臺灣博碩士論文加值系統

阿茲海默症(Alzheimer’s disease)乃屬老年人之神經退化性疾病。其主因為澱粉樣Beta蛋白(Amyloid β-protein, Aβ)於腦皮質產生異常之聚集(polymerization)及堆積(aggregation)，導致神經細胞凋亡、以及進行性記憶和認知能力之損傷。
牛樟芝學名為Antrodia cinnamomea，乃屬台灣特有之菇菌類，主要生長於海拔200-200公尺之闊葉林中。富含生物活性成分，而以三萜類化合物居多。文獻顯示，牛樟芝具有抗癌、抗氧化、保肝、以及保護神經等生物活性。
本研究使用Aβ25-35對PC12細胞株誘發細胞毒性，並以牛樟芝酒精萃取物探討其保護效果。其使用之方法為評估Aβ之聚集，胞內鈣離子之遷移，NO、ROS、MDA、TNF-α之水平、Bax/Bcl-2比以及Cleaved caspase-3、8、9活性等各因子隨時間與濃度變化之情形。證諸Aβ25-35誘導PC12細胞株損傷之實驗中，其PC12細胞株存活率穫得改善、胞內鈣離子以及ROS受到抑制，NO、TNF-α、及MDA等水平有效之減少，Bax/ Bcl-2比及Cleaved caspase-3、8、9活性之下降，發現牛樟芝酒精萃取物確可明顯抑制Aβ25-35對PC12細胞株之損傷。另者，若以酒精萃取物預先處理PC12細胞株，亦可達某些程度之保護功能。

Alzheimer's disease, occurring mostly in the elderly, is a neurodegenerative disease. Pathological findings have revealed its etiology is mainly due to the abnormal aggregation and accumulation of Amyloid β-protein (Aβ) in the cerebral cortex, inducing neuronal apoptosis and progressive loss of memory and cognitive abilities.
Antrodia cinnamomea (A. cinnamomea) (AC) is a unique mushroom species found in Taiwan. Its favored habitant mainly is the broad-leaved plants flourishing at altitude 200-2000 meters deep in the mountain area. It contains huge amount of biologically active ingredients, mostly triterpenoids. AC has become popular with its anticancer, antioxidant, neuroprotective, and hepatoprotective effects.
The effect of the ethanolic extract of AC (EEAC) to protect the PC12 cell line against the cytotoxicity induced by Aβ25-35 was evaluated. The parameters examined included the Aβ aggregation status, the intracellular Ca2+ shift, levels of cytosolic ROS, MDA, NO, TNF-α, ratio Bax/ Bcl-2, and the Cleaved caspase-3, 8, 9. EEAC inhibited aggregation of Aβ25-35 as revealed by the Congo Red and Thioflavin T assays. It improved cell viability and decreased the levels of intracellular Ca2+, ROS, NO, TNF-α, MDA, ratio Bax/ Bcl-2, and Ceaved caspase-3, 8, 9.
We suggest AC can be a feasible alternative adjuvant neuroprotective medicine.

