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研究生:賴彥勳
研究生(外文):Yen-Hsun Lai
論文名稱:蓮蓬萃取物應用於保肝護腎之研究
論文名稱(外文):The study of application of lotus seedpod extracts on hepatic and renal protection
指導教授:陳璟賢陳璟賢引用關係
學位類別:碩士
校院名稱:中山醫學大學
系所名稱:營養學系碩士班
學門:醫藥衛生學門
學類:營養學類
論文種類:學術論文
論文出版年:2017
畢業學年度:105
語文別:中文
論文頁數:147
中文關鍵詞:非酒精性脂肪肝疾病慢性腎臟疾病蓮蓬氧化壓力細胞凋亡纖維化
外文關鍵詞:non-alcoholic fatty liver diseasechronic kidney diseaselotus seedpod extractsoxidative stresscell apoptosisfibrosis
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蓮蓬(lotus seedpod)為傳統中藥材,研究顯示具有抗氧化、抗老化與抗發炎作用,本實驗室先前的研究顯示蓮蓬對於肝腎損傷可能具有改善效果,但是蓮蓬在保肝護腎作用上仍需進一步研究。在保肝細胞實驗中,透過油酸(oleic acid, OA)誘導人類肝細胞株HepG2細胞損傷,而蓮蓬萃取物(lotus seedpod extracts, LSE)與其主要功效成分表沒食子兒茶素(epigallocatechin, EGC)可以增加HepG2細胞存活率並減少細胞中脂肪堆積;此外oleic acid誘導氧化壓力與細胞凋亡的增加,在LSE或EGC的給予下,皆能降低氧化壓力與抑制細胞凋亡來減少肝細胞損傷,分子數據顯示LSE的抗凋亡作用可能通過線粒體途徑介導。在護腎動物實驗中,則透過10週連續餵食0.2% 腺嘌呤(adenine)誘導C57BL/6 小鼠產生腎損傷,並於第5週開始餵食1%與2% LSE直到第10週實驗結束。與誘導組相較之下,LSE能降低尿素氮(BUN)、肌酸酐(Creatinine, CRE)與發炎因子tumor necrosis factor-α (TNF-α)與interleukin 6 (IL-6)表現量,並且LSE可以增加腎臟總抗氧化能力與抗氧化酵素Glutathione peroxidase (GPx)、Glutathione reductase (GR)、catalase、Superoxide Dismutase (SOD) 活性並且減少脂質過氧化。另外LSE還能抑制腎臟纖維化及纖維化相關因子(TGF-β1、PAI-1、α-SMA、COL1A2)蛋白表現。研究結果顯示LSE具有潛力發展成為改善NAFLD與CKD的保健食品。
Lotus seedpod, which is rich in flavonoid, is one of the traditional Chinese herbal medicines. Previous studies have shown that lotus seedpod possess antioxidant, anti-aging, and anti-inflammatory activities. However, the hepatic and renal protective effects of lotus seedpod are still unknown. In this study, we examined the heptoprotective effect of lotus seedpod extracts (LSE) and its main components epigallocatechin (EGC) in vitro. Firstly, oleic acid (OA) is used to induce the phenotype of non-alcoholic fatty liver disease (NAFLD) in human hepatic HepG2 cells. LSE dose-dependently improved the OA-induced loss of viability and lipid accumulation of HepG2 cells. Furthermore, LSE and EGC showed potential in reducing OA-induced occurrence of apoptosis confirmed by morphological and biochemical features, including an increase in oxidative stress, apoptotic bodies formation and caspase-3 activation. Molecular data showed the anti-apoptotic effect of LSE might be mediated via mitochondrial pathway. On the other hand, to investigate the protective effect and molecular mechanism of LSE on adenine-induced chronic kidney disease (CKD) mice in vivo, C57BL/6JNar1 mice were treated with 0.2% adenine, an inducer of chronic kidney injury (CKD) for 4 weeks, and then treated LSE (1% or 2%) for another 6 weeks. After 10 weeks, mice serum and kidney of mice were collected for further studies. The results showed that serum levels of blood urea nitrogen (BUN) and creatinine (CRE) in adenine-treated mice were increased as compared with control group. 1% and 2% LSE could decrease both levels when compared with the adenine alone group. In inflammatory cytokines analysis, we found that serum level of tumor necrosis factor (TNF)- α was significant increased after adenine induction, while 2% of LSE could reduce the serum level. In determination of oxidative stress in kidney, adenine could increase thiobarbituric acid relative substances (TBARS) level, while LSE treatments could significantly decrease oxidative stress level in mice. In measurement of antioxidant enzyme activity, adenine also decrease glutathione peroxidase (GPx) activity, glutathione (GSH) level, glutathione reductase (GR), catalase and superoxide dismutase (SOD) activity in kidney tissues, while LSE treatments could increase these enzyme activities. Furthermore, adenine-induced renal morphology fibrosis and fibrosis related proteins (TGF-β1, PAI-1, α-SMA, COL1A2) were decreased after treated with LSE. Our data imply that LSE potentially could be developed as an anti-NAFLD and anti-CKD agents in future.
