烏靈參之生物活性成分研究

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Title:	烏靈參之生物活性成分研究 Bioactive Constituents from Wu-Ling-Shen, a Termite Associated Xylaria nigripes YMJ653
Authors:	張榮純 Chang, Jung-Chun
Contributors:	林若凱
Keywords:	黑柄炭角菌;倍半萜;類;誘發型一氧化氮合成酶;第二型環氧合酶;基質金屬蛋白酵素 Xylaria nigripes;Sesquiterpene;iNOS;COX-2;MMP
Date:	2015-07-16
Issue Date:	2020-08-28 14:39:48 (UTC+8)
Abstract:	白蟻巢菌圃 (fungus comb or garden) 中包含許多種微生物，在生態演替中扮演重要的角色，尤其是炭角菌屬 (Xylaria spp.) 的真菌，而且，該菌屬的子實體 (fruiting body) 長久以來就被使用於中國傳統醫藥作為鎮靜、催眠藥或用於增強記憶的用藥，意謂著該類真菌為活性化合物的潛在來源。因此選擇黑柄炭角菌 Xylaria nigripes YMJ653 進行發酵培養及其二次代謝物研究。從液態發酵液純化分離出 13 個化合物，經一系列的光譜解析始確認結構，其中有9個新化合物，分別是6個eremophilane-type sesquiterpene類化合物 nigriterpene A-F (1-6);1 個 guaiane-type sesquiterpene 類化合物 (+)-epi-guaidiol A (12) 和 1 個 ambrosanolide-type sesquiterpene 類化合物 (+)-ambrosanoli-10,11-diol (13);1 個 aromatic 類化合物 2-(hydroxymethyl)-3-pentylphenol (11)，還有 4 個已知化合物，分別是 2 個 benzofuran-type aromatic 類化合物 fomannoxin alcohol (7) 和 fomannoxin (8);以及其他的 3-butyl-7-hydroxyphthalide (9) 及 scytalone (10)。在活性試驗上，以 BV-2 細胞株探討 13 個化合物純質 (1-13) 對脂多醣(LPS) 誘導發炎蛋白之影響，結果發現化合物3同時可抑制誘發型一氧化氮合成酶 (iNOS) 和第二型環氧合酶 (COX-2) 的生成，且具有顯著效果,與未誘發組相比較，其 iNOS 蛋白表現為 1.9 ± 1.1 倍，COX-2 蛋白表現為 2.4 ± 0.3 倍。另以 HTP-1 細胞株探討化合物 6 在不同濃度下，對於基質金屬蛋白酵素-9 (MMP-9) 的抑制及細胞毒殺活性，結果顯現隨化合物濃度增加使得 MMP-9 的活性漸次降低，以及細胞毒殺活性逐漸增加。 The fungus comb of Odontotermes formosanus contains many microbes, especially Xylaria sp., whose growth and metabolic activity are likely to play important roles in the termite neet. And, the fruiting bodies of Xylaria species have long been used in traditional Chinese medicine as sedative-hypnotics or memory-enhancing drugs, suggesting a potential source for medicinally useful compounds. Thus, Xylaria nigripes YMJ653 was selected for fermentation and investigation on its bioactive principles. Six new eremophilane-type sesquiterpenes nigriterpene A-F (1-6), one new guaiane-type sesquiterpenes (+)-epi-guaidiol A (12) , one new ambrosanolide-type sesquiterpene (+)-ambrosanoli-10,11-diol (13), one new aromatic 2-(hydroxymethyl)-3-pentylphenol (11), together with previously reported two benzofuran-type aromatics fomannoxin alcohol (7) and fomannoxin (8), as well as 3-butyl-7-hydroxyphthalide (9) and scytalone (10) were isolated from liquid state fermented broths of Xylaria nigripes YMJ653. The effect of compounds 1-13 on the inhibition of inducibe nitric oxide synthase (iNOS) and cyclooxygeneas-2 (COX-2) production in lipopolysaccharide (LPS)-activated BV-2 cells was further evaluated. Compound 3 possessed stronger effect on iNOS and COX-2 inhibition, with 1.9 ± 1.1 folds on iNOS and 2.4 ± 0.3 folds on COX-2 which compared with non-LPS-induced BV-2 cells. The effect of compound 6 on the inhibition of MMP-9 activation in LPS-induced THP-1 cells was further evaluation, and it showed significant inhibitory effect on MMP-9 and cytotoxicity in a does-dependent manner.
Description:	碩士指導教授:林若凱委員:盧重光委員:蕭哲志委員:李慶國
Data Type:	thesis
Appears in Collections:	[Graduate Institute of Pharmacognosy Science] Dissertation/Thesis

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