臺灣博碩士論文加值系統

目錄
指導教授推薦書
口試委員會審定書
致謝 iii
中文摘要 v
英文摘要 vii
目錄 ix
圖目錄 xii
表目錄 xvii
第一章 緒論 1
第一節 前言 1
第二節 與 HNE 有相關之疾病 3
第三節 HNE抑制劑 31
第四節 野牡丹簡介及文獻回顧 40
第五節 研究背景與動機 64
第二章 實驗方法與設計 65
第一節 實驗設計 65
第二節 實驗儀器與材料 67
第三節 藥品與溶劑 70
第四節 野牡丹之萃取與分離純化 71
第五節 Casuarinin的製備 75
第六節 生物活性測定 78
第七節 檢量線建立 81
第八節 統計分析 81
第三章 實驗結果 82
第一節 候選中藥之篩選 82
第二節 野牡丹分離與純化 84
第三節 Casuarinin 的製備 91
第四節 野牡丹指紋圖譜之建立 100
第五節 結構解析 105
第四章 討論 146
第五章 結論 159
第六章 參考資料 162
第七章 附錄 185

圖目錄
Fig. 1-1 人類正常肺泡（左側）和ARDS患者肺泡示意圖 9
Fig. 1-2 COPD治療的潛在目標 13
Fig. 1-3 PMNs在腫瘤中的功能 16
Fig. 1-4 導致腎損傷之因素 18
Fig. 1-5 PR3在發炎反應及免疫系統中的角色 24
Fig. 1-6 嗜中性白血球絲胺酸蛋白酶在發炎反應中的機制 26
Fig. 1-7 嗜中性白血球反應機制 30
Fig. 1-8 Sivelestat 和 HNE 的交互作用 33
Fig. 1-9 Alvelestat 結構圖 34
Fig. 1-10 AE-3763 結構圖 35
Fig. 1-11 GW311616A 結構圖 35
Fig. 1-12 ZD-0892 結構圖 36
Fig. 1-13 野牡丹藥材圖 41
Fig. 2 實驗設計流程圖 66
Fig. 3-1 Casuarinin及劃分層 2MDE1、2MDE2 之 HPLC 層析圖比對結果圖 95
Fig. 3-2 Casuarinin 之 HPLC 層析圖 101
Fig. 3-3 Gallic acid 之 HPLC 層析圖 101
Fig. 3-4 Protocatechuic acid 之 HPLC 層析圖 102
Fig. 3-5 野牡丹指紋圖譜 102
Fig. 3-6 Casuarinin 檢量線 (calibration curve) 104
Fig. 3-7 3-Methoxy-4-hydroxyphenol-1-O-β-D-(6′-O-galloy-l)- glucopyranoside 結構圖 107
Fig. 3-8 3-Methoxy-4-hydroxyphenol-1-O-β-D-(6′-O-galloy-l)- glucopyranoside 之 ESI-MS 圖譜 108
Fig. 3-9 3-Methoxy-4-hydroxyphenol-1-O-β-D-(6′-O-galloy-l)- glucopyranoside 之1H-NMR 圖譜 (400MHz, CD3OD) 109
Fig. 3-10 3-Methoxy-4-hydroxyphenol-1-O-β-D-(6′-O-galloy-l)- glucopyranoside 之 13C-NMR 圖譜 (100MHz, CD3OD) 110
Fig. 3-11 3-Methoxy-4-hydroxyphenol-1-O-β-D-(6′-O-galloy-l)- glucopyranoside 之 1H-13C HSQC 圖譜 (400MHz, CD3OD) 111
Fig. 3-12 3-Methoxy-4-hydroxyphenol-1-O-β-D-(6′-O-galloy-l)- glucopyranoside 之 1H-13C COSY 圖譜 (400MHz, CD3OD)
112
Fig. 3-13 3-Methoxy-4-hydroxyphenol-1-O-β-D-(6′-O-galloy-l)- glucopyranoside 之 1H-13C HMBC 圖譜 (400MHz, CD3OD) 113
Fig. 3-14 Casuarinin 結構圖 117
Fig. 3-15 Casuarinin 之 ESI-MS 圖譜 119
Fig. 3-16 Casuarinin 之 1H-NMR 圖譜 (400MHz, CD3OD) 120
Fig. 3-17 Casuarinin 之 13C-NMR 圖譜 (100MHz, CD3OD) 121
Fig. 3-18 Casuarinin 之 1H-13C HSQC 圖譜 (400MHz, CD3OD) 122
Fig. 3-19 Casuarinin 之 1H-1H COSY 圖譜 (400MHz, CD3OD)
123
Fig. 3-20 Casuarinin 之 1H-13C HMBC 圖譜 (400MHz, CD3OD) 124
Fig. 3-21 Ferulaldehyde 結構圖 126
Fig. 3-22 Ferulaldehyde 之 1H-NMR 圖譜 (400MHz, CD3OD)
127
Fig. 3-23 Ferulaldehyde 之 1H-1H NOESY 圖譜 (400MHz, CD3OD) 128
Fig. 3-24 Sinapaldehyde 結構圖 130
Fig. 3-25 Sinapaldehyde 之 1H-NMR 圖譜 (400MHz, CD3Cl3)
131
Fig. 3-26 Sinapaldehyde 之 13C-NMR 圖譜 (100MHz, CD3Cl3)
132
Fig. 3-27 Sinapaldehyde 之 1H-1H NOESY 圖譜 (400MHz, CD3Cl3) 133
Fig. 3-28 Ellagic acid 結構圖 135
Fig. 3-29 Ellagic acid 之 1H-NMR 圖譜 (400MHz, CD3OD) 136
Fig. 3-30 Ellagic acid 之 13C-NMR 圖譜 (100MHz, CD3OD) 137
Fig. 3-31 Gallic acid 結構圖 139
Fig. 3-32 Gallic acid 之 1H-NMR 圖譜 (400MHz, CD3OD) 140
Fig. 3-33 Gallic acid 之 13C-NMR 圖譜 (100MHz, CD3OD) 141
Fig. 3-34 Protocatechuic acid 結構圖 143
Fig. 3-35 Protocatechuic acid 之 1H-NMR 圖譜 (100MHz, CD3OD) 144
Fig. 3-36 Protocatechuic acid 之 13C-NMR 圖譜 (100MHz, CD3OD) 145
Fig. 4-1 王不留行 (左) 及野牡丹 (右) 藥材比較圖 147
Fig. 4-2 Arimoniin (左) 及 Pedunculagin (右) 結構圖 150
Fig. 4-3 Caffeic acid、Quinic acid、3,5-Dicaffeoylquinic acid 結構圖 152
Fig. 4-4 Tannin 類化合物分類圖 152
Fig. 4-5 1,2,3,4,6-pentagalloyl-glucose 結構圖 153
Fig. 4-6 HHDP (左) 及 Ellagic acid (右) 結構圖 154
Fig. 4-7 Flavan-3-ol (左) 及 Catechin (右) 結構圖 154
Fig. 4-8 Stenophyllanin C 結構圖 155
Fig. 4-9 Arimoniin (左) 及 Pedunculagin (右) 分子嵌合圖 156
Fig. 5-1 野牡丹分離純化之流程圖 (1) 160
Fig. 5-2 野牡丹分離純化之流程圖 (2) 161
Appendix Fig. A-1 野牡丹 DNA 之分析結果 185
Appendix Fig. A-2 候選中草藥之篩選 186
Appendix Fig. A-3 Casuarinin 檢量線 188