目錄

目錄 I
圖表目錄 VII
中文摘要 IX
Abstract XI
縮寫檢索表 XIII
第一章、緒論 1
第二章、文獻探討 2
2.1 肝臟生理與功能 2
2.1.1 肝臟介紹 2
2.1.2 肝臟生理功能 4
2.1.3 肝損傷及肝臟疾病 6
2.2 非酒精性脂肪肝疾病(Non-alcoholic Fatty Liver Disease, NAFLD) 9
2.2.1 介紹 9
2.2.3 發生原因 10
2.3 油酸(Oleic acid, OA) 15
2.3.1 油酸介紹 15
2.3.2 機轉 16
2.4 蓮蓬(Lotus seedpod) 17
2.4.1 蓮蓬介紹 17
2.4.2 蓮蓬成分與功效 18
2.4.3 表沒食子兒茶素(Epigallocatechin, EGC) 19
2.5 細胞凋亡(Apoptosis) 20
2.5.1 細胞凋亡介紹 20
2.5.2 外在路徑(Extrinsic pathway) 20
2.5.3 內在路徑(Intrinsic pathway) 21
2.6 細胞自噬(Autophagy) 22
2.6.1 細胞自噬介紹 22
2.6.2 自噬機轉 23
2.7 腎臟生理與功能 25
2.7.1 腎臟介紹 25
2.7.2 腎臟生理功能 27
2.8 慢性腎臟疾病 (Chronic kidney disease, CKD) 31
2.8.1 慢性腎臟疾病介紹 31
2.8.2 慢性腎臟疾病惡化原因 33
2.9 腺嘌呤(Adenine) 34
2.9.1 腺嘌呤介紹 34
2.9.2 腺嘌呤誘導CKD之機轉 35
2.10 腎臟纖維化(Renal fibrosis) 36
2.10.1 纖維化介紹 36
2.10.1 纖維化機轉 37
第三章、實驗架構與流程 39
第四章、材料與方法 40
4.1 實驗儀器與藥品試劑 40
4.1.1 實驗儀器與設備 40
4.1.2 實驗藥品與試劑 41
4.1.3 油酸(Oleic acid)配置 44
4.1.4 蓮蓬萃取物(Lotus seedpod extracts, LSE)配製 44
4.1.5 表沒食子兒茶素(Epigallocatechin, EGC)製備 45
4.2 實驗細胞株培養 45
4.2.1 細胞株來源 45
4.2.2 培養基與緩衝液配置 45
4.2.3 解凍細胞 46
4.2.4 繼代培養 47
4.2.5 細胞計數 47
4.2.6 冷凍細胞 48
4.3 細胞存活試驗(cell viability) 48
4.4 油紅(oil red o)染色 49
4.5 尼羅紅(Nile red)染色 50
4.6 活性氧物質(ROS)生成分析(DCFDA staining) 50
4.7 細胞自噬分析(acidic vesicular organelles stain, AVO stain) 51
4.8 蛋白質萃取與定量 52
4.9 西方墨點法(western blotting) 53
4.10 細胞凋亡分析(DAPI stain) 56
4.11 細胞凋亡分析-雙染色法(Annexin V/7-AAD stain) 56
4.12 粒線體膜電位分析(JC1 stain-Mitochondrial Membrane Potential Assay) 57
4.13 粒線體分離(Mitochondrial isolation) 58
4.14 實驗動物 59
4.14.1 實驗動物 59
4.14.2 實驗設計與流程 59
4.14.3 血清收集 60
4.14.4 臟器收集與均質液製作 60
4.15 血清生化值分析 60
4.16 促發炎細胞因子(Proinflammatory cytokine)測定 61
4.17 組織抗氧化能力分析 62
4.17.1 麩胱甘肽過氧化物酶(Glutathione peroxidase, GPx)活性測定 62
4.17.2 麩胱甘肽還原酶(Glutathione reductase, GRd)活性測定 63
4.17.3 麩胱甘肽(Glutathione, GSH)含量測定 63
4.17.4 過氧化氫酶 (catalase)活性測定 64
4.17.5 超氧化物歧化酶(Superoxide Dismutase, SOD)活性測定 65
4.17.6 總抗氧化能力測定(Trolox equivalent antioxidant capacity) 66
4.17.7 脂質過氧化測定(Thiobarbituric acid reactive substances) 66
4.18 蘇木素-伊紅染色(hematoxylin and eosin stain, H&E stain) 67
4.19 膠原纖維染色(Masson''s trichrome stain) 68
4.20 統計方法 69
第五章、實驗結果 70
5.1 探討不同濃度OA 與LSE合併處理下對於HepG2細胞存活率影響 70
5.2 探討LSE對OA誘導的脂肪堆積的影響 70
5.3 探討LSE對OA誘導的ROS增加的影響 71
5.4 探討LSE對OA誘導的自噬(autophagy)的影響 72
5.5 探討LSE對OA誘導的自噬蛋白表現之影響 73
5.6 探討LSE對OA誘導的細胞凋亡(apoptosis)的影響 74
5.7 探討LSE對OA誘導的粒線體膜電位改變的影響 74
5.8 探討LSE對OA誘導的內在路徑凋亡相關蛋白的影響 75
5.9 探討LSE對OA誘導的凋亡蛋白酶(caspase)蛋白表現之影響 76
5.10 探討LSE對腺嘌呤誘導的小鼠腎臟外觀與重量的影響 77
5.11 探討LSE對腺嘌呤誘導的小鼠血清生化數值的影響 78
5.12 探討LSE對腺嘌呤誘導的小鼠發炎因子的影響 79
5.13 探討LSE對腺嘌呤誘導的C57BL/6 mice抗氧化酵素與脂質過氧化的影響 80
5.14 探討LSE對腺嘌呤誘導的小鼠腎臟組織病理切片的影響 81
5.15 探討LSE對腺嘌呤誘導的小鼠腎臟纖維化相關蛋白的影響 82
第六章、討論 84
6.1 LSE對於OA誘導的脂肪性肝損傷的保護作用 84
6.2 LSE對於腺嘌呤誘導的晚期CKD的保護作用 91
第七章、結論 95
第八章、參考文獻 96

圖表目錄
附圖一:肝小葉結構[4] 3
附圖二:NAFLD/NASH的疾病進程[25] 10
附圖三:肝臟脂肪堆積[28] 12
附圖四:氧化壓力與NASH進展[30] 13
附圖五:油酸結構[41] 16
附圖六:外在與內在路徑的示意圖[89] 22
附圖七:自噬小體的形成[92] 24
附圖八:腎臟位置與結構[94] 26
附圖九:腎元結構[96] 27
附表一:KDIGO指南[111] 31
附表二:依據GFR的CKD分級[111] 32
附表三:GFR與白蛋白尿與ESRD風險的相關性[112] 32
附圖十:腺嘌呤結構[114] 34
附圖十一:腺嘌呤代謝[115] 35
附圖十二:纖維化機轉[124] 38
附表四:10%下層膠與上層膠配方 (2片) 54


Table1. Effect of LSE on serum biochemical values of mice induced by adenine. 107
Figure 1. Effects of OA, LSE, EGC in combination on HepG2 cell viabilty. 108
Figure 2. Effects of LSE or EGC on the OA-induced intracellular lipid accumulation. 110
Figure 3. Effects of LSE or EGC on OA-induced an increase in ROS content in HepG2 cells. 111
Figure 4. Effects of LSE or EGC on OA-induced HepG2 cell autophagy. 114
Figure 5. Effects of LSE or EGC on classⅠPI3K/Akt/mTOR signal OA-treated HepG2 cells. 115
Figure 6. Effect of LSE or EGC on expression of autophagy-related proteins in OA-treated HepG2 cells. 116
Figure 7. Effects of LSE or EGC on OA-induced HepG2 cell apoptosis. 118
Figure 8. Effects of LSE or EGC on OA-induced mitochondrial membrane depolarization in HepG2 cells. 119
Figure 9. Effects of LSE or EGC on expression of bcl-2 family proteins in OA-treated HepG2 cells. 120