目錄
中文摘要……………………………………………………………………………1
英文摘要……………………………………………………………………………3
縮寫表………………………………………………………………………………5
目錄…………………………………………………………………………………8
表目錄………………………………………………………………………………12
圖目錄………………………………………………………………………………13
第一章 前言………………………………………………………………………16
第二章 文獻回顧…………………………………………………………………18
2.1 阿茲海默症…………………………………………………………………18
2.2 β-amyloid與阿茲海默症…………………………………………………20
2.3 Amyloid precursor protein…………………………………………23
2.4 β-amyloid生成……………………………………………………………23
2.5 β-amyloid結構……………………………………………………………25
2.6 β-amyloid aggregation………………………………………………25
2.7牛樟芝………………………………………………………………………29
第三章 研究目的及實驗架構……………………………………………………32
3.1 研究目的……………………………………………………………………32
3.2 實驗架構……………………………………………………………………33
第四章 實驗材料…………………………………………………………………34
4.1 實驗材料：牛樟芝酒精萃取物……………………………………………34
4.2 實驗細胞株…………………………………………………………………34
4.3 實驗試劑……………………………………………………………………35
4.3.1 化學試劑…………………………………………………………35
4.3.2 細胞培養試劑……………………………………………………37
4.3.3 西方轉漬試劑……………………………………………………37
4.3.4 細胞耗材…………………………………………………………38
4.4 實驗設備……………………………………………………………………38
第五章 實驗方法…………………………………………………………………41
5.1 化學成分分析………………………………………………………………41
5.1.1 HPLC分析…………………………………………………………41
5.1.2 總酚類化合物含量之測定………………………………………41
5.1.3 總類黃酮含量之測定……………………………………………42
5.1.4 粗三萜含量之測定……………………………………42
5.1.5 還原力測定………………………………………………………43
5.1.6 DPPH自由基清除能力測定………………………………………44
5.2 PC12 cells培養與保存…………………………………………………45
5.2.1 細胞培養液配製…………………………………………………45
5.2.2 完全培養液配製…………………………………………………45
5.2.3 非完全培養液配製………………………………………………45
5.2.4 PC12 cells之培養………………………………………………46
5.2.5 PC12 cells保存…………………………………………………46
5.2.6 PC12 cells細胞解凍……………………………………………47
5.3 β-amyloid25-35 (Aβ25-35)聚集之效果……………………………48
5.3.1 β-amyloid25-35備製…………………………………………48
5.3.2 牛樟芝酒精萃取物(ACEE)備製…………………………………48
5.3.3 Congo Red染色分析Aβ25-35聚合之情形……………………48
5.3.4 Thioflavin T assay分析Aβ25-35聚集之情形……………49
5.4保護作用之機制評估………………………………………………………50
5.4.1 細胞存活率測定…………………………………………………50
5.4.1.1 β-amyloid25-35之細胞毒性………………………………50
5.4.1.2 牛樟芝酒精萃取物(ACEE)之細胞毒性……………………51
5.4.1.3 ACEE對Aβ25-35細胞毒性之保護作用……………………52
5.4.2 細胞內發炎測定…………………………………………………53
5.4.2.1 一氧化氮生成量………………………………………………53
5.4.2.2 TNF-α生成量…………………………………………………54
5.4.2.3 胞內鈣離子測定………………………………………………55
5.4.2.4 胞內ROS含量…………………………………………………56
5.4.2.5 MDA測定………………………………………………………56
5.4.3 蛋白質定性與定量分析…………………………………………58
5.4.3.1 蛋白質萃取……………………………………………………58
5.4.3.2 蛋白質定量……………………………………………………59
5.4.3.3 聚丙烯醯胺膠體電泳法………………………………………59
5.4.3.4 西方墨點法……………………………………………………60
5.8 統計分析……………………………………………………………………61
第六章 實驗結果與討論………………………………………………………62
6.1 牛樟芝酒精萃取物化學成分分析…………………………………………62
6.1.1 HPLC成分分析……………………………………………………62
6.1.2 牛樟芝酒精萃取物之產率及化學組成…………………………62
6.2 化學氧化力測定……………………………………………………………63
6.2.1 還原力……………………………………………………………63
6.2.2 清除DPPH自由基能力……………………………………………63
6.3 β-amyloid25-35 (Aβ25-35)聚集之檢測……………………………64
6.3.1 利用Congo Red染色分析Aβ25-35 聚合之情形………………64
6.3.2 Thioflavin T assay分析Aβ25-35聚集之螢光表現量……64
6.4 保護作用之機制評估……………………………………………………65
6.4.1 細胞存活率測定…………………………………………………65
6.4.1.1 β-amyloid25-35 (Aβ25-35)之細胞毒性………………65
6.4.1.2 牛樟芝酒精萃取物(ACEE)之細胞毒性……………………66
6.4.1.3 ACEE對Aβ25-35細胞毒性之保護作用……………………66
6.4.2 抗發炎活性………………………………………………………67
6.4.2.1 一氧化氮生成量………………………………………………67
6.4.2.2 TNF-α生成量…………………………………………………68
6.4.2.3 胞內鈣離子濃度測定…………………………………………68
6.4.2.4 胞內ROS含量…………………………………………………69
6.4.2.5 MDA濃度測定…………………………………………………70
6.4.2.6 ACEE對Aβ25-35影響Bax/ BcL-2蛋白表現量之調節功
能………………………………………………………………70
6.4.2.7 ACEE對Aβ25-35影響Cleaved caspase-3蛋白表現量之
調節功能………………………………………………………71
第七章 結論………………………………………………………………………72
第八章 參考文獻…………………………………………………………………73
第九章 附表………………………………………………………………………81
第十章 附圖………………………………………………………………………84

