白藜蘆醇抗發炎

白藜蘆醇是一種天然多酚類、類黃酮類物質，存在於許多食用植物。許多體外實驗與動物實驗顯示白藜蘆醇具許多生物活性，可促進健康與提昇運動表現，包括：抗氧化、抗發炎與提昇粒線體的生合成作用。然而迄今無補充白藜蘆醇對人類運動表現影響之研究。期待透過本研究了解，白藜蘆醇是否能提昇耐力跑的成績、提昇最大攝氧量與降低半程馬拉松運動所致的氧化壓力與發炎現象。本研究以16名20-25歲、男性長跑選手作為本實驗的受試者。本實驗設計採隨機、雙盲、安慰劑對照、交叉(randomized, double-blind, placebo-controlled, crossover)模式，膠囊排空期為8週。每位受試者均需連續4週，每日服用：(一)1000 mg白藜蘆醇或 (二)500 mg白藜蘆醇與500 mg安慰劑或 (三)1000 mg安慰劑。增補4週後，受試者在跑步機上跑步，前5公里速度為70 % V ‧ O2max，剩下16公里受試者視自己體能狀況，自行操控平坡電動跑步機速度（儘可能加快速度），記錄21公里耐力跑所需的時間，並於增補前、後，測量最大攝氧量 (V ‧O2max )。分別於增補前、運動前、運動後立即點、運動後第1、2、24、48、72小時以肘前靜脈抽血，分析血漿中發炎指標 (interleukin-6, interleukin-1 receptor antagonist, and C-reactive protein)、8-Iso-prostaglandin F2α (脂質氧化指標)、protein carbonyl (蛋白質氧化指標)、8-hydroxy-2'-deoxyguanosine (DNA氧化指標)、catalase (內源性酶類抗氧化劑)、glutathione (內源性非酶類抗氧化劑)與白藜蘆醇的濃度。

狀態	已完成
有效的開始/結束日期	8/1/11 → 12/31/12

https://www.grb.gov.tw/search/planDetail?id=2351257&docId=371979

(1)Oparil, S. and Oberman, A. Nontraditional cardiovascular risk factors.
American Journal of Medical Science,193-207,1999.
(2)Yang, C.S.,Landau, J.M., Huang, M.T., Newmark, H.L. Inhibition of carcinogenesis by dietary polyphenolic compounds.Annu.Rev.Nutr.21,
381-406,2001.
(3)Giugliano,D.,Ceriello,A., Paolisso,G.Diabetes mellitus, hypertension, and cardiovascular disease:Which role for oxidative stress .
Metabolism:Clicinal and Experimental 44:363-368,1995.
(4)Halliwell,B.,Gutteridge,J.M.C.,Cross,C.E.Free radicals,antioxidants, and human disease :Where are we now ?The Journal of Laboratory and
Clinical Mediciane 119:598-620,1992.
(5)Giugliano,D.,Ceriello,A., Paolisso,G.Diabetes mellitus, hypertension, and cardiovascular disease:Which role for oxidative stress .
Metabolism:Clicinal and Experimental 44:363-368,1995.
(6)Yang, C.S.,Landau, J.M., Huang, M.T., Newmark, H.L. Inhibition of carcinogenesis by dietary polyphenolic compounds.Annu.Rev.Nutr.21,
381-406,2001..
(7)Yang, C.S.,Landau, J.M., Huang, M.T., Newmark, H.L. Inhibition of carcinogenesis by dietary polyphenolic compounds.Annu.Rev.Nutr.21,
381-406,2001..
(8)Cao,Y.,Cao,R.,Brakenhielm,E.Antiangiogenic mechanisms of dietderived polyphenols.J.Nutr.Biochem.13,380-390,2002.
(9)Yang, C.S.,Landau, J.M., Huang, M.T., Newmark, H.L. Inhibition of carcinogenesis by dietary polyphenolic compounds.Annu.Rev.Nutr.21,
381-406,2001.
(10)Jang, M., Cai, L., Udeani, G.O., Slowing, K.V., Thomas, C.F., Beecher, C.W.W.,Fong,H.H.S.,Farnsworth,N.R.,Kinghorn,A.D.,Mehta,R.G.,Moon,R.C., Pezzutro,J.M.Cancer chemopreventive activity of resveratrol,a
natural product derived from graps.Science 275,218-220,1997.