Figure 10. Effects of LSE or EGC on expression of cytochrome c proteins in OA-treated HepG2 cells. 121
Figure 11. Effects of LSE or EGC on expression of PARP-1 protein in OA-treated HepG2 cells. 123
Figure 12. Overview of pathways for LSE inhibited OA-induced liver injury 124
Figure 13. Effect of LSE on serum level of cytokines in mice induced by adenine. 125
Figure 14. Effect of LSE on serum antioxidant enzymes level in mice induced by adenine. 127
Figure 15. Effect of LSE on kidney histopathology in mice induced by adenine. 129
Figure 16. Effect of LSE on expression of fibrosis protein in mice induced by adenine. 130
Figure 17. Overview of pathways for LSE inhibited adenine-induced kindey injury 131
1.Abdel-Misih, S.R.Z. and M. Bloomston, Liver Anatomy. The Surgical clinics of North America, 2010. 90(4): p. 643-653.
2.Feldman, M., L.S. Friedman, and L.J. Brandt, Sleisenger and Fordtran’s Gastrointestinal and Liver Disease PATHOPHYSIOLOGY•DIAGNOSIS•MANAGEMENT 10th Edition. 2016.
3.Rutkauskas, S., V. Gedrimas, J. Pundzius, G. Barauskas, and A. Basevicius, Clinical and anatomical basis for the classification of the structural parts of liver. Medicina (Kaunas), 2006. 42(2): p. 98-106.
4.Péter, B. and E. Péter. Transzdifferenciáció és regeneratív medicina. 2011.
5.Xie, G., X. Wang, L. Wang, L. Wang, R.D. Atkinson, et al., Role of differentiation of liver sinusoidal endothelial cells in progression and regression of hepatic fibrosis in rats. Gastroenterology, 2012. 142(4): p. 918-927.e6.
6.Benedetti, A., C. Bassotti, K. Rapino, L. Marucci, and A.M. Jezequel, A morphometric study of the epithelium lining the rat intrahepatic biliary tree. J Hepatol, 1996. 24(3): p. 335-42.
7.Smith, J.P. and T.E. Solomon, Cholecystokinin and pancreatic cancer: the chicken or the egg? American Journal of Physiology - Gastrointestinal and Liver Physiology, 2014. 306(2): p. G91-G101.
8.Rui, L., Energy Metabolism in the Liver. Comprehensive Physiology, 2014. 4(1): p. 177-197.
9.Font-Burgada, J., S. Shalapour, S. Ramaswamy, B. Hsueh, D. Rossell, et al., Hybrid Periportal Hepatocytes Regenerate the Injured Liver without Giving Rise to Cancer. Cell, 2015. 162(4): p. 766-79.
10.Kandel, S.E. and J.N. Lampe, Role of Protein–Protein Interactions in Cytochrome P450-Mediated Drug Metabolism and Toxicity. Chemical Research in Toxicology, 2014. 27(9): p. 1474-1486.
11.Johnson, E.F., J.P. Connick, J.R. Reed, W.L. Backes, M.C. Desai, et al., Correlating Structure and Function of Drug-Metabolizing Enzymes: Progress and Ongoing Challenges. Drug Metabolism and Disposition, 2014. 42(1): p. 9-22.
12.Bogdanos, D.P., B. Gao, and M.E. Gershwin, Liver Immunology. Comprehensive Physiology, 2013. 3(2): p. 567-598.
13.Invernizzi, P., Liver auto-immunology: The paradox of autoimmunity in a tolerogenic organ. Journal of Autoimmunity, 2013. 46: p. 1-6.
14.衛生福利部, 民國105年死因結果摘要表. 民國106年.
15.Kew, M.C., Hepatitis viruses (other than hepatitis B and C viruses) as causes of hepatocellular carcinoma: an update. J Viral Hepat, 2013. 20(3): p. 149-57.
16.Zhang, N., Y. Hu, C. Ding, W. Zeng, W. Shan, et al., Salvianolic acid B protects against chronic alcoholic liver injury via SIRT1-mediated inhibition of CRP and ChREBP in rats. Toxicology Letters, 2017. 267: p. 1-10.
17.Theile, D., W.E. Haefeli, H.K. Seitz, G. Millonig, J. Weiss, et al., Association of liver stiffness with hepatic expression of pharmacokinetically important genes in alcoholic liver disease. Alcohol Clin Exp Res, 2013. 37 Suppl 1: p. E17-22.
18.Katsagoni, C.N., M. Georgoulis, G.V. Papatheodoridis, D.B. Panagiotakos, and M.D. Kontogianni, Effects of lifestyle interventions on clinical characteristics of patients with non-alcoholic fatty liver disease: A meta-analysis. Metabolism, 2017. 68: p. 119-132.
19.Day, C.P. and O.F. James, Steatohepatitis: a tale of two "hits"? Gastroenterology, 1998. 114(4): p. 842-5.
