臺灣博碩士論文加值系統

山竹 (Garcinia mangostana Linn.) 為藤黃科 (Guttiferae) 植物，由於其果肉清香甜美被民眾稱之為”果后”，主要產地為東南亞等熱帶地區；果殼具清涼解熱及止瀉，外敷可促進傷口癒合等功效，是當地常用的草藥。
文獻指出山竹的萃取物具有多重活性，而果殼部分是 xanthones 的主要來
源；xanthones 具有抗氧化、抗腫瘤、抗發炎及抗微生物等活性。
本實驗的目的為分離山竹果殼中各種結構之xanthones 類成分，並進
行抗發炎及抗菌活性評估，以探討不同取代基的xanthone 衍生物其活性與
結構的相關性；另一部分則同時建立定量各種活性成分之HPLC 分析方法，
利用XTerra MS C18 管柱及保護管柱，移動相0.1 % HCOOH-CH3CN，比
較市售各種山竹膳食補充品之成分含量差異。
取山竹果殼萃取物以丙酮進行震盪萃取後，以不同矽膠管柱進行分離
及純化成分並建立HPLC 分析定量方法。以LPS 誘導RAW 264.7 細胞株
產生NO 的模式，評估體外抗發炎活性，並利用三種菌株Streptococcus
mutans, Staphylococcus aureus, 及Propionibacterium acnes 以培養液稀釋法評估各成分之抗菌活性。
由山竹果殼中純化出十六種成分包括α-mangostin, γ-mangostin,
β-mangostin, 9-hydroxycalabaxanthone, gartanin, 8-deoxygartanin, garcinone C, 1,7-dihydroxy-2-(3-methylbut-2-enyl)-3-methoxyxanthone (GM-G), mangostenol, mangostingone, northyriol, 11-hydroxy-1-isomangostin, quercetin, protocatechuic acid 及二個首次發現於山竹果殼之新成分，分別命
名為garcinone F 及garcinone G。抗發炎活性結果顯示在濃度為10 μg/ ml下，γ-mangostin, 11-hydroxy-1-isomangostin, garcinone C, mangostenol 及mangostingone 初步評估具有抗發炎之活性。抗菌活性結果顯示，α-mangostin, 9-hydroxycalabaxanthone, β-mangostin, γ-mangostin,mangostenol 及mangostingone 對三株菌皆具有抗菌活性。
山竹是一個xanthone 衍生工廠，含量為所有植物之冠，比較這些同骨
架、不同取代基之化學成分：garcinone C, mangostenol 具有抗發炎活性；9-hydroxycalabaxanthone, mangostingone 具有抗菌活性，
9-hydroxycalabaxanthoneu 抑制S. mutans 不亞於α-mangostin，MIC 為3.82μM，IC50 為21.18 μM，這些微量成分亦有相當的抗發炎及抗菌活性。
成分分析結果顯示，本實驗建立山竹之HPLC 分析法不論是同日內或
異日間結果，山竹成分之變異係數皆小於3 %；及利用α-mangostin 及
γ-mangostin 兩種山竹果殼中的主成分測定添加回收率之結果，回收率皆大
於95 %，確認本實驗的分析方法之準確性佳，且具有再現性。定量方面，
檢量線之相關係數 (r2) 均大於0.999，表示線性關係良好，山竹成分之最
小偵測濃度可達0.032 μg/ ml，適合作為山竹膳食補充品中成分標示之依據；以上這些成分可作為未來保健食品開發的指標之一。

Natural products were widely used as traditional medicines around the world. Many tropical plants have been indentified to have interesting therapeutic potential
and biological activity. Mangosteen (Garcinia mangostana Linn.) belongs to the family of Guttiferae, cultivated in the tropical rainforest of the Southeast Asia countries. People in these countries have used the hulls of mangosteen as a traditional medicine for the treatment of trauma, diarrhea, and skin infections. Xanthones are identified as the major bioactive compounds of the mangosteen fruit hulls which have been confirmed to exhibit anti-microbial, anti-inflammatory, anti-oxidative, and anti-viral activities.
Xanthone derivatives were separated from mangosteen fruit hulls. And the assessments of anti-inflammatory and antibacterial activities were studied by the different substituents of xanthone derivatives and compared their structure activity relationships. Furthermore, we establish a quantitative HPLC analysis method on detecting the active components with the use of XTerra MS C18 column and
protected column, mobile phase of 0.1% HCOOH-CH3CN. The differences among the commercially available products were examined.
The mangosteen fruit hulls extract was dissolved in acetone with ultrasonic bath before the separation and purification. Sixteen components were isolated from fruit
hulls of mangosteen, including α-mangostin, γ-mangostin, β-mangostin, 9-hydroxycalabaxanthone, gartanin, 8-deoxygartanin, garcinone C, mangostenol,
mangostingone, 11-hydroxy-1-isomangostin, quercetin,
1,7-dihydroxy-2-(3-methylbut-2-enyl)-3-methoxyxanthone, northyriol, protocatechuic acid and two new compounds named garcinone F and garcinone G. Components of the mangosteen fruit hulls inhibited nitric oxide (NO) production from lipopolysaccharide (LPS)-stimulated RAW 264.7 cells to assess the in vitro anti-inflammatory activity. Components were further tested for antimicrobial activities by broth dilution method showed inhibition on the growth of Streptococcus mutans, Staphylococcus aureus, and Propionibacterium acnes.
γ-Mangostin, 11-hydroxy-1-isomangostin, garcinone C, mangostenol, and mangostingone showed anti-inflammatory activity at concentration of 10 μg/ ml. α-mangostin, 9-hydroxycalabaxanthone, β-mangostin, γ-mangostin, mangostenol, and mangostingone have antibacterial activity. 9-hydroxycalabaxanthoneu inhibited S. mutans as much as α-mangostin, MIC: 3.82 μM, IC50: 21.18 μM. These results
provide a marker substance profile for the future development of dietary supplement.
In conclusion, we established an accurate and reproducible quantitative analysis method and demonstrated that the results of the interday or intraday, mangosteen
composition of the coefficient of variation were less than 3 %, and the results of recovery were greater than 95%. On the aspect of quantitative analysis, the calibration
curve of the correlation coefficient (r2) was greater than 0.999-indicating a good linear relationship, and the limit of detection concentration of mangosteen components was
as low as 0.032 μg / ml. This method was suitable for the determination of xanthones and its structural related derivatives in dietary supplements contained mangosteen hull
extract. Future study on their pharmacological effects is of the interesting perspective.

