Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/52014
標題: 毛蕊花苷及其衍生物對於影響心血管疾病部份因素之研究:血液流變、內皮細胞發炎及高血壓
Studies of acteoside and its derivatives on selected aspects of cardiovascular disease: hemorheology, endothelial inflammation and hypertension
作者: Chen, Chao-Hsiang
陳兆祥
關鍵字: Hyperbaric oxygen
血液流變
Hemorheology
Acteoside
Cell adhesion molecules
Hypertension
毛蕊花苷血管內皮附著分子
高血壓
出版社: 食品暨應用生物科技學系所
引用: Chapter 1 Ay, H., Topal, T., Uysal, B., Ozler, M., Oter, S., Korkmaz, A. and Dundar, K., 2007. Time-dependent course of hyperbaric oxygen-induced oxidative effects in rat lung and erythrocytes. Clin Exp Pharmacol Physiol 34, 787-791. Birkofer, L., Kaiser, C. and Thomas, U., 1968. Acteoside and neoacteoside: sugar esters from Syringa vulgaris (L.). Z Naturforsch B 23, 1051-1058. Burns, R.C., Rivera-Nieves, J., Moskaluk, C.A., Matsumoto, S., Cominelli, F. and Ley, K., 2001. Antibody blockade of ICAM-1 and VCAM-1 ameliorates inflammation in the SAMP-1/Yit adoptive transfer model of Crohn''s disease in mice. Gastroenterology 121, 1428-1436. Cecchi, E., Mannini, L. and Abbate, R., 2009. Role of hyperviscosity in cardiovascular and microvascular diseases. G Ital Nefrol 26 Suppl 46, 20-29. Chang, C.Y., Liang, H.J., Chow, S.Y., Chen, S.M. and Liu, D.Z., 2007. Hemorheological mechanisms in Alzheimer''s disease. Microcirculation 14, 627-634. Chen, C.H., Song, T.Y., Liang, Y.C. and Hu, M.L., 2009. Acteoside and 6-O-acetylacteoside downregulate cell adhesion molecules induced by IL-1beta through inhibition of ERK and JNK in human vascular endothelial cells. J Agric Food Chem 57, 8852-8859. Chiou, W.F., Lin, L.C. and Chen, C.F., 2004. Acteoside protects endothelial cells against free radical-induced oxidative stress. J Pharm Pharmacol 56, 743-748. Cho, Y.I., Mooney, M.P. and Cho, D.J., 2008. Hemorheological disorders in diabetes mellitus. J Diabetes Sci Technol 2, 1130-1138. Coussens, L.M. and Werb, Z., 2002. Inflammation and cancer. Nature 420, 860-867. Eisenberg, S., 1966. Blood viscosity and fibrinogen concentration following cerebral infarction. Circulation 33, II10-14. Erdem, T.Y., Ercan, M., Ugurlu, S., Balci, H., Acbay, O. and Gundogdu, S., 2008. Plasma viscosity, an early cardiovascular risk factor in women with subclinical hypothyroidism. Clin Hemorheol Microcirc 38, 219-225. Feher, G., Koltai, K., Kesmarky, G., Szapary, L., Juricskay, I. and Toth, K., 2006. Hemorheological parameters and aging. Clin Hemorheol Microcirc 35, 89-98. Grotta, J., Ackerman, R., Correia, J., Fallick, G. and Chang, J., 1982. Whole blood viscosity parameters and cerebral blood flow. Stroke 13, 296. Halliwell, B., 2007. Flavonoids: a re-run of the carotenoids story? Novartis Found Symp 282, 93-101; discussion 101-104, 212-108. Hausmann, M., Obermeier, F., Paper, D.H., Balan, K., Dunger, N., Menzel, K., Falk, W., Schoelmerich, J., Herfarth, H. and Rogler, G., 2007. In vivo treatment with the herbal phenylethanoid acteoside ameliorates intestinal inflammation in dextran sulphate sodium-induced colitis. Clin Exp Immunol 148, 373-381. Huang, C.G., Shang, Y.J., Zhang, J., Zhang, J.R., Li, W.J. and Jiao, B.H., 2008. Hypouricemic effects of phenylpropanoid glycosides acteoside of Scrophularia ningpoensis on serum uric acid levels in potassium oxonate pretreated Mice. Am J Chin Med 36, 149-157. Hwang, Y.P., Kim, H.G., Choi, J.H., Park, B.H., Jeong, M.H., Jeong, T.C. and Jeong, H.G., 2011. Acteoside inhibits PMA-induced matrix metalloproteinase-9 expression via CaMK/ERK- and JNK/NF-kappaB-dependent signaling. Mol Nutr Food Res 55 suppl 1, S103-S116. Inoue, M., Sakuma, Z., Ogihara, Y. and Saracoglu, I., 1998. Induction of apoptotic cell death in HL-60 cells by acteoside, a phenylpropanoid glycoside. Biol Pharm Bull 21, 81-83. Jimenez, C. and Riguera, R., 1994. Phenylethanoid glycosides in plants: structure and biological activity. Nat Prod Rep 11, 591-606. Khodabandehlou, T., Boisseau, M.R. and Le Devehat, C., 2004. Blood rheology as a marker of venous hypertension in patients with venous disease. Clin Hemorheol Microcirc 30, 307-312. Koo, K.A., Kim, S.H., Oh, T.H. and Kim, Y.C., 2006. Acteoside and its aglycones protect primary cultures of rat cortical cells from glutamate-induced excitotoxicity. Life Sci 79, 709-716. Koo, K.A., Sung, S.H., Park, J.H., Kim, S.H., Lee, K.Y. and Kim, Y.C., 2005. In vitro neuroprotective activities of phenylethanoid glycosides from Callicarpa dichotoma. Planta Med 71, 778-780. Lee, K.J., Woo, E.R., Choi, C.Y., Shin, D.W., Lee, D.G., You, H.J. and Jeong, H.G., 2004. Protective effect of acteoside on carbon tetrachloride-induced hepatotoxicity. Life Sci 74, 1051-1064. Lee, K.W., Kim, H.J., Lee, Y.S., Park, H.J., Choi, J.W., Ha, J. and Lee, K.T., 2007. Acteoside inhibits human promyelocytic HL-60 leukemia cell proliferation via inducing cell cycle arrest at G0/G1 phase and differentiation into monocyte. Carcinogenesis 28, 1928-1936. Lee, K.Y., Jeong, E.J., Lee, H.S. and Kim, Y.C., 2006. Acteoside of Callicarpa dichotoma attenuates scopolamine-induced memory impairments. Biol Pharm Bull 29, 