Resveratrol as an anti-inflammatory and anti-aging agent: Mechanisms and clinical implications

Molecular Nutrition and Food Research

Volumn 49, Issue 5, 2005, Pages 405-430

  De La Lastra, Catalina Alarcón ^a   Villegas, Isabel ^a  

^a UNIVERSITY OF SEVILLE   (Spain)

Author keywords

Anti ageing; Anti inflammatory; Resveratrol; Review

Indexed keywords

RESVERATROL;

ANTIAGING ACTIVITY; ANTIINFLAMMATORY ACTIVITY; BERRY; BIOAVAILABILITY; CANCER PREVENTION; CARCINOGENESIS; CARDIOVASCULAR SYSTEM; CELL ACTIVATION; CHEMOPROPHYLAXIS; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DOWN REGULATION; DRUG ACTIVITY; DRUG CLEARANCE; ENZYME INHIBITION; GRAPE; HUMAN; IMMUNOCOMPETENT CELL; INFLAMMATION; LIFESPAN; LIVER; NERVOUS SYSTEM; NONHUMAN; PEANUT; REVIEW; TUMOR GROWTH; TUMOR PROMOTION; YEAST;

AGING; ANTI-INFLAMMATORY AGENTS; BIOLOGICAL AVAILABILITY; FRUIT; HUMANS; LONGEVITY; MACROPHAGES; MAST CELLS; MONOCYTES; NEUTROPHILS; PLANTS; PROSTAGLANDIN-ENDOPEROXIDE SYNTHASES; STILBENES; TRANSCRIPTION FACTORS; WINE;

ARACHIS HYPOGAEA; VITACEAE; VITIS SP.;

EID: 20344407841     PISSN: 16134125     EISSN: None     Source Type: Journal    
DOI: 10.1002/mnfr.200500022     Document Type: Review

References (228)

1. Leiro, J., Álvarez, E., Arranz, J. A., Laguna, R., et al., Effects of cis-resveratrol on inflammatory murine macrophages: antioxidant activity and downregulation of inflammatory genes. J. Leukoc. Biol. 2004, 75, 1156-1165.
2. Fremont, L., Biological effects of resveratrol. Life Sci. 2000, 66, 663-673.
3. Pervaiz, S., Resveratrol: from grapevines to mammalian biology. FASEB J. 2003, 17, 1975-1985.
4. Renaud, S. C., De Lorgeril, M., Wine, alcohol, platelets and the French paradox for coronary heart disease. Lancet 1992, 339, 1523-1526.
5. Soleas, G. J., Diamandis, E. P., Goldberg, D. M., Wine as a biological fluid: history, production, and role in disease prevention. J. Clin. Lab. Anal. 1997, 11, 287-313.
6. Kaldas, M. I., Walle, U. K., Walle, T., Resveratrol transport and metabolism by human intestinal Caco-2 cells. J. Pharm. Pharmacol. 2003, 55, 307-312.
7. Ignatowicz, E., Baer-Dubowska, W., Resveratrol, a natural chemopreventive agent against degenerative diseases. Pol. J. Pharmacol. 2001, 53, 557-569.
8. Hao, H. D., He, L. R., Mechanisms of cardiovascular protection by resveratrol. J. Med. Food 2004, 7, 290-298.
9. Szewczuk, L. M., Penning, T. M., Mechanism-based inactivation of COX-1 by red wine m-hydroquinones: a structure-activity relationship study. J. Nat. Prod. 2004, 67, 1778-1782.
10. Landrault, N., Poucheret, P., Ravel, P., Gasc, F., et al., Antioxidant capacities and phenolics levels of French wines from different varieties and vintages. J. Agric. Food Chem. 2001, 49, 3341-3348.
11. Peng, Y., Chu, Q., Liu, F., Ye, J., Determination of phenolic constituents of biological interest in red wine by capillary electrophoresis with electrochemical detection. J. Agric. Food Chem. 2004, 52, 153-156.
12. López-Vélez, M., Martínez-Martínez, F., Del Valle-Ribes, C., The study of phenolic compounds as natural antioxidants in wine. Crit. Rev. Food Sci. Nutr. 2003, 43, 233-244.
13. Soleas, G. J., Diamandis, E. P., Goldberg, D. M., Resveratrol: a molecule whose time has come? And gone? Clin. Biochem. 1997, 30, 91-113.
14. Jang, M., Cai, L., Udeani, G. O., Slowing, K. V., et al., Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 1997, 275, 218-220.
15. Roemer, K., Mahyar-Roemer, M., The basis for the chemopreventive action of resveratrol. Drugs of Today 2002, 38, 571-580.
16. Aziz, M. H., Kumar, R., Ahmad, N., Cancer chemoprevention by resveratrol: in vitro and in vivo studies and the underlying mechanisms (review). Int. J. Oncol. 2003, 23, 17-28.
17. Masoro, E. J., Caloric restriction and aging: an update. Exp. Gerontol. 2000, 35, 299-305.
18. Koubova, J., Guarente, L., How does calorie restriction work? Genes Dev. 2003, 17, 313-321.
19. Hall, S. S., In vino vitalis? Compounds activate life-extending genes. Science 2003, 301, 1165.
20. Red wine ingredient make yeast live longer. [www.nature.com/nsu/030825/ 030825-1.html].
21. Creasy, L. L., Cofee, M., Phytoalexin production potential of grape berries. J. Am. Soc. Hort. Sci. 1988, 113, 230-234.
22. Langcake, P., Pryce, R. J., The production of resveratrol by Vitis vinifera and other members of the vitaceae as a response to infection or injury. Physiol. Plant. Pathol. 1976, 9, 77-86.
23. Jeandet, P., Bessis, R., Gautheron, B., The production of resveratrol (3,5,4′-trihydroxystilbene) by grape berries in different developmental stages. Am. J. Enol. Vitic. 1991, 42, 41-46.
24. Vrhovsek, U., Eder, R., Wendelin, S., The occurrence of trans-resveratrol in Slovenian red and white wines. Acta Aliment. 1995, 24, 203-212.