1. Adrian M. Isaacs, David B. Senn, Menglan Yuan, James P.
Shine, and Bruce A. Yankner. Acceleration of Amyloid β-Peptide Aggregation by Physiological Concentrations of Calcium. J Biol Chem. Author manuscript; available in PMC 2006.
2. Aming Zhang, Wei Qi, Theresa A. Good, and Erik J. Fernandez. Structural Differences between Aβ(1-40) Intermediate Oligomers and Fibrils Elucidated by Proteolytic Fragmentation and Hydrogen/ Deuterium Exchange. Biophysical Journal, 2009.
3. Ana Villa, Maria JesuÂs Latasa and Angel Pascual. Nerve growth factor modulates the expression and secretion of β-amyloid precursor protein through different mechanisms in PC12 cells. Journal of Neurochemistry, 2001.
4. Asad Jan, Ozgun Gokce, Ruth Luthi-Carter, and Hilal A. Lashuel. The Ratio of Monomeric to Aggregated Forms of Aβ40 and Aβ42 Is an Important Determinant of Amyloid-β Aggregation, Fibrillogenesis, and Toxicity. J Biol Chem, 2008.
5. Barbara J. Blanchard, Albert Chen, Leslie M. Rozeboom, Kate A. Stafford, Peter Weigele, and Vernon M. Ingram. Efficient reversal of Alzheimer’s disease fibril formation and elimination of neurotoxicity by a small molecule. PNAS, 2004.
6. Brookmeyer R, Gray S, Kawas C. Projections of Alzheimer’s disease in the United States and the public health impact of delaying disease onset. Am J Public Health, 1998.
7. Chang-Yu Chen; Tsu-Kung Lin; Yi-Chuang Chang; Yi-Fen Wang; Huey-Wen Shyu; Kuan-Hua Lin; Miao-Chen Choua Nickel(II)-Induced Oxidative Stress, Apoptosis, G2/M Arrest, and Genotoxicity in Normal Rat Kidney Cells. Journal of Toxicology and Environmental Health, 2010.
8. Cheng Chang Ho, Alaganandam Kumaran, Lucy Sun Hwang. Bio-assay guided isolation and identification of anti-Alzheimer active compounds from the root of Angelica sinensis. Food Chemistry, 2009.
9. Chi-Tai Yeh, Yerra Koteswara Rao, Chih-Jung Yao, Chuan-Feng Yeh, Chi-Han Li, Shuang-En Chuang, John H.T. Luong, Gi-Ming Lai, Yew-Min Tzeng. Cytotoxic triterpenes from Antrodia camphorata and their mode of action in HT-29 human colon cancer cells. Cancer Letters, 2009.
10. Daniel Payette, Jun Xie, Qing Guo. The amyloid beta ion channel hypothesis of Alzheimer’s disease. Neuropsychiatric Disease and Treatment, 2007.
11. Daniel I. Orellana, Rodrigo A. Quintanilla, Ricardo B. Maccioni. Neuroprotective effect of TNFα against the β-amyloid neurotoxicity mediated by CDK5 kinase. Biochimica et Biophysica Acta, 2007.