71-74. Letcher, R.L., Chien, S., Pickering, T.G., Sealey, J.E. and Laragh, J.H., 1981. Direct relationship between blood pressure and blood viscosity in normal and hypertensive subjects. Role of fibrinogen and concentration. Am J Med 70, 1195-1202. Li, H., Chou, G.X., Wang, Z.T. and Hu, Z.B., 2006. HPLC determination of acteoside in Radix Rehmanniae. Zhongguo Zhong Yao Za Zhi 31, 822-824. Li, J.S., Zhang, W., Kang, Z.M., Ding, S.J., Liu, W.W., Zhang, J.H., Guan, Y.T. and Sun, X.J., 2009. Hyperbaric oxygen preconditioning reduces ischemia-reperfusion injury by inhibition of apoptosis via mitochondrial pathway in rat brain. Neuroscience 159, 1309-1315. Maffei Facino, R., Carini, M., Aldini, G., Berti, F. and Rossoni, G., 1999. Panax ginseng administration in the rat prevents myocardial ischemia-reperfusion damage induced by hyperbaric oxygen: evidence for an antioxidant intervention. Planta Med 65, 614-619. Merrill, E.W., 1969. Rheology of blood. Physiol Rev 49, 863 888. Misiakos, E.P., Kouraklis, G., Agapitos, E., Perrea, D., Karatzas, G., Boudoulas, H. and Karayannakos, P.E., 2001. Expression of PDGF-A, TGFb and VCAM-1 during the developmental stages of experimental atherosclerosis. Eur Surg Res 33,264-269. Norris, P., Poston, R.N., Thomas, D.S., Thornhill, M., Hawk, J. and Haskard, D.O., 1991. The expression of endothelial leukocyte adhesion molecule-1 (ELAM-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in experimental cutaneous inflammation: a comparison of ultraviolet B erythema and delayed hypersensitivity. J Invest Dermatol 96, 763-770. Ohno, T., Inoue, M., Ogihara, Y. and Saracoglu, I., 2002. Antimetastatic activity of acteoside, a phenylethanoid glycoside. Biological & pharmaceutical bulletin 25, 666. Ouyang, M.A., Wang, H.Q., Chen, Z.L. and Yang, C.R., 1996. Triterpenoid glycosides from Ilex kudincha. Phytochemistry 43, 443-445. Shacter, E. and Weitzman, S.A., 2002. Chronic inflammation and cancer. Oncology (Williston Park) 16, 217-226, 229; discussion 230-212. Tai, C.J., Chen, C.H., Chen, H.H. and Liang, H.J., Differential effect of high dietary fat intakes on haemorheological parameters in rats. Br J Nutr 103, 977-983. ten Hacken, N.H., Postma, D.S., Bosma, F., Drok, G., Rutgers, B., Kraan, J. and Timens, W., 1998. Vascular adhesion molecules in nocturnal asthma: a possible role for VCAM-1 in ongoing airway wall inflammation. Clin Exp Allergy 28, 1518-1525. Weber, S.U., Koch, A., Kankeleit, J., Schewe, J.C., Siekmann, U., Stuber, F., Hoeft, A. and Schroder, S., 2009. Hyperbaric oxygen induces apoptosis via a mitochondrial mechanism. Apoptosis 14, 97-107. Wong, I.Y., He, Z.D., Huang, Y. and Chen, Z.Y., 2001a. Antioxidative activities of phenylethanoid glycosides from Ligustrum purpurascens. J Agric Food Chem 49, 3113-3119. Wong, I.Y., Huang, Y., He, Z.D., Lau, C.W. and Chen, Z.Y., 2001b. Relaxing effects of Ligstrum purpurascens extract and purified acteoside in rat aortic rings. Planta Med 67, 317-321. Wu, Y.T., Lin, L.C., Sung, J.S. and Tsai, T.H., 2006. Determination of acteoside in Cistanche deserticola and Boschniakia rossica and its pharmacokinetics in freely-moving rats using LC-MS/MS. J Chromatogr B Analyt Technol Biomed Life Sci 844, 89-95. Xiong, Q., Hase, K., Tezuka, Y., Namba, T. and Kadota, S., 1999. Acteoside inhibits apoptosis in D-galactosamine and lipopolysaccharide-induced liver injury. Life Sci 65, 421-430. Xu, C., Li, C.Y. and Kong, A.N., 2005. Induction of phase I, II and III drug metabolism/transport by xenobiotics. Arch Pharm Res 28, 249-268. Zhao, J., Liu, T., Ma, L., Yan, M., Zhao, Y., Gu, Z. and Huang, Y., 2009. Protective effect of acteoside on immunological liver injury induced by Bacillus Calmette-Guerin plus lipopolysaccharide. Planta Med 75, 1463-1469. Zhao, T., Guo, J., Li, H., Huang, W., Xian, X., Ross, C.J., Hayden, M.R., Wen, Z. and Liu, G., 2006. Hemorheological abnormalities in lipoprotein lipase deficient mice with severe hypertriglyceridemia. Biochem Biophys Res Commun 341, 1066-1071. Chapter 2 Ay, H., Topal, T., Uysal, B., Ozler, M., Oter, S., Korkmaz, A. and Dundar, K., 2007. Time-dependent course of hyperbaric oxygen-induced oxidative effects in rat lung and erythrocytes. Clin Exp Pharmacol Physiol 34, 787-791. Cecchi, E., Mannini, L. and Abbate, R., 2009. Role of hyperviscosity in cardiovascular and microvascular diseases. G Ital Nefrol 26 Suppl 46, 20-29. Chang, C.Y., Liang, H.J., Chow, S.Y., Chen, S.M. and Liu, D.Z., 2007. Hemorheological mechanisms in Alzheimer''s disease. Microcirculation 14, 627-634. Cheng, H.C., Chan, C.M., Tsay, H.S., Liang, H.J., Liang, Y.C. and Liu, D.Z., 2007. Improving effects of epigallocatechin-3-gallate on hemorheological abnormalities of aging Guinea pigs. Circ J 71, 597-603. Chiou, W.F., Lin, L.C. and Chen, C.F., 2004. Acteoside protects endothelial cells against free radical-induced oxidative stress. J Pharm Pharmacol 56, 743-748. Cho, Y.I., Mooney, M.P. and Cho, D.J., 2008. Hemorheological disorders in diabetes mellitus. J Diabetes Sci Technol 2, 1130-1138. Chung, T.W., Yu, J.J. and Liu, D.Z., 1998. Reducing lipid peroxidation stress of