Challenges of translating basic research into therapeutics: Resveratrol as an example

Journals of Gerontology - Series A Biological Sciences and Medical Sciences

Volumn 67 A, Issue 2, 2012, Pages 158-167

  Smoliga, James M ^a   Vang, Ole ^b   Baur, Joseph A ^c  

^a MARYWOOD UNIVERSITY   (United States)

^b ROSKILDE UNIVERSITY   (Denmark)

^c UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

Clinical trials; Metabolism; Nutraceutical; Polyphenol; Translational

Indexed keywords

ANIMALIA;

ANTIOXIDANT; RESVERATROL; STILBENE DERIVATIVE;

AGING; ANIMAL; ARTICLE; BIOAVAILABILITY; CLINICAL TRIAL (TOPIC); DRUG EFFECT; HUMAN; METABOLISM; TRANSLATIONAL RESEARCH;

AGING; ANIMALS; ANTIOXIDANTS; BIOLOGICAL AVAILABILITY; CLINICAL TRIALS AS TOPIC; HUMANS; STILBENES; TRANSLATIONAL MEDICAL RESEARCH;

EID: 84856171338     PISSN: 10795006     EISSN: 1758535X     Source Type: Journal    
DOI: 10.1093/gerona/glr062     Document Type: Article

References (102)

