sun C., Zhang F., Ge X., Yan T., Chen X., Shi X., et al. SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B. Cell Metab 2007, 6:307-319.
37. Aubin M.C., Lajoie C., Clement R., Gosselin H., Calderone A., Perrault L.P. Female rats fed a high-fat diet were associated with vascular dysfunction and cardiac fibrosis in the absence of overt obesity and hyperlipidemia: therapeutic potential of resveratrol. J Pharmacol Exp Ther 2008, 325:961-968.
38. Dolinsky V.W., Rueda-Clausen C.F., Morton J.S., Davidge S.T., Dyck J.R. Continued postnatal administration of resveratrol prevents diet-induced metabolic syndrome in rat offspring born growth restricted. Diabetes 2011, 60:2274-2284.
39. Kim S., Jin Y., Choi Y., Park T. Resveratrol exerts anti-obesity effects via mechanisms involving down-regulation of adipogenic and inflammatory processes in mice. Biochem Pharmacol 2011, 81:1343-1351.
40. Sharma S., Misra C.S., Arumugam S., Roy S., Shah V., Davis J.A., et al. Antidiabetic activity of resveratrol, a known SIRT1 activator in a genetic model for type-2 diabetes. Phytother Res 2010, 25:67-73.
41. Li Y., Xu S., Giles A., Nakamura K., Lee J.W., Hou X., et al. Hepatic overexpression of SIRT1 in mice attenuates endoplasmic reticulum stress and insulin resistance in the liver. FASEB J 2011, 25:1664-1679.
42. Kitada M., Kume S., Imaizumi N., Koya D. Resveratrol improves oxidative stress and protects against diabetic nephropathy through normalization of Mn-SOD dysfunction in AMPK/SIRT1-independent pathway. Diabetes 2011, 60:634-643.
43. Minakawa M., Kawano A., Miura Y., Yagasaki K. Hypoglycemic effect of resveratrol in type 2 diabetic model db/db mice and its actions in cultured L6 myotubes and RIN-5F pancreatic beta-cells. J Clin Biochem Nutr 2011, 48:237-244.
44. Shang J., Chen L.L., Xiao F.X. Resveratrol improves high-fat induced nonalcoholic fatty liver in rats. Zhonghua Gan Zang Bing Za Zhi 2008, 16:616-619.
45. Rocha K.K., Souza G.A., Ebaid G.X., Seiva F.R., Cataneo A.C., Novelli E.L. Resveratrol toxicity: effects on risk factors for atherosclerosis and hepatic oxidative stress in standard and high-fat diets. Food Chem Toxicol 2009, 47:1362-1367.
46. Rivera L., Moron R., Zarzuelo A., Galisteo M. Long-term resveratrol administration reduces metabolic disturbances and lowers blood pressure in obese Zucker rats. Biochem Pharmacol 2009, 77:1053-1063.
47. Rodgers J.T., Lerin C., Haas W., Gygi S.P., Spiegelman B.M., Puigserver P. Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature 2005, 434:113-118.
48. Mayers J.R., Iliff B.W., Swoap S.J. Resveratrol treatment in mice does not elicit the bradycardia and hypothermia associated with calorie restriction. FASEB J 2009, 23:1032-1040.
49. Lee J.H., Song M.Y., Song E.K., Kim E.K., Moon W.S., Han M.K., et al. Overexpression of SIRT1 protects pancreatic beta-cells against cytokine toxicity by suppressing the nuclear factor-kappaB signaling pathway. Diabetes 2009, 58:344-351.
50. Shang J., Chen L.L., Xiao F.X., Sun H., Ding H.C., Xiao H. Resveratrol improves non-alcoholic fatty liver disease by activating AMP-activated protein kinase. Acta Pharmacol Sin 2008, 29:698-706.
51. Szkudelski T. Resveratrol inhibits insulin secretion from rat pancreatic islets. Eur J Pharmacol 2006, 552:176-181.
52. Scarlatti F., Sala G., Somenzi G., Signorelli P., Sacchi N., Ghidoni R. Resveratrol induces growth inhibition and apoptosis in metastatic breast cancer cells via de novo ceramide signaling. FASEB J 2003, 17:2339-2341.