20.Milić, S., D. Lulić, and D. Štimac, Non-alcoholic fatty liver disease and obesity: Biochemical, metabolic and clinical presentations. World Journal of Gastroenterology : WJG, 2014. 20(28): p. 9330-9337.
21.Cholankeril, G., R. Patel, S. Khurana, and S.K. Satapathy, Hepatocellular carcinoma in non-alcoholic steatohepatitis: Current knowledge and implications for management. World J Hepatol, 2017. 9(11): p. 533-543.
22.Singh, S., G.N. Kuftinec, and S. Sarkar, Non-alcoholic Fatty Liver Disease in South Asians: A Review of the Literature. Journal of Clinical and Translational Hepatology, 2017. 5(1): p. 76-81.
23.Hsu, C.S. and J.H. Kao, Non-alcoholic fatty liver disease: an emerging liver disease in Taiwan. J Formos Med Assoc, 2012. 111(10): p. 527-35.
24.Ota, T., T. Takamura, S. Kurita, N. Matsuzawa, Y. Kita, et al., Insulin Resistance Accelerates a Dietary Rat Model of Nonalcoholic Steatohepatitis. Gastroenterology, 2007. 132(1): p. 282-293.
25.Kitade, H., G. Chen, Y. Ni, and T. Ota, Nonalcoholic Fatty Liver Disease and Insulin Resistance: New Insights and Potential New Treatments. Nutrients, 2017. 9(4): p. 387.
26.Dongiovanni, P., B. Donati, R. Fares, R. Lombardi, R.M. Mancina, et al., PNPLA3 I148M polymorphism and progressive liver disease. World Journal of Gastroenterology : WJG, 2013. 19(41): p. 6969-6978.
27.Postic, C. and J. Girard, Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice. The Journal of Clinical Investigation, 2008. 118(3): p. 829-838.
28.Browning, J.D. and J.D. Horton, Molecular mediators of hepatic steatosis and liver injury. Journal of Clinical Investigation, 2004. 114(2): p. 147-152.
29.Koutsari, C. and M.D. Jensen, Thematic review series: patient-oriented research. Free fatty acid metabolism in human obesity. J Lipid Res, 2006. 47(8): p. 1643-50.
30.Basaranoglu, M., G. Basaranoglu, and H. Sentürk, From fatty liver to fibrosis: A tale of “second hit”. World Journal of Gastroenterology : WJG, 2013. 19(8): p. 1158-1165.
31.Robertson, G., I. Leclercq, and G.C. Farrell, Nonalcoholic steatosis and steatohepatitis. II. Cytochrome P-450 enzymes and oxidative stress. Am J Physiol Gastrointest Liver Physiol, 2001. 281(5): p. G1135-9.
32.Caldwell, S.H., R.H. Swerdlow, E.M. Khan, J.C. Iezzoni, E.E. Hespenheide, et al., Mitochondrial abnormalities in non-alcoholic steatohepatitis. Journal of Hepatology, 1999. 31(3): p. 430-434.
33.Nassir, F. and J.A. Ibdah, Role of Mitochondria in Nonalcoholic Fatty Liver Disease. International Journal of Molecular Sciences, 2014. 15(5): p. 8713-8742.
34.Hensley, K., Y. Kotake, H. Sang, Q.N. Pye, G.L. Wallis, et al., Dietary choline restriction causes complex I dysfunction and increased H(2)O(2) generation in liver mitochondria. Carcinogenesis, 2000. 21(5): p. 983-9.
35.Feldstein, A.E., N.W. Werneburg, A. Canbay, M.E. Guicciardi, S.F. Bronk, et al., Free fatty acids promote hepatic lipotoxicity by stimulating TNF-alpha expression via a lysosomal pathway. Hepatology, 2004. 40(1): p. 185-94.
36.Dinu, M., G. Pagliai, A. Casini, and F. Sofi, Mediterranean diet and multiple health outcomes: an umbrella review of meta-analyses of observational studies and randomised trials. Eur J Clin Nutr, 2017.
37.Kontogianni, M.D., N. Tileli, A. Margariti, M. Georgoulis, M. Deutsch, et al., Adherence to the Mediterranean diet is associated with the severity of non-alcoholic fatty liver disease. Clinical Nutrition, 2014. 33(4): p. 678-683.
38.Gelli, C., M. Tarocchi, L. Abenavoli, L. Di Renzo, A. Galli, et al., Effect of a counseling-supported treatment with the Mediterranean diet and physical activity on the severity of the non-alcoholic fatty liver disease. World Journal of Gastroenterology, 2017. 23(17): p. 3150-3162.
39.Lassailly, G., R. Caiazzo, F. Pattou, and P. Mathurin, Perspectives on Treatment for Nonalcoholic Steatohepatitis. Gastroenterology, 2016. 150(8): p. 1835-1848.
40.Oseini, A.M. and A.J. Sanyal, Therapies in non-alcoholic steatohepatitis (NASH). Liver Int, 2017. 37 Suppl 1: p. 97-103.
41.Oleic Acid. 2016.
42.Ricchi, M., M.R. Odoardi, L. Carulli, C. Anzivino, S. Ballestri, et al., Differential effect of oleic and palmitic acid on lipid accumulation and apoptosis in cultured hepatocytes. J Gastroenterol Hepatol, 2009. 24(5): p. 830-40.
43.Liao, C.C., T.T. Ou, H.P. Huang, and C.J. Wang, The inhibition of oleic acid induced hepatic lipogenesis and the promotion of lipolysis by caffeic acid via up-regulation of AMP-activated kinase. J Sci Food Agric, 2014. 94(6): p. 1154-62.
44.Chang, J.J., M.J. Hsu, H.P. Huang, D.J. Chung, Y.C. Chang, et al., Mulberry anthocyanins inhibit oleic acid induced lipid accumulation by reduction of lipogenesis and promotion of hepatic lipid clearance. J Agric Food Chem, 2013. 61(25): p. 6069-76.
