Progress 12/15/02 to 12/14/05

Outputs
Red wine was shown to protect the immune system from damage caused by free radicals generated due to the consumption of alcohol. The bioactive compounds in wine were shown to influence the proliferation and lifespan of cancer cells in culture. More importantly, the whole food was shown to be more effective than single compounds derived from the wine. We noted synergistic effects on cancer cell death among compounds found in muscadine wine: quercetin, ellagic acid and resveratrol. Finally, when transgenic animals prone to Alzheimer's disease were given wine for 7 months and compared to animals given ethanol or water, their ability to learn was better than the controls. The effect of the disease on spatial learning was attenuated by wine consumption and the formation of beta amyloid plaques in the brain was reduced. Fractionation of the wine showed that the active fraction did not contain resveratrol, a novel result in light of the fact that resveratrol has received much publicity recently in the literature.

Impacts
Muscadine grapes (Vitis rotundifolia) have a unique chemical composition relative to other Vitis genuses. We hypothesized that this grape would have unique health benefits relative to other grapes. Information on this grape would benefit Florida grape growers by providing marketing information to share with consumers. We have a longstanding relationship with the Florida Grape Growers Association; attending and speaking at their annual meetings. The muscadine grape has been shown to have antioxidant, anti-cancer and promote neurological health.

Publications

• Mertens-Talcott, S.U., Bomser, J.A., Romero, C., Talcott, S.T., and Percival, S.S. Ellagic acid potentiates the effect of quercetin on p21waf1/cip1, p53 and MAP-kinases without affecting intracellular generation of reactive oxygen species in vitro. J.Nutr. 135(3):609-14, 2005
• Wang J, Ho L, Zhao Z, Seror I, Humala N, Dickstein DL, Thiyagarajan M, Percival SS, Talcott ST, Pasinetti GM. Moderate consumption of Cabernet Sauvignon attenuates A-beta neuropathology in a mouse model of Alzheimer's disease. FASEB J. 2006 Nov;20(13):2313-20.
• Mertens-Talcott S.U., Lee J.H., Percival S.S., Talcott S.T. Induction of cell death in Caco-2 human colon carcinoma cells by ellagic acid rich fractions from muscadine grapes (Vitis rotundifolia). J Agric Food Chem. 54:5336-43, 2006
• Mertens-Talcott, S.U. and Percival, S.S. Ellagic acid and quercetin interact synergistically with resveratrol in the induction of apoptosis, and cause transient cell cycle arrest in human leukemia cells. Cancer Letters 218:141-151, 2005.
• Mertens-Talcott, S.U. Talcott, S.T., Percival, S.S. Low concentrations of quercetin and ellagic acid synergistically influence proliferation, cytotoxity and apoptosis in MOLT-4 human leukemia cells, J Nutr 133:2669-2674, 2003.
• Percival, S.S. and C.A. Sims. Red wine modifies the effects of alcohol on immune function in the mouse. J. Nutrition, 130:1091-1094, 2000.
• Percival, S.S. and Talcott, S.T., 2003 Dietary Importance of Wines. IN: The Encyclopedia of Food Sciences and Nutrition, 2nd edition. Ed. in chief: B. Caballero, Elsevier Science Ltd. 6209-6217.
• Susan S. Percival, Charles A. Sims, Stephen T. Talcott, 2002 Immune Benefits of Consuming Red Muscadine Wine FSHN 02-4.

Progress 10/01/04 to 09/30/05

Outputs
Muscadine grapes have unique phytochemicals compared to other grape species. We know, for example that muscadine grapes have more ellagic acid than other grape species and glycosylate their anthocyanins in a different positions compared to vinifera species. Our research has shown that muscadine wine and isolated extracts and isolated compounds from the muscadine grape are effective anticancer agents, at least in cells in culture. Combinations of muscadine grape-derived phenolics are more effective in causing cancer cell death than the single compounds alone. Interactions between ellagic acid, quercetin and resveratrol are more effective in promoting cancer cell death yet promoting survival of normal fibroblasts. In animal feeding studies, muscadine wine consumption was associated with protection of the mouse immune function. The liver metabolic enzyme profile was judged to be anti-cancer with two fold higher phase 1 enzymes but 10 fold higher phase 2 enzymes.

Impacts
The phytochemical composition of muscadine wine is an important concept for growers and wine makers in the Southeast. Muscadine grapes are resistant to Pierce's disease, which is a disease that results in death of vinifera plants when grown in the south. If the prevalence of Pierce's disease spreads across traditional grape-growing regions, muscadine grapes will become of greater economic importance on a national level. Not only does the composition affect the flavor or the wine, but it affects the health benefits as well. The information derived from this research can be used by the producers to market their products and increase sales of this particular grape species. The synergistic interaction of two wine components suggests that whole foods are more healthful than the single components. Moreover, removal of the glycosides from the wines resulted in a marked change in their benefits. The results of both of these studies encourage the consumption of foods rather than the extracts, modifications, or single compounds derived from the foods.