目錄 I
圖目錄 VII
表目錄 X
附圖目錄 XII
附表目錄 XVIII
縮寫表 XIX
中文摘要 XXI
英文摘要 XXIII
第一章 前言 1
一、 引序 1
二、 山竹簡介 1
三、 本實驗採用之山竹活性評估 6
(一) 抗發炎 6
1. 脂多醣Lipopolysaccharides (LPS) 與巨噬細胞 7
2. 發炎與巨噬細胞 7
(二) 抗菌 10
1. 變異鏈球菌 (Streptococcus mutans) 10
2. 金黃色葡萄球菌 (Staphylococcus aureus) 11
3. 痤瘡桿菌 (Propionibacterium acnes) 12
四、 文獻回顧 13
(一) Xanthones 黃色酮簡介 13
(二) 山竹之成分 13
(三) 山竹成分活性回顧 15
1. Xanthones及其衍生物 15
2. Flavonoids 20
第二章 實驗材料與方法 23
一、 材料 23
二、 試驗細胞及菌株 24
三、 化學試劑及培養液 24
四、 分離管柱及管柱填充劑 26
五、 儀器設備 27
六、 實驗架構 28
七、 山竹果殼活性成分之分離 29
(一) 新鮮山竹果殼成分之分離 29
(二) 山竹萃取物之成分分離 30
八、 山竹果殼之抗發炎活性評估 42
(一) 樣品溶液製備 42
(二) RAW 264.7細胞培養 42
(三) 細胞毒性之測定 43
(四) LPS誘導RAW 264.7細胞株 44
九、 山竹果殼之抗菌活性評估 46
(一) 初步篩選山竹萃取物 46
(二) S. mutans, S. aureus及P. acnes三種菌株培養條件 47
(三) 培養液稀釋法 47
十、 山竹果殼成分之HPLC分析 50
(一) 層析條件 50
(二) 檢量線之製作 51
(三) 定量方法之確效 51
(四) 添加回收率試驗 51
(五) 山竹萃取物之成分含量分析 52
十一、 山竹成分快速劃分方法之開發 53
(一) 樣品溶液製備 55
(二) 儀器設備 55
(三) 低壓層析步驟 56
(四) HPLC鑑定之條件 56
(五) Sephadex LH-20管柱連接ESI-MS進行快速鑑定成分 56
第三章 結果與討論 58
第一節 山竹成分之結構鑑定 58
一、 山竹果殼純化之成分 58
(一) GM-A之圖譜解析 58
(二) GM-B之圖譜解析 59
(三) GM-C之圖譜解析 62
(四) GM-I之圖譜解析 63
(五) GM-E之圖譜解析 65
(六) GM-F之圖譜解析 66
(七) GM-D之圖譜解析 68
(八) GM-H之圖譜解析 69
(九) GM-J之圖譜解析 72
(十) GM-K之圖譜解析 73
(十一) GM-G之圖譜解析 75
(十二) GM-P之圖譜解 76
(十三) GM-O之圖譜解析 78
(十四) GM-M之圖譜解析 78
(十五) GM-N之圖譜解析 81
(十六) GM-Q之圖譜解析 84
二、 XANTHONE類成分之NMR訊號特徵 87
第二節 山竹成分之抗發炎活性 90
一、 山竹成分之細胞毒性 90
二、 山竹成分抑制NO含量測定 90
三、 抗發炎活性評估 90
第三節 山竹成分之抗菌活性 92
一、 山竹萃取物之抗菌活性 92
二、 山竹成分抑制S. mutans之活性 92
三、 山竹成分抑制S. aureus之活性 94
四、 山竹成分抑制P. acnes之活性 95
五、 山竹抗菌活性之綜合探討 95
第四節 活性成分之定量分析 96
一、 山竹果殼指紋圖譜之建立及成分化合物HPLC分析 96
二、 山竹果殼中各成分之定量 102
(一) 成分檢量線之製作 102
(二) 確認實驗準確度 103
(三) 山竹萃取物及市售品之成分含量分析 104
第五節 山竹成分快速劃分方法之開發 107
一、 山竹果殼粗萃物經Sephadex LH-20管柱分離後的分佈 107
二、 ESI/ MS鑑定山竹果殼粗萃物之xanthones 108
第四章 結論 112
一、 山竹成分快速劃分方法之開發 112
二、 山竹果殼成分之綜合活性比較 112
三、 山竹果殼中xanthone衍生物可能生合成路徑 113
參考文獻 116
附表 S1
附圖 S11

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