1. Feral CC, Neels JG, Kummer C, Slepak M, Olefsky JM, Ginsberg MH. Blockade of alpha4 integrin signaling ameliorates the metabolic consequences of high-fat diet-induced obesity. Diabetes. 2008;57:1842-1851.
2. Lu M, Patsouris D, Li P, et al. A new antidiabetic compound attenuates inflammation and insulin resistance in Zucker diabetic fatty rats. Am J Physiol Endocrinol Metab. 2010;298:E1036-E1048.
3. Patsouris D, Li PP, Thapar D, Chapman J, Olefsky JM, Neels JG. Ablation of CD11c-positive cells normalizes insulin sensitivity in obese insulin resistant animals. Cell Metab. 2008;8:301-309.
4. Narkar VA, Downes M, Yu RT, et al. AMPK and PPARdelta agonists are exercise mimetics. Cell. 2008;134:405-415.
5. Jaskelioff M, Muller FL, Paik JH, et al. Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature. 2011;469:102-106.
6. Gonzalez-Suarez E, Geserick C, Flores JM, Blasco MA. Antagonistic effects of telomerase on cancer and aging in K5-mTert transgenic mice. Oncogene. 2005;24:2256-2270. (Pubitemid 40516592)
7. Elsea SH, Lucas RE. The mousetrap: what we can learn when the mouse model does not mimic the human disease. ILAR J. 2002;43:66-79. (Pubitemid 135743763)
8. Talmadge JE, Singh RK, Fidler IJ, Raz A. Murine models to evaluate novel and conventional therapeutic strategies for cancer. Am J Pathol. 2007;170:793-804. (Pubitemid 47339349)
9. Kalra EK. Nutraceutical-definition and introduction. AAPS PharmSci. 2003;5:E25.
10. Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov. 2006;5:493-506. (Pubitemid 44136961)
11. Siemann EH, Creasy LL. Concentration of the phytoalexin resveratrol in wine. Am J Eno Vitic. 1992;43:49-52.
12. Jang M, Cai L, Udeani GO, et al. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science. 1997;275:218-220. (Pubitemid 127696281)
13. Howitz KT, Bitterman KJ, Cohen HY, et al. Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature. 2003;425:191-196. (Pubitemid 37150899)
14. Wood JG, Rogina B, Lavu S, et al. Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature. 2004;430:686-689. (Pubitemid 39061685)
15. Agarwal B, Baur JA. Resveratrol and life extension. Ann N Y Acad Sci. 2011;1215:138-143.
16. Bass TM, Weinkove D, Houthoofd K, Gems D, Partridge L. Effects of resveratrol on lifespan in Drosophila melanogaster and Caenorhabditis elegans. Mech Ageing Dev. 2007;128:546-552. (Pubitemid 47498522)
17. Valenzano DR, Terzibasi E, Genade T, Cattaneo A, Domenici L, Cellerino A. Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Curr Biol. 2006;16:296-300. (Pubitemid 43190229)
18. Pervaiz S, Holme AL. Resveratrol: its biologic targets and functional activity. Antioxid Redox Signal. 2009;11:2851-2897.
19. Athar M, Back JH, Kopelovich L, Bickers DR, Kim AL. Multiple molecular targets of resveratrol: anti-carcinogenic mechanisms. Arch Biochem Biophys. 2009;486:95-102.
20. Baur JA, Pearson KJ, Price NL, et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006;444:337-342. (Pubitemid 44764104)
21. Lagouge M, Argmann C, Gerhart-Hines Z, et al. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. Cell. 2006;127:1109-1122. (Pubitemid 44894520)
22. Das M, Das DK. Resveratrol and cardiovascular health. Mol Aspects Med. 2010;31:503-512.
23. Cui X, Jin Y, Hofseth AB, et al. Resveratrol suppresses colitis and colon cancer associated with colitis. Cancer Prev Res (Phila). 2010;3:549-559.
24. Roy P, Kalra N, Prasad S, George J, Shukla Y. Chemopreventive potential of resveratrol in mouse skin tumors through regulation of mitochondrial and PI3K/AKT signaling pathways. Pharm Res. 2009;26:211-217.
25. Csiszar A, Labinskyy N, Olson S, et al. Resveratrol prevents monocrotaline-induced pulmonary hypertension in rats. Hypertension. 2009;54:668-675.
26. Sanchez-Fidalgo S, Cardeno A, Villegas I, Talero E, de la Lastra CA. Dietary supplementation of resveratrol attenuates chronic colonic inflammation in mice. Eur J Pharmacol. 2010;633:78-84.
27. Vang O, Das DK. Resveratrol and health. Ann N Y Acad Sci. 2011;1215.
28. Vang O, Ahmad N, Baile CA, et al. What is new for an old molecule? Systematic review and recommendations on the use of resveratrol. PLoS ONE. In press.
