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研究生: 田安然
Tien, An-Jan
論文名稱: 抗發炎中草藥之開發應用與機轉
The Development, Application, and Mechanism of Anti-inflammatory Traditional Herbal Medicine
指導教授: 鄭劍廷
Chien, Chiang-Ting
學位類別: 博士
Doctor
系所名稱: 生命科學系
Department of Life Science
論文出版年: 2018
畢業學年度: 106
語文別: 英文
論文頁數: 70
中文關鍵詞: Antrodia cinnamomeaHepatic inflammationFibrosisHepatocarcinogenesisReactive oxygen speciesAntcin KN-nitrosodiethylaminearterial thrombosisICAM-1monacolin KMonascus Adlayplatelet
英文關鍵詞: Antrodia cinnamomea, Hepatic inflammation, Fibrosis, Hepatocarcinogenesis, Reactive oxygen species, Antcin K, N-nitrosodiethylamine, arterial thrombosis, ICAM-1, monacolin K, Monascus Adlay, platelet
DOI URL: http://doi.org/10.6345/DIS.NTNU.SLS.027.2018.D01
論文種類: 學術論文
相關次數: 點閱:151下載:15
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  • 無中文摘要

    Traditional Chinese herbal medicine has been widely used for thousands of years for health promotion, disease prevention and treatment. the clinical effect of Traditional Chinese herbal medicine is remarkable, but the mechanism of those herbal medicine are incompletely clear. In our study, we chose two famous and widely used herbal medicine to explore the mechanism by determine the anti-inflammatory and anti-oxidant effect. We chose Antrodia cinnamomea and Monascus Adlay as the study subject.
    Antrodia cinnamomea (A. cinnamomea), a popular medicinal mushroom in Taiwan, is widely used for prevention or treatment of liver diseases. Systematic studies on the anti-inflammatory effect of A. cinnamomea and its molecular mechanisms have not yet been fully investigated. HPLC fingerprint analysis identified seven ergostane-type triterpenoids from A. cinnamomea water extract (ACW) including highest content of Antcin K (AC), Antcin C, Antcin H, Dehydrosulphurenic acid, Antcin B, Antcin A and Dehydroeburicoic acid. Here, we explored the effects and mechanisms of ACW and the highest content AC on N-nitrosodiethylamine (DEN) induced liver inflammation, fibrosis and carcinogenesis in rats. In in vitro study, we found ACW and AC dose-dependently scavenged O2-., H2O2 and HOCl amount by a chemiluminescence analyzer. In in vivo experiment, oral intake ACW and AC significantly inhibited DEN-enhanced hepatocellular inflammation, fibrosis and carcinoma by pathologic observation, the elevated bile and liver reactive oxygen species (ROS) amounts, plasma γ-glutamyl transpeptidase, and oxidative stress including 3-nitrotyrosine, 4-hydroxynonenal and Kuppfer cell infiltration (ED-1 stains) in the inflammatory livers. DEN enhanced nuclear factor-B (NF-B) translocation, whereas ACW and AC suppressed DEN-enhanced NF-B translocation through the inhibition of its upstream signaling of p85/phosphoinositide-3-kinase, mitogen activated protein kinase and CYP2E1 expression. In conclusion, DEN can induce hepatocellular inflammation, fibrosis and carcinoma through the increase in NF-B translocation to nucleus and oxidative injury. ACW and its active component, Antcin K, counteract DEN-induced hepatic injury and inflammation by the protective and therapeutic mechanisms of a direct scavenging ROS activity and an upregulation of antioxidant defense mechanisms.