45.Gómez-Lechón, M.J., M.T. Donato, A. Martínez-Romero, N. Jiménez, J.V. Castell, et al., A human hepatocellular in vitro model to investigate steatosis. Chemico-Biological Interactions, 2007. 165(2): p. 106-116.
46.Park, E.-J., A.Y. Lee, S.-H. Chang, K.-N. Yu, J.-H. Kim, et al., Role of p53 in the cellular response following oleic acid accumulation in Chang liver cells. Toxicology Letters, 2014. 224(1): p. 114-120.
47.Wu, C.H., M.C. Lin, H.C. Wang, M.Y. Yang, M.J. Jou, et al., Rutin inhibits oleic acid induced lipid accumulation via reducing lipogenesis and oxidative stress in hepatocarcinoma cells. J Food Sci, 2011. 76(2): p. T65-72.
48.Lee, J.S., S. Shukla, J.-A. Kim, and M. Kim, Anti-Angiogenic Effect of Nelumbo nucifera Leaf Extracts in Human Umbilical Vein Endothelial Cells with Antioxidant Potential. PLoS ONE, 2015. 10(2): p. e0118552.
49.Paudel, K.R. and N. Panth, Phytochemical Profile and Biological Activity of Nelumbo nucifera. Evidence-based Complementary and Alternative Medicine : eCAM, 2015. 2015: p. 789124.
50.享綠文化事業有限公司, 臺南縣蓮花產業文化資訊館導覽手冊. 2001.
51.李時珍, 本草綱目. 1596.
52.Liao, C.-H. and J.-Y. Lin, Lotus (Nelumbo nucifera Gaertn) plumule polysaccharide ameliorates pancreatic islets loss and serum lipid profiles in non-obese diabetic mice. Food and Chemical Toxicology, 2013. 58: p. 416-422.
53.Ohkoshi, E., H. Miyazaki, K. Shindo, H. Watanabe, A. Yoshida, et al., Constituents from the leaves of Nelumbo nucifera stimulate lipolysis in the white adipose tissue of mice. Planta Med, 2007. 73(12): p. 1255-9.
54.Zhu, M.Z., W. Wu, L.L. Jiao, P.F. Yang, and M.Q. Guo, Analysis of Flavonoids in Lotus (Nelumbo nucifera) Leaves and Their Antioxidant Activity Using Macroporous Resin Chromatography Coupled with LC-MS/MS and Antioxidant Biochemical Assays. Molecules, 2015. 20(6): p. 10553-65.
55.Lee, B., M. Kwon, J.S. Choi, H.O. Jeong, H.Y. Chung, et al., Kaempferol Isolated from Nelumbo nucifera Inhibits Lipid Accumulation and Increases Fatty Acid Oxidation Signaling in Adipocytes. J Med Food, 2015. 18(12): p. 1363-70.
56.Tang, C.C., W.L. Lin, Y.J. Lee, Y.C. Tang, and C.J. Wang, Polyphenol-rich extract of Nelumbo nucifera leaves inhibits alcohol-induced steatohepatitis via reducing hepatic lipid accumulation and anti-inflammation in C57BL/6J mice. Food Funct, 2014. 5(4): p. 678-87.
57.Liu, C.M., C.L. Kao, H.M. Wu, W.J. Li, C.T. Huang, et al., Antioxidant and anticancer aporphine alkaloids from the leaves of Nelumbo nucifera Gaertn. cv. Rosa-plena. Molecules, 2014. 19(11): p. 17829-38.
58.Lin, R.-J., M.-H. Wu, Y.-H. Ma, L.-Y. Chung, C.-Y. Chen, et al., Anthelmintic Activities of Aporphine from Nelumbo nucifera Gaertn. cv. Rosa-plena against Hymenolepis nana. International Journal of Molecular Sciences, 2014. 15(3): p. 3624-3639.
59.Liu, S., D. Li, B. Huang, Y. Chen, X. Lu, et al., Inhibition of pancreatic lipase, α-glucosidase, α-amylase, and hypolipidemic effects of the total flavonoids from Nelumbo nucifera leaves. Journal of Ethnopharmacology, 2013. 149(1): p. 263-269.
60.Yang, W.M., K.J. Shim, M.J. Choi, S.Y. Park, B.-J. Choi, et al., Novel effects of Nelumbo nucifera rhizome extract on memory and neurogenesis in the dentate gyrus of the rat hippocampus. Neuroscience Letters, 2008. 443(2): p. 104-107.
61.Ling, Z.Q., B.J. Xie, and E.L. Yang, Isolation, characterization, and determination of antioxidative activity of oligomeric procyanidins from the seedpod of Nelumbo nucifera Gaertn. J Agric Food Chem, 2005. 53(7): p. 2441-5.
62.Xiao, J.S., B.J. Xie, Y.P. Cao, H. Wu, Z.D. Sun, et al., Characterization of oligomeric procyanidins and identification of quercetin glucuronide from lotus ( Nelumbo nucifera Gaertn.) seedpod. J Agric Food Chem, 2012. 60(11): p. 2825-9.
63.林韋帆, Analysis Of Polyphenols In Hibiscus sabdariffa, Nelumbinis Receptaculum And Graptopelaum Paraguayense By HPLC. 2012.
64.Luo, X., M. Chen, Y. Duan, W. Duan, H. Zhang, et al., Chemoprotective action of lotus seedpod procyanidins on oxidative stress in mice induced by extremely low-frequency electromagnetic field exposure. Biomedicine & Pharmacotherapy, 2016. 82: p. 640-648.
65.Yin, C., X. Luo, Y. Duan, W. Duan, H. Zhang, et al., Neuroprotective effects of lotus seedpod procyanidins on extremely low frequency electromagnetic field-induced neurotoxicity in primary cultured hippocampal neurons. Biomedicine & Pharmacotherapy, 2016. 82: p. 628-639.
66.Duan, Y., H. Zhang, B. Xie, Y. Yan, J. Li, et al., Whole body radioprotective activity of an acetone–water extract from the seedpod of Nelumbo nucifera Gaertn. seedpod. Food and Chemical Toxicology, 2010. 48(12): p. 3374-3384.