25. Romero-Perez, A. I., Lamuela-Raventos, R. M., Waterhouse, A. L., Delatorreboronat, M. C., Levels of cis- and trans-resveratrol and their glucosides in white and rose Vitis vinifera wines from Spain. J. Agric. Food Chem. 1996, 44, 2124-2128.
26. Goldberg, D. M., Yan, J., Ng, E., Diamandis, E. P., et al., A global survey of trans-resveratrol concentrations in commercial wines. Am. J. Enol. Viti. 1995, 46, 159-165.
27. McMurtrey, K. D., Minn, J., Pobanz, K., Schultz, T. P., Analysis of red wines for resveratrol using direct injection high-pressure liquid chromatography with electrochemical detection. J. Agric. Food Chem. 1994, 42, 2077-2080.
28. Pezet, R., Pont, V., Cuenat, P., Method to determine resveratrol and pterostilbene in grape berries and wines using high-perfomance liquid chromatography and highly sensitive fluorimetric detection. J. Chromatogr. A 1994, 663, 191-197.
29. Ector, B. J., Magee, J. B., Hegwood, C. P., Coign, M. J., Resveratrol concentration in muscadine berries, juice, pomance, purees, seeds and wines. Am. J. Enol. Vitic. 1996, 47, 57-62.
30. Daniel, O., Meier, M. S., Schlatter, J., Frischknecht, P., Selected phenolic compounds in cultivated plants: ecologic functions, health implications and modulation by pesticides. Environ. Health Perspect. 1999, 107 (Suppl. 1), 109-114.
31. Soleas, G. J., Goldberg, D. M., Karumachiri, A., Diamandis, E. P., Influence of viticultural and oenological factors on changes in cis- and trans-resveratrol in commercial wines. J. Wine Res. 1995, 6, 107-121.
32. Romero-Perez, A.I., Ibern-Gomez, M., Lamuela-Raventos, R., de La Torre-Boronat, M. C., Piceid, the major resveratrol derivative in grape juices. J. Agric. Food Chem. 1999, 47, 1533-1536.
33. Ribeiro de Lima, M. T., Waffo-Teguo, P., Teissedre, P. L., Pujolas, A., et al., Determination of stilbenes (trans-astringin, cis- and trans-piceid, and cis- and trans-resveratrol) in Portuguese wines. J. Agric. Food Chem. 1999, 47, 2666-2670.
34. Goldberg, D. M., Does wine work? Clin. Chem. 1995, 41, 14-16.
35. Sanders, T. H., McMichael, R. W., Hendrix, K. W., Occurrence of resveratrol in edible peanuts. J. Agric. Food Chem. 2000, 48, 1243-1246.
36. Wang, Y., Catana, C., Yang, Y., Roderick, R., et al., An LC-MS method for analyzing total resveratrol in grape juice, cranberry juice, and in wine. J. Agric. Food Chem. 2000, 50, 431-435.
37. Bertelli, A. A., Giovanni, L., Stradi, R., Urien, S., et al., Kinetics of trans- and cis-resveratrol (3,4′,5-trihydroxystilbene) after red wine oral administration in rats. Int. J. Clin. Pharmacol. Res. 1996, 16, 77-81.
38. Andlauer, W., Kolb, J., Siebert, K., Furst, P., Assessment of resveratrol bioavailability in the perfused small intestine of the rat. Drugs Exp. Clin. Res. 2000, 26, 47-55.
39. Soleas, G. J., Angelini, M., Grass, L., Diamandis, E. P., et al., Absorption of trans-resveratrol in rats. Methods Enzymol. 2001, 335, 145-154.
40. Yu, C., Shin, Y. G., Chow, A., Li, Y., et al., Human, rat and mouse metabolism of resveratrol. Pharm. Res. 2002, 19, 1907-1914.
41. Goldberg, D. M., Yan, J., Soleas, G. J., Absorption of three wine-related polyphenols in three different matrices by healthy subjects. J. Clin. Biochem. 2003, 36, 79-87.
42. 14C]-trans-resveratrol, a cancer chemopreventive polyphenol, in mouse tissues after oral administration. Life Sci. 2003, 72, 2219-2233.
43. Meng, X., Maliakal, P., Lu, H., Lee, M.-J., et al., Urinary and plasma levels of resveratrol and quercetin in humans, mice and rats after ingestion of pure compounds and grape juice. J. Agric. Food Chem. 2004, 52, 935-942.
44. Marier, J. F., Vachon, P., Gritsas, A., Zhang, J., et al., 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.
45. Kuhnle, G., Spencer, J. P. E., Chowrimootoo, G., Schroeter, H., et al., Resveratrol is absorbed in the small intestine as resveratrol glucuronide. Biochem. Biophys. Res. Commun. 2000, 272, 212-217.
46. Juan, M. E., Buenafuente, J., Casals, I., Planas, J. M., Plasmatic levels of trans-resveratrol in rats. Food Res. Int. 2002, 35, 195-199.
47. De Santi, C., Pietrabissa, A., Mosca, F., Pacifici, G. M., Glucuronidation of resveratrol, a natural product present in grape and wine, in the human liver. Xenobiotica 2000, 30, 1047-1054.
48. De Santi, C., Pietrabissa, A., Spisni, R., Mosca, F., et al., Sulphation of resveratrol, a natural product present in grape and wine, in the human liver and duodenum. Xenobiotica 2000, 30, 609-617.
49. Aumont, V., Krisa, S., Battaglia, E., Netter, P., et al., Regioselective and stereospecific glucuronidation of trans- and cis-resveratrol in human. Arch. Biochem. Biophys. 2001, 393, 281-289.
50. Gescher, A. J., Steward, W. P., Relationship between mechanisms, bioavailability, and preclinical chemopreventive efficacy of resveratrol: a conundrum. Cancer Epidemiol. Biomarkers Prev. 2003, 12, 953-957.
51. Soleas, G. J., Yan, J., Goldberg, D. M., Measurement of trans-resveratrol, (+)-catechin, and quercetin in rat and human blood and urine by gas chromatography with mass selective detection. Methods Enzymol. 2001, 335, 130-145.
52. Walle, T., Hsieh, F., DeLegge, M. H., Oatis, J. E. Jr., et al., High absorption but very low bioavailability of oral resveratrol in humans. Drug Metab. Dispos. 2004, 32, 1377-1382.