erythrocyte membrane by alpha-tocopherol nicotinate plays an important role in improving blood rheological properties in type 2 diabetic patients with retinopathy. Diabet Med 15, 380-385. Delazar, A., Sabzevari, A., Mojarrab, M., Nazemiyeh, H., Esnaashari, S., Nahar, L., Razavi, S.M. and Sarker, S.D., 2008. Free-radical-scavenging principles from Phlomis caucasica. J Nat Med 62, 464-466. Ercan, M., Koksal, C., Konukoglu, D., Bozkurt, A.K. and Onen, S., 2003. Impaired plasma viscosity via increased cholesterol levels in peripheral occlusive arterial disease [correction of disase]. Clin Hemorheol Microcirc 29, 3-9. Erdem, T.Y., Ercan, M., Ugurlu, S., Balci, H., Acbay, O. and Gundogdu, S., 2008. Plasma viscosity, an early cardiovascular risk factor in women with subclinical hypothyroidism. Clin Hemorheol Microcirc 38, 219-225. Falco, C., Vaya, A., Simo, M., Contreras, T., Santaolaria, M. and Aznar, J., 2005. Influence of fibrinogen levels on erythrocyte aggregation determined with the Myrenne aggregometer and the Sefam erythro-aggregometer. Clin Hemorheol Microcirc 33, 145-151. Feher, G., Koltai, K., Kesmarky, G., Szapary, L., Juricskay, I. and Toth, K., 2006. Hemorheological parameters and aging. Clin Hemorheol Microcirc 35, 89-98. Goto, H., Shimada, Y., Sekiya, N., Yang, Q., Kogure, T., Mantani, N., Hikiami, H., Shibahara, N. and Terasawa, K., 2004. Effects of Keishi-bukuryo-gan on vascular function and hemorheological factors in spontaneously diabetic (WBN/kob) rats. Phytomedicine 11, 188-195. Halliwell, B., 2007. Flavonoids: a re-run of the carotenoids story? Novartis Found Symp 282, 93-101; discussion 101-104, 212-108. Halliwell, B., 2009. The wanderings of a free radical. Free Radic Biol Med 46, 531-542. Hausmann, M., Obermeier, F., Paper, D.H., Balan, K., Dunger, N., Menzel, K., Falk, W., Schoelmerich, J., Herfarth, H. and Rogler, G., 2007. In vivo treatment with the herbal phenylethanoid acteoside ameliorates intestinal inflammation in dextran sulphate sodium-induced colitis. Clin Exp Immunol 148, 373-381. Hou, W.C., Tsay, H.S., Liang, H.J., Lee, T.Y., Wang, G.J. and Liu, D.Z., 2007. Improving abnormal hemorheological parameters in aging guinea pigs by water-soluble extracts of Salvia miltiorrhiza Bunge. J Ethnopharmacol 111, 483-489. Huang, S.Y., Jeng, C., Kao, S.C., Yu, J.J. and Liu, D.Z., 2004. Improved haemorrheological properties by Ginkgo biloba extract (Egb 761) in type 2 diabetes mellitus complicated with retinopathy. Clin Nutr 23, 615-621. Khodabandehlou, T., Boisseau, M.R. and Le Devehat, C., 2004. Blood rheology as a marker of venous hypertension in patients with venous disease. Clin Hemorheol Microcirc 30, 307-312. Kim, H.J., Lee, J.H., Kim, S.J., Oh, G.S., Moon, H.D., Kwon, K.B., Park, C., Park, B.H., Lee, H.K., Chung, S.Y., Park, R. and So, H.S., Roles of NADPH oxidases in cisplatin-induced reactive oxygen species generation and ototoxicity. J Neurosci 30, 3933-3946. Kim, S.S., Son, Y.O., Chun, J.C., Kim, S.E., Chung, G.H., Hwang, K.J. and Lee, J.C., 2005. Antioxidant property of an active component purified from the leaves of paraquat-tolerant Rehmannia glutinosa. Redox Rep 10, 311-318. Letcher, R.L., Chien, S., Pickering, T.G., Sealey, J.E. and Laragh, J.H., 1981. Direct relationship between blood pressure and blood viscosity in normal and hypertensive subjects. Role of fibrinogen and concentration. Am J Med 70, 1195-1202. Li, J.S., Zhang, W., Kang, Z.M., Ding, S.J., Liu, W.W., Zhang, J.H., Guan, Y.T. and Sun, X.J., 2009. Hyperbaric oxygen preconditioning reduces ischemia-reperfusion injury by inhibition of apoptosis via mitochondrial pathway in rat brain. Neuroscience 159, 1309-1315. Liang, Y.C., Lin-shiau, S.Y., Chen, C.F. and Lin, J.K., 1997. Suppression of extracellular signals and cell proliferation through EGF receptor binding by (-)-epigallocatechin gallate in human A431 epidermoid carcinoma cells. J Cell Biochem 67, 55-65. Lin, Y.L., Tsai, S.H., Lin-Shiau, S.Y., Ho, C.T. and Lin, J.K., 1999. Theaflavin-3,3''-digallate from black tea blocks the nitric oxide synthase by down-regulating the activation of NF-kappaB in macrophages. Eur J Pharmacol 367, 379-388. Maffei Facino, R., Carini, M., Aldini, G., Berti, F. and Rossoni, G., 1999. Panax ginseng administration in the rat prevents myocardial ischemia-reperfusion damage induced by hyperbaric oxygen: evidence for an antioxidant intervention. Planta Med 65, 614-619. Martinez, M., Vaya, A., Server, R., Santaolaria, M. and Aznar, J., 1998. Erythrocyte elongation index measured on a Rheodyn SSD laser diffractometer. Influence of the hematocrit. Clin Hemorheol Microcirc 19, 255-257. Nourooz-Zadeh, J., Ziegler, D., Sohr, C., Betteridge, J.D., Knight, J. and Hothersall, J., 2006. The use of pholasin as a probe for the determination of plasma total antioxidant capacity. Clin Biochem 39, 55-61. Obata, T., 2006. Nitric oxide and MPP+-induced hydroxyl radical generation. J Neural Transm 113, 1131-1144. Pham, T.Q., Cormier, F., Farnworth, E., Tong, V.H. and Van Calsteren, M.R., 2000. Antioxidant properties of crocin from Gardenia jasminoides