67.Zhang, H., Y. Cheng, X. Luo, and Y. Duan, Protective effect of procyanidins extracted from the lotus seedpod on immune function injury induced by extremely low frequency electromagnetic field. Biomedicine & Pharmacotherapy, 2016. 82: p. 364-372.
68.Wu, Q., S. Li, X. Li, Y. Sui, Y. Yang, et al., Inhibition of Advanced Glycation Endproduct Formation by Lotus Seedpod Oligomeric Procyanidins through RAGE-MAPK Signaling and NF-kappaB Activation in High-Fat-Diet Rats. J Agric Food Chem, 2015. 63(31): p. 6989-98.
69.Wu, Q., H. Chen, Z. Lv, S. Li, B. Hu, et al., Oligomeric procyanidins of lotus seedpod inhibits the formation of advanced glycation end-products by scavenging reactive carbonyls. Food Chemistry, 2013. 138(2–3): p. 1493-1502.
70.Wu, Q., S. Li, X. Li, X. Fu, Y. Sui, et al., A Significant Inhibitory Effect on Advanced Glycation End Product Formation by Catechin as the Major Metabolite of Lotus Seedpod Oligomeric Procyanidins. Nutrients, 2014. 6(8): p. 3230-3244.
71.Mengyan, Z., Protection of Lotus Seedpod Proanthocyanidins on Organs and Tissues under High-intensity Excercise. The Open Biomedical Engineering Journal, 2015. 9: p. 296-300.
72.Duan, Y., H. Xu, X. Luo, H. Zhang, Y. He, et al., Procyanidins from Nelumbo nucifera Gaertn. Seedpod induce autophagy mediated by reactive oxygen species generation in human hepatoma G2 cells. Biomedicine & Pharmacotherapy, 2016. 79: p. 135-152.
73.蔡佩旻, The effect of lotus seedpod extracts on lipopolysaccharide-induced liver inflammation in vivo and in vitro. 2015.
74.黃筱尹, In vitro and in vivo protective effect of Lotus seedpod extract against acetaminophen-induced liver injury. 2016.
75.黃登琪, Lotus seedpod extracts improved metabolic syndrome and reduced lipid accumulation in hepatocytes. 2015.
76.李庭暄, The study of inhibitory effect of lotus seedpod extract on melanogenesis. 2014.
77.王廷軒, Beta cell protective effects of lotus seedpod extracts against oxidative injury in vitro and in vivo. 2015.
78.Singh, B.N., S. Shankar, and R.K. Srivastava, Green tea catechin, epigallocatechin-3-gallate (EGCG): mechanisms, perspectives and clinical applications. Biochemical pharmacology, 2011. 82(12): p. 1807-1821.
79.Yang, C. and H. Wang, Cancer Preventive Activities of Tea Catechins. Molecules, 2016. 21(12): p. 1679.
80.Chen, X.Q., X.B. Wang, R.F. Guan, J. Tu, Z.H. Gong, et al., Blood anticoagulation and antiplatelet activity of green tea (-)-epigallocatechin (EGC) in mice. Food Funct, 2013. 4(10): p. 1521-5.
81.Ravindranath, M.H., V. Ramasamy, S. Moon, C. Ruiz, and S. Muthugounder, Differential Growth Suppression of Human Melanoma Cells by Tea (Camellia sinensis) Epicatechins (ECG, EGC and EGCG). Evidence-based Complementary and Alternative Medicine : eCAM, 2009. 6(4): p. 523-530.
82.Lin, S.-C., W.-C. Li, J.-W. Shih, K.-F. Hong, Y.-R. Pan, et al., The tea polyphenols EGCG and EGC repress mRNA expression of human telomerase reverse transcriptase (hTERT) in carcinoma cells. Cancer Letters, 2006. 236(1): p. 80-88.
83.Unno, K., A. Hara, A. Nakagawa, K. Iguchi, M. Ohshio, et al., Anti-stress effects of drinking green tea with lowered caffeine and enriched theanine, epigallocatechin and arginine on psychosocial stress induced adrenal hypertrophy in mice. Phytomedicine, 2016. 23(12): p. 1365-1374.
84.Hu, J., D. Zhou, and Y. Chen, Preparation and antioxidant activity of green tea extract enriched in epigallocatechin (EGC) and epigallocatechin gallate (EGCG). J Agric Food Chem, 2009. 57(4): p. 1349-53.
85.Ogborne, R.M., S.A. Rushworth, and M.A. O’Connell, Epigallocatechin activates haem oxygenase-1 expression via protein kinase Cδ and Nrf2. Biochemical and Biophysical Research Communications, 2008. 373(4): p. 584-588.
86.Kim, H.-S., M.J. Quon, and J.-a. Kim, New insights into the mechanisms of polyphenols beyond antioxidant properties; lessons from the green tea polyphenol, epigallocatechin 3-gallate(). Redox Biology, 2014. 2: p. 187-195.
87.Obara, K., K. Ukai, and T. Ishikawa, Mechanism of potentiation by tea epigallocatechin of contraction in porcine coronary artery: The role of protein kinase Cδ-mediated CPI-17 phosphorylation. European Journal of Pharmacology, 2011. 668(3): p. 414-418.
88.Kimball, J.W., Kimball''s Biology Pages : Apoptosis. 2014.
89.Guo, H., L. Chen, H. Cui, X. Peng, J. Fang, et al., Research Advances on Pathways of Nickel-Induced Apoptosis. International Journal of Molecular Sciences, 2016. 17(1): p. 10.
90.Elmore, S., Apoptosis: A Review of Programmed Cell Death. Toxicologic pathology, 2007. 35(4): p. 495-516.
91.Rashid, H.-O., R.K. Yadav, H.-R. Kim, and H.-J. Chae, ER stress: Autophagy induction, inhibition and selection. Autophagy, 2015. 11(11): p. 1956-1977.
92.Xie, Y., R. Kang, X. Sun, M. Zhong, J. Huang, et al., Posttranslational modification of autophagy-related proteins in macroautophagy. Autophagy, 2015. 11(1): p. 28-45.