53. Aziz M.H., Nihal M., Fu V.X., Jarrard D.F., Ahmad N. Resveratrol-caused apoptosis of human prostate carcinoma LNCaP cells is mediated via modulation of phosphatidylinositol 3'-kinase/Akt pathway and Bcl-2 family proteins. Mol Cancer Ther 2006, 5:1335-1341.
54. Palsamy P., Subramanian S. Ameliorative potential of resveratrol on proinflammatory cytokines, hyperglycemia mediated oxidative stress, and pancreatic beta-cell dysfunction in streptozotocin-nicotinamide-induced diabetic rats. J Cell Physiol 2010, 224:423-432.
55. Kahn B.B., Flier J.S. Obesity and insulin resistance. J Clin Invest 2000, 106:473-481.
56. Goodpaster B.H., Kelley D.E., Wing R.R., Meier A., Thaete F.L. Effects of weight loss on regional fat distribution and insulin sensitivity in obesity. Diabetes 1999, 48:839-847.
57. Macarulla M.T., Alberdi G., Gomez S., Tueros I., Bald C., Rodriguez V.M., et al. Effects of different doses of resveratrol on body fat and serum parameters in rats fed a hypercaloric diet. J Physiol Biochem 2009, 65:369-376.
58. Fujitaka K., Otani H., Jo F., Jo H., Nomura E., Iwasaki M., et al. Modified resveratrol Longevinex improves endothelial function in adults with metabolic syndrome receiving standard treatment. Nutr Res 2011, 31:842-847.
59. Barger J.L., Kayo T., Vann J.M., Arias E.B., Wang J., Hacker T.A., et al. A low dose of dietary resveratrol partially mimics caloric restriction and retards aging parameters in mice. PLoS One 2008, 3:e2264.
60. Szkudelska K., Nogowski L., Szkudelski T. Resveratrol and genistein as adenosine triphosphate-depleting agents in fat cells. Metabolism 2010, 60:720-729.
61. Szkudelska K., Nogowski L., Szkudelski T. Resveratrol, a naturally occurring diphenolic compound, affects lipogenesis, lipolysis and the antilipolytic action of insulin in isolated rat adipocytes. J Steroid Biochem Mol Biol 2009, 113:17-24.
62. Kennedy A., Overman A., Lapoint K., Hopkins R., West T., Chuang C.C., et al. Conjugated linoleic acid-mediated inflammation and insulin resistance in human adipocytes are attenuated by resveratrol. J Lipid Res 2009, 50:225-232.
63. Cucciolla V., Borriello A., Oliva A., Galletti P., Zappia V., Della Ragione F. Resveratrol: from basic science to the clinic. Cell Cycle 2007, 6:2495-2510.
64. Aggarwal B.B., Bhardwaj A., Aggarwal R.S., Seeram N.P., Shishodia S., Takada Y. Role of resveratrol in prevention and therapy of cancer: preclinical and clinical studies. Anticancer Res 2004, 24:2783-2840.
65. Lu J., Ho C.H., Ghai G., Chen K.Y. Resveratrol analog, 3,4,5,4'-tetrahydroxystilbene, differentially induces pro-apoptotic p53/Bax gene expression and inhibits the growth of transformed cells but not their normal counterparts. Carcinogenesis 2001, 22:321-328.
66. Araujo J.R., Goncalves P., Martel F. Chemopreventive effect of dietary polyphenols in colorectal cancer cell lines. Nutr Res 2011, 31:77-87.
67. Huang C., Ma W.Y., Goranson A., Dong Z. Resveratrol suppresses cell transformation and induces apoptosis through a p53-dependent pathway. Carcinogenesis 1999, 20:237-242.
68. Mnjoyan Z.H., Fujise K. Profound negative regulatory effects by resveratrol on vascular smooth muscle cells: a role of p53-p21(WAF1/CIP1) pathway. Biochem Biophys Res Commun 2003, 311:546-552.
69. Mousa S.S., Mousa S.A. Effect of resveratrol on angiogenesis and platelet/fibrin-accelerated tumor growth in the chick chorioallantoic membrane model. Nutr Cancer 2005, 52:59-65.
70. Poussier B., Cordova A.C., Becquemin J.P., Sumpio B.E. Resveratrol inhibits vascular smooth muscle cell proliferation and induces apoptosis. J Vasc Surg 2005, 42:1190-1197.