     Monascus Adlay (MA) prepared from fungal fermentation of Monascus purpureus inoculating with cooked adlay contains high content of monakolin K (MK) and phenolic compounds. We explored whether MA and MK improve FeCl3-induced arterial thrombosis in rats. The rats were divided into control, FeCl3-treated rat carotid artery occlusion (TTO), TTO determined with one-week MA, and TTO determined with one-week MK. We compared MA or MK effects on oxidative stress by chemiluminescence amplification and immunohistochemistry, TTO by a transonic system, NFB, ICAM-1, endoplasmic reticulum stress CHOP and Nrf2 signaling by western blotting. MA or MK efficiently depressed O2-, H2O2 and HOCl levels, platelet activation and aggregation and H2O2-enhanced ICAM-1 and VCAM-1 expression in the endothelial cells. FeCl3 significantly increased NFB p65, 3-nitrotyrosine, CHOP and ICAM-1 expression, and decreased nuclear Nrf2 translocation and induces arterial thrombus formation. MA or MK pretreatment significantly elongated the level of FeCl3-induced TTO compared to TTO group, significantly decreased proinflammatory NF-B/ICAM-1 signaling, endoplasmic reticulum stress CHOP expression and decreased thrombotic area. MA or MK significantly preserved nuclear Nrf2 translocation. MA and MK exerted a similar protective effect in attenuating thrombus formation. We suggest MA is better than MK to improve FeCl3-induced arterial thrombosis.
    Through the study about Monascus Adlay (MA) and Antrodia cinnamomea, we found that anti-inflammatory and anti-oxidative effect are one of the main mechanism of Traditional herbal medicine. We can explore more about the mechanisms of the other traditional herbal medicine to discover the secret of Chinese Medicine.

    1. Abstract 3 2. Introduction 5 3. Materials and Methods 9 3.1 Chemicals 9 3.2 Experimental model of liver injury 10 3.3 In vivo and in vitro chemiluminescence recording for ROS activity 11 3.4 Inflammation, ED-1, 3-NT, 4-HNE, apoptosis and autophagy in the liver 13 3.5 Western Blotting for p85, MAPK and CYP2E1 in the livers 15 3.6 Preparation of Monascus adlay (MA) 16 3.7 Animals and MA Treatments 17 3.8 FeCl3-induced carotid arterial time to occlusion (TTO) 17 3.9 Grouping 18 3.10 Lucigenin-Enhanced Chemiluminescence (CL) Counts 18 3.11 Soluble form of Vascular ICAM-1 and ROS assay 19 3.12 In situ demonstration of ROS production and amount in the carotid artery 19 3.13 Immunoblot analysis for NFB, 3-NT, ICAM-1, CHOP, and Nrf2 20 3.14 Preparation of Platelet Suspensions for Platelet activation and aggregation 21 3.15 Expression of ICAM-1 and VCAM-1 on ROS-treated endothelial cells 22 3.16 Statistical analyses 23 4. Final Results 23 4.1 Ingredients of A. cinnamomea fruiting body 23 4.2 Scavenging O2-., H2O2 and HOCl ability by ACW and AC 24 4.3 Exploring Anti-inflammatory effect of AC and ACW by 3-NT and 4-HNE stain and ED-1 infiltration 24 4.4 Anti-fibrosis effect of AC and ACW 25 4.5 ACW or AC treatment inhibiting NF-κB mediated inflammation 25 4.6 inhibition of phosphorylated p85, phosphorylated MAPK and CYP2E1 expression by AC or ACW 26 4.7 Reducing DEN-evoked apoptosis and autophagy by AC and ACW in the livers 26 4.8 MA or MK pretreatment delays FeCl3-induced TTO 42 4.9 MA or MK reduces FeCl3-induced arterial thrombosis and endothelial 3-NT and ICAM-1 43 4.10 MK or MK inhibited platelet activation and aggregation and endothelial ICAM-1 and VCAM-1 expression 45 4.11 Scavenging O2-., H2O2 and HOCl ability by MA and MK 47 4.12 MA or MK treatment on FeCl3-enhanced arterial ROS and sICAM-1 levels 49 4.13 MA or MK on 3-NT, ICAM-1, CHOP and n-Nrf2 expression in FeCl3-treated arteries 51 5. Discussion 52 6. Conclusion 62 7. 未來展望: 63 8. References 64 9. 個人介紹 70

    [1] Kudo, M. Surveillance, diagnosis, treatment, and outcome of liver cancer in Japan. Liver Cancer. 4: 39-50, 2015.
