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ResveratrolThe compound is found in the skin of red grapes and as a constituent of red wine, which has some to suggest that the compound may contribute to the so-called "French Paradox". French Paradox refers to the fact that people in France suffer relatively low incidence of coronary heart disease, despite their diet being rich in saturated fats. Another group of compounds in red wine under research for this purpose are specific polyphenols, oligomeric procyanidins, that many believe offer a great degree of protection to human blood-vessel cells. In terms of anti aging, the compound has been found in several animal studies to extend life, with the worm C. elegans, and the fruit fly Drosophila melanogaster. With a fish species of Nothobranchius furzeri, the maximum life extension was by 59%, and median lifespan by 56%. In a first mammal (with mice) study, published in Nature, November 2006, results showed that obese mice provided with resveratrol lived an average of 15% longer than obese mice not provided the supplement. Exactly how the compound has these anti aging effects are not fully understood, but according to some scientists, they appear to mimic several of the biochemical effects of calorie restriction. Specifically, this translates into lipase inhibition, by reducing the absorption of fat through intestinal walls. Interestingly, one study indicates that resveratrol activates SIRT1 and PGC-1¦Á and improve functioning of the mitochondria, which may be a significant contributing factor. Currently, there is a lot of research ongoing with the compound, specifically when it comes to the compounds effects on human subjects. No direct conclusions can be derived from the animal studies done so far. Resveratrol - StudiesGu X, Creasy L, Kester A, et al., Capillary electrophoretic determination of resveratrol in wines. J Agric Food Chem 47:3323-3277, 1999. Leiro J, Arranz JA, Fraiz N, Sanmartin ML, Quezada E, Orallo F. Effect of cis-resveratrol on genes involved in nuclear factor kappa B signaling. Int Immunopharmacol. 2005 Feb;5(2):393-406. Y.J. Chun, M.Y. King, F.P. Guengerich, Resveratrol is a selective human cytochrome P450 1A1 inhibitor, Biochem. Biophys. Res. Commun. 262 (1999) 20¨C24. Benitez DA, Pozo-Guisado E, Alvarez-Barrientos A, Fernandez-Salguero PM, Castellon EA (Oct 18 2006). "Mechanisms involved in resveratrol-induced apoptosis and cell cycle arrest in prostate cancer-derived cell lines". Journal of Andrology. Parker JA, Arango M, Abderrahmane S, Lambert E, Tourette C, Catoire H, N¨¦ri C. Resveratrol rescues mutant polyglutamine cytotoxicity in C. elegans and mammalian neurons. Nature Genetics 2005 ; 4 : 349-50. Olson ER, Naugle JE, Zhang X, Bomser JA, Meszaros JG. Inhibition of cardiac fibroblast proliferation and myofibroblast differentiation by resveratrol. Am J Physiol Heart Circ Physiol 2005 Mar;288(3):H1131-8. Riles WL, Erickson J, Nayyar S, Atten MJ, Attar BM, Holian O (21 Sep 2006). "Resveratrol engages selective apoptotic signals in gastric adenocarcinoma cells". World Journal of Gastroenterology 12 (35). Sareen D, van Ginkel PR, Takach JC, Mohiuddin A, Darjatmoko SR, Albert DM, Polans AS (Sep 2006). "Mitochondria as the primary target of resveratrol-induced apoptosis in human retinoblastoma cells". Investigative Ophthamology & Visual Science 47 (9). Tang HY, Shih A, Cao HJ, Davis FB, Davis PJ, Lin HY (Aug 2006). "Resveratrol-induced cyclooxygenase-2 facilitates p53-dependent apoptosis in human breast cancer cells" 5 (8). Aziz MH, Nihal M, Fu VX, Jarrard DF, Ahmad N (May 2006). "Resveratrol-caused apoptosis of human prostate carcinoma LNCaP cells is mediated via modulation of phosphatidylinositol 3'-kinase/Akt pathway and Bcl-2 family proteins". Molecular Cancer Therapeutics 5 (5). 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." Current Biology 2006 Feb 7;16 (3):296-300. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA. "Resveratrol improves health and survival of mice on a high-calorie diet" Nature 2006. Cell, Vol 127, 1109-1122, 15 December 2006; Resveratrol Improves Mitochondrial Function and Protects against Metabolic Disease by Activating SIRT1 and PGC-1¦Á. Kaeberlein et al. Substrate-specific activation of sirtuins by resveratrol. J Biol Chem. 2005 Apr 29; 280(17):17038-45. Heredia A, Davis C, Redfield R. Synergistic inhibition of HIV-1 in activated and resting peripheral blood mononuclear cells, monocyte-derived macrophages, and selected drug-resistant isolates with nucleoside analogues combined with a natural product, resveratrol. J Acquir Immune Defic Syndr. 2000 Nov 1;25(3):246-55. Faith SA, Sweet TJ, Bailey E, Booth T, Docherty JJ. Resveratrol suppresses nuclear factor-kappaB in herpes simplex virus infected cells. Antiviral research 2006 Jul 14. Palamara AT, Nencioini L, Aquilano K, et al. Inhibition of influenza A virus replication by resveratrol. Journal of Infectious Diseases May 2005 15;191(10):1719-29. Gehm BD, McAndrews JM, Chien P, Jameson JL. Resveratrol, a polyphenolic compound found in grapes and wine, is an agonist for the estrogen receptor. Proc. National. Academy of Sciences 1997 Dec 9;94(25):14138-43. Bowers JL, Tyulmenkov VV, Jernigan SC, Klinge CM. Resveratrol acts as a mixed agonist/antagonist for estrogen receptors alpha and beta. Endocrinology 2000 Oct;141(10):3657-67. Gescher AJ, Steward WP. Relationship between mechanisms, bioavailibility, and preclinical chemopreventive efficacy of resveratrol: a conundrum., Cancer Epidemiol Biomarkers Prev. 2003;12(10):953-957.
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