- 學位論文
第一部分 松針層孔菌二次代謝產物與生物活性之研究 第二部分 胡氏肉桂葉部之化學成分及降血糖活性之研究
Part I Secondary Metabolites and Bioactivities from the Fungus, Porodaedalea pini Part II Chemical constituents and anti-hyperglycemic activity from the leaves of Cinnamomum macrostemon
摘要
第一部分: 松針層孔菌二次代謝產物與生物活性之研究 松針層孔菌 (Porodaedalea pini (Brot.) Murrill)為刺革菌科的真菌，主要分布於北半球溫熱帶區域，會造成常見的紅環腐爛或是白斑，為森林中重要的干擾劑，經篩選過後發現，其發酵液具有調節雄性激素受體 (androgen receptor, AR)的活性。利用生物活性導向分離試驗及圖譜分析法，由松針層孔菌之乙酸乙酯萃取物中分離得到八個化合物，其中包含三個新化合物—piniphenol A (PP-1), piniphenol B (PP-2)及piniphenol C (PP-3)，以及五個已知化合物。piniphenol A (PP-1)具有中度的調節雄性激素活性；另一方面，也發現piniphenol A (PP-1)具有中度抑制NO產生的活性，IC50值為60.0 μM 。 第二部分: 胡氏肉桂葉部之化學成分及降血糖活性之研究 胡氏肉桂 (Cinnamomum macrostemon Hayata)是樟科 (Lauraceae)樟屬 (Cinnamomum)的常綠中喬木，為台灣固有種。經由初步SGLT抑制活性篩選，從約60種樟科植物的甲醇萃取物中，發現胡氏肉桂的甲醇萃取物最具SGLT抑制活性。利用生物活性導向分離試驗及光譜分析法，由胡氏肉桂的活性水層分離得到15個化合物，包含1個megastigmane類新化合物—cinnamacroside以及14個已知化合物，包含11個flavonoids, 以及benzenoid、lignan、coumarin各一個.。於乙酸乙酯層萃取物分離得到21個已知化合物。其中活性水層得到的活性化合物kaempferol-3-O-β-D-glucopyranosyl-(1→4)-α-L-rhamnopyranosyl-7-O-α-L-rhamno-pyranoside (PP-8) 及kaempferol-3-O-(2"-β-D-glucopyranosyl)-α-L-rhamnopyranoside (PP-10) 對dual SGLT1/SGLT2顯示具有100% 抑制活性
並列摘要
Part I. Secondary metabolites from the fungus, Porodaedalea pini A fungus Porodaedalea pini (Brot.) Murrill (Phellinus pini) (Hymenochaetaceae), which causes tree diseases commonly known as “red ring rot” or “white speck”, is an important forest disturbance agent and plays a key role in habitat formation for several forest animals. P. pini was processed through liquid-state fermentation, and its liquid fermentate showed androgen regulation (AR) activity based on the preliminary screening. Bioassay-guided fractionation of the active ethyl acetate-soluble layer of the liquid fermentate of P. pini led to the isolation of three new aromatic compounds, piniphenol A (PP-1), piniphenol B (PP-2), and piniphenol C (PP-3) along with five known compounds, 4-vinylphenol (PP-4) and 4-hydroxybenzaldehyde (PP-5), 2-methoxy-2-(4'-hydroxyphenyl)ethanol (PP-6), 2,3-dihydroxypropyl acetate (PP-7), and phenol (PP-8). The structures of these compounds were elucidated by spectral analysis. Among the isolates, piniphenol A (PP-1) showed moderate androgen antagonism activity with 0.42 μM. On the other hand, PP-1 showed moderate NO inhibitory activity with IC50 value of 60.0 μM as well. Part II. Chemical constituents and anti-hyperglycemic activity from the leaves of Cinnamomum macrostemon Glucose transport and metabolism are tightly associated with diseases including diabetes. Sodium-coupled glucose co-transporters (SGLTs), SGLT1 and SGLT2 are important for intestinal absorption and renal reabsorption of glucose, respectively. Previous study reported that dual SGLT1/SGLT2 inhibitor as adjunct therapy to insulin in type 1 diabetes mellitus can improve glycemic control and overcome the side effect, such as hypoglycemia and weight loss. Cinnamomum macrostemon Hayata is a medium-sized evergreen tree, endemic to Taiwan and grows at medium to high altitudes. Approximately 60 species of Lauraceae plants have been screened for the SGLT inhibitory activity, and C. macrostemon was shown as the most active species. Bioassay-guided fractionation of the active water-soluble layer led to the isolation of one new megastigmane, cinnamacroside and fourteen known compounds, including eleven flavonoids, one benzenoid, one lignan, and one coumarin. Twenty-one known compounds were also isolated from ethyl acetate-soluble layer, including three steroids, three benzenoids, eight lignans, one amide, one quinone, and three flavonoids. Among the isolates from the active water-soluble layer, kaempferol-3-O-β-D-glucopyranosyl-(1→4)-α-L-rhamnopyranosyl-7-O-α-L-rhamno-pyranoside (CM-8) and kaempferol-3-O-(2"-β-D-glucopyranosyl)-α-L-rhamnopyranoside (CM-10) showed 100% inhibitory activity toward dual SGLT1/SGLT2.