29. Marier JF, Vachon P, Gritsas A, Zhang J, Moreau JP, Ducharme MP. Metabolism and disposition of resveratrol in rats: extent of absorption, glucuronidation, and enterohepatic recirculation evidenced by a linked-rat model. J Pharmacol Exp Ther. 2002;302:369-373. (Pubitemid 34680460)
30. Walle T, Hsieh F, DeLegge MH, Oatis JE Jr., Walle UK. High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab Dispos. 2004;32:1377-1382. (Pubitemid 39564557)
31. Wang D, Hang T, Wu C, Liu W. Identification of the major metabolites of resveratrol in rat urine by HPLC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci. 2005;829:97-106. (Pubitemid 41773470)
32. Almeida L, Vaz-da-Silva M, Falcao A, et al. Pharmacokinetic and safety profile of transresveratrol in a rising multiple-dose study in healthy volunteers. Mol Nutr Food Res. 2009;53:S7-S15.
33. Boocock DJ, Patel KR, Faust GE, et al. Quantitation of trans-resveratrol and detection of its metabolites in human plasma and urine by high performance liquid chromatography. J Chromatogr B Analyt Technol Biomed Life Sci. 2007;848:182-187. (Pubitemid 46464044)
34. Narayanan NK, Nargi D, Randolph C, Narayanan BA. Liposome encapsulation of curcumin and resveratrol in combination reduces prostate cancer incidence in PTEN knockout mice. Int J Cancer. 2009;125:1-8.
35. Vitaglione P, Sforza S, Galaverna G, et al. Bioavailability of trans-resveratrol from red wine in humans. Mol Nutr Food Res. 2005;49:495-504. (Pubitemid 40780396)
36. Waite KA, Sinden MR, Eng C. Phytoestrogen exposure elevates PTEN levels. Hum Mol Genet. 2005;14:1457-1463. (Pubitemid 40823455)
37. Pearce VP, Sherrell J, Lou Z, Kopelovich L, Wright WE, Shay JW. Immortalization of epithelial progenitor cells mediated by resveratrol. Oncogene. 2008;27:2365-2374. (Pubitemid 351521093)
38. Calabrese EJ, Mattson MP, Calabrese V. Resveratrol commonly displays hormesis: occurrence and biomedical significance. Hum Exp Toxicol. 2010;29:980-1015.
39. Pearson KJ, Baur JA, Lewis KN, et al. Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab. 2008;8:157-168.
40. Dudley J, Das S, Mukherjee S, Das DK. Resveratrol, a unique phytoalexin present in red wine, delivers either survival signal or death signal to the ischemic myocardium depending on dose. J Nutr Biochem. 2009;20:443-452.
41. Reagan-Shaw S, Nihal M, Ahmad N. Dose translation from animal to human studies revisited. FASEB J. 2008;22:659-661. (Pubitemid 351348146)
42. Brown VA, Patel KR, Viskaduraki M, et al. Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics, and effect on the insulin-like growth factor axis. Cancer Res. 2010;70:9003-9011.
43. Williams LD, Burdock GA, Edwards JA, Beck M, Bausch J. Safety studies conducted on high-purity trans-resveratrol in experimental animals. Food Chem Toxicol. 2009;47:2170-2182.
44. Baur JA. Biochemical effects of SIRT1 activators. Biochim Biophys Acta. 2010;1804:1626-1634.
45. Majumdar AP, Banerjee S, Nautiyal J, et al. Curcumin synergizes with resveratrol to inhibit colon cancer. Nutr Cancer. 2009;61:544-553.
46. Mikstacka R, Rimando AM, Ignatowicz E. Antioxidant effect of trans-resveratrol, pterostilbene, quercetin and their combinations in human erythrocytes in vitro. Plant Foods Hum Nutr. 2010;65:57-63.
47. Kowalczyk MC, Kowalczyk P, Tolstykh O, Hanausek M, Walaszek Z, Slaga TJ. Synergistic effects of combined phytochemicals and skin cancer prevention in SENCAR mice. Cancer Prev Res (Phila). 2010;3:170-178.
48. Zamin LL, Filippi-Chiela EC, Dillenburg-Pilla P, Horn F, Salbego C, Lenz G. Resveratrol and quercetin cooperate to induce senescence-like growth arrest in C6 rat glioma cells. Cancer Sci. 2009;100:1655-1662.
49. Park HJ, Yang JY, Ambati S, et al. Combined effects of genistein, quercetin, and resveratrol in human and 3T3-L1 adipocytes. J Med Food. 2008;11:773-783.
50. Revel A, Raanani H, Younglai E, et al. Resveratrol, a natural aryl hydrocarbon receptor antagonist, protects lung from DNA damage and apoptosis caused by benzo[a]pyrene. J Appl Toxicol. 2003;23:255-261. (Pubitemid 36950295)