53. Bianchini, F., Vainio, H., Wine and resveratrol: mechanisms of cancer prevention? Eur. J. Cancer Prev. 2003, 12, 417-425.
54. Asensi, M., Medina, I., Ortega, A., Carretero, J., et al., Inhibition of cancer growth by resveratrol is related to its low bioavailability. Free Radical Biol. Med. 2002, 33, 387-398.
55. Belguendouz, L., Fremont, L., Linard, A., Resveratrol inhibits metal iondependent and independent peroxidation of porcine low-density lipoproteins. Biochem. Pharmacol. 1997, 53, 1347-1355.
56. Khan, M. A., Muzammil, S., Musarrat, J., Differential binding of tetracyclines with serum albumin and induced structural alterations in drug-bound protein. Int. J. Biol. Macromol. 2002, 30, 243-249.
57. Jannin, B., Menzel, M., Berlot, J. P., Delmas, D., et al., Transport of resveratrol, a cancer chemopreventive agent, cellular targets: plasmatic protein binding and cell uptake. Biochem. Pharmacol. 2004, 68, 1113-1118.
58. Blache, D., Rustan, I., Durand, P., Lesgards, G., et al., Gas chromatographic analysis of resveratrol in plasma, lipoproteins and cells after in vitro incubations. J. Chromatogr. B 1997, 702, 103-110.
59. Belguendouz, L., Fremont, L., Gozzelino, M. T., Interaction of trans-resveratrol with plasma proteins. Biochem. Pharmacol. 1998, 55, 811-816.
60. Lamuela-Raventos, R. M., Covas, M. I., Fito, M., Marrugat, J., et al., Detection of dietary antioxidant phenolic compounds in human LDL. Clin. Chem. 1999, 45, 1870-1872.
61. Bertelli, A., Bertelli, A. A., Gozzini, A., Giovannini, L., Plasma and tissue resveratrol concentrations and pharmacological activity. Drugs Exp. Clin. Res. 1998, 24, 133-138.
62. Lançon, A., Delmas, D., Osman, H., Thénot, J. P., et al., Human hepatic cell uptake of resveratrol: involvement of both passive diffusion and carrier-mediated process. Biochem. Biophys. Res. Commun. 2004, 316, 1132-1137.
63. De Santi, C., Pietrabissa, A., Spisni, R., Mosca, F., et al., Sulphation of resveratrol, a natural compound present in wine, and its inhibition by natural flavonoids. Xenobiotica 2000, 30, 857-866.
64. Potter, G. A., Patterson, L. H., Wanogho, E., Perry, P. J., et al., The cancer preventative agent resveratrol is converted to the anticancer agent piceatannol by the cytochrome P450 enzyme CYP1B1. Br. J. Cancer 2002, 86, 774-778.
65. Piver, B., Fer, M., Vitrac, X., Merillon, J. M., et al., Involvement of cytochrome P450 1A2 in the biotransformation of trans-resveratrol in human liver microsomes. Biochem. Pharmacol. 2004, 68, 773-782.
66. Wang, L. X., Heredia, A., Song, H., Zhang, Z., et al., Resveratrol glucuronides as the metabolites of resveratrol in humans: characterization, synthesis, and anti-HIV activity. J. Pharm. Sci. 2004, 93, 2448-2457.
67. Zhou, S., Koh, H. L., Gao, Y., Gong, Z. Y., et al., Herbal bioactivation: the good, the bad and the ugly. Life Sci. 2004, 74, 935-968.
68. Ciolino, H. P., Daschner, P. J., Yeh, G. C., Resveratrol inhibits transcription of CYP1A1 in vitro by preventing activation of the aryl hydrocarbon receptor. Cancer Res. 1998, 58, 5707-5712.
69. Ciolino, H. P., Yeh, G. C., Inhibition of aryl hydrocarbon-induced cytochrome P-450 1A1 enzyme activity and CYP 1A1 expression by resveratrol. Mol. Pharmacol. 1999, 56, 760-767.
70. Chun, Y. J., Kim, M. Y., Guengerich, F. P., Resveratrol is a selective human cytochrome P450 1A1 inhibitor. Biochem. Biophys. Res. Commun. 1999, 262, 20-24.
71. Chang, T. K., Lee, W. B., Ko, H. H., Trans-resveratrol modulates the catalytic activity and mRNA expression of the procarcinogen-activating human cytochrome P450 1B1. Can. J. Physiol. Pharmacol. 2000, 78, 874-881.
72. Chang, T. K., Chen, J., Lee, W. B., Differential inhibition and inactivation of human CYP1 enzymes by trans-resveratrol: evidence for mechanism based inactivation of CYP1A2. J. Pharmacol. Exp. Ther. 2001, 299, 874-882.
73. Yu, C., Shin, Y. G., Kosmeder, J. W., Pezzuto, J. M., et al., Liquid chromatography/tandem mass spectrometric determination of inhibition of human cytochrome P450 isozymes by resveratrol and resveratrol-3-sulfate. Rapid Commun. Mass Spectrom. 2003, 17, 307-313.
74. Chan, W. K., Nguyen, L. T., Miller, V. P., Harris, R. Z., Mechanism-based inactivation of human cytochrome P450 3A4 by grapefruit juice and red wine. Life Sci. 1998, 62, 135-142.
75. Chan, W. K., Delucchi, A. B., Resveratrol, a red wine constituent, is a mechanism-based inactivator of cytochrome P450 3A4. Life Sci. 2000, 67, 3103-3112.
76. Piver, B., Berthou, F., Dreano, Y., Lucas, D., Inhibition of CYP3A, CYP1A and CYP2E1 activities by resveratrol and other non volatile red wine components. Toxicol. Lett. 2001, 125, 83-91.
77. Bailey, D. G., Malcolm, J., Arnold, O., Spence, J. D., Grapefruit juice-drug interactions. Br. J. Clin. Pharmacol. 1998, 46, 101-110.
78. Kane, G. C., Lipsky, J. J., Drug-grapefruit juice interactions. Mayo Clin. Proc. 2000, 75, 933-942.
79. Becquemont, L., Verstuyft, C., Kerb, R., Brinkmann, U., et al., Effect of grapefruit juice on digoxin pharmacokinetics in humans. Clin. Pharmacol. Ther. 2001, 70, 311-316.