12. Der-Zen Liu, Hong-Jen Liang, Chien-Ho Chen, Ching-Hua Sub, Tzong-Huei Lee, Chun-Ting Huang, Wen-Chi Hou, Shyr-Yi Lin, Wen-Bin Zhong, Pei-Jung Lin, Ling-Fang Hung, Yu-Chih Liang. Comparative anti-inflammatory characterization of wild fruiting body, liquid-state fermentation, and solid-state culture of Taiwanofungus camphoratus in microglia and the mechanism of its action. Journal of Ethnopharmacology, 2007.
13. Donggun Sul, Hyo-Shin Kim, Eun-Kyung Cho, Min Lee, Hyun Sook Kim, Woon-Won Jung, KwangWoo Hwang, So-Young Park. 2,3,7,8-TCDD neurotoxicity in neuroblastoma cells is caused by increased oxidative stress, intracellular calcium levels, and tau phosphorylation. Toxicology, 2009.
14. Donggeun Sul, Hyo-Shin Kim, Dongho Lee, Seong Soo Joo, Kwang Woo Hwang, So-Young Park. Protective effect of caffeic acid against beta-amyloid-induced neurotoxicity by the inhibition of calcium influx and tau phosphorylation. Life Sciences, 2009.
15. Fadi Massoud, and Serge Gauthier. Update on the Pharmacological Treatment of Alzheimer’s Disease. Current Neuropharmacology, 2010.
16. Feng-Lin Hsu, Cheng-Jen Chou, Yi-Chieh Chang, Tun-Tschu Chang, Mei-Kuang Lu. Promotion of hyphal growth and underlying chemical changes in Antrodia camphorata by host factors from Cinnamomum camphora. International Journal of Food Microbiology, 2006.
17. Gal Bitan, Marina D. Kirkitadze, Aleksey Lomakin, Sabrina S. Vollers, George B. Benedek and David B. Teplow. Amyloid β-protein (Aβ) assembly: Aβ40 and Aβ42 oligomerize through distinct pathways. PNAS, 2003.
18. Gang Li, Rong Ma, Chengfang Huang, Qiang Tang, Qin Fu, Hui Liu, Benrong Hu, Jizhou Xiang. Protective effect of erythropoietin on β-amyloid-induced PC12 cell death through antioxidant mechanisms. Neuroscience Letters, 2008.
19. Giuseppe Verdile, Samuel E Gandy, Ralph N. Martins. The Role of Presenilin and its Interacting Proteins in the Biogenesis of Alzheimer’s Beta Amyloid. Neurochem Res, 2007.
20. Hai-Ying Zhang, Yi-Heng Liu, Hong-Quan Wang, Jie-Hua Xu, Hai-Tao Hu. Puerarin protects PC12 cells against β-amyloid-induced cell injury. Cell Biology International, 2008.
21. Han-Kyu Lee, Pravir Kumar, Qinghao Fu, Kenneth M. Rosen, and Henry W. Querfurth. The Insulin/ Akt Signaling Pathway Is Targeted by Intracellular β-Amyloid. Molecular Biology of the Cell, 2009.
22. Harald Hampel, Yong Shen, Dominic M. Walshd Paul Aisen, Les M. Shaw, Henrik Zetterberg, John Q. Trojanowskif, and Kaj Blennow. Biological markers of amyloid β-related mechanisms in Alzheimer’s diseas. Exp Neurol. Author manuscript; available in PMC, 2010.
23. Hardy J, Gwinn-Hardy K. Genetic classification of primary neurodegenerative disease. Science, 1998.
24. Hui Zheng and Edward H Koo. The amyloid precursor protein: beyond amyloid. Molecular Neurodegeneration, 2006.
25. Jia-Ming Chang, Yi-Ru Lee, Le-Mei Hung, Sheng-Yung Liu, Mao-Tien Kuo, Wu-Che Wen and Peini Chen. An Extract of Antrodia camphorata Mycelia Attenuates the Progression of Nephritis in Systemic Lupus Erythematosus–Prone NZB/W F1 Mice. eCAM Advance Access published, 2008.
26. Jie-Ping Fan, Chao-Hong He. Simultaneous quantification of three major bioactive triterpene acids in the leaves of Diospyros kaki by high-performance liquid chromatography method. Journal of Pharmaceutical and Biomedical Analysis, 2006.