    [2] Liao, Y.J., C.C. Fang, , C.H. Yen, S.M. Hsu, C.K. Wang, S.F. Huang, Y.C. Liang, Y.Y. Lin, Y.T. Chu and Y.M. Arthur Chen. Niemann-Pick type C2 protein regulates liver cancer progression via modulating ERK1/2 pathway: Clinicopathological correlations and therapeutical implications. Int. J. Cancer. 137: 1341-1351, 2015.
    [3] Ahn, B., B.S. Han, D.J. Kim and H. Ohshima. Immunohistochemical localization of inducible nitric oxide synthase and 3-nitrotyrosine in rat liver tumors induced by N-nitrosodiethylamine. Carcinogenesis. 20: 1337-1344, 1999.
    [4] Boitier, E., M. Merad-Boudia, C. Guguen-Guillouzo, N. Defer, I. Ceballos-Picot, J.P. Leroux, and C. Marsac. Impairment of the mitochondrial respiratory chain activity in diethynitrosamine-induced rat hepatomas: possible involvement of oxygen free radicals. Cancer Res. 55: 3028-3035, 1995.
    [5] Chen, K.H., B.R. Lin, C.T. Chien and C.H. Ho. Emblica officinalis Gaertn. Attentuates N-nitrosodiethylamine-induced apoptosis, autophagy, and inflammation in rat livers. J Med Food. 14: 746-755, 2011.
    [6] Sakurai, T., M. Kudo, A. Umemura, G. He, A.M. Elsharkawy, E. Seki and M. Karin. p38α inhibits liver fibrogenesis and consequent hepatocarcinogenesis by curtailing accumulation of reactive oxygen species. Cancer Research. 73: 215-224, 2013.
    [7] Loguercio, C. and A. Federico. Oxidative stress in viral and alcoholic hepatitis. Free Rad Biol Med. 34: 1-10, 2003.
    [8] Nieto, N., S.L. Friedman and A.I. Cederbaum. Stimulation and proliferation of primary rat hepatic stellate cells by cytochrome P450 2E1-derived reactive oxygen species. Hepatology. 35: 62-73, 2002.
    [9] Yu, H.J., B.R. Lin, H.S. Lee, C.T. Shun, C.C. Yang, T.Y. Lai, C.T. Chien and S.M. Hsu. Sympathetic vesicovascular reflex induced by acute urinary retention evokes proinflammatory and proapoptotic injury in rat liver. Am J Physiol Renal Physiol. 288: F1005-1014, 2005.
    [10] Yang, C.C., C.A. Yao, J.C. Yang and C.T. Chien. Sialic acid rescues repurified lipopolysaccharide-induced acute renal failure via inhibiting TLR4/PKC/gp91-mediated endoplasmic reticulum stress, apoptosis, autophagy, and pyroptosis signaling. Toxicol Sci. 141: 155-165, 2014.
    [11] Gao, M., P.Y. Yeh, Y.S. Lu, C.H. Hsu, K.F. Chen, W.C. Lee, W.C. Feng, C.S. Chen, M.L. Kuo and A.L. Cheng. OSU-03012, a novel celecoxib derivative, induces reactive oxygen species-related autophagy in hepatocellular carcinoma. Cancer Res. 68: 9348-9357, 2008.
    [12] Yu, T., Y.J. Lee, H.M. Yang, S. Han, J.H. Kim, Y. Lee, C. Kim, M.H. Han, M.Y. Kim, J.Lee, and J.Y. Cho. Inhibitory effect of Sanguisorba officinalis ethanol extract on NO and PGE₂ production is mediated by suppression of NF-κB and AP-1 activation signaling cascade. J Ethnopharmacol. 134: 11-17, 2011.
    [13] Chang, T.T. and W.N. Chou. Antrodia cinnamomea reconsidered and A. salmonea sp. nov. on Cunninghamia konishii in Taiwan. Botanic Bull Acad Sin. 45: 347–352, 2004.
    [14] Chen, C.H., S.W. Yang and Y.C. Shen. New steroid acids from Antrodia cinnamomea, a fungal parasite of Cinnamomum micranthum. J Nat Prod. 58: 1655-1661, 1995.