80. Sigusch, H., Henschel, L., Kraul, H., Merkel, U., et al., Lack of effect of grapefruit juice on diltiazem bioavailability in normal subjects. Pharmazie 1994, 49, 675-679.
81. Vincent, J., Harris, S. I., Foulds, G., Dogolo, L. C., et al., Lack of effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of amlodipine. Br. J. Clin. Pharmacol. 2000, 50, 455-463.
82. Dresser, G. K., Bailey, D. G., The effects of fruit juices on drug disposition: a new model for drug interactions. Eur. J. Clin. Invest. 2003, 33 (Suppl. 2), 10-16.
83. Paine, M. F., Criss, A. B., Watkins, P. B., Two major grapefruit juice components differ in intestinal CYP3A4 inhibition kinetic and binding properties. Drug Metab. Dispos. 2004, 32, 1146-1153.
84. Lin, S. J., Defossez, P. A., Guarente, L., Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science 2000, 289, 2126-2128.
85. Kaeberlein, M., McVey, M., Guarente, L., The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev. 1999, 13, 2570-2580.
86. Lin, S. J., Kaeberlein, M., Andalis, A. A., Sturzt, L. A., et al., Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration. Nature 2002, 418, 344-348.
87. Anderson, R. M., Bitterman, K. J., Wood, J. G., Medvedik, O., et al., Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae. Nature 2003, 423, 181-185.
88. Guarente, L., Sir2 links chromatin silencing, metabolism, and aging. Genes Dev. 2000, 14, 1021-1026.
89. Gasser, S. C. M., The molecular biology of the SIR proteins. Gene 2001, 279, 1-16.
90. Tissenbaum, H. A., Guarente, L., Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 2001, 410, 227-230.
91. Rogina, B., Helfand, S. L., Frankel, S., Longevity regulation by Drosophila Rpd3 deacetylase and caloric restriction. Science 2002, 298, 1745.
92. Denu, J. M., Linking chromatin function with metabolic networks: Sir2 family of NAD(+)-dependent deacetylases. Trends Biochem. Sci. 2003, 28, 41-48.
93. Howitz, K. T., Bitterman, K. J., Cohen, H. Y., Lamming, D. W., et al., Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 2003, 425, 191-196.
94. Corder, R., Crozier, A., Kroon, P. A., Drinking your health? It's too early to say. Nature 2003, 426, 119.
95. Wood, J. G., Rogina, B., Lavu, S., Howitz, K., et al., Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 2004, 430, 686-689.
96. Bauer, J. H., Goupil, S., Garber, G. B., Helfand, S. L., An accelerated assay for the identification of lifespan-extending interventions in Drosophila melanogaster. Proc. Natl. Acad. Sci. USA 2004, 101, 12980-12985.
97. Vaziri, H., Dessain, S. K., Ng Eaton, E., Imai, S. I., et al., hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell 2001, 107, 149-159.
98. Luo, J., Nikolaev, A. Y., Imai, S., Chen, D., et al., Negative control of p53 by Sir2a promotes cell survival under stress. Cell 2001, 107, 137-148.
99. Langley, E. P. M., Pearson, M., Faretta, M., Bauer, U. M., et al., Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence. EMBO J. 2002, 21, 2383-2396.
100. Ferguson, L. R., Role of plant polyphenols in genomic stability. Mutat. Res. 2001, 475, 89-111.
101. Nicolini, G., Rigolio, R., Miloso, M., Bertelli, A. A., et al., Anti-apoptotic effect of transresveratrol on paclitaxel-induced apoptosis in the human neuroblastoma SH-SY5Y cell line. Neurosci. Lett. 2001, 302, 41-44.
102. Dong, Z., Molecular mechanism of the chemopreventive effect of resveratrol. Mutat. Res. 2003, 523-524, 145-150.
103. Picard, F., Kurtev, M., Chung, N., Topark-Ngarm, A., et al., Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature 2004, 429, 771-776.
104. Tontonoz, P., Hu, E., Spiegelman, B. M., Stimulation of adipogenesis in fibroblasts by PPARg2, a lipid-activated transcription factor. Cell 1994, 79, 1147-1156.
105. Berger, J., Moller, D. E., The mechanisms of action of PPARs. Annu. Rev. Med. 2002, 53, 409-435.
106. Wahli, W., Peroxisome proliferator-activated receptors (PPARs): from metabolic control to epidermal wound healing. Swiss Med. WKLY 2002, 132, 83-91.
107. Alarcón de la Lastra, C., Sánchez-Fidalgo, S., Villegas, I., Motilva, V., New pharmacological perspectives and therapeutic potential of PPAR-γ agonists. Curr. Pharm. Des. 2004, 10, 3505-3524.
108. Barak, Y., Nelson, M. C., Ong, E. S., Jones, Y. Z., et al., PPAR γ is required for placental, cardiac, and adipose tissue development. Mol. Cell 1999, 4, 585-595.
109. Torra, I. P., Chinetti, G., Duval, C., Fruchart, J. C., et al., Peroxisome proliferator-activated receptors: from transcriptional control to clinical practice. Curr. Opin. Lipidol. 2001, 12, 245-254.
110. Blüher, M., Kahn, B. B., Kahn, C. R., Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 2003, 299, 572-574.
111. Geboes, K., From inflammation to lesion. Acta Gastroenterol. Belg. 1994, 57, 273-284.
112. Rodríguez, F. J., Fisiopatología de la inflamación, in: Consejo General de Colegios Oficiales de Farmacéuticos (Ed.), Avances en Farmacología y Farmacoterapia. Módulo III: Avances en Inmunología, Inflamación y Dolor, Acción Médica, S. A., Madrid 2003, pp. 49-74.
113. Wang, S. C., Rossignol, D. P., Christ, W. J., Geller, D. A., et al., Suppression of lipopolysaccharide-induced macrophage nitric oxide and cytokine production in vitro by a novel lipopolysaccharide antagonist. Surgery 1994, 116, 339-346.