93.Alan J. Wein, M., PhD (Hon), L.R.K. FACS, MD, A.W.P. MBA, MD, PhD, and M. Craig A. Peters, Campbell-Walsh Urology. 2012.
94.J. Gordon Betts, T.J.C., et al, OpenStax College, Anatomy and Physiology. OpenStax CNX. . 2017.
95.de Boer, A., J.M. Hoogduin, P.J. Blankestijn, X. Li, P.R. Luijten, et al., 7 T renal MRI: challenges and promises. Magma (New York, N.y.), 2016. 29: p. 417-433.
96.Mullins, L.J., B.R. Conway, R.I. Menzies, L. Denby, and J.J. Mullins, Renal disease pathophysiology and treatment: contributions from the rat. Disease Models & Mechanisms, 2016. 9(12): p. 1419-1433.
97.Cheng, H. and R.C. Harris, The glomerulus- a view from the outside- the podocyte. The international journal of biochemistry & cell biology, 2010. 42(9): p. 1380-1387.
98.Zhuo, J.L. and X.C. Li, Proximal Nephron. Comprehensive Physiology, 2013. 3(3): p. 1079-1123.
99.Dantzler, W.H., A.T. Layton, H.E. Layton, and T.L. Pannabecker, Urine-Concentrating Mechanism in the Inner Medulla: Function of the Thin Limbs of the Loops of Henle. Clinical Journal of the American Society of Nephrology : CJASN, 2014. 9(10): p. 1781-1789.
100.Subramanya, A.R. and D.H. Ellison, Distal Convoluted Tubule. Clinical Journal of the American Society of Nephrology : CJASN, 2014. 9(12): p. 2147-2163.
101.Staruschenko, A., Regulation of transport in the connecting tubule and cortical collecting duct. Comprehensive Physiology, 2012. 2: p. 1541-1584.
102.Sparks, M.A., S.D. Crowley, S.B. Gurley, M. Mirotsou, and T.M. Coffman, Classical Renin-Angiotensin System in Kidney Physiology. Comprehensive Physiology, 2014. 4(3): p. 1201-1228.
103.Sequeira-Lopez, M.L.S., V.K. Nagalakshmi, M. Li, C.D. Sigmund, and R.A. Gomez, Vascular versus tubular renin: role in kidney development. American Journal of Physiology - Regulatory, Integrative and Comparative Physiology, 2015. 309(6): p. R650-R657.
104.Adams, J.S. and M. Hewison, Update in Vitamin D. The Journal of Clinical Endocrinology and Metabolism, 2010. 95(2): p. 471-478.
105.Prasad, N. and D. Bhadauria, Renal phosphate handling: Physiology. Indian Journal of Endocrinology and Metabolism, 2013. 17(4): p. 620-627.
106.Blaine, J., M. Chonchol, and M. Levi, Renal Control of Calcium, Phosphate, and Magnesium Homeostasis. Clinical Journal of the American Society of Nephrology : CJASN, 2015. 10(7): p. 1257-1272.
107.Noguchi, C.T., L. Wang, H.M. Rogers, R. Teng, and Y. Jia, Survival and proliferative roles of erythropoietin beyond the erythroid lineage. Expert reviews in molecular medicine, 2008. 10: p. e36-e36.
108.Arcasoy, M.O., Non-erythroid effects of erythropoietin. Haematologica, 2010. 95(11): p. 1803-1805.
109.Couser, W.G., G. Remuzzi, S. Mendis, and M. Tonelli, The contribution of chronic kidney disease to the global burden of major noncommunicable diseases. Kidney International, 2011. 80(12): p. 1258-1270.
110.吳寬墩., 邱淑媞., 林裕峰., 郭耿南., and 許銘能., 台灣慢性腎臟病臨床診療指引. 2015.
111.National Guideline, C., KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. 2013.
112.Fraser, S.D.S. and T. Blakeman, Chronic kidney disease: identification and management in primary care. Pragmatic and Observational Research, 2016. 7: p. 21-32.
113.Hallan, S.I., K. Matsushita, Y. Sang, B.K. Mahmoodi, C. Black, et al., Age and the Association of Kidney Measures with Mortality and End-Stage Renal Disease. JAMA : the journal of the American Medical Association, 2012. 308(22): p. 2349-2360.
114.Raczyńska, E.D. and M. Makowski, Geometric consequences of electron delocalization for adenine tautomers in aqueous solution. Journal of Molecular Modeling, 2014. 20(6): p. 2234.
115.Johnson, R.J., E.A. Gaucher, Y.Y. Sautin, G.N. Henderson, A.J. Angerhofer, et al., The Planetary Biology of Ascorbate and Uric acid and their Relationship with the Epidemic of Obesity and Cardiovascular Disease. Medical hypotheses, 2008. 71(1): p. 22-31.
116.Maiuolo, J., F. Oppedisano, S. Gratteri, C. Muscoli, and V. Mollace, Regulation of uric acid metabolism and excretion. International Journal of Cardiology, 2016. 213: p. 8-14.
117.Santana, A.C., S. Degaspari, S. Catanozi, H. Delle, L. de Sa Lima, et al., Thalidomide suppresses inflammation in adenine-induced CKD with uraemia in mice. Nephrol Dial Transplant, 2013. 28(5): p. 1140-9.
118.Chen, Z., X. Liu, G. Yu, H. Chen, L. Wang, et al., Ozone therapy ameliorates tubulointerstitial inflammation by regulating TLR4 in adenine-induced CKD rats. Ren Fail, 2016. 38(5): p. 822-30.
119.Ali, B.H., S.A. Adham, M. Al Za’abi, M.I. Waly, J. Yasin, et al., Ameliorative Effect of Chrysin on Adenine-Induced Chronic Kidney Disease in Rats. PLoS ONE, 2015. 10(4): p. e0125285.
120.Schinner, E., V. Wetzl, and J. Schlossmann, Cyclic nucleotide signalling in kidney fibrosis. International Journal of Molecular Sciences, 2015. 16(2): p. 2320-2351.