Ellis and study of the reactions of crocin with linoleic acid and crocin with oxygen. J Agric Food Chem 48, 1455-1461. Reinhart, W.H. and Singh, A., 1990. Erythrocyte aggregation: the roles of cell deformability and geometry. Eur J Clin Invest 20, 458-462. Rizvi, S.I., Zaid, M.A., Anis, R. and Mishra, N., 2005. Protective role of tea catechins against oxidation-induced damage of type 2 diabetic erythrocytes. Clin Exp Pharmacol Physiol 32, 70-75. Schmid-Schonbein, H., Ruef, P. and Linderkamp, O., 1996. The shear stress diffractometer Rheodyn SSD for determination of erythrocyte deformability. I. Principles of operation and reproducibility. Clinical hemorheology 16, 745-748. Sen, T., Dutta, A. and Chatterjee, A., Epigallocatechin-3-gallate (EGCG) downregulates gelatinase-B (MMP-9) by involvement of FAK/ERK/NFkappaB and AP-1 in the human breast cancer cell line MDA-MB-231. Anticancer Drugs 21, 632-644. Shahat, A.A., Nazif, N.M., Abousetta, L.M., Ibrahim, N.A., Cos, P., Van Miert, S., Pieters, L. and Vlietinck, A.J., 2005. Phytochemical investigation and antioxidant activity of Duranta repens. Phytother Res 19, 1071-1073. Sugisawa, A. and Umegaki, K., 2002. Physiological concentrations of (-)-epigallocatechin-3-O-gallate (EGCg) prevent chromosomal damage induced by reactive oxygen species in WIL2-NS cells. J Nutr 132, 1836-1839. Syed, D.N., Afaq, F., Kweon, M.H., Hadi, N., Bhatia, N., Spiegelman, V.S. and Mukhtar, H., 2007. Green tea polyphenol EGCG suppresses cigarette smoke condensate-induced NF-kappaB activation in normal human bronchial epithelial cells. Oncogene 26, 673-682. Tai, C.J., Chen, C.H., Chen, H.H. and Liang, H.J., Differential effect of high dietary fat intakes on haemorheological parameters in rats. Br J Nutr 103, 977-983. Tipoe, G.L., Leung, T.M., Hung, M.W. and Fung, M.L., 2007. Green tea polyphenols as an anti-oxidant and anti-inflammatory agent for cardiovascular protection. Cardiovasc Hematol Disord Drug Targets 7, 135-144. Umegaki, K., Sugisawa, A., Yamada, K. and Higuchi, M., 2001. Analytical method of measuring tea catechins in human plasma by solid-phase extraction and HPLC with electrochemical detection. J Nutr Sci Vitaminol (Tokyo) 47, 402-408. Vignes, M., Maurice, T., Lante, F., Nedjar, M., Thethi, K., Guiramand, J. and Recasens, M., 2006. Anxiolytic properties of green tea polyphenol (-)-epigallocatechin gallate (EGCG). Brain Res 1110, 102-115. Wang, H., Xu, Y., Yan, J., Zhao, X., Sun, X., Zhang, Y., Guo, J. and Zhu, C., 2009. Acteoside protects human neuroblastoma SH-SY5Y cells against beta-amyloid-induced cell injury. Brain Res 1283, 139-147. Weber, S.U., Koch, A., Kankeleit, J., Schewe, J.C., Siekmann, U., Stuber, F., Hoeft, A. and Schroder, S., 2009. Hyperbaric oxygen induces apoptosis via a mitochondrial mechanism. Apoptosis 14, 97-107. Wells, P.G., Kim, P.M., Laposa, R.R., Nicol, C.J., Parman, T. and Winn, L.M., 1997. Oxidative damage in chemical teratogenesis. Mutat Res 396, 65-78. Xu, C., Li, C.Y. and Kong, A.N., 2005. Induction of phase I, II and III drug metabolism/transport by xenobiotics. Arch Pharm Res 28, 249-268. Yang, C.S., Chen, L., Lee, M.J., Balentine, D., Kuo, M.C. and Schantz, S.P., 1998. Blood and urine levels of tea catechins after ingestion of different amounts of green tea by human volunteers. Cancer Epidemiol Biomarkers Prev 7, 351-354. Zhang, A., Zhu, Q.Y., Luk, Y.S., Ho, K.Y., Fung, K.P. and Chen, Z.Y., 1997. Inhibitory effects of jasmine green tea epicatechin isomers on free radical-induced lysis of red blood cells. Life Sci 61, 383-394. Zhao, C., Dodin, G., Yuan, C., Chen, H., Zheng, R., Jia, Z. and Fan, B.T., 2005. "In vitro" protection of DNA from Fenton reaction by plant polyphenol verbascoside. Biochim Biophys Acta 1723, 114-123. Zhao, T., Guo, J., Li, H., Huang, W., Xian, X., Ross, C.J., Hayden, M.R., Wen, Z. and Liu, G., 2006. Hemorheological abnormalities in lipoprotein lipase deficient mice with severe hypertriglyceridemia. Biochem Biophys Res Commun 341, 1066-1071. Zheng, J., Wang, X., Li, H., Gu, Y., Tu, P. and Wen, Z., 2009. Improving abnormal hemorheological parameters in ApoE-/- mice by Ilex kudingcha total saponins. Clin Hemorheol Microcirc 42, 29-36. Chapter 3 Ahmad, M., 1986. Naturally occurring acteoside from Buddleja davidii. J Pharm 4, 65-68. Barnes, J., Anderson, L.A., Phillipson, J.D. and Library, R., 2007. Herbal medicines. Pharmaceutical Press London. Blankenberg, S., Barbaux, S. and Tiret, L., 2003. Adhesion molecules and atherosclerosis. Atherosclerosis 170, 191-203. Brigelius-Flohe, R., Banning, A., Kny, M. and Bol, G.F., 2004. Redox events in interleukin-1 signaling. Arch Biochem Biophys 423, 66-73. Chen, Y., Li, K.S. and Xie, T.G., 1995. Hypotensive action of the extract of kudingcha dongqingye. Chin. Tradit. Herb. Drugs 26, 250-252. Chiou, W.F., Lin, L.C. and Chen, C.F., 2004. Acteoside protects endothelial cells against free radical-induced oxidative stress. J Pharm Pharmacol 56, 743-748. Chun, J.C., Cheol Kim, J., Taek Hwang, I. and Eun Kim, S., 2002. Acteoside from Rehmannia glutinosa nullifies paraquat activity