114. Rainger, G. E., Rowley, A. F., Nash, G. B., Adhesion-dependent release of elastase from human neutrophils in a novel, flow-based model: specificity of different chemotactic agents. Blood 1998, 92, 4819-4827.
115. Nathan, C., Points of control in inflammation. Nature 2002, 420, 846-852.
116. Vietor, I., Schwenger, P., Li, W., Schlessinger, J., et al., Tumor necrosis factor-induced activation and increased tyrosine phosphorylation of mitogen-activated protein (MAP) kinase in human fibroblasts. J. Biol. Chem. 1993, 268, 18994-18999.
117. Fulgenzi, A., Bertelli, A. A., Magni, E., Ferrero, E., et al., In vivo inhibition of TNFα-induced vascular permeability by resveratrol. Transplant. Proc. 2001, 33, 2341-2343.
118. Baggiolini, M., Loetscher, P., Moser, B., Interleukin-8 and the chemokine family. Int. J. Immunopharmacol. 1995, 17, 103-108.
119. Donnelly, L. E., Newton, R., Kennedy, G. E., Fenwick, P. S., et al., Anti-inflammatory effects of resveratrol in lung epithelial cells: molecular mechanisms. Am. J. Physiol. Lung. Cell Mol. Physiol. 2004, 287, L774-L783.
120. Hart, P. H., Regulation of the inflammatory response in asthma by mast cell products. Immunol. Cell Biol. 2001, 79, 149-153.
121. Baolin, L., Inami, Y., Tanaka, H., Inagaki, N., et al., Resveratrol inhibits the release of mediators from bone marrow-derived mouse mast cells in vitro. Planta Med. 2004, 70, 305-309.
122. Levy, J. H., The human inflammatory response. J. Cardiovasc. Pharmacol. 1996, 27 (Suppl. 1), S31-S37.
123. Simon, S. I., Goldsmith, H. L., Leukocyte adhesion dynamics in shear flow. Ann. Biomed. Eng. 2002, 30, 315-332.
124. Cavallaro, A., Ainis, T., Bottari, C., Fimiani, V., Effect of resveratrol on some activities of isolated and in whole blood human neutrophils. Physiol. Res. 2003, 52, 555-562.
125. Panés, J., Granger, N., Leukocyte-endothelial cell interactions: molecular mechanisms and implications in gastrointestinal disease. Gastroenterology 1998, 114, 1066-1090.
126. Cronstein, B. N., Weissmann, G., The adhesion molecules of inflammation. Arthritis Rheum. 1993, 36, 147-157.
127. Ferrero, M. E., Bertelli, A. A. E., Pellegatta, F., Fulgenzi, A., et al., Phytoalexin resveratrol (3,4′,5-trihydroxystilbene) modulates granulocyte and monocyte endothelial adhesion. Transplant. Proc. 1998, 30, 4191-4193.
128. Bertelli, A. A., Baccalini, R., Battaglia, E., Falchi, M., Ferrero, M. E., Resveratrol inhibits TNF alpha-induced endothelial cell activation. Therapie 2001, 56, 613-616.
129. Chung, A. W., Jurasz, P., Hollenberg, M. D., Radomski, M. W., Mechanisms of action of proteinase-activated receptor agonists on human platelets. Br. J. Pharmacol. 2002, 135, 1123-1132.
130. Kaneider, N. C., Mosheimer, B., Reinisch, N., Patsch, J. R., Wiedermann, C. J., Inhibition of thrombin-induced signaling by resveratrol and quercetin: effects on adenosine nucleotide metabolism in endothelial cells and platelet-neutrophil interactions. Thromb. Res. 2004, 114, 185-194.
131. Kaneider, N. C., Egger, P., Dunzendorfer, S., Noris, P., et al., Reversal of thrombin-induced deactivation of CD39/ATP-Dase in endothelial cells by HMG-CoA reductase inhibition: effects on Rho-GTPase and adenosine nucleotide metabolism. Arterioscler. Thromb. Vasc. Biol. 2002, 22, 894-900.
132. Kawashima, Y., Nagasawa, T., Ninomiya, H., Contribution of ecto-5V-nucleotidase to the inhibition of platelet aggregation by human endothelial cells. Blood 2000, 96, 2157-2162.
133. Wallace, J. L., Ma, L., Inflammatory mediators in gastrointestinal defense and injury. Exp. Biol. Med. 2001, 226, 1003-1015.
134. Rotondo, S., Rajtar, G., Manarini, S., Celardo, A., et al., Effect of trans-resveratrol, a natural polyphenolic compound, on human polymorphonuclear leukocyte function. Br. J. Pharmacol. 1998, 123, 1691-1699.
135. McClintock, S. D., Till, G. O., Smith, M. G., Ward, P. A., Protection from half-mustard-gas-induced acute lung injury in the rat. J. Appl. Toxicol. 2002, 22, 257-262.
136. Tou, J., Urbizo, C., Resveratrol inhibits the formation of phosphatidic acid and diglyceride in chemotactic peptide- or phorbol ester-stimulated human neutrophils. Cell Signal. 2001, 13, 191-197.
137. Harlan, J. M., Neutrophil-mediated vascular injury. Acta Med. Scand. 1987, Suppl. 715, 123-129.
138. DiPietro, L., Wound healing: the role of the macrophage and other immune cells. Shock 1995, 4, 233-240.
139. Fritsch, C., Simon-Assmann, P., Kedinger, M., Evans, G. S., Cytokines modulate fibroblast phenotype and epithelial-stroma interactions in rat intestine. Gastroenterology 1997, 112, 826-838.
140. Tsai, S. H., Lin-Shiau, S. Y., Lin, J. K., Suppression of nitric oxide synthase and the down-regulation of the activation of NFκB in macrophages by resveratrol. Br. J. Pharmacol. 1999, 126, 673-680.
141. Wadsworth, T. L., Koop, D. R., Effects of the wine polyphenolics quercetin and resveratrol on pro-inflammatory cytokine expression in RAW 264.7 macrophages. Biochem. Pharmacol. 1999, 57, 941-949.
142. Matsuda, H., Kageura, T., Morikawa, T., Toguchida, I., et al., Effects of stilbene constituents from rhubarb on nitric oxide production in lipopolysaccharide-activated macrophages. Bioorg. Med. Chem. Lett. 2000, 10, 323-327.