51. Ungvari Z, Bagi Z, Feher A, et al. Resveratrol confers endothelial protection via activation of the antioxidant transcription factor Nrf2. Am J Physiol Heart Circ Physiol. 2010;299:H18-H24.
52. Iggo N, Winearls CG, Davies DR. The development of cast nephropathy in multiple myeloma. QJM. 1997;90:653-656. (Pubitemid 27483425)
53. Loftus P. Glaxo Ends Study of 'Red-Wine' Drug, No More Studies Planned The Wall Street Journal. New York: Dow Jones Newswires; 2010.
54. Pezzuto JM. Resveratrol as an inhibitor of carcinogenesis. Pharm Biol. 2008;46:443-573. (Pubitemid 351882326)
55. Miller RA, Harrison DE, Astle CM, et al. Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. J Gerontol A Biol Sci Med Sci. 2010;66:191-201.
56. De Angelis C, Drazen JM, Frizelle FA, et al. Clinical trial registration: a statement from the International Committee of Medical Journal Editors. N Engl J Med. 2004;351:1250-1251. (Pubitemid 39296312)
57. McGauran N, Wieseler B, Kreis J, Schuler YB, Kolsch H, Kaiser T. Reporting bias in medical research-a narrative review. Trials. 2010;11:37.
58. Gardiner P, Sarma DN, Low Dog T, et al. The state of dietary supplement adverse event reporting in the United States. Pharmacoepidemiol Drug Saf. 2008;17:962-970.
59. Kennedy J. Herb and supplement use in the US adult population. Clin Ther. 2005;27:1847-1858. (Pubitemid 41815236)
60. Gardiner P, Graham R, Legedza AT, Ahn AC, Eisenberg DM, Phillips RS. Factors associated with herbal therapy use by adults in the United States. Altern Ther Health Med. 2007;13:22-29. (Pubitemid 46427629)
61. Rietjens IM, Slob W, Galli C, Silano V. Risk assessment of botanicals and botanical preparations intended for use in food and food supplements: emerging issues. Toxicol Lett. 2008;180:131-136.
62. Boon H, Hirschkorn K, Griener G, Cali M. The ethics of dietary supplements and natural health products in pharmacy practice: a systematic documentary analysis. Int J Pharm Pract. 2009;17:31-38.
63. FDA. Guidance for Industry: Botanical Drug Products. Rockville, MD: U.S. Department of Health and Human Services; 2004.
64. U.S. Department of Health and Human Services. Dietary Supplement Health and Education Act of 1994. http://www.health.gov/dietsupp/ch1.htm. Accessed March 2, 2011.
65. Mashour GA, Forman SA, Campagna JA. Mechanisms of general anesthesia: from molecules to mind. Best Pract Res Clin Anaesthesiol. 2005;19:349-364. (Pubitemid 40753804)
66. Hemmings HC Jr., Akabas MH, Goldstein PA, Trudell JR, Orser BA, Harrison NL. Emerging molecular mechanisms of general anesthetic action. Trends Pharmacol Sci. 2005;26:503-510. (Pubitemid 41338560)
67. Saniova B, Drobny M. Consciousness and general anaesthesia: a recent view. Neuro Endocrinol Lett. 2008;29:822-830.
68. Ishizawa Y. Mechanisms of anesthetic actions and the brain. J Anesth. 2007;21:187-199. (Pubitemid 46692012)
69. Aftab N, Likhitwitayawuid K, Vieira A. Comparative antioxidant activities and synergism of resveratrol and oxyresveratrol. Nat Prod Res. 2010;24:1726-1733.
70. Bereswill S, Munoz M, Fischer A, et al. Anti-inflammatory effects of resveratrol, curcumin and simvastatin in acute small intestinal inflammation. PLoS One. 2010;5:e15099.
71. Chow HH, Garland LL, Hsu CH, et al. Resveratrol modulates drug- and carcinogen-metabolizing enzymes in a healthy volunteer study. Cancer Prev Res (Phila). 2010;3:1168-1175.
72. Xiong S, Salazar G, Patrushev N, Alexander RW. FoxO1 mediates an auto-feedback loop regulating SIRT1 expression. J Biol Chem. 2011;286:5289-5299.
73. Fullerton MD, Steinberg GR. SIRT1 takes a backseat to AMPK in the regulation of insulin sensitivity by resveratrol. Diabetes. 2010;59:551-553.
74. Wendeburg L, de Oliveira AC, Bhatia HS, Candelario-Jalil E, Fiebich BL. Resveratrol inhibits prostaglandin formation in IL-1beta-stimulated SK-N-SH neuronal cells. J Neuroinflammation. 2009;6:26.
75. Rodgers JT, Lerin C, Gerhart-Hines Z, Puigserver P. Metabolic adaptations through the PGC-1 alpha and SIRT1 pathways. FEBS Lett. 2008;582:46-53. (Pubitemid 350297246)