    [15] Chen, S.C., M.K. Lu, J.J. Cheng and D.L. Wang. Antiangiogenic activities of polysaccharides isolated from medicinal fungi. FEMS Microbiol Lett. 249: 247-254, 2005.
    [16] Cheng, J.J., N.K. Huang, T.T. Chang, D.L. Wang and M.K. Lu. Study for anti-angiogenic activities of polysaccharides isolated from Antrodia cinnamomea in endothelial cells. Life Sci. 76: 3029-3042, 2005.
    [17] Hsu, Y.L., P.L. Kuo, C.Y. Cho, W.C. Ni, T.F. Tzeng, L.T. Ng, Y.H. Kuo and C.C. Lin. Antrodia cinnamomea fruiting bodies extract suppresses the invasive potential of human liver cancer cell line PLC/PRF/5 through inhibition of nuclear factor kappaB pathway. Food Chem Toxicol. 45: 1249-1257, 2007.
    [18] Lu, M.K., J.J. Cheng, W.L. Lai, Y.R. Lin and N.K. Huang. Adenosine as an active component of Antrodia cinnamomea that prevents rat PC12 cells from serum deprivation-induced apoptosis through the activation of adenosine A(2A) receptors. Life Sci. 79: 252-258, 2006.
    [19] Lu, M.K., J.J. Cheng, W.L. Lai, Y.J. Lin and N.K. Huang. Fermented Antrodia cinnamomea extract protects rat PC12 cells from serum deprivation-induced apoptosis: the role of the MAPK family. J Agric Food Chem. 56: 865-874, 2008.
    [20] Huang, Y.L., Y.L. Chu, C.T. Ho, J.G. Chung, C.I. Lai, Y.C. Su, Y.H. Kuo and L.Y. Sheen. Antcin K, an active triterpenoid from the fruiting bodies of basswood-cultivated Antrodia cinnamomea, inhibits metastasis via suppression of integrin-mediated adhesion, migration, and invasion in human hepatoma cells. J Agric Food Chem. 63: 4561-4569, 2015.
    [21] Shen, Y.C., Y.H. Wang, Y.C. Chou, C.F. Chen, L.C. Lin, T.T. Chang, J.H. Tien and C.J. Chou. Evaluation of the anti-inflammatory activity of zhankuic acids isolated from the fruiting bodies of Antrodia camphorata. Planta Med. 70: 310–314, 2004.
    [22] Lu, M.C., M. El-Shazly, T.Y. Wu, Y.C. Du, T.T. Chang, C.F. Chen, Y.M. Hsu, K.H. Lai, C.P. Chiu, F.R. Chang and Y.C. Wu. Recent research and development of Antrodia cinnamomea. Pharmacol Therap. 139: 124–156, 2013.
    [23] Huang, C.H., Y.Y. Chang, C.W. Liu, W.Y. Kang, Y.L. Lin, H.C. Chang and Y.C. Chen. Fruiting body of Niuchangchih (Antrodia camphorata) protects livers against chronic alcohol consumption damage. J Agric Food Chem. 58: 3859–3866, 2010.
    [24] Lin, T. Y., S. C. Chien, Y. H. Kuo and S. Y. Wang. Distinguishing between R- and S-antcin C and their cytotoxicity. Nat Prod Comm. 7: 835–836, 2012.
    [25] Carter-Kent, C., L.M. Yerian, E.M. Brunt, P. Angulo, R. Kohli, S.C. Ling, S.A. Xanthakos, P.F. Whitington, P. Charatcharoenwitthaya, J. Yap, R. Lopez, A.J. McCullough and A.E. Feldstein. Nonalcoholic steatohepatitis in children: a multicenter clinicopathological study. Hepatology. 50: 1113-1120, 2009.
    [26] Yang, C.M., Y.J. Zhou, R.J. Wang and M.L. Hu. Anti-angiogenic effects and mechanisms of polysaccharides from Antrodia cinnamomea with different molecular weights. J Ethnopharmacol. 123: 407-412, 2009.
