Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Bioorg Med Chem. 2013 Jul 1;21(13):3866-72. doi: 10.1016/j.bmc.2013.04.004. Epub 2013 Apr 13.
The addition of a DNA methyltransferase inhibitor, 5-azacytidine, to Aspergillus sydowii fungus culture broth changed its secondary metabolites profile. Analysis of the culture broth extract led to the isolation of three new bisabolane-type sesquiterpenoids: (7S)-(+)-7-O-methylsydonol (1), (7S,11S)-(+)-12-hydroxysydonic acid (2) and 7-deoxy-7,14-didehydrosydonol (3), along with eight known compounds. The isolated compounds were evaluated for their anti-diabetic and anti-inflammatory activities. Among the isolates, (S)-(+)-sydonol (4) did not only potentiate insulin-stimulated glucose consumption but also prevented lipid accumulation in 3T3-L1 adipocytes. Additionally, (S)-(+)-sydonol (4) exhibited significant anti-inflammatory activity through inhibiting superoxide anion generation and elastase release by fMLP/CB-induced human neutrophils. This is the first report on isolating a secondary metabolite with anti-diabetic and anti-inflammatory activities from microorganisms.
氮杂胞苷的添加改变了蛹虫草真菌培养液的次生代谢产物谱。对培养液提取物的分析导致了三种新的倍半萜类化合物的分离：（7S）-（+）-7-O-甲基蛹虫草醇（1）、（7S，11S）-（+）-12-羟基蛹虫草酸（2）和 7-去氧-7,14-二脱水蛹虫草醇（3），以及八种已知化合物。对分离得到的化合物进行了抗糖尿病和抗炎活性评价。在所分离的化合物中，（S）-（+）-蛹虫草醇（4）不仅增强了胰岛素刺激的葡萄糖消耗，而且还防止了 3T3-L1 脂肪细胞中的脂质积累。此外，（S）-（+）-蛹虫草醇（4）通过抑制 fMLP/CB 诱导的人中性粒细胞中超氧阴离子生成和弹性蛋白酶释放，表现出显著的抗炎活性。这是首次从微生物中分离出具有抗糖尿病和抗炎活性的次生代谢产物的报道。