71. Shankar S., Singh G., Srivastava R.K. Chemoprevention by resveratrol: molecular mechanisms and therapeutic potential. Front Biosci 2007, 12:4839-4854.
72. Imamura G., Bertelli A.A., Bertelli A., Otani H., Maulik N., Das D.K. Pharmacological preconditioning with resveratrol: an insight with iNOS knockout mice. Am J Physiol Heart Circ Physiol 2002, 282:H1996-H2003.
73. Das S., Cordis G.A., Maulik N., Das D.K. Pharmacological preconditioning with resveratrol: role of CREB-dependent Bcl-2 signaling via adenosine A3 receptor activation. Am J Physiol Heart Circ Physiol 2005, 288:H328-H335.
74. Das S., Tosaki A., Bagchi D., Maulik N., Das D.K. Resveratrol-mediated activation of cAMP response element-binding protein through adenosine A3 receptor by Akt-dependent and -independent pathways. J Pharmacol Exp Ther 2005, 314:762-769.
75. Zhao X.Y., Li G.Y., Liu Y., Chai L.M., Chen J.X., Zhang Y., et al. Resveratrol protects against arsenic trioxide-induced cardiotoxicity in vitro and in vivo. Br J Pharmacol 2008, 154:105-113.
76. Chen C.J., Yu W., Fu Y.C., Wang X., Li J.L., Wang W. Resveratrol protects cardiomyocytes from hypoxia-induced apoptosis through the SIRT1-FoxO1 pathway. Biochem Biophys Res Commun 2009, 378:389-393.
77. Usta E., Mustafi M., Walker T., Ziemer G. Resveratrol suppresses apoptosis in intact human cardiac tissue-in vitro model simulating extracorporeal circulation. J Cardiovasc Surg (Torino) 2011, 52:399-409.
78. Wang K., Klionsky D.J. Mitochondria removal by autophagy. Autophagy 2011, 7:297-300.
79. Eskelinen E.L., Reggiori F., Baba M., Kovacs A.L., Seglen P.O. Seeing is believing: the impact of electron microscopy on autophagy research. Autophagy 2011, 7:935-956.
80. Gonzalez C.D., Lee M.S., Marchetti P., Pietropaolo M., Towns R., Vaccaro M.I., et al. The emerging role of autophagy in the pathophysiology of diabetes mellitus. Autophagy 2011, 7:2-11.
81. Tanabe F., Yone K., Kawabata N., Sakakima H., Matsuda F., Ishidou Y., et al. Accumulation of p62 in degenerated spinal cord under chronic mechanical compression: functional analysis of p62 and autophagy in hypoxic neuronal cells. Autophagy 2011, 7:1462-1471.
82. Sui X., Jin L., Huang X., Geng S., He C., Hu X. p53 signaling and autophagy in cancer: a revolutionary strategy could be developed for cancer treatment. Autophagy 2011, 7:565-571.
83. Isaka Y., Kimura T., Takabatake Y. The protective role of autophagy against aging and acute ischemic injury in kidney proximal tubular cells. Autophagy 2011, 7:1085-1087.
84. Przyklenk K., Undyala V.V., Wider J., Sala-Mercado J.A., Gottlieb R.A., Mentzer R.M. Acute induction of autophagy as a novel strategy for cardioprotection: getting to the heart of the matter. Autophagy 2011, 7:432-433.
85. Opipari A.W., Tan L., Boitano A.E., Sorenson D.R., Aurora A., Liu J.R. Resveratrol-induced autophagocytosis in ovarian cancer cells. Cancer Res 2004, 64:696-703.
86. Kueck A., Opipari A.W., Griffith K.A., Tan L., Choi M., Huang J., et al. Resveratrol inhibits glucose metabolism in human ovarian cancer cells. Gynecol Oncol 2007, 107:450-457.
87. Scarlatti F., Maffei R., Beau I., Codogno P., Ghidoni R. Role of non-canonical Beclin 1-independent autophagy in cell death induced by resveratrol in human breast cancer cells. Cell Death Differ 2008, 15:1318-1329.