    [27] Lin, Y.W., J.H. Pan, R.H. Liu, Y.H. Kuo, L.Y. Sheen and B.H. Chiang. The 4-acetylantroquinonol B isolated from mycelium of Antrodia cinnamomea inhibits proliferation of hepatoma cells. J Sci Food & Agric. 90: 1739-1744, 2010.
    [28] Chu, Y.C., R.M. Yang, T.T. Chang and J.C. Chou. Fructification of Antrodia cinnamomea was strain dependent in malt extract media and involved specific gene expression. J Agric Food Chem. 58: 257-261, 2010.
    [29] Han, H.F., N. Nakamura, F. Zuo, A. Hirakawa, T. Yokozawa and M. Hattori. Protective effects of a neutral polysaccharide isolated from the mycelium of Antrodia cinnamomea on Propionibacterium acnes and lipopolysaccharide induced hepatic injury in mice. Chem Pharm Bull (Tokyo). 54: 496-500, 2006.
    [30] Yu, Y.L., I.H. Chen, K.Y. Shen, R.Y. Huang, W.R. Wang, C.J. Chou, T.T. Chang and C.L. Chu. A triterpenoid methyl antcinate K isolated from Antrodia cinnamomea promotes dendritic cell activation and Th2 differentiation. Eur J Immunol. 39:2482-2491, 2009.
    [31] Phuong do, T., C.M. Ma, M. Hattori and J.S. Jin. Inhibitory effects of antrodins A-E from Antrodia cinnamomea and their metabolites on hepatitis C virus protease. Phytotherapy Res. 23: 582-584, 2009.
    [32] Wu, M.D., M.J. Cheng, B.C. Wang, Y.J. Yech, J.T. Lai, Y.H. Kuo, G.F. Yuan and I.S. Chen. Maleimide and maleic anhydride derivatives from the mycelia of Antrodia cinnamomea and their nitric oxide inhibitory activities in macrophages. J Nat Prod. 71: 1258-1261, 2008.
    [33] Kuo, P.L., Y.L. Hsu, C.Y. Cho, L.T. Ng, Y.H. Kuo and C.C. Lin. Apoptotic effects of Antrodia cinnamomea fruiting bodies extract are mediated through calcium and calpain-dependent pathways in Hep 3B cells. Food Chem Toxicol. 44: 1316-1326, 2006
    [34] Yeh, C.H., H.S. Chiang and C.T. Chien. Hyaluronic acid ameliorates bladder hyperactivity via theinhibition of H2O2-enhanced purinergic and muscarinic signaling in the rat. Neurourol.Urodyn. 29: 765–770, 2010.
    [35] Li, P.C., C.F. Shaw, T.F. Kuo and C.T. Chien. Inducible nitric oxide synthase evoked nitric oxide counteracts capsaicin-induced airway smooth muscle contraction, but exacerbates plasma extravasation. Neurosci. Lett. 378: 117–122, 2005
    [36] Malakul, W., K. Ingkaninan, P. Sawasdee and O.L. Woodman. The ethanolic extract of Kaempferia parviflora reduces ischaemic injury in rat isolated hearts. J. Ethnopharmacol. 137: 184–191, 2011.
    [37] Yamanaka, N., O. Oda and S. Nagao. Nitric oxide released from zwitterionic polyamine/NO adducts inhibits Cu2þ-induced low density lipoprotein oxidation. FEBS Letters 398: 53–56, 1996.
    [38] Bau YS and Mo C F: The uses and culturing methods of Monascus purpureus Went. New Asia College Academy Annual 1975; 17:335-357.
    [39] Aniya Y, Yokomakura T, Yonamine M, Nagamine T and Nakanishi H: Protective effect of the mold Monascus anka against acetaminophen-induced liver toxicity in rats. The Japanese Journal of Pharmacology 1998; 78:79-82.
    [40] Ma J, Li Y, Ye Q, Li J, Hua Y, Ju D, Zhang D, Cooper R and Chang M: Constituents of red yeast rice, a traditional Chinese food and medicine. Journal of Agricultural and Food Chemistry 2000; 48: 5220-5225.