(11)Yang, C.S., Chung, J.Y.,Yang, G., Chhabra, S.K.,Lee, M.J. Tea and tea polyphenols in cancer prevention.J.Nutr.130,472S-478S,2000.
(12)Jang, D.S., Kang,B.S., Ryu, S.Y., Chang, I.M., Min,K.R. , Kim,Y.
Inhibitory effects of resveratrol analogs on unopsonized zymosan-induced oxygen radical production. Biochemical Pharmacology 57: 705-712,1999.
(13)Joseph A. Baur1*, Kevin J. Pearson2*, Nathan L. Price2, Hamish A. Jamieson7, Carles Lerin8, Avash Kalra2, Vinayakumar V. Prabhu3, Joanne S. Allard2, Guillermo Lopez-Lluch9, Kaitlyn Lewis2, Paul J. Pistell2, Suresh Poosala4, Kevin G. Becker3, Olivier Boss10, Dana Gwinn11, Mingyi Wang5, Sharan Ramaswamy6, Kenneth W. Fishbein6,
Richard G. Spencer6, Edward G. Lakatta5, David Le Couteur7,
Reuben J. Shaw11, Placido Navas9, Pere Puigserver8, Donald K.
Ingram2,12, Rafael de Cabo2 & David A. Sinclair1. Resveratrol
improves health and survival of mice on a high-calorie diet.
Nature Vol444 nNovember 2006.
(14)Schroder, G., Brown, J.W.S., Schroder, J. Molecular analysis of resveratrol synthase. Eur. J. Biochem. 172, 161-169,1998.
(15)Soleas, G.J., Diamandis, E.P., Goldberg, D.M. Resveratrol: a molecule whose time has come? And gone? Clin. Biochem. 30, 91-113,1997.
(16)Ross, J.A.,Kasum, C.M. Dietary flavonoids: bioavailability, metabolic effects,and safety. Annu. Rev. Nutr. 22, 19-34,2002.
(17)Jang, M., Cai, L., Udeani, G.O., Slowing, K.V., Thomas, C.F., Beecher, C.W.W.,Fong,H.H.S.,Farnsworth,N.R.,Kinghorn,A.D.,Mehta,R.G.,Moon,R.C.,Pezzutro,J.M.Cancer chemopreventive activity of resveratrol,a
natural product derived from graps.Science 275,218-220,1997.
(18)Park, J.W.,Choi, Y.J.,Jang, M.A., Lee, Y.S., Jun, D.Y., Suh,S.I.,Baek,
W.K.,Suh,M.H., Jin, I.N., Kwon, T. K.Chemopreventive agent
Resveratrol, a natural product derived from graps,reversibly inhibits progression through S and G2 phases of the cell cycye in U937 cells.
Cancer Res.163,43-49,2001.
(19)Fremont, L. Biological effects of resveratrol. Life Sci.66,663-673,2000.
(20)Lipkin, M., Reddy, B., Newmark, H.,Lamprecht, S.A. Dietary factors in human colorectal cancer. Annu. Rev. Nutr. 19, 545-586,1999.
(21)Key, T.J., Allen, N.E., Spencer, E.A., Travis, R.C. The effect of diet on risk of cancer. Lancet 360, 861-868,2002.
(22)Jankun, J., Selman, S.H., Swiercz, R. Why drinking green tea could prevent cancer. Nature 387, 561,1997.
(23)Knight,J.A.Disease related to oxygen-derived free radicals .
Ann.Clin.Lab.Sci.25,111-121,1995.
(24)Chapman,M.L.,Rubin,B.R., Gracy,R.W.Increased carbonyl content of proteins in synorial fluid from patients with rheumatoid arthritis.J.Rheumatol.16,15-19,1989.
(25)Ghiselli,A.Aromatic hydroxylation.Salicylic acid as a probe for
measuring hydroxyl radical production .Methods in Molecular Biology.
108,89-100,1998.
(26)Wang, M.J.,Lin, W.W.,Chen, H.L.,Chang, Y.H.,Ou, H.C.,Kuo, J.S., Jeng,K.C. Silymarin protects dopaminergic neurons against Lipopolysaccharide-Induced neurotoxicity by inhibiting microglia activation.Eur.J.Neurosci.16:2103-2112,2002.
(27)Marletta M .A. Cell.78,927-930,1994.
(28)May,J.M.Is ascorbic acid an antioxidant for the plasma membrane?
Faseb J,13,995-1006,1999.