27. Jie Shen and Raymond J. Kelleher. The presenilin hypothesis of Alzheimer’s disease: Evidence for a loss-of-function pathogenic mechanism. PNAS, 2007.
28. Jung-Hee Jang, Young-Joon Surh. AP-1 mediates β-amyloid-induced iNOS expression in PC12 cells via the ERK2 and p38 MAPK signaling pathways. Biochemical and Biophysical Research Communications, 2005.
29. Jung-Hee Jang, Young-Joon SurhT. β-Amyloid-induced apoptosis is associated with cyclooxygenase-2 up-regulation via the mitogen-activated protein kinase–NF-κB signaling pathway. Free Radical Biology & Medicine, 2005.
30. Kazuko Shimada, Kuniko Fujikawa, Keiko Yahara, and Takashi Nakamura. Antioxidative Properties of Xanthan on the Autoxidation of Soybean Oil in Cyclodextrin Emulsion. J. Agric. Food Chem, 1992.
31. Madamanchi Geethangili and Yew-Min Tzeng. Review of Pharmacological Effects of Antrodia camphorata and ts Bioactive Compounds. eCAM Advance Access published, 2009.
32. Marino B. Arnao, Antonio Cano, Manuel Acosta. The hydrophilic and lipophilic contribution to total antioxidant activity. Food Chemistry, 2001.
33. Masaki Wakabayashi and Katsumi Matsuzaki. Formation of Amyloids by Aβ1–42 on NGF-differentiated PC12 Cells: Roles of Gangliosides and Cholesterol. J. Mol. Biol, 2007.
34. M. Bisaglia, V. Venezia, P. Piccioli, S. Stanzione, C. Porcile, C. Russo, F. Mancini, C. Milanese, G. Schettini. Acetaminophen protects hippocampal neurons and PC12 cultures from amyloid β-peptides induced oxidative stress and reduces NF-γB activation. Neurochemistry International, 2002.
35. Mei-Kuang Lu, Jing-Jy Cheng, Wen-Lin Lai, Yen-Ru Lin, Nai-Kuei Huang. Adenosine as an active component of Antrodia cinnamomea that prevents rat PC12 cells from serum deprivation-induced apoptosis through the activation of adenosine A2a receptors. Life Sciences, 2006.
36. Michio Hashimoto, Hossain Md Shahdat, Masanori Katakura, Yoko Tanabe, Shuji Gamoh. Effects of docosahexaenoic acid on in vitro amyloid beta peptide25–35 fibrillation. Biochimica et Biophysica Acta , 2009.
37. Ming-Tsung Liu, Hsueh-Meei Huang, Kee-Ching G. Jeng, Shou-Chung Ou, Jon-Son Kuo. Induction of cytokine genes and IL-1α by chemical hypoxia in PC12 cells. Life Sciences, 2000.
38. M.R.H. Krebs, E.H.C. Bromley, A.M. Donald. The binding of thioflavin-T to amyloid fibrils: localization and implications. Journal of Structural Biology, 2005.
39. Myung-Min Choi, Eun-A. Kim, Hoh-Gyu Hahn, Kee Dal Nam, Seung-Ju Yang , Soo Young Choi, Tae Ue Kim, Sung-Woo Cho, Jae-Wan Huh. Protective effect of benzothiazole derivative KHG21834 on amyloid β-induced neurotoxicity in PC12 cells and cortical and mesencephalic neurons. Toxicology, 2007.
40. Myung-Sunny Kim, Hong-Seob So, Ji-Sun Park, Kang-Min Lee, Byung-Soon Moon, Ho-Sub Lee, Tae-Young Kim, Seong-Keun Moon, Raekil Park. Hwansodan protects PC12 cells against serum-deprivation-induced apoptosis via a mechanism involving Ras and mitogen-activated protein (MAP) kinase pathway. M.-S. Kim et al. / General Pharmacology, 2000.