121.Wynn, T.A. and T.R. Ramalingam, Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nature Medicine, 2012. 18(7): p. 1028-1040.
122.Nogueira, A., M. JoÃO Pires, and P. Alexandra Oliveira, Pathophysiological Mechanisms of Renal Fibrosis: A Review of Animal Models and Therapeutic Strategies. In Vivo, 2017. 31(1): p. 1-22.
123.Meng, X.-M., P.M.-K. Tang, J. Li, and H.Y. Lan, TGF-β/Smad signaling in renal fibrosis. Frontiers in Physiology, 2015. 6: p. 82.
124.Schinner, E., V. Wetzl, A. Schramm, F. Kees, P. Sandner, et al., Inhibition of the TGFβ signalling pathway by cGMP and cGMP‐dependent kinase I in renal fibrosis. FEBS Open Bio, 2017. 7(4): p. 550-561.
125.Lan, H.Y., Diverse Roles of TGF-β/Smads in Renal Fibrosis and Inflammation. International Journal of Biological Sciences, 2011. 7(7): p. 1056-1067.
126.Sun, K., X. Xie, Y. Liu, Z. Han, X. Zhao, et al., Autophagy lessens ischemic liver injury by reducing oxidative damage. Cell & Bioscience, 2013. 3: p. 26-26.
127.Cursio, R., P. Colosetti, and J. Gugenheim, Autophagy and Liver Ischemia-Reperfusion Injury. BioMed Research International, 2015. 2015: p. 417590.
128.Li, L., J. Tan, Y. Miao, P. Lei, and Q. Zhang, ROS and Autophagy: Interactions and Molecular Regulatory Mechanisms. Cell Mol Neurobiol, 2015. 35(5): p. 615-21.
129.Vida, A., J. Márton, E. Mikó, and P. Bai, Metabolic roles of poly(ADP-ribose) polymerases. Seminars in Cell & Developmental Biology, 2017. 63: p. 135-143.
130.Reiss, A.B., I. Voloshyna, J. DeLeon, N. Miyawaki, and J. Mattana, Cholesterol Metabolism in CKD. American journal of kidney diseases : the official journal of the National Kidney Foundation, 2015. 66(6): p. 1071-1082.
131.Bechmann, L.P., R.A. Hannivoort, G. Gerken, G.S. Hotamisligil, M. Trauner, et al., The interaction of hepatic lipid and glucose metabolism in liver diseases. Journal of Hepatology, 2012. 56(4): p. 952-964.
132.Kwanten, W.J., W. Martinet, P.P. Michielsen, and S.M. Francque, Role of autophagy in the pathophysiology of nonalcoholic fatty liver disease: A controversial issue. World Journal of Gastroenterology : WJG, 2014. 20(23): p. 7325-7338.
133.Niso-Santano, M., S.A. Malik, F. Pietrocola, J.M. Bravo-San Pedro, G. Mariño, et al., Unsaturated fatty acids induce non-canonical autophagy. The EMBO Journal, 2015. 34(8): p. 1025-1041.
134.Lavallard, V.J. and P. Gual, Autophagy and Non-Alcoholic Fatty Liver Disease. BioMed Research International, 2014. 2014: p. 120179.
135.Ma, Y., J. Zhang, Q. Zhang, P. Chen, J. Song, et al., Adenosine induces apoptosis in human liver cancer cells through ROS production and mitochondrial dysfunction. Biochem Biophys Res Commun, 2014. 448(1): p. 8-14.
136.Siddiqui, M.A., J. Ahmad, N.N. Farshori, Q. Saquib, S. Jahan, et al., Rotenone-induced oxidative stress and apoptosis in human liver HepG2 cells. Mol Cell Biochem, 2013. 384(1-2): p. 59-69.
137.Gomez-Lechon, M.J., M.T. Donato, A. Martinez-Romero, N. Jimenez, J.V. Castell, et al., A human hepatocellular in vitro model to investigate steatosis. Chem Biol Interact, 2007. 165(2): p. 106-16.
138.Chen, D.F. and C.H. Wang, [The relationship between the opening of mitochondrial permeability transition pores of cultured hepatocytes with their apoptoses in a non-alcoholic fatty liver disease model]. Zhonghua Gan Zang Bing Za Zhi, 2007. 15(11): p. 837-9.
139.Ma, Y., J. Zhang, Q. Zhang, P. Chen, J. Song, et al., Adenosine induces apoptosis in human liver cancer cells through ROS production and mitochondrial dysfunction. Biochemical and Biophysical Research Communications, 2014. 448(1): p. 8-14.
140.Chistiakov, D.A., I.A. Sobenin, V.V. Revin, A.N. Orekhov, and Y.V. Bobryshev, Mitochondrial Aging and Age-Related Dysfunction of Mitochondria. BioMed Research International, 2014. 2014: p. 238463.
141.Zhang, J., K. Huang, K.L. O''Neill, X. Pang, and X. Luo, Bax/Bak activation in the absence of Bid, Bim, Puma, and p53. Cell Death & Disease, 2016. 7(6): p. e2266.
142.Ba, X. and N.J. Garg, Signaling Mechanism of Poly(ADP-Ribose) Polymerase-1 (PARP-1) in Inflammatory Diseases. The American Journal of Pathology, 2011. 178(3): p. 946-955.
143.Zhang, F., S.S. Lau, and T.J. Monks, A Dual Role for Poly(ADP-Ribose) Polymerase-1 
During Caspase-Dependent Apoptosis. Toxicological Sciences, 2012. 128(1): p. 103-114.
144.Bianchi, S., A. Baronti, R. Cominotto, and R. Bigazzi, [Lipid metabolism abnormalities in Chronic Kidney Disease]. G Ital Nefrol, 2016. 33(S68).
145.Pasalic, D., N. Marinkovic, and L. Feher-Turkovic, Uric acid as one of the important factors in multifactorial disorders – facts and controversies. Biochemia Medica, 2012. 22(1): p. 63-75.
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