    [41] Tseng YH, Yang JH, Chang HL and Mau JL: Taste quality of monascal adlay. Journal of Agricultural and Food Chemistry 2004; 52: 297-2300.
    [42] Tseng YH, Yang JH, Chang HL, Lee YL and Mau JL: Antioxidant properties of methanolic extracts from monascal adlay. Food Chemistry 2006; 97:375-381.
    [43] Lavi R, Zhu XY, Chade AR, Lin J, Lerman A and Lerman LO: (2010). Simvastatin decreases endothelial progenitor cell apoptosis in the kidney of hypertensive hypercholesterolemic pigs. Arteriosclerosis,Thrombosis, and Vascular Biology 2010; 30: 976-983.
    [44] Kuo CC, Chiang W, Liu GP, Chien YL, Chang JY, Lee CK, Lo JM, Huang SL, Shih MC and Kuo YH: 2,2'-Diphenyl-picrylhydrazyl radical-scavenging active components from adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) hulls. Journal of Agricultural and Food Chemistry 2002; 50: 5850-5855.
    [45] Yao HT, Lin JH, Chiang MT, Chiang W, Luo MN, and Lii CK: (2011). Suppressive effect of the ethanolic extract of adlay bran on cytochrome p-450 enzymes in rat liver and lungs. Journal of Agricultural and Food Chemistry, 59, 4306-4314.
    [46] Lubos E, Handy DE and Loscalzo J: Role of oxidative stress and nitric oxide in atherothrombosis. Frontiers in Bioscience 2008; 13:5323-44.
    [47] Matsui T, Oda E, Higashimoto Y, Yamagishi S: Glyceraldehyde-derived pyridinium (GLAP) evokes oxidative stress and inflammatory and thrombogenic reactions in endothelial cells via the interaction with RAGE. Cardiovascular Diabetology 2015; 14:1.
    [48] Li PC, Tsai WH and Chien CT. Dietary Monascus adlay supplements facilitate suppression of cigarette smoke-induced pulmonary endoplasmic reticulum stress, autophagy, apoptosis and emphysema-related PLGF in the rat. Food Chemistry 2013 136:765-774.
    [49] Cirillo P, De Rosa S, Pacileo M, Gargiulo A, Angri V, Fiorentino I, Prevete N, Petrillo G, De Palma R, Leonardi A, De Paulis A, Chiariello M: Human urotensin II induces tissue factor and cellular adhesion molecules expression in human coronary endothelial cells: an emerging role for urotensin II in cardiovascular disease. Journal of Thrombosis and Haemostasis 2008 6:726-736.
    [50] Huang DW, Kuo YH, Lin FY, Lin YL and Chiang W: Effect of Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) Testa and its phenolic components on Cu2+-treated low-density lipoprotein (LDL) oxidation and lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages. Journal of Agricultural and Food Chemistry 2009; 57:2259-2266.
    [51] Chen HJ, Shih CK, Hsu HY and Chiang W: Mast cell-dependent allergic responses are inhibited by ethanolic extract of adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) testa. Journal of Agricultural and Food Chemistry 2010; 58: 2596-2601.
    [52] Chen HH, Chiang W, Chang JY, Chien YL, Lee CK, Liu KJ, Cheng YT, Chen TF, Kuo YH, Kuo CC: Antimutagenic constituents of Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf) with potential cancer chemopreventive activity. Journal of Agricultural and Food Chemistry 2011; 59: 6444-6452.
    [53] Ghanayem BI, Long PH, Ward SM, Chanas B, Nyska M, Nyska A. Hemolytic anemia, thrombosis, and infarction in male and female F344 rats following gavage exposure to 2-butoxyethanol. Experimental and Toxicologic Pathology 2001 53:97-105.
    [54] Chien CT, Lee PH, Chen CF, Ma MC, Lai MK and Hsu SM: De novo demonstration and co-localization of freeradical production and apoptosis formation in rat kidney subjected to ischemia/reperfusion. Journal of the American Society of Nephrology 2001; 12: 973-982.