in Cucumis sativus. Pesticide Biochemistry and Physiology 72, 153-159. Clarkson, C., Staerk, D., Hansen, S.H., Smith, P.J. and Jaroszewski, J.W., 2006. Identification of major and minor constituents of Harpagophytum procumbens (Devil''s claw) using HPLC-SPE-NMR and HPLC-ESIMS/APCIMS. J Nat Prod 69, 1280-1288. Delazar, A., Sabzevari, A., Mojarrab, M., Nazemiyeh, H., Esnaashari, S., Nahar, L., Razavi, S.M. and Sarker, S.D., 2008. Free-radical-scavenging principles from Phlomis caucasica. J Nat Med 62, 464-466. Dunne, A. and O''Neill, L.A., 2003. The interleukin-1 receptor/Toll-like receptor superfamily: signal transduction during inflammation and host defense. Sci STKE 2003, re3. Gutierrez, J., Ballinger, S.W., Darley-Usmar, V.M. and Landar, A., 2006. Free radicals, mitochondria, and oxidized lipids: the emerging role in signal transduction in vascular cells. Circ Res 99, 924-932. Hausmann, M., Obermeier, F., Paper, D.H., Balan, K., Dunger, N., Menzel, K., Falk, W., Schoelmerich, J., Herfarth, H. and Rogler, G., 2007. In vivo treatment with the herbal phenylethanoid acteoside ameliorates intestinal inflammation in dextran sulphate sodium-induced colitis. Clin Exp Immunol 148, 373-381. Heinecke, J.W., Baker, L., Rosen, H. and Chait, A., 1986. Superoxide-mediated modification of low density lipoprotein by arterial smooth muscle cells. J Clin Invest 77, 757-761. Hiramatsu, K., Rosen, H., Heinecke, J.W., Wolfbauer, G. and Chait, A., 1987. Superoxide initiates oxidation of low density lipoprotein by human monocytes. Arteriosclerosis 7, 55-60. Hwang, Y.S., Jeong, M., Park, J.S., Kim, M.H., Lee, D.B., Shin, B.A., Mukaida, N., Ellis, L.M., Kim, H.R., Ahn, B.W. and Jung, Y.D., 2004. Interleukin-1beta stimulates IL-8 expression through MAP kinase and ROS signaling in human gastric carcinoma cells. Oncogene 23, 6603-6611. Iademarco, M.F., McQuillan, J.J., Rosen, G.D. and Dean, D.C., 1992. Characterization of the promoter for vascular cell adhesion molecule-1 (VCAM-1). J Biol Chem 267, 16323-16329. Kang, K.H., Huh, H., Kim, B.K. and Lee, C.K., 1999. An antiviral furanoquinone from Paulownia tomentosa Steud. Phytother Res 13, 624-626. Kaur, J., Dhaunsi, G.S. and Turner, R.B., 2004. Interleukin-1 and nitric oxide increase NADPH oxidase activity in human coronary artery smooth muscle cells. Med Princ Pract 13, 26-29. Kim, S.S., Son, Y.O., Chun, J.C., Kim, S.E., Chung, G.H., Hwang, K.J. and Lee, J.C., 2005. Antioxidant property of an active component purified from the leaves of paraquat-tolerant Rehmannia glutinosa. Redox Rep 10, 311-318. Kitagawa, S., Tsukamoto, H., Hisada, S. and Nishide, S., 1984. Studies on the chinese crude drug forsythiae fructus. VII: A new caffeoyl glycoside from Forsythia viridissima. Chemical and pharmaceutical bulletin 32, 1209-1213. Koo, K.A., Kim, S.H., Oh, T.H. and Kim, Y.C., 2006. Acteoside and its aglycones protect primary cultures of rat cortical cells from glutamate-induced excitotoxicity. Life Sci 79, 709-716. Koo, K.A., Sung, S.H., Park, J.H., Kim, S.H., Lee, K.Y. and Kim, Y.C., 2005. In vitro neuroprotective activities of phenylethanoid glycosides from Callicarpa dichotoma. Planta medica 71, 778. Lee, J.H., Lee, J.Y., Kang, H.S., Jeong, C.H., Moon, H., Whang, W.K., Kim, C.J. and Sim, S.S., 2006a. The effect of acteoside on histamine release and arachidonic acid release in RBL-2H3 mast cells. Arch Pharm Res 29, 508-513. Lee, J.Y., Woo, E.R. and Kang, K.W., 2005. Inhibition of lipopolysaccharide-inducible nitric oxide synthase expression by acteoside through blocking of AP-1 activation. J Ethnopharmacol 97, 561-566. Lee, K.W., Kim, H.J., Lee, Y.S., Park, H.J., Choi, J.W., Ha, J. and Lee, K.T., 2007. Acteoside inhibits human promyelocytic HL-60 leukemia cell proliferation via inducing cell cycle arrest at G0/G1 phase and differentiation into monocyte. Carcinogenesis 28, 1928-1936. Lee, K.Y., Jeong, E.J., Lee, H.S. and Kim, Y.C., 2006b. Acteoside of Callicarpa dichotoma attenuates scopolamine-induced memory impairments. Biol Pharm Bull 29, 71-74. Liu, D.Z., Liang, H.J., Chen, C.H., Lin, S.Y., Zhong, W.B., Ho, F.M., Hou, W.C., Lo, J.L., Ho, Y.S., Lin, P.J., Hung, L.F. and Liang, Y.C., 2007. Switch activation of PI-PLC downstream signals in activated macrophages with wortmannin. Biochim Biophys Acta 1773, 869-879. Lockyer, J.M., Colladay, J.S., Alperin-Lea, W.L., Hammond, T. and Buda, A.J., 1998. Inhibition of nuclear factor-kappaB-mediated adhesion molecule expression in human endothelial cells. Circ Res 82, 314-320. Marx, N., Sukhova, G.K., Collins, T., Libby, P. and Plutzky, J., 1999. PPARalpha activators inhibit cytokine-induced vascular cell adhesion molecule-1 expression in human endothelial cells. Circulation 99, 3125-3131. Meager, A., 1999. Cytokine regulation of cellular adhesion molecule expression in inflammation. Cytokine Growth Factor Rev 10, 27-39. Mendes, A.F., Caramona, M.M., Carvalho, A.P. and Lopes, M.C., 2003. Hydrogen peroxide mediates interleukin-1beta-induced AP-1 activation in articular chondrocytes: implications for the regulation of iNOS expression. Cell Biol Toxicol 