143. Leiro, J., Alvarez, E., Garcia, D., Orallo, F., Resveratrol modulates rat macrophage functions. Int. Immunopharmacol. 2002, 2, 767-774.
144. Zhong, M., Cheng, G. F., Wang, W. J., Guo, Y., et al., Inhibitory effect of resveratrol on interleukin 6 release by stimulated peritoneal macrophages of mice. Phytomedicine 1999, 6, 79-84.
145. Culpitt, S. V., Rogers, D. F., Fenwick, P. S., Shah, P., et al., Inhibition by red wine extract, resveratrol, of cytokine release by alveolar macrophages in COPD. Thorax 2003, 58, 942-946.
146. Higgs, G. A., Moncada, S., Salmon, J. A., Seager, K., The source of thromboxane and prostaglandins in experimental inflammation. Br. J. Pharmacol. 1985, 89, 1162-1188.
147. Shigematsu, S., Ishida, S., Hara, M., Takahashi, N., et al., Resveratrol, a red wine constituent polyphenol, prevents superoxide-dependent inflammatory responses induced by ischemia/reperfusion, platelet-activating factor, or oxidants. Free Radic. Biol. Med. 2003, 34, 810-817.
148. Kimura, Y., Okuda, H., Kubo, M., Effects of stilbenes isolated from medicinal plants on arachidonate metabolism and degranulation in human polymorphonuclear leukocytes. J. Ethnopharmacol. 1995, 45, 131-139.
149. Hogaboam, C. M., Bissonnette, E. Y., Chin, B. C., Befus, A. D., et al., Prostaglandins inhibit inflammatory mediator release from rat mast cells. Gastroenterology 1993, 104, 122-129.
150. Wertheim, W. A., Kunkel, S. L., Standiford, T. J., Burdick, M. D., et al., Regulation of neutrophil-derived IL-8: the role of prostaglandin E2, dexamethasone, and IL-4. J. Immunol. 1993, 151, 2166-2175.
151. Chandrasekharan, N. V., Dai, H., Roos, K. L., Evanson, N. K., et al., COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc. Natl. Acad. Sci. USA 2002, 99, 13926-13931.
152. Davies, N. M., Good, R. L., Roupe, K. A., Yáñez, J. A., Cyclooxygenase-3: axiom, dogma, anomaly, enigma or splice error? - not as easy as 1, 2, 3. J. Pharm. Pharmaceut. Sci. 2004, 7, 217-226.
153. Dinchuk, J. E., Liu, R. Q., Trzaskos, J. M., COX-3: in the wrong frame in mind. Immunol. Lett. 2003, 86, 121.
154. Vane, J. R., Botting, R. M., Mechanism of action of nonsteroidal anti-inflammatory drugs. Am. J. Med. 1998, 104, 2S-8S.
155. Fournier, D. B., Gordon, G. B., COX-2 and colon cancer: potential targets for chemoprevention. J. Cell Biochem. Suppl. 2000, 34, 97-102.
156. Bakhle, Y. S., COX-2 and cancer: a new approach to an old problem. Br. J. Pharmacol. 2201, 134, 1137-1150.
157. Gupta, R. A., DuBois, R. N., Colorectal cancer prevention and treatment by inhibition of cyclooxygenase-2. Nature Rev. 2001, 1, 11-21.
158. Szewczuk, L. M., Forti, L., Stivala, L. A., Penning, T. M., Resveratrol is a peroxidase-mediated inactivator of COX-1 but not COX-2. J. Biol. Chem. 2004, 279, 22727-22737.
159. Subbaramaiah, K., Chung, W. J., Michaluart, P., Telang, N., et al., Resveratrol inhibits cyclooxygenase-2 transcription and activity in phorbol ester-treated human mammary epithelial cells. J. Biol. Chem. 1998, 273, 21875-21882.
160. Martínez, J., Moreno, J. J., Effect of resveratrol, a natural polyphenolic compound, on reactive oxygen species and prostaglandin production. Biochem. Pharmacol. 2000, 59, 865-870.
161. Martín, A. R., Villegas, I., La Casa, C., Alarcón de la Lastra, C., Resveratrol, a polyphenol found in grapes, suppresses oxidative damage and stimulates apoptosis during early colonic inflammation in rats. Biochem. Pharmacol. 2004, 67, 1399-1410.
162. Shigeta, J., Takahashi, S., Okabe, S., Role of cyclooxygenase-2 in the healing of gastric ulcers in rats. J. Pharmacol. Exp. Ther. 1998, 286, 1383-1390.
163. Schmassmann, A., Peskar, B. M., Stettler, C., Netzer, P., et al., Effects of inhibition of prostaglandin endoperoxide synthase-2 in chronic gastrointestinal ulcer models in rats. Br. J. Pharmacol. 1998, 123, 795-804.
164. Nissen, N. N., Polverini, P. J., Koch, A. E., Volin, M. V., et al., Vascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing. Am. J. Pathol. 1998, 152, 1445-1452.
165. Khanna, S., Venojarvi, M., Roy, S., Sharma, N., et al., Dermal wound healing properties of redox-active grape seed proanthocyanidins. Free Radic. Biol. Med. 2002, 33, 1089-1096.
166. Brzozowski, T., Konturek, P. C., Konturek, S. J., Sliwowski, Z., et al., Classic NSAID and selective cyclooxygenase (COX)-1 and COX-2 inhibitors in healing of chronic gastric ulcers. Microsc. Res. Tech. 2001, 53, 343-353.
167. Goodwin, J. S., Ceuppens, J., Regulation of the immune response by prostaglandins. J. Clin. Immunol. 1983, 3, 295-315.
168. Tsujii, M., DuBois, R. N., Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell 1995, 83, 493-501.
169. 2 in human colon cancer cells. Cancer Res. 1998, 58, 362-366.
170. Tsujii, M., Kawano, S., Tsuji, S., Sawaoka, H., et al., Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 1998, 93, 705-716.
171. Gupta, R. A., Tejada, L. V., Tong, B. J., Das, S. K., et al., Cyclooxygenase-1 is overexpressed and promotes angiogenic growth factor production in ovarian cancer. Cancer Res. 2003, 63, 906-911.