(29)Hong, S.Y.,Hwang, K.Y.,Lee,E.Y.,Eun,S.W.,Cho,S.R.,Han,C.S.,Park,Y.H., Chang,S.K. Effect of vitamin C on plasma total antioxidant status in patients with paraquat intoxication.Toxical Lett,126,51-59,2002.
(30)Uchida, L., Nomura, y. Effect of vitamin C depletion on serum cholesterol and lipoprotein levels in ODS(od/od) rats unable to synthesize ascorbic.J Nutr. 120:1140-1147,1990.
(31)Gastaldello,K.,Vereerstraeten,A.,Nzame-Nze,T.,Vanherweghem,J.L., Tielemans,C. Resistance to erythropoietin in iron-overloaded heamodialysis patients can be overcome by ascorbic acid administration.Nephrol Dial Transplant,10 Suppl 6,44-47,1995.
(32)Eiselt,J.,Racek,J.,Trefil,L.,Opatrny,K. Effects of a vitamin E-modified dialysis membrane and vitamin C infusion on oxidative stress in hemodialysis patients.Artif Organs,25,430-436,2001.
(33) Satoh,K. Serum lipid peroxide in cerebrovascular disorders determined by a new colorimetric method. Clin. Chim. Acta. 90: 37-43,1978.
(34)Muus,P.,Bonta,I.L.,Den,Oudsten,S.A.Plasma levels of malondialdehyde,a product of cyclo-oxygenase-dependent and independent lipid peroxidaiton inrheumatoid arthritis: a correction with disease activity. Prostaglandins med. 2: 63-65,1979.
(35) Chia, L.S., Thompson, J.E.,Moscarello, M. A. X-ray diffraction evidence for myelin disorder in brain from humans with Alzheimer’s disease. Biochim. Biophys. Acta 775: 308-312,1984.
(36)Hagihara, M., Nishigaki, I., Maseki, M., Yagi, K. Age-dependent changes in lipid peroxide levels in the lipoprotein fractions of human serum.
J. Gerontol. 39: 269-272,1984.
(37)Tiwaskar, H.V., Suryakar, A.N., Ambekar, J.G.,Makhija, S. J. Alteration in the levels of serum lipid peroxide, cyclooxygenase activity and free fatty acids in bronchial asthma. Indian J. Chest Dis. Allied Sci. 28: 122-125,1986.
(38)Esterbauer, H. Cytotoxicity and genotoxicity of lipid-oxidation products. Am. J. Clin. Nutr. 57: 779S-786S,1993.
(39)Mazière, C., Conte, M.A., Degonville, J., Ali, D.,Mazière, J.C. Cellular enrichment with polyunsaturated fatty acids induces an oxidative stress and activates the transcription factors AP1 and NFkB. Biochim. Biophys. Res. Commun. 265:116-122,1999.
(40)Halliwell, B. and Chirico, S. Lipid peroxidation: its mechanism, measurement, and signficance. Am. J. Clin. Nutr. 57: 715-725,1993.
(41)Halliwell, B. and Chirico, S. Lipid peroxidation: its mechanism, measurement, and signficance. Am. J. Clin. Nutr. 57: 715-725,1993.
(42)Halliwell, B. and Chirico, S. Lipid peroxidation: its mechanism, measurement, and signficance. Am. J. Clin. Nutr. 57: 715-725,1993.
(43)Galliard, T. Techniques for overcome problems of lipolytic enzymes and lipoxygenases in the preparation of plant organelles. Methods Enzymol, vol. 31,pp. 520-528,1974.
(44)Esterbauer, H. Cytotoxicity and genotoxicity of lipid-oxidation products. Am.J. Clin. Nutr. 57: 779S-786S,1993.
(45)Kowalski, D. P., Feeley, R. M.,Jones, D. P. Use of exogenous glutathione for metabolism of peroxidized methyl linoleate in rat small intestine. J. Nutr. 120: 1115-1121,1990.
(46)Spiteller, G. Linoleic acid peroxidation-the dominant lipid peroxidation process in low density lipoprotein and its relationship to chronic diseases. Chem. Phys.Lipids 95: 105-162,1998.
(47)Halliwell, B. and Gutteridge, J. M. C. Antioxidant defenses. In: Free radicals in biology and medicine. Oxford University Press, New York, USA,3rd ed., pp. 105-245. 1999.
(48)Jang, D.S., Kang,B.S., Ryu, S.Y., Chang, I.M., Min,K.R. , Kim,Y.