表目錄
Table 1-1 Berlin definition 5
Table 1-2 具有 HNE 抑制活性的天然物 37
Table 3-1 野牡丹水萃物之產量產率結果 83
Table 3-2 野牡丹水萃物之 HNE 活性評估結果 83
Table 3-3 水萃物分層萃取之產量產率與HNE活性評估結果 84
Table 3-4 MDE 分離純化之產量產率與HNE活性評估結果 85
Table 3-5 MDE2分離純化之產量產率與HNE活性評估結果 86
Table 3-6 MDE2-2分離純化之產量與產率與HNE活性評估結果 87
Table 3-7 MDE4分離純化之產量與產率與 HNE 活性評估結果 88
Table 3-8 MDE4-4分離純化之產量與產率與 HNE 活性評估結果 89
Table 3-9 MDE4-3分離純化之產量與產率與 HNE 活性評估結果 90
Table 3-10 新水萃物萃取之產量產率與HNE活性評估結果 92


Table 3-11 新水萃物分層萃取產量產率與HNE活性評估結果
93
Table 3-12 2MDE 分離純化之產量產率結果 94
Table 3-13 2MDE1 分離純化之產量產率 96
Table 3-14 2MDE1-2 分離純化之產量產率 97
Table 3-15 七個化合物 HNE、PR3及CG 抑制活性測試結果
99
Table 3-16 不同濃度之casuarinin 層析峰面積 104
Table 3-17 3-Methoxy-4-hydroxyphenol-1-O-β-D-(6′-O-galloy-l)-glucopyranoside 1H 、13C 和 HMBC 圖譜數據整理表 (400 MHz, CD3OD) 107
Table 3-18 Casuarinin 1H 、13C 和 HMBC 圖譜數據整理表 (400MHz, CD3OD) 117
Table 3-19 Ferulaldehyde 1H 和13C 圖譜數據整理表 (400MHz, CD3OD) 126
Table 3-20 Sinapaldehyde 1H 和13C 圖譜數據整理表 (400MHz, CD3Cl3) 130
Table 3-21 Ellagic acid 1H 和13C 圖譜數據整理表 (400MHz, CD3OD) 135
Table 3-22 Gallic acid 1H 和13C 圖譜數據整理表 (400MHz, CD3OD) 139
Table 3-23 Protocatechuic acid 1H 和13C 圖譜數據整理表 (400MHz, CD3OD) 143
Appendix Table A-1 椿皮 (Ailanthus altissima) 之水萃物產量產率及 HNE 活性評估結果 187
Appendix Table A-2 王不留行 (Vaccaria segetalis) 水萃物 HNE 活性評估結果 187

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