88. Lin C.J., Lee C.C., Shih Y.L., Lin T.Y., Wang S.H., Lin Y.F., et al. Resveratrol enhances the therapeutic effect of temozolomide against malignant glioma in vitro and in vivo by inhibiting autophagy. Free Radic Biol Med 2012, 52:377-391.
89. Lekli I., Ray D., Mukherjee S., Gurusamy N., Ahsan M.K., Juhasz B., et al. Co-ordinated autophagy with resveratrol and gamma-tocotrienol confers synergetic cardioprotection. J Cell Mol Med 2010, 14:2506-2518.
90. Gurusamy N., Lekli I., Mukherjee S., Ray D., Ahsan M.K., Gherghiceanu M., et al. Cardioprotection by resveratrol: a novel mechanism via autophagy involving the mTORC2 pathway. Cardiovasc Res 2010, 86:103-112.
91. Mukherjee S., Ray D., Lekli I., Bak I., Tosaki A., Das D.K. Effects of Longevinex (modified resveratrol) on cardioprotection and its mechanisms of action. Can J Physiol Pharmacol 2010, 88:1017-1025.
92. Hsu K.F., Wu C.L., Huang S.C., Wu C.M., Hsiao J.R., Yo Y.T., et al. Cathepsin L mediates resveratrol-induced autophagy and apoptotic cell death in cervical cancer cells. Autophagy 2009, 5:451-460.
93. Puissant A., Robert G., Fenouille N., Luciano F., Cassuto J.P., Raynaud S., et al. Resveratrol promotes autophagic cell death in chronic myelogenous leukemia cells via JNK-mediated p62/SQSTM1 expression and AMPK activation. Cancer Res 2010, 70:1042-1052.
94. Signorelli P., Munoz-Olaya J.M., Gagliostro V., Casas J., Ghidoni R., Fabrias G. Dihydroceramide intracellular increase in response to resveratrol treatment mediates autophagy in gastric cancer cells. Cancer Lett 2009, 282:238-243.
95. Mauthe M., Jacob A., Freiberger S., Hentschel K., Stierhof Y.D., Codogno P., et al. Resveratrol-mediated autophagy requires WIPI-1-regulated LC3 lipidation in the absence of induced phagophore formation. Autophagy 2011, 7:1448-1461.
96. Marino G., Morselli E., Bennetzen M.V., Eisenberg T., Megalou E., Schroeder S., et al. Longevity-relevant regulation of autophagy at the level of the acetylproteome. Autophagy 2011, 7:647-649.
97. Ohta K., Mizuno A., Ueda M., Li S., Suzuki Y., Hida Y., et al. Autophagy impairment stimulates PS1 expression and gamma-secretase activity. Autophagy 2010, 6:345-352.
98. Song L.H., Pan W., Yu Y.H., Quarles L.D., Zhou H.H., Xiao Z.S. Resveratrol prevents CsA inhibition of proliferation and osteoblastic differentiation of mouse bone marrow-derived mesenchymal stem cells through an ER/NO/cGMP pathway. Toxicol In Vitro 2006, 20:915-922.
99. Dai Z., Li Y., Quarles L.D., Song T., Pan W., Zhou H., et al. Resveratrol enhances proliferation and osteoblastic differentiation in human mesenchymal stem cells via ER-dependent ERK1/2 activation. Phytomedicine 2007, 14:806-814.
100. Lei M., Liu S.Q., Liu Y.L. Resveratrol protects bone marrow mesenchymal stem cell derived chondrocytes cultured on chitosan-gelatin scaffolds from the inhibitory effect of interleukin-1beta. Acta Pharmacol Sin 2008, 29:1350-1356.
101. Gu J., Wang C.Q., Fan H.H., Ding H.Y., Xie X.L., Xu Y.M., et al. Effects of resveratrol on endothelial progenitor cells and their contributions to reendothelialization in intima-injured rats. J Cardiovasc Pharmacol 2006, 47:711-721.
102. Gurusamy N., Ray D., Lekli I., Das D.K. Red wine antioxidant resveratrol-modified cardiac stem cells regenerate infarcted myocardium. J Cell Mol Med 2010, 14:2235-2239.