    [55] Chien CT, Fan SC, Lin SC, Kuo CC, Yang CH, Yu TY, Lee SP, Cheng DY and Li PC: Glucagon-like peptide-1 receptor agonist activation ameliorates venous thrombosis-induced arteriovenous fistula failure in chronic kidney disease. Thrombosis and Haemostasis 2014; 112:1051-1064.
    [56] Chien CT, Fan SC, Lin SC, Kuo CC, Yang CH, Yu TY, Lee SP, Cheng DY, and Li PC. Glucagon-like peptide-1 receptor agonist activation ameliorates venous thrombosis-induced arteriovenous fistula failure in chronic kidney disease. Thrombosis and Haemostasis 2014 112:1051-1064.
    [57] Ampofo E, Müller I, Dahmke IN, Eichler H, Montenarh M, Menger MD, and Laschke MW. Role of protein kinase CK2 in the dynamic interaction of platelets, leukocytes and endothelial cells during thrombus formation. Thrombosis Research 2015 136:996-1006.
    [58] Huang Z, Zuo L, Zhang Z, Liu J, Chen J, Dong L, and Zhang J. 3,3'-Diindolylmethane decreases VCAM-1 expression and alleviates experimental colitis via a BRCA1-dependent antioxidant pathway. Free Radical Biolology and Medicine 2011 50:228-236.
    [59] Chien CT, Chang WT, Chen HW, Wang TD, Liou SY, Chen TJ, Chang YL, Lee YT and Hsu SM: Ascorbate supplement reduces oxidative stress in dyslipidemic patients undergoing apheresis. Arteriosclerosis, Thrombosis, and Vascular Biology 2004; 24:1111–1117.
    [60] Kurz KD, Main BW, Sandusky GE: Rat model of arterial thrombosis induced by ferric chloride. Thrombis Research 1990; 60:269-280.
    [61] Lee CM, Chien CT, Chang PY, Hsieh MY, Jui HY, Liau CS, Hsu SM and Lee YT : High-density lipoprotein antagonizes oxidized low-density lipoprotein by suppressing oxygen free-radical formation and preserving nitric oxide bioactivity. Atherosclerosis. 2005; 183:251-258.
    [62] Kuo DC, Hsu SP and Chien CT: Partially hydrolyzed guar gum supplement reduces high-fat diet increased blood lipids and oxidative stress and ameliorates FeCl3-induced acute arterial injury in hamsters. Journal of Biomedical Science 2009; 16:15-20.
    [63] Schäfer A, Schulz C, Fraccarollo D, Tas P, Leutke M, Eigenthaler M, Seidl S, Heider P, Ertl G, Massberg S and Bauersachs J: The CX3C chemokine fractalkine induces vascular dysfunction by generation of superoxide anions. Arteriosclerosis, Thrombosis, and Vascular Biology 2007; 27: 55-62.
    [64] Tedgui A and Mallat Z: Anti-inflammatory mechanisms in the vascular wall. Circulation Research 2001; 88:877-887.
    [65] Kaneider NC, Egger P, Dunzendorfer S, and Wiedermann CJ. Rho-GTPase-dependent platelet-neutrophil interaction affected by HMG-CoA reductase inhibition with altered adenosine nucleotide release and function. Arteriosclerosis, Thrombosis, and Vascular Biology 2002; 22:1029-1035.
    [66] Owens AP 3rd, Passam FH, Antoniak S, Marshall SM, McDaniel AL, Rudel L, Williams JC, Hubbard BK, Dutton JA, Wang J, Tobias PS, Curtiss LK, Daugherty A, Kirchhofer D, Luyendyk JP, Moriarty PM, Nagarajan S, Furie BC, Furie B, Johns DG, Temel RE, and Mackman N. Monocyte tissue factor-dependent activation of coagulation in hypercholesterolemic mice and monkeys is inhibited by simvastatin. Journal of Clinical Investigation 2012; 122:558-568.
    [67] Spadaccio C, De Marco F, Di Domenico F, Coccia R, Lusini M, Barbato R, Covino E, and Chello M. Simvastatin attenuates the endothelial pro-thrombotic shift in saphenous vein grafts induced by Advanced glycation endproducts. Thrombosis Research 2014; 133:418-425.

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