19, 203-214. Middleton, E., Jr., Kandaswami, C. and Theoharides, T.C., 2000. The effects of plant flavonoids on mammalian cells: implications for inflammation, heart disease, and cancer. Pharmacol Rev 52, 673-751. Miyase, T., Koizumi, A., Ueno, A., Noro, T., Kuroyanagi, M., Fukushima, S., Akiyama, Y. and Takemoto, T., 1982. Studies on the acyl glycosides from Leucoseptrum japonicum (Miq.) Kitamura et Murata. Chem Pharm Bull 30, 2732-2737. Moore, K.P., Darley-Usmar, V., Morrow, J. and Roberts, L.J., 2nd, 1995. Formation of F2-isoprostanes during the oxidation of human low density lipoprotein by peroxynitrite. Adv Prostaglandin Thromboxane Leukot Res 23, 225-227. Nakashima, Y., Raines, E.W., Plump, A.S., Breslow, J.L. and Ross, R., 1998. Upregulation of VCAM-1 and ICAM-1 at atherosclerosis-prone sites on the endothelium in the ApoE-deficient mouse. Arterioscler Thromb Vasc Biol 18, 842-851. Ouyang, M.A., Wang, H.Q., Chen, Z.L. and Yang, C.R., 1996. Triterpenoid glycosides from Ilex kudincha. Phytochemistry 43, 443-445. Rao, Y.K., Fang, S.H., Hsieh, S.C., Yeh, T.H. and Tzeng, Y.M., 2009. The constituents of Anisomeles indica and their anti-inflammatory activities. J Ethnopharmacol 121, 292-296. Shahat, A.A., Nazif, N.M., Abousetta, L.M., Ibrahim, N.A., Cos, P., Van Miert, S., Pieters, L. and Vlietinck, A.J., 2005. Phytochemical investigation and antioxidant activity of Duranta repens. Phytother Res 19, 1071-1073. Sticher, O. and Lahloub, M.F., 1982. Phenolic glycosides of Paulownia tomentosa bark. Planta Med 46, 145-148. Suk, F.M., Chen, C.H., Lin, S.Y., Cheng, C.J., Yen, S.J., Hung, L.F., Liu, D.Z. and Liang, Y.C., 2009. 15-deoxy-Delta(12,14)-prostaglandin J(2) inhibits fibrogenic response in human hepatoma cells. Toxicol Lett 187, 22-27. Szmitko, P.E., Wang, C.H., Weisel, R.D., de Almeida, J.R., Anderson, T.J. and Verma, S., 2003. New markers of inflammation and endothelial cell activation: Part I. Circulation 108, 1917-1923. Terry, R.W., Kwee, L., Levine, J.F. and Labow, M.A., 1993. Cytokine induction of an alternatively spliced murine vascular cell adhesion molecule (VCAM) mRNA encoding a glycosylphosphatidylinositol-anchored VCAM protein. Proc Natl Acad Sci U S A 90, 5919-5923. Wang, H., Xu, Y., Yan, J., Zhao, X., Sun, X., Zhang, Y., Guo, J. and Zhu, C., 2009. Acteoside protects human neuroblastoma SH-SY5Y cells against beta-amyloid-induced cell injury. Brain Res 1283, 139-147. Wilmer, W.A., Tan, L.C., Dickerson, J.A., Danne, M. and Rovin, B.H., 1997. Interleukin-1beta induction of mitogen-activated protein kinases in human mesangial cells. Role of oxidation. J Biol Chem 272, 10877-10881. Wong, I.Y., He, Z.D., Huang, Y. and Chen, Z.Y., 2001. Antioxidative activities of phenylethanoid glycosides from Ligustrum purpurascens. J Agric Food Chem 49, 3113-3119. Wyk, B.E., Oudtshoorn, B. and Gericke, N., 1997. Medicinal plants of South Africa. Medicinal plants of South Africa. Zhao, C., Dodin, G., Yuan, C., Chen, H., Zheng, R., Jia, Z. and Fan, B.T., 2005. "In vitro" protection of DNA from Fenton reaction by plant polyphenol verbascoside. Biochim Biophys Acta 1723, 114-123. Chapter 4 Ahmad, M. and Aftab, K., 1995. Hypotensive action of syringin from Syringa vulgaris. Phytotherapy Research 9, 452-454. Ahmad, M., Rizwani, G.H., Aftab, K., Ahmad, V.U., Gilani, A.H. and Ahmad, S.P., 1995. Acteoside: A new antihypertensive drug. Phytotherapy Research 9, 525-527. Berry, C.E. and Hare, J.M., 2004. Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications. J Physiol 555, 589-606. Birkofer, L., Kaiser, C. and Thomas, U., 1968. [Acteoside and neoacteoside: sugar esters from Syringa vulgaris (L.)]. Z Naturforsch B 23, 1051-1058. Bouloumie, A., Bauersachs, J., Linz, W., Scholkens, B.A., Wiemer, G., Fleming, I. and Busse, R., 1997. Endothelial dysfunction coincides with an enhanced nitric oxide synthase expression and superoxide anion production. Hypertension 30, 934-941. Chen, C.H., Song, T.Y., Liang, Y.C. and Hu, M.L., 2009. Acteoside and 6-O-acetylacteoside downregulate cell adhesion molecules induced by IL-1beta through inhibition of ERK and JNK in human vascular endothelial cells. J Agric Food Chem 57, 8852-8859. Chiou, W.F., Lin, L.C. and Chen, C.F., 2004. Acteoside protects endothelial cells against free radical-induced oxidative stress. J Pharm Pharmacol 56, 743-748. Cuzzocrea, S., Mazzon, E., Dugo, L., Di Paola, R., Caputi, A.P. and Salvemini, D., 2004. Superoxide: a key player in hypertension. FASEB J 18, 94-101. Fotherby, M.D. and Panayiotou, B., 1999. Antihypertensive therapy in the prevention of stroke: what, when and for whom? Drugs 58, 663-674. Hou, W.C., Chen, H.J. and Lin, Y.H., 2003. Antioxidant peptides with Angiotensin converting enzyme inhibitory activities and applications for Angiotensin converting enzyme purification. J Agric Food Chem 51, 1706-1709. Huang, C.G., Shang, Y.J., Zhang, J., Zhang, J.R., Li, W.J. and Jiao, B.H., 2008. Hypouricemic effects of phenylpropanoid glycosides acteoside of Scrophularia ningpoensis on serum uric acid levels in potassium oxonate-pretreated Mice. Am J Chin