41. Nacira Darghal, Arlette Garnier-Suillerot, Milena Salerno. Mechanism of thioflavin T accumulation inside cells overexpressing P-glycoprotein or multidrug resistance-associated protein: Role of lipophilicity and positive charge. Biochemical and Biophysical Research Communications, 2006.
42. Nai-Kuei Huang, Yun-Lian Lin, Jing-Jy Cheng, Wen-Lin Lai. Gastrodia elata prevents rat pheochromocytoma cells from serum-deprived apoptosis: the role of the MAPK family. Life Sciences, 2004.
43. Naidu A, Quon D, Cordell B. Beta-Amyloid peptide produced in vitro is degraded byproteinases released by cultured cells. J Biol Chem, 1995.
44. Olga Simakova and Nelson J. Arispe. The Cell-Selective Neurotoxicity of the Alzheimer’s Aβ Peptide Is Determined by Surface Phosphatidylserine and Cytosolic ATP Levels. Membrane Binding Is Required for Aβ Toxicity. The Journal of Neuroscience, 2007.
45. Philip Thomas and Michael Fenech. A review of genome mutation and Alzheimer’s disease. Mutagenesis, 2007.
46. Ponte P , Gonzalez-DeWhitt P, Schilling J, Miller J, Hsu D, Greenberg B, Davis K, Wallace W, Lieberburg I, Fuller F. A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors. Nature, 1988.
47. Richard C. Li, Farzan Pouranfar, Seung Kwan Lee, Matthew W. Morris, Yang Wang,and David Gozal. Neuroglobin protects PC12 cells against β-amyloid-induced cell injury. Neurobiol Aging. Author manuscript; available in PMC, 2009.
48. Ritu Khurana, Chris Coleman, Cristian Ionescu-Zanetti, Sue A. Carter, Vinay Krishna, Rajesh K. Grover, Raja Roy, Shashi Singh. Mechanism of thioflavin T binding to amyloid fibrils. Journal of Structural Biology, 2005.
49. Rong Ma, Nian Xiong, Chengfang Huang, Qiang Tang, Benrong Hu, Jizhou Xiang a, Gang Li. Erythropoietin protects PC12 cells from β-amyloid25–35-induced apoptosis via PI3K/ Akt signaling pathway. Neuropharmacology, 2009.
50. Sandy Shuo Zhao, Kelvin Sze-Yin Leung. Quality evaluation of mycelial Antrodia camphorata using high-performance liquid chromatography (HPLC) coupled with diode array detector and mass spectrometry (DAD-MS). Zhao and Leung Chinese Medicine, 2010.
51. Sarah L Cole and Robert Vassar. The Alzheimer's disease β-secretase enzyme, BACE1. Molecular Neurodegeneration, 2007.
52. Sasidhar Yallampalli, Maria-Adelaide Micci, Giulio Taglialatela. Ascorbic acid prevents β-amyloid-induced intracellular calcium increase and cell death in PC12 cells. Neuroscience Letters, 1998.
53. Scott A. Small and Karen Duff1. Linking Aβ and Tau in Late-Onset Alzheimer’s Disease: A Dual Pathway Hypothesis. Neuron, 2008.
54. Selkoe DJ. The molecular pathology of Alzheimer's disease. Neuron, 1991.
55. Silvia Biocca, Antonino Cattaneo and Pietro Calissano.A macromolecular structure favouring microtubule assembly in NGF-differentiated pheochromocytoma cells (PC12). The EMBO Journal, 1983.
56. Sun Young Lee, Tae Youl Ha, Dong Ju Son, Sung Ran Kim, Jin Tae Hong. Effect of sesaminol glucosides on β-amyloid-induced PC12 cell death through antioxidant mechanisms. Neuroscience Research, 2005.
57. Soottawat Benjakul, Wittayachai Lertittikul, Friedrich Bauer. Antioxidant activity of Maillard reaction products from a porcine plasma protein–sugar model system. Food Chemistry, 2005.
58. Tierney MC, Szalai JP, Snow WG, et al. A prospective study of the clinical utility of ApoE genotype in the prediction of outcome in patients with memory impairment. Neurology, 1996.