Inhibitory effects of resveratrol analogs on unopsonized zymosan-induced oxygen radical production. Biochemical Pharmacology 57: 705-712,1999.
(49)Ohkawa, H., Ohishi,N., Yagi, K. Assay for lipid peroxides in animal
tissues by thiobarbituric acid reaction. Anal. Biochem.,95: 351-358, 1979.
(50)Olas, B., Wachowicz, J., Saluk-Juszczak, Zieliñski, T. Effects of resveratrol, a natural polyphenolic compound, on platelet activation induced by endotoxin or thrombin. Thrombosis Research 107: 141-145.
(51)Iijima, K., Yoshizumi, M., Ouchi.,Y. Effect of red wine polyphenols on vascular smooth muscle cell function －molecular mechanism of the ‘French paradox’. Mechanisms of Ageing and Development 123: 1033-1039,2002.
(52)Pendurthi, U.R. and Rao, L.V.M. Resveratrol suppresses agonist-induced monocyte adhesion to cultured human endothelial cells.
Thrombosis Research 106: 243-248,2002.

(53)El-Mowafy, A.M. Resveratrol activates membrane-bound guanylyl cyclase in coronary arterial smooth muscle: A novel signaling mechanism
in support of coronary protection. Biochemical and Biophysical Research Communications 291: 1218-1224,2002.
(54)Fulgenzi, A., Bertelli, A.A.E., Magni,E., Ferrero, E., Ferrero, M.E.
In vivo inhibition of TNFα-induced vascular permeability by
resveratrol. Transplantation Proceedings 33: 2341-2343,2001.
(55)Zern, T.L., West, K.L., Fernandez, M.L. Grape polyphenols
decrease plasma triglycerides and cholesterol accumulation in the aorta of ovariectomized guinea pigs. The Journal of Nutrition 133:2268-2272,2003.
(56)Hung, L.M., Su, M.J., Chen, J.K. Resveratrol protects myocardial ischemia-reperfusion injury through both NO-dependent and
NO-independent mechanisms. Free Radical Biology and Medicine 36: 774-781,2004.
(57)Mellors, A. and Tappel.,A.L. The inhibition of mitochondria by
ubiquinone and ubiquinol. The Journal of Biological Chemistry 241:4353-4356,1966.
(58)Frankel, E.N., Waterhouse, A.L., Kinsella, J.E. Inhibition of
human LDL oxidation by resveratrol. Lancet 341: 1103-1104,1993.
(59)Stivala, L.A., Savio, M., Carafoli, F., Perucca, P., Bianchi, L., Maga,G.,
Forti, L., Pagnoni, U.M., Albini, A., Prosperi, E., Vannini, V.
Specific structural determinants are responsible for the antioxidant activity and the cell cycle effects of resveratrol. The Journal of Biological Chemistry 276: 22586-22594,2001.
(60)Lorenz, P., Roychowdhury, S., Engelmann, M., Wolf, G., Horn, T.F.W.
Oxyresveratrol and resveratrol are potent antioxidants and free
radical scavengers: effect on nitrosative and oxidative stress derived from
microglial cells. Nitric Oxide 9: 64-76,2003.
(61)Hung, L.M., Su, M.J., Chu, W.K., Chiao, C.W., Chan, W.F.,
Chen. J.K. The protective effect of resveratrols on
ischaemia-reperfusion injuries of rat hearts is correlated with antioxidant
efficacy. British Journal of Pharmacology 135: 1627-1634,2002.
(62)Stojanoviæ, S., Sprinz, H., Brede, O. Efficiency and mechanism of the antioxidant action of trans-resveratrol and its analogues in the radical liposome oxidation. Archives of Biochemistry and Biophysics 391: 79-89,2001.
(63)Hung, L.M.,Chen, J.K., Huang, S.S., Lee, R.S., Su, M.J. Cardioprotective effect of resveratrol, a natural antioxidant derived from grapes. Cardiovascular Research 47: 549-555,2000.
(64)Hung, L.M.,Chen, J.K., Huang, S.S., Lee, R.S., Su, M.J. Cardioprotective effect of resveratrol, a natural antioxidant derived from grapes. Cardiovascular Research 47: 549-555,2000.
(65)Bell, D., Jackson, M., Nicoll, J.J., Millar, J., Muir,A.L. Inflammatory response, neutrophil activation, and free radical production after acute myocardial infarction: effect of thrombolytic treatment. British Heart Journal 63: 82-87,1990.