76. Uttamchandani M, Wang J, Yao SQ. Protein and small molecule microarrays: powerful tools for high-throughput proteomics. Mol Biosyst. 2006;2:58-68.
77. Perel P, Roberts I, Sena E, et al. Comparison of treatment effects between animal experiments and clinical trials: systematic review. BMJ. 2007;334:197.
78. Pound P, Ebrahim S, Sandercock P, Bracken MB, Roberts I. Where is the evidence that animal research benefits humans? BMJ. 2004;328:514-517. (Pubitemid 38293622)
79. de Jong M, Maina T. Of mice and humans: are they the same? Implications in cancer translational research. J Nucl Med. 2010;51:501-504.
80. Dumke CL, Mark Davis J, Angela Murphy E, et al. Successive bouts of cycling stimulates genes associated with mitochondrial biogenesis. Eur J Appl Physiol. 2009;107:419-427.
81. Davis JM, Murphy EA, Carmichael MD, Davis B. Quercetin increases brain and muscle mitochondrial biogenesis and exercise tolerance. Am J Physiol Regul Integr Comp Physiol. 2009;296:R1071-R1077.
82. Nieman DC, Henson DA, Maxwell KR, et al. Effects of quercetin and EGCG on mitochondrial biogenesis and immunity. Med Sci Sports Exerc. 2009;41:1467-1475.
83. Nieman DC, Williams AS, Shanley RA, et al. Quercetin's influence on exercise performance and muscle mitochondrial biogenesis. Med Sci Sports Exerc. 2010;42:338-345.
84. Davis JM, Carlstedt CJ, Chen S, Carmichael MD, Murphy EA. The dietary flavonoid quercetin increases VO(2max) and endurance capacity. Int J Sport Nutr Exerc Metab. 2010;20:56-62.
85. Bigelman KA, Fan EH, Chapman DP, Freese EC, Trilk JL, Cureton KJ. Effects of six weeks of quercetin supplementation on physical performance in ROTC cadets. Mil Med. 2010;175:791-798.
86. Gerhart-Hines Z, Rodgers JT, Bare O, et al. Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha. EMBO J. 2007;26:1913-1923. (Pubitemid 46624046)
87. Ji L, Dickman JR, Kang C, Koening R. Exercise-induced hormesis may help healthy aging. Dose Response. 2010;8:73-79.
88. Ji L, Gomez-Cabrera M-C, Vina J. Exercise and hormesis: activation of cellular antioxidant signaling pathway. Ann N Y Acad Sci. 2006;1067:425-435. (Pubitemid 43806355)
89. Gomez-Cabrera M-C, Domenech E, Romagnoli M, et al. Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance. Am J Clin Nutr. 2008;87:142-149.
90. Teixeira VH, Valente HF, Casal SI, Marques AF, Moreira PA. Antioxidants do not prevent postexercise peroxidation and may delay muscle recovery. Med Sci Sports Exerc. 2009;41:1752-1760.
91. Day C. Thiazolidinediones: a new class of antidiabetic drugs. Diabet Med. 1999;16:179-192.
92. Graham DJ, Ouellet-Hellstrom R, MaCurdy TE, et al. Risk of acute myocardial infarction, stroke, heart failure, and death in elderly Medicare patients treated with rosiglitazone or pioglitazone. JAMA. 2010;304:411-418.
93. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007;356:2457-2471. (Pubitemid 46919772)
94. Cohen D. Rosiglitazone: what went wrong? BMJ. 2010;341:c4848.
95. Berman J. Clinical development of dietary supplements: the perils of starting at phase III. Fitoterapia. 2010:80-84.
96. Woolf AD, Watson WA, Smolinske S, Litovitz T. The severity of toxic reactions to ephedra: comparisons to other botanical products and national trends from 1993-2002. Clin Toxicol (Phila). 2005;43:347-355. (Pubitemid 41428767)
97. Cohen PA, Ernst E. Safety of herbal supplements: a guide for cardiologists. Cardiovasc Ther. 2010;28:246-253.
98. MacDonald L, Foster BC, Akhtar H. Food and therapeutic product interactions-a therapeutic perspective. J Pharm Pharm Sci. 2009;12:367-377.
99. Boocock DJ, Faust GES, Patel KR, et al. Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemoprotective agent. Cancer Epidemiol Biomarkers Prev. 2007;16:1246-1252. (Pubitemid 46984966)
100. O'Connor AB. Building comparative efficacy and tolerability into the FDA approval process. JAMA. 2010;303:979-980.
101. Allan GM, Korownyk C, LaSalle K, et al. Do randomized controlled trials discuss healthcare costs? PLoS One. 2010;5:e12318.
102. Distefano JK, Watanabe RM. Pharmacogenetics of anti-diabetes drugs. Pharmaceuticals (Basel). 2010;3:2610-2646.