Med 36, 149-157. Institute of Laboratory Animal, R. and National Research, C., 1996. Guide for the care and use of laboratory animals. National Academy Press Washington, DC. Koo, K.A., Kim, S.H., Oh, T.H. and Kim, Y.C., 2006. Acteoside and its aglycones protect primary cultures of rat cortical cells from glutamate-induced excitotoxicity. Life Sci 79, 709-716. Koo, K.A., Sung, S.H., Park, J.H., Kim, S.H., Lee, K.Y. and Kim, Y.C., 2005. In vitro neuroprotective activities of phenylethanoid glycosides from Callicarpa dichotoma. Planta Med 71, 778-780. Lee, K.Y., Jeong, E.J., Lee, H.S. and Kim, Y.C., 2006. Acteoside of Callicarpa dichotoma attenuates scopolamine-induced memory impairments. Biol Pharm Bull 29, 71-74. Li, H., Chou, G.X., Wang, Z.T. and Hu, Z.B., 2006. [HPLC determination of acteoside in Radix Rehmanniae]. Zhongguo Zhong Yao Za Zhi 31, 822-824. Lin, C.L., Lin, S.Y., Lin, Y.H. and Hou, W.C., 2006. Effects of tuber storage protein of yam (Dioscorea alata cv. Tainong No. 1) and its peptic hydrolyzates on spontaneously hypertensive rats. Journal of the Science of Food and Agriculture 86, 1489-1494. Lin, S.Y., Wang, C.C., Lu, Y.L., Wu, W.C. and Hou, W.C., 2008. Antioxidant, anti-semicarbazide-sensitive amine oxidase, and anti-hypertensive activities of geraniin isolated from Phyllanthus urinaria. Food Chem Toxicol 46, 2485-2492. Liu, D.Z., Liang, Y.C., Lin, S.Y., Lin, Y.S., Wu, W.C., Hou, W.C. and Su, C.H., 2007. Antihypertensive activities of a solid-state culture of Taiwanofungus camphoratus (Chang-chih) in spontaneously hypertensive rats. Biosci Biotechnol Biochem 71, 23-30. Mark, K.S. and Davis, T.P., 2000. Stroke: development, prevention and treatment with peptidase inhibitors. Peptides 21, 1965-1973. Nakazono, K., Watanabe, N., Matsuno, K., Sasaki, J., Sato, T. and Inoue, M., 1991. Does superoxide underlie the pathogenesis of hypertension? Proc Natl Acad Sci USA 88, 10045-10048. Ohno, T., Inoue, M., Ogihara, Y. and Saracoglu, I., 2002. Antimetastatic activity of acteoside, a phenylethanoid glycoside. Biol Pharm Bull 25, 666-668. Ong, S.L.H., Vickers, J.J., Zhang, Y., McKenzie, K.U.S., Walsh, C.E. and Whitworth, J.A., 2007. Role of xanthine oxidase in dexamtehasone induced hypertension in rats. Clinical and Experimental Pharmacology and Physiology 34, 517-519. Ouyang, M.A., Wang, H.Q., Chen, Z.L. and Yang, C.R., 1996. Triterpenoid glycosides from Ilex kudincha. Phytochemistry 43, 443-445. Rao, Y.K., Fang, S.H., Hsieh, S.C., Yeh, T.H. and
摘要: 心血管疾病為許多影響心臟及血管之各種疾病的通稱,也為美國男女性主要致死的原因之一。異常血液流變,血管內皮細胞發炎以及高血壓是誘發心血管疾病的三大主因。本論文分成三大部份,第一部份是建立了一個評估高壓氧對血液流變參數之影響的體外試驗模型。使用密閉良好的高壓氧艙模擬自由基的攻擊環境。進行全血粘度,紅血球膜脂質過氧化,紅血球變形度等血液流變參數的研究。實驗結果顯示隨著氧分壓的增加 (1.0,1.5,2.0和2.5 atm) 和曝露時間的增加 (4,8,12和16小時)導致超氧陰離子的產生並引發全血粘度及紅血球膜脂質過氧化增加,同時亦伴隨紅血球變形能力降低。此外,我們更進一步利用已知的抗氧化劑兒茶素(如EGCG, ECG及EGC),驗證兒茶素對高壓氧誘發之異常血液流變。實驗結果顯示兒茶素可顯著減少全血中超氧陰離子、全血黏度以及紅血球膜之脂質過氧化減少並且可顯著提高紅血球變形度,有效強度依次為EGCG、ECG、EGC。接著,本研究利用上述所建立之體外異常血液流變模式做為天然物之篩檢。天然物包括毛蕊花苷及其結構類似物6-O-Acetylacteoside。毛蕊花苷 (Acteoside)屬於苯乙醇苷類化合物,是許多藥用植物及苦茶中的活性成份。結果顯示添加毛蕊花苷或6-O-Acetylacteoside之全血,可顯著降低全血中超氧陰離子含量以及紅血球膜之脂質過氧化,以及可顯著提高紅血球變形度。 在動脈粥狀硬化過程以及內皮細胞發炎反應,細胞附著分子(CAMs)扮演著重要角色。活體外研究指出,毛蕊花苷具有抗發炎之特性,然而對於毛蕊花苷及其結構類似物如 isoacteoside和6-O-acetylacteoside是否可抑制發炎反應及動脈粥狀硬化過程中細胞附著分子的表現仍不清楚。因此在第二部份我們探討毛蕊花苷及其結構類似物對於白血球細胞附著於人類臍靜脈內皮細胞之抑制效果以及對於促發炎細胞激素 IL-1β 所誘導之血管內皮細胞表現黏著分子如 ICAM-1及VCAM-1 表現之影響。結果證實毛蕊花苷及其結構類似物 isoacteoside 和6-O-acetylacteoside,在人類臍靜脈內皮細胞中,可抑制經由IL-1β所引起的細胞附著分子 ICAM-1及VCAM-1的表現,同時其抑制的活性強度依次是6-O-acetylacteoside >毛蕊花苷 > isoacteoside。此外毛蕊花苷及 6-O-acetylacteoside 也都呈劑量相關性的抑制 VCAM-1 基因啟動區的活性,並與降低訊息分子 ERK 及 JNK 的磷酸化有關。 研究指出毛蕊花苷經由靜脈注射給予正常血壓之大鼠,可有效降低其收縮壓及舒張壓。然而對於毛蕊花苷經由管餵的方式給予大鼠是否也是有降血壓之作用,目前所知甚少,因此在第三部份我們以自發性高血壓大鼠為實驗模式,探討毛蕊花苷及其衍生物Isoacteoside是否具有降血壓之功效。結果顯示,毛蕊花苷 (10 mg/kg BW)可顯著降低自發性高血壓大鼠之收縮壓及舒張壓,但Isoacteoside則無降血壓之效果。此外毛蕊花苷及Isoacteoside均具有抑制血管收縮素轉化酶、抑制黃嘌呤氧化酶及捕捉DPPH自由基之能力。綜合以上結果,我們認為毛蕊花苷的降血壓作用可能與抑制血管收縮素氧化酶有關,而與其抗氧化能力無關,然而對於毛蕊花苷之降血壓機制則需在未來更進一步探討。 歸納以上結果,本論文建置了一種篩檢天然物改善異常血液流變之體外試驗模型,實驗結果證實毛蕊花苷對於高壓氧所誘發之異常血液流變參數具有明顯改善效果,包括降低紅血球膜脂質過氧化,提高紅血球變形能力。此外在內皮細胞毛蕊花苷可顯著抑制促發炎細胞激素 IL-1β 所誘導之血管內皮細胞附著分子的表現,而花蕊花苷也具有降血壓枝效果。因此未來毛蕊花苷開發成一預防心血管疾病之保健食品或藥品應具有很大之潛能。
Cardiovascular disease, a common name for a variety of diseases that affect heart and blood vessels, is a major killer of women and men in the United States. Hemorheologic abnormality parameters, vascular endothelial cell inflammation and hypertension are the three main causes on the induction of cardiovascular disease. In the first part of this thesis, we established an in vitro model to evaluate the influence of hyperbaric oxygen (HBO) on hemorheological parameters. A well-sealed chamber with HBO was used to simulate an environment of free radical attacks. Hemorheological parameters, including whole blood viscosity, erythrocyte membrane lipid peroxidation, and erythrocyte deformability, were investigated. Results show that an increase in oxygen partial pressure (1.0, 1.5, 2.0 and 2.5 atm) and exposure time (4, 8, 12 and 16 h) led to elevated levels of superoxide and viscosity of whole blood, enhanced lipid peroxidation in erythrocyte membranes, as well as decreased erythrocyte