172. Balkwill, F., Mantovani, A., Inflammation and cancer: back to Virchow? Lancet 2001, 357, 539-545.
173. Coussens, L. M., Werb, Z., Inflammation and cancer. Nature 2002, 420, 860-867.
174. Eling, T. E., Thompson, D. C., Foureman, G. L., Curtis, J. F., et al., Prostaglandin H synthase and xenobiotic oxidation. Annu. Rev. Pharmacol. Toxicol. 1990, 30, 1-45.
175. Wiseman, H., Halliwell, B., Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer. Biochem. J. 1996, 313, 17-29.
176. Nikolic, D., van Breemen, R. B., DNA oxidation induced by cyclooxygenase-2. Chem. Res. Toxicol. 2001, 14, 351-354.
177. Anderson, W. F., Umar, A., Hawk, E. T., Cyclooxygenase inhibition in cancer prevention and treatment. Expert Opin. Pharmacother. 2003, 4, 2193-2204.
178. Murias, M., Handler, N., Erker, T., Pleban, K., et al., Resveratrol analogues as selective cyclooxygenase-2 inhibitors: synthesis and structure-activity relationship. Bioorg. Med. Chem. 2004, 12, 5571-5578.
179. Dubuisson, J. G., Dyess, D. L., Gaubatz, J. W., Resveratrol modulates human mammary epithelial cell O-acetyltransferase, sulfotransferase, and kinase activation of the heterocyclic amine carcinogen N-hydroxy-PhIP. Cancer Lett. 2002, 182, 27-32.
180. 2 is protected by the antioxidants melatonin, N(1)-acetyl-N-(2)-formyl-5- methoxykynuramine, resveratrol and uric acid. Int. J. Biochem. Cell Biol. 2001, 33, 775-783.
181. Damianaki, A., Bakogeorgou, E., Kampa, M., Notas, G., et al., Potent inhibitory action of red wine polyphenols on human breast cancer cells. J. Cell Biochem. 2000, 78, 429-441.
182. Sgambato, A., Ardito, R., Faraglia, B., Boninsegna, A., et al., Resveratrol, a natural phenolic compound, inhibits cell proliferation and prevents oxidative DNA damage. Mutat. Res. 2001, 496, 171-180.
183. 3. Free Radic. Biol. Med. 1999, 26, 1531-1537.
184. Bhat, K. P., Kosmeder II, J. M., Pezzuto, J. M., Biological effects of resveratrol. Antioxid. Redox Signal 2001, 3, 1041-1064.
185. Ciolino, H. P., Yeh, G. C., The effects of resveratrol on CYP1A1 expression and aryl hydrocarbon receptor function in vitro. Adv. Exp. Med. Biol. 2001, 492, 183-193.
186. Dorai, T., Aggarwal, B. B., Role of chemopreventive agents in cancer therapy (mini-review). Cancer Lett. 2004, 215, 129-140.
187. Garcia-Garcia, J., Micol, V., de Godos, A., Gomez-Fernandez, J. C., The cancer chemopreventive agent resveratrol is incorporated into model membranas and inhibits protein kinase C alpha activity. Arch. Biochem. Biophys. 1999, 372, 382-388.
188. Subbaramaiah, K., Dannenberg, A. J., Cyclooxygenase-2: a molecular target for chemoprevention and treatment. Trends Pharmacol. Sci. 2003, 24, 96-102.
189. Ragione, F. D., Cucciolla, V., Borriello, A., Pietra, V. D., et al., Resveratrol arrests the cell division cycle at S/G2 phase transition. Biochem. Biophys. Res. Commun. 1998, 250, 53-58.
190. Schneider, Y., Vincent, F., Duranton, B., Badolo, L., et al., Anti-proliferative effect of resveratrol, a natural component of grapes and wine, on human colonic cancer cells. Cancer Lett. 2000, 158, 85-91.
191. Park, J. W., Choi, Y. J., Jang, M. A., Lee, Y. S., et al., Chemopreventive agent resveratrol, a natural product derived from grapes, reversibly inhibits progression through S and G2 phases of the cell cycle in U937 cells. Cancer Lett. 2001, 163, 43-49.
192. Joe, A. K., Liu, H., Suzui, M., Vural, M. E., et al., Resveratrol induces growth inhibition, S-phase arrest, apoptosis, and changes in biomarker expression in several human cancer cell lines. Clin. Cancer Res. 2002, 8, 893-903.
193. Clement, M. V., Hirpara, J. L., Chawdhury, S. H., Pervaiz, S., Chemo-preventive agent resveratrol, a natural product derived from grapes, triggers CD95 signalling-dependent apoptosis in human tumor cells. Blood 1998, 92, 996-1002.
194. Fontecave, M., Lepoivre, M., Elleingand, E., Gerez, C., et al., Resveratrol, a remarkable inhibitor of ribonucleotide reductase. FEBS Lett. 1998, 421, 277-279.
195. Mgbonyebi, O. P., Russo, J., Russo, I. H., Anti-proliferative effect of synthetic resveratrol on human breast epithelial cells. Int. J. Oncol. 1998, 12, 865-869.
196. Lu, R., Serrero, G., Resveratrol, a natural product derived from grape, exhibits anti-estrogenic activity and inhibits the growth of human breast cancer cells. J. Cell Physiol. 1999, 179, 297-304.
197. Levenson, A. S., Gehm, B. D., Pearce, S. T., Horiguchi, J., et al., Resveratrol acts as an oestrogen receptor (ER) agonist in breast cancer cells stably transfected with ERα. Int. J. Cancer 2003, 104, 587-596.
198. Gehm, B. D., McAndrews, J. M., Chien, P. Y., Jameson, J. L., Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Proc. Natl. Acad. Sci. USA 1997, 94, 14138-14143.
199. Schmitt, E., Lehmann, L., Metzler, M., Stopper, H., Hormonal and genotoxic activity of resveratrol. Toxicol. Lett. 2002, 136, 133-142.
200. Mahyar-Roemer, M., Katsen, A., Mestres, P., Roemer, K., Resveratrol induces colon tumor cell apoptosis independently of p53 and precede by epithelial differentiation, mitochondrial proliferation and membrane potential collapse. Int. J. Cancer 2001, 94, 615-622.