(66)Salkowski, C.A., Detore, G., McNally,R., Vogel,S.N. Regulation of inducible nitric oxide synthase messenger RNA expression and nitric oxide production by lipopolysaccharide in vivo:The roles of macrophages, endogenous IFN-gamma and TNF receptor-1-mediated signaling. The Journal of Immunology 158:905-912,1997.
(67)Pendurthi, U.R., Williams, J.T., Rao,L.V.M. Resveratrol, a polyphenolic compound found in wine, inhibits tissue factor expression in vascular cells: A possible mechanism for the cardiovascular benefits associated with moderate consumption of wine. Arteriosclerosis, Thrombosis, and Vascular Biology 19: 419-426,1999.
(68)Wadsworth, T.L. and Koop,D.R. Effects of the wine polyphenolics quercetin and resveratrol on pro-inflammatory cytokine expression in RAW 264.7 macrophages. Biochemical Pharmacology57: 941-949,1999.
(69)Cho, D.I., Koo, N.Y., Chung, W.J., Kim, T.S., Ryu, Y., Im, S.Y.,
Kim,K.M. Effects of resveratrol-related hydroxystilbenes on
the nitric oxide production in macrophage cells: Structural requirements
and mechanism of action. Life Science 71: 2071-2082,2002.
(70)Tsai, S.H., Lin-Shiau, S.Y., Lin,J.K. Suppression of nitric oxide synthase and the down-regulation of the activation of NF-κB in macrophages by resveratrol. British Journal of Pharmacology 126:673-680,1999.
(71)Halliwell, B. Reactive oxygen species and the central nervous system.
J. Neurochem. 59: 1609-1619, 1992.
(72)Halliwell, B. and Gutteridge, J. M. C. Antioxidant defenses. In: Free radicals in biology and medicine. Oxford University Press, New York, USA,3rd ed., pp. 105-245. 1999.
(73)Rhee, S. G., Bae, Y. S., Lee, S. R., Kwon, J. Hydrogen peroxide: a key messenger that modulates protein phosphorylation through
cysteine oxidation. Sci. STKE. 10: PE1-5, 2000.
(74)Allen, R. G. and Tresini, M. Oxidative stress and gene regulation.
Free Rad. Biol. & Med., 28: 463-499, 2000.
(75)Joe ,B., Lokesh,BR. Role of capsaicin, curcumin and dietary n-3 fatty acids in lowering the generation of reactive oxygen species in rat peritoneal macrophages.Biochim Biophys Acta 1224:255-63,1994.
(76)Starsser, E.M., Wessner,B., Manhart ,N.,Roth E. The relationship between the anti-inflammatory effects of curcumin and cellular glutathione cotent in myelomonocytic cells. Biochem Pharmacol., 70:552-9,2005.
(77)Hung, L.M.,Chen, J.K., Huang, S.S., Lee, R.S., Su, M.J. Cardioprotective effect of resveratrol, a natural antioxidant derived from grapes. Cardiovascular Research 47: 549-555,2000.
(78)Stivala, L.A., Savio, M., Carafoli, F., Perucca, P., Bianchi, L., Maga,G.,
Forti, L., Pagnoni, U.M., Albini, A., Prosperi, E., Vannini, V.
Specific structural determinants are responsible for the antioxidant activity and the cell cycle effects of resveratrol. The Journal of Biological Chemistry 276: 22586-22594,2001.
(79)Halliwell, B. and Chirico, S. Lipid peroxidation: its mechanism, measurement, and signficance. Am. J. Clin. Nutr. 57: 715-725,1993.
(80)Frankel, E.N., Waterhouse, A.L., Kinsella, J.E. Inhibition of human LDL oxidation by resveratrol. Lancet 341: 1103-1104,1993
(81)Ray, P.S., Maulik, G.A., Cordis, A.A.E., Bertelli, A.The red wine antioxidant resveratrol protects isolated rat hearts from ischemia reperfusion injury. Free Radical Biology and Medicine 27:160-169 ,1999.
(82)Stivala, L.A., Savio, M., Carafoli, F., Perucca, P., Bianchi, L., Maga,G.,
Forti, L., Pagnoni, U.M., Albini, A., Prosperi, E., Vannini, V. Specific structural determinants are responsible for the antioxidant activity and the cell cycle effects of resveratrol. The Journal of Biological Chemistry 276: 22586-22594,2001.
.