103. Lu K.H., Chen Y.W., Tsai P.H., Tsai M.L., Lee Y.Y., Chiang C.Y., et al. Evaluation of radiotherapy effect in resveratrol-treated medulloblastoma cancer stem-like cells. Childs Nerv Syst 2009, 25:543-550.
104. Shankar S., Nall D., Tang S.N., Meeker D., Passarini J., Sharma J., et al. Resveratrol inhibits pancreatic cancer stem cell characteristics in human and KrasG12D transgenic mice by inhibiting pluripotency maintaining factors and epithelial-mesenchymal transition. PLoS One 2011, 6:e16530.
105. Pandey P.R., Okuda H., Watabe M., Pai S.K., Liu W., Kobayashi A., et al. Resveratrol suppresses growth of cancer stem-like cells by inhibiting fatty acid synthase. Breast Cancer Res Treat 2010, 130:387-398.
106. Chen T., Shen L., Yu J., Wan H., Guo A., Chen J., et al. Rapamycin and other longevity-promoting compounds enhance the generation of mouse induced pluripotent stem cells. Aging Cell 2011, 10:908-911.
107. Bordone L., Guarente L. Calorie restriction, SIRT1 and metabolism: understanding longevity. Nat Rev Mol Cell Biol 2005, 6:298-305.
108. Howitz K.T., Bitterman K.J., Cohen H.Y., Lamming D.W., Lavu S., Wood J.G., et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 2003, 425:191-196.
109. Knutson M.D., Leeuwenburgh C. Resveratrol and novel potent activators of SIRT1: effects on aging and age-related diseases. Nutr Rev 2008, 66:591-596.
110. Pacholec M., Bleasdale J.E., Chrunyk B., Cunningham D., Flynn D., Garofalo R.S., et al. SRT1720, SRT2183, SRT1460, and resveratrol are not direct activators of SIRT1. J Biol Chem 2010, 285:8340-8351.
111. Burnett C., Valentini S., Cabreiro F., Goss M., Somogyvari M., Piper M.D., et al. Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila. Nature 2011, 477:482-485.
112. Hwang Y.P., Choi J.H., Han E.H., Kim H.G., Wee J.H., Jung K.O., et al. Purple sweet potato anthocyanins attenuate hepatic lipid accumulation through activating adenosine monophosphate-activated protein kinase in human HepG2 cells and obese mice. Nutr Res 2011, 31:896-906.
113. Kubota K., Sumi S., Tojo H., Sumi-Inoue Y., I-Chin H., Oi Y., et al. Improvements of mean body mass index and body weight in preobese and overweight Japanese adults with black Chinese tea (Pu-Erh) water extract. Nutr Res 2011, 31:421-428.
114. Wang P., Xu T.Y., Guan Y.F., Tian W.W., Viollet B., Rui Y.C., et al. Nicotinamide phosphoribosyltransferase protects against ischemic stroke through SIRT1-dependent adenosine monophosphate-activated kinase pathway. Ann Neurol 2011, 69:360-374.
115. Wang P., Zhang R.Y., Song J., Guan Y.F., Xu T.Y., Du H., et al. Loss of AMP-activated protein kinase-alpha2 impairs the insulin-sensitizing effect of calorie restriction in skeletal muscle. Diabetes 2012, 61:1051-1061.
116. Lage R., Dieguez C., Vidal-Puig A., Lopez M. AMPK: a metabolic gauge regulating whole-body energy homeostasis. Trends Mol Med 2008, 14:539-549.
117. Centeno-Baez C., Dallaire P., Marette A. Resveratrol inhibition of inducible nitric oxide synthase in skeletal muscle involves AMPK but not SIRT1. Am J Physiol Endocrinol Metab 2011, 301:E922-E930.
118. Canto C., Jiang L.Q., Deshmukh A.S., Mataki C., Coste A., Lagouge M., et al. Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle. Cell Metab 2010, 11:213-219.
119. Canto C., Gerhart-Hines Z., Feige J.N., Lagouge M., Noriega L., Milne J.C., et al. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature 2009, 458:1056-1060.
120. Park S.J., Ahmad F., Philp A., Baar K., Williams T., Luo H., et al. Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell 2012, 148:421-433.
121. Timmers S., Konings E., Bilet L., Houtkooper R.H., van de Weijer T., Goossens G.H., et al. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab 2011, 14:612-622.