201. Hsieh, T. C., Juan, G., Darzynkiewicz, Z., Wu, J. M., Resveratrol increases nitric oxide synthase, induces accumulation of p53 and p21(WAF1/CIP1), and suppresses cultured bovine pulmonary artery endothelial cell proliferation by perturbing progression through S and G2. Cancer Res. 1999, 59, 2596-2601.
202. 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.
203. Lu, J., Ho, C. H., Ghai, G., Chen, K. Y., Resveratrol analog, 3,4,5,4′-tetrahydroxystilbene, differentially induces proapoptotic p53/Bax gene expression and inhibits the growth of transformed cells but not their normal counterparts. Carcinogenesis 2001, 22, 321-328.
204. She, Q. B., Bode, A. M., Ma, W. Y., Chen, N. Y., et al., Resveratrol-induced activation of p53 and apoptosis is mediated by extracellular-signal-regulated protein kinases and p38 kinase. Cancer Res. 2001, 61, 1604-1610.
205. Narayanan, B. A., Narayanan, N. K., Re, G. G., Nixon, D. W., Differential expression of genes induced by resveratrol in LNCaP cells: P53-mediated molecular targets. Int. J. Cancer 2003, 104, 204-212.
206. Surh, Y. J., Hurh, Y. J., Kang, J. Y., Lee, G., et al., Resveratrol, an antioxidant present in red wine, induces apoptosis in human promyelocytic leukaemia (HL-60) cells. Cancer Lett. 1999, 140, 1-10.
207. Tessitore, L., Davit, A., Sarotto, I., Caderni, G., Resveratrol depresses the growth of colorectal aberrant crypt foci by affecting bax and p21CIP expression. Carcinogenesis 2000, 21, 1619-1622.
208. Bode, A. M., Dong, Z., Mitogen-activated protein kinase activation in UV-induced signal transduction. Sci. STKE 2003, 167, RE2.
209. Bode, A. M., Dong, Z., in: Bao, Y., Fenwick, R. (Eds.), Phytochemicals in Health and Disease, Marcel Dekker, New York 2004, pp. 257-284.
210. Chun, K. S., Surh, Y. J., Signal transduction pathways regulating cyclooxygenase-2 expression: potencial molecular targets for chemoprevention. Biochem. Pharmacol. 2004, 68, 1089-1100.
211. Kundu, J. K., Surh, Y. J., Molecular basis of chemoprevention by resveratrol: NF-κB and AP-1 as potential targets. Mutat. Res. 2004, 555, 65-80.
212. Lee, F. S., Hagler, J., Chen, Z. J., Maniatis, T., Activation of the IκB alpha kinase complex by MEKK1, a kinase of the JNK pathway. Cell 1997, 88, 213-222.
213. Schwanger, P., Alpert, D., Skolnik, E. Y., Vilcek, J., Activation of p38 mitogen-activated protein kinase by sodium salicylate leads to inhibition of tumor necrosis factor-induced IκBa phosphorylation and degradation. Mol. Cell. Biol. 1998, 18, 78-84.
214. Karin, M., The beginning of the end: IκB kinase (IKK) and NfκB activation. J. Biol. Chem. 1999, 274, 27339-27342.
215. Bode, A. M., Dong, Z., Targeting signal transduction pathways by chemopreventive agents (review). Mutat. Res. 2004, 555, 33-51.
216. Garg, A., Aggarwal, B. B., Nuclear transcription factor-κB as a target for cancer drug development. Leukemia 2002, 16, 1053-1068.
217. Bharti, A. C., Aggarwal, B. B., Nuclear factor-κB and cancer: its role in prevention and therapy. Biochem. Pharmacol. 2002, 64, 883-888.
218. Manna, S. K, Mukhopadhyay, A., Aggarwal, B. B., 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. 2000, 164, 6509-6519.
219. Mouria, M., Gukovskaya, A. S., Jung, Y., Buechler, P., et al., Food-derived polyphenols inhibit pancreatic cancer growth through mitochondrial cytochrome C release and apoptosis. Int. J. Cancer 2002, 98, 761-769.
220. Holmes-McNary, M., Baldwin Jr., A. S., Chemopreventive properties of trans-resveratrol are associated with inhibition of activation of the IκB kinase. Cancer Res. 2000, 60, 3477-3483.
221. Eferl, R., Wagner, E. F., AP-1: a double edged sword in tumorigenesis. Nat. Rev. Cancer 2003, 3, 859-868.
222. Shen, F., Chen, S. J., Dong, X. J., Zhong, H., et al., Suppression of IL-8 gene transcription by resveratrol in phorbol ester treated human monocytic cells. J. Asian Nat. Prod. Res. 2003, 5, 151-157.
223. Surh, Y. J., Molecular mechanisms of chemopreventive effects of selected dietary and medicinal phenolic substances. Mutat. Res. 1999, 428, 305-327.
224. Woo, J.-H., Lim, J. H., Kim, Y.-H., Suh, S.-I., et al., Resveratrol inhibits phorbol myristate acetate-induced matrix metalloproteinase-9 expression by inhibiting JNK and PKC δ signal transduction. Oncogene 2004, 23, 1845-1853.
225. Lee, P. P., Hwang, J. J., Murphy, G., Ip, M. M., Functional significance of MMP-9 in tumor necrosis factor-induced proliferation and branching morphogenesis of mammary epithelial cells. Endocrinology 2000, 141, 3764-3773.
226. Waas, E. T., Lomme, R. M., DeGroot, J., Wobbes, T., et al., Tissue levels of active matrix metalloproteinase-2 and -9 in colorectal cancer. Br. J. Cancer 2002, 86, 1876-1883.
227. Sato, H., Seiki, M., Regulatory mechanism of 92 kDa type IV collagenase gene expression which is associated with invasiveness of tumor cells. Oncogene 1993, 8, 395-405.
228. Inoue, H., Jiang, X. F., Katayama, T., Osada, S., et al., Brain protection by resveratrol and fenofibrate against stroke requires peroxisome proliferator-activated receptor-α in mice. Neurosci. Lett. 2003, 352, 203-206.