deformability. We then used some well-known catechin antioxidants, such as epigallocatechin gallate (EGCG), (-)-epicatechin 3-gallate (ECG), and (-)-epigallocatechin (EGC) to verify the feasibility on abnormal hemorheological parameters induced by hyperbaric oxygen. We found that EGCG, ECG, and EGC (0.1, 0.5 and 1.0 μM) effectively ameliorated hemorheologic abnormality and enhanced erythrocyte deformability. Moreover, we used the established model for evaluating the ameliorative effect of phenylethanoid glycosides, such as acteoside and 6-O-acetylacteoside, on hemorheological abnormality. We found that acteoside exhibited stronger ameliorative effect on hemorheologic abnormality induced by HBO treatment than that of 6-O-acetylacteoside. Cell adhesion molecules (CAMs) play an important role on atherosclerosis and vascular endothelial cell inflammation. Acteoside has been shown to possess anti-inflammatory properties in vitro. However, it is unclear whether acteoside and similar compounds may inhibit the expression of CAMs. In the second part of this thesis, we examined the inhibitory effects of acteoside, isoacteoside and 6-O-acetylacteoside on leukocyte adhesion to human umbilical vein endothelial cells (HUVECs) and the expression of ICAM-1 andVCAM-1 induced by a pro-inflammatory cytokine, IL-1β. We found that acteoside, isoacteoside and 6-Oacetylacteoside possessed an inhibitory effect on IL-1β-activated expression of intercellular CAM-1 (ICAM-1) and vascular CAM-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs). The inhibitory potency was 6-O-acetylacteoside > acteoside > isoacteoside. Moreover, Acteoside and 6-O-acetylacteoside also dose-dependently inhibit VCAM-1 gene promoter activity in IL-1β-activated HUVECs. In addition, we investigated the effect of acteoside and 6-O-acetylacteoside on phosphorylation of activation of ERK, JNK, and p38, all of which participate in the expression of ICAM-1 and VCAM-1. The inhibition of acteoside and 6-O-acetylacteoside on IL-1β-activated expression of CAMs was manifested by decreased phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK). These results indicated that acteoside and 6-O-acetylacteoside exert potential anti-inflammatory activities in vascular endothelium by inhibiting the expression of CAMs, primarily through decreased phosphorylation of ERK and JNK. Acteoside has been shown to induce a dose-dependent decrease in systolic blood pressure (SBP) and diastolic blood pressure (DBP) following its intravenous injection into normotensive anaesthetized Wistar rats. However, it is unclear whether oral supplementation of Acteoside is useful for blood pressure regulation in vivo and few studies have compared side-by-side the in vivo antihypertensive activities of Acteoside and its structurally related compounds such as Isoacteoside. Therefore, in the third part of this thesis, we investigated the antihypertensive activities of Acteoside and its structural isomer, isoacteoside, in spontaneously hypertensive rats (SHR) and their in vitro effects on angiotensin-converting enzyme (ACE) activity and in vitro antioxidant activities. Results revealed that orally administrated a signal dose (10 mg/kg BW) of Acteoside, but not Isoacteoside, significantly lowered systolic blood pressure (SBP) and diastolic blood pressure (DBP) over a 24-h period. Both Acteoside and Isoacteoside significantly inhibited the activities of ACE, but the effects of Acteoside were stronger than those of Isoacteoside. Both compounds scavenged DPPH radical and inhibited xanthine oxidase to a similar extent, whereas Isoacteoside was more effective than Acteoside in scavenging superoxide radicals (IC50 = 38.5 μM and 66.0 μM, respectively). These results demonstrate that Acteoside but not Isoacteoside exhibits antihypertensive effects in SHR, and that the effect of Acteoside is primarily related to its inhibition of ACE but not its antioxidant activities. Further studies on the potential antihypertensive effects of Acteoside are warranted. In summary, this dissertation has established an in vitro model for screening or assessing the efficacy of functional foods and drugs in the prevention or improvement of hemorheologic abnormality. The inhibitory role of acteoside on HBO-induced hemorheologic abnormality parameters has significant improvements, such as the reduction on erythrocyte membrane lipid peroxidation, and the increase of erythrocyte deformability. In addition, acteoside was also found to inhibit endothelial cell inflammation through inhibition the expression of CAMs induced by IL-1β. Moreover, acteoside exhibits antihypertensive effects in SHR. Therefore, acteoside possess potential to be developed as functional food and drug on the prevention of cardiovascular disease.
URI: http://hdl.handle.net/11455/52014
其他識別: U0005-2507201109491400
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-2507201109491400
Appears in Collections:食品暨應用生物科技學系

文件中的檔案:

取得全文請前往華藝線上圖書館

Show full item record
 
TAIR Related Article
 
Citations:


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.