59. Vincenzo Fogliano, Veronica Verde, Giacomino Randazzo, and Alberto Ritieni. Method for Measuring Antioxidant Activity and Its Application to Monitoring the Antioxidant Capacity of Wines. J. Agric. Food Chem, 1999.
60. Wei Qi, Aming Zhang, Dhara Patel, Sungmun Lee, Jamie L. Harrington, Liming Zhao, David Schaefer, Theresa A. Good, and Erik J. Fernandez. Simultaneous Monitoring of Peptide Aggregate Distributions, Structure, and Kinetics Using Amide Hydrogen Exchange: Application to Aβ1–40 Fibrillogenesis. Biotechnol Bioeng., 2008.
61. Woojin Kim and Michael H. Hecht. Mutations Enhance the Aggregation Propensity of the Alzheimer’s Aβ Peptide. J. Mol. Biol., 2008.
62. Xiao-Lan Qi, Jin Xiu, Ke-Ren Shan, Yan Xiao, Ran Gu, Ru-Yu Liu, Zhi-Zhong Guan. Oxidative stress induced by beta-amyloid peptide1–42 is involved in the altered composition of cellular membrane lipids and the decreased expression of nicotinic receptors in human SH-SY5Y neuroblastoma cells. Neurochemistry International, 2005.
63. Xiaoyu Liu, Kedi Xu, Ming Yan, Yongping Wang, Xiaoxiang Zheng. Protective effects of galantamine against Aβ-induced PC12 cell apoptosis by preventing mitochondrial dysfunction and endoplasmic reticulum stress. Neurochemistry International, 2010.
64. Yair Porat, Adel Abramowitz and Ehud Gazit. Inhibition of Amyloid Fibril Formation by Polyphenols: Structural Similarity and Aromatic Interactions as a Common Inhibition Mechanism. Chem Biol Drug Des, 2006.
65. You-Cheng Hseu, Fang-Yang Wu, Jia-Jiuan Wu, Jing-Yi Chen, Wen-Huei Chang, Fung-Jou Lu, Yu-Ching Lai, Hsin-Ling Yang. Anti-inflammatory potential of Antrodia Camphorata through inhibition of iNOS, COX-2 and cytokines via the NF-γB pathway. International Immunopharmacology, 2005.
66. You-Cheng Hseu, Ssu-Ching Chen, Pei-Chuan Tsai, Chee-Shan Chen, Fung-Jou Lu, Nai-Wen Chang, Hsin-Ling Yang. Inhibition of cyclooxygenase-2 and induction of apoptosis in estrogen-nonresponsive breast cancer cells by Antrodia camphorate. Food and Chemical Toxicology, 2007.
67. Yong Hoon Park1, Young-Jin Kim, Il Hong Son1, and Hyun Duk Yang1. Inhibition of β-amyloid1-40 Peptide Aggregation and Neurotoxicity by Citrate. Korean J Physiol Pharmaco, 2009.
68. Yu-Jen Chen, Po-Ching Cheng, Ching-Nan Lin, Hui-Fen Liao, Yu-Yawn Chen, Chin-Chu Chen, Kin-Mu Lee. Polysaccharides from Antrodia camphorata mycelia extracts possess immunomodulatory activity and inhibits infection of Schistosoma mansoni. International Immunopharmacology, 2008.
69. Yun-Lian Lin, Yi-Chao Lee, Chuen-Lin Huang, Wen-Lin Lai, Yen-Ru Lin, Nai-Kuei Huang. Ligusticum chuanxiong prevents rat pheochromocytoma cells from serum deprivation-induced apoptosis through a protein kinase A-dependent pathway. Journal of Ethnopharmacology, 2007.
70. Z.-Z. Guan, H. Miao, J.-Y. Tian, C. Unger, A. Nordberg, and X. Zhang. Suppressed expression of nicotinic acetylcholine receptors by nanomolar β-amyloid peptides in PC12 cells. J Neural Transm, 2001.