Publications

• Mertens-Talcott, S.U., Lee, J-H, Percival, S.S. and Talcott, S.T. 2006 Alterations of vital cellular parameters and induction of apoptosis in Cacao-2 human colon carcinoma cells by ellagic acids-rich fractions from muscadine grapes (Vitis rotundifolia), submitted.
• Mertens-Talcott, S.U., Bomser, J.A., Romero, C., Talcott, S.T., and Percival, S.S. 2005. Ellagic acid potentiates the effect of quercetin on p21waf1/cip1, p53 and MAP-kinases without affecting intracellular generation of reactive oxygen species in vitro. J.Nutr. 135(3):609-14.
• Mertens-Talcott, S.U. and Percival, S.S. 2005. Ellagic Acid and Quercetin Interact Synergistically with Resveratrol in the Induction of Apoptosis, and Cause Transient Cell Cycle Arrest in Human Leukemia Cells. Cancer Letters 218:141-151.
• Minor R. and Percival, SS, 2005 Polyphenolic modulation of p53-mediated apoptosis in human fibroblasts. FASEB J. 19: A#598.16
• Mertens-Talcott, S.U. Bomser, JA, Talcott ST Percival, SS 2004 Quercetin and Ellagic Acid Act Synergistically in the Induction of Apoptosis and p21WAF1/CIP1-involved Signal Transduction in Human MOLT-4 Leukemia Cells FASEB J 18:A#270.4
• Nantz, MP, Rowe, CA, Mertens-Talcott, SU, Percival, SS 2005 Damage to immune cells by ethanol is prevented in mice consuming red wine. FASEB J 18:A#597.2

Progress 10/01/02 to 10/01/03

Outputs
The objective of this research will investigate the health benefits of a unique grape genus, Vitis rotundifolia. 1.Compare phytochemical composition of muscadine and cabernet wines. 2.Determine health benefits of muscadine and cabernet wine compare to ethanol and water in mice. a. Immune modulating activity b. Anti-inflammatory activity c. Modulation of phase I and phase II detoxification enzymes in the liver and the intestine. Results 1.The phytochemical composition has been completed. Muscadine is unique compared to cabernet in that it contains ellagic acid, a potent anti-cancer agent. Because of this result, we performed some anti-neoplastic transformation assays as well as cancer cell line proliferation and cell cycle studies. 2.Muscadine wine was shown to inhibit neoplastic transformation in the benzo[a]pyrene induction assay. The size, number, and invasiveness of the foci were reduced by muscadine compared to cabernet or the control. 3.Investigations between two muscadine wine phytonutrients, quercetin and ellagic acid, showed a synergistic interaction in inhibition of the cell cycle and induction of apoptosis in human leukemic cells. 4.Investigations comparing cabernet wine and muscadine wine indicate that both wines are beneficial in inhibiting cell cycle progression and inducing apoptosis in human colon carcinoma cells. Moreover, removal of the glycosides from the phenolic compounds radically changed the benefits. Plans for the coming year 1.Second study with mice and inflammation will be performed. 2.Further work with cell culture and anti-cancer activity will be performed. Partnerships and collaborations Within the FSHN Department, a strong collaboration exists between Food Chemistry and Nutrition Sciences. We partnered with University of Arkansas to prepare the cabernet wine. We also collaborate with Dr. Josh Bomser at Ohio State University on alterations in intracellular signaling by the wine phytonutrients. Education and training http://edis.ifas.ufl.edu/pdffiles/FS/FS08500.pdf

Impacts
Expected impact 1.The composition of the muscadine wine is an important concept for growers and wine makers in the state of Florida and the Southeast. Not only does the composition affect the flavor or the wine, but it affects the health benefits as well. The information here can be used by the producers to market their products and increase sales of this particular grape species. 2.The synergistic interaction of two wine components suggests that whole foods are more healthful than the single components. Moreover, removal of the glycosides from the wines resulted in a marked change in their benefits. The results of both of these studies encourage the consumption of foods rather than the extracts, modifications, or single compounds derived from the foods.

Publications

• Refereed Publications Percival, S.S. and Talcott, S.T.2003 Dietary Importance of Wines. IN: The Encyclopedia of Food Sciences and Nutrition, 2nd edition. Ed. in chief: B. Caballero, Elsevier Science Ltd. pp6209-6217.
• Mertens-Talcott, S.U. Talcott, S.T., Percival, S.S. 2003 Low concentrations of quercetin and ellagic acid synergistically influence proliferation, cytotoxity, and apoptosis in MOLT-4 human leukemia cells, J Nutr 133:2669-2674.
• Abstracts Rowe, C.A. Gallo, L., Mertens, S.U., Nantz, M.P., Percival, S.S., 2003 Inhibition of neoplastic transformation by two red wine grape species, FASEB J: A1109.
• Mertens, S.U., Talcott, S.T., Percival, S.S.2003 Low concentrations of quercetin and ellagic acid influence proliferation, cytotoxity and apoptosis in MOLT-4 human leukemic cell in a synergistic manner, FASEB J: A1109.
• Mertens-Talcott, SU, Talcott, ST, Percival, SS. July 2003 Polyphenolics from Red Muscadine and Cabernet Wines Influence Vital Cell Parameters and Induce Apoptosis in Human Leukemia Cells. IFT Technical Abstract.