臺灣博碩士論文加值系統

牛樟芝(Antrodia cinnamomea)為臺灣特有種藥用真菌，天然情況下只生長在牛樟木中空的樹幹內，現今已有椴木栽培、液態、固態和皿培式培養等生產方式，並被證明具有抗發炎和抗癌作用等活性。透過評估固態培養牛樟芝(ANCI)抗發炎活性，期望能提供未來開發ANCI成為抗發炎藥物的依據。
在初步的抗發炎試驗中，固態培養牛樟芝菌絲體的乙醇萃取物(ANCI-E)在50~100 μg/ml 時可以抑制脂多醣(LPS)誘導巨噬細胞RAW 264.7的一氧化氮(NO)產生。將ANCI-E溶於水中以氯仿分配萃取後，分別獲得氯仿層(ANCI-C)和水層(ANCI-W)。經活性試驗發現ANCI-C在25-100 μg/ml 能顯著抑制LPS 誘導RAW 264.7之NO的產生，因此，進行ANCI-C的成分分離和鑑定並評估其抗發炎活性。ANCI-C分別採用管柱層析、薄層層析和高效液相色譜法進行分離，共得到11個化合物。以化合物光譜數據與文獻比對確認結構為4,7-dimethoxy-5-methyl-1,3-benzodioxole (1)、1,2-dihydroxy-3,6-dimethoxy-4-methylbenzene (2)、antrodin B (3)、24-methylenelanost-8-en-3-ol (4)、dehydroeburicoic acid (5)、antcin A (6)、ubiquinone-3 (7)、4-acetylantroquinonol B (8)、antrocamol LT2 (9)、4-acetylantrocamol LT3 (10) 與 4-acetylantroquinonol K (11)。
將分離的化合物進行抗發炎活性評估，結果顯示3、6與7在10和30 μM 及2、8、9、10與11在30 μM時均能抑制LPS刺激RAW 264.7細胞的NO產生，而在細胞訊息傳遞機制探討則發現ANCI-C在25-100 μg/ml時會顯著抑制誘導型一氧化氮合成酶(iNOS)的表達，以及在50-100 μg/ml 時也會顯著抑制環氧合酶-2(COX-2)的表達，推測ANCI之抗發炎機制可能經由抑制iNOS及COX-2來達成，其餘化合物之作用機制正在進行中。

Antrodia cinnamomea is a well known medicinal fungus that is native to Taiwan. In natural circumstances, it only grows in the hollow trunk of Cinnamomum kanehirae. Now it can be cultured by wood cultivation, liquid fermentation, solid-state fermentation, and petri-cultivation. Pharmaceutical study showed that it exhibited anti-inflammatory and anticancer activities. By evaluating the anti-inflammatory activity of solid-state fermented Antrodia cinnamomea mycelium (ANCI), this study can provide a scientific data for developing ANCI as an anti-inflamatory agent in the furture.
In a investigation for anti-inflammatory compound of potential therapeutic value, we found the ethanol extract of solid-state fermented A. cinnamomea mycelium (ANCI-E) can inhibited NO production on lipopolysaccharide (LPS)-induced RAW 264.7 macrophages at 50~100 μg/ml. The ANCI-E were dissolved with water and partitioned with chloroform to obtain chloroform and water layer. The chloroform layer of ANCI (ANCI-C) displayed the inhibition effect on NO production of LPS-induced RAW 264.7 cells at 25-100 μg/ml, significantly. Therefore, aims of this study were to isolate and identify the bioactive constituents of ANCI-C, and to assess their anti-inflammatory activities. The chloroform layer was separated by using column, thin-layer, and high performance liquid chromatography, to obtain eleven compounds. Their structures were characterized by spectroscopic analysis, and comparison with the literature data, and named as 4,7-dimethoxy-5-methyl-1,3-benzodioxole (1), 1,2-dihydroxy-3,6-dimethoxy-4-
methylbenzene (2), antrodin B (3), 24-methylenelanost-8-en-3-ol (4), dehydroeburicoic acid (5), antcin A (6), ubiquinone-3 (7), 4-acetylantroquinonol B (8), antrocamol LT2 (9), 4-acetylantrocamol LT3 (10) and 4-acetylantroquinonol K (11).
Eleven compounds were assessed the anti-inflammatory activities. The results showed that 3, 6, and 7 (10, and 30 μM ), and 2, 8, 9, 10, and 11 (30 μM) can inhibit nitric oxide (NO) production on LPS-stimulated RAW 264.7 cells, significantly. The ANCI-C also showed the inhibition effects on inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. The mechanism of compounds are still needed to clarity.

摘要.....i
Abstract.....ii
誌謝.....iv
目錄.....v
表目錄.....vii
圖目錄.....viii
附圖目錄.....ix
第一章 緒論.....1
1-1 前言.....1
1-2 牛樟芝介紹.....3
1-3 研究目的.....4
第二章 文獻回顧.....5
2-1 牛樟芝化學成分回顧.....5
2-2 牛樟芝藥理活性回顧.....41
2-3 牛樟芝專利檢索.....51
第三章 化學成分抽取與分離.....53
第四章 化合物之結構鑑定.....56
4-1 4-acetylantroquinonol B (8)之結構鑑定.....56
4-2 Antrocamol LT2 (9)之結構鑑定.....58
4-3 4-acetylantrocamol LT3 (10)之結構鑑定.....60
4-4 4-acetylantroquinonol K (11)之結構定.....62
第五章 活性試驗結果與討論.....64
5-1 牛樟芝粗萃物、氯仿層和水層對LPS誘導RAW 264.7之細胞存活率試驗.....64
5-2 牛樟芝粗萃物、氯仿層和水層對LPS誘導RAW 264.7 cells的抑制NO表現.....65
5-3 化合物1-11對LPS誘導RAW 264.7之細胞存活率試驗.....66
5-4 化合物1-11對LPS誘導RAW 264.7 cells的抑制NO表現.....67
5-5 牛樟芝氯仿層對LPS誘導RAW 264.7 cells蛋白表達之影響.....68
第六章 實驗方法.....69
6-1實驗材料與儀器.....69
6-2 萃取、分離與純化.....73
6-3 細胞培養方法.....75
6-4 藥理活性測試方法.....76
6-5 西方墨點法.....77
6-6 數據分析.....81
6-7 化合物之物理及光譜數據.....82
第七章 結論.....86
參考文獻.....87
Extended Abstract.....106

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