海洋来源土曲霉中丁烯酸内酯成分的分离及其抗神经炎症活性评价

Isolation of butyric acid lactone compounds from marine-derived Aspergillus terreus and evaluation of their anti-neuroinflammatory activity

摘要:

目的 探讨南海来源土曲霉 Aspergillus terreus 中的丁烯酸内酯成分及其体外抗神经炎症活性。 方法 采用正相、反相硅胶柱层析和半制备高效液相色谱等分离方法对Aspergillus terreus大米发酵提取物进行分 离纯化，通过核磁共振波谱、质谱和电子圆二色光谱计算的方法对获得的单体化合物进行结构鉴定，并测试化合物 对脂多糖（LPS）诱导BV-2小胶质细胞中NO释放的抑制作用，分别设置空白对照组、模型组（加入LPS）、给药组（加 入LPS和化合物）和阳性对照组（加入LPS和地塞米松）。结果 分离鉴定了6个丁烯酸内酯化合物1 ~ 6，包括1个 新化合物 1。与空白对照组比较，模型组 LPS诱导的 BV-2细胞中 NO 含量显著升高（P < 0.001）；与模型组比较，化 合物2 ~ 4和6细胞培养液中NO含量均显著降低（P < 0.001或0.05），但是化合物5细胞培养液中的NO含量无显著 差异（P > 0.05）。结论 从海洋真菌 Aspergillus terreus中发现 1个新的丁烯酸内酯化合物（化合物 1）；化合物 2 ~ 4 和6具有较弱的抗神经炎症活性。

Abstract:

Objective To investigate into the butenolides and their anti- neuroinflammatory activities derived from the marine-associated fungus Aspergillus terreus. Methods Normal-phase and reversed-phase silica gel column chromatography and semi-preparative high performance liquid chromatography were employed to isolate the compounds; Structural elucidation was determined using nuclear magnetic resonance spectroscopy (NMR), mass spectrometry (MS), and calculated and experimental electronic circular dichroism (ECD) data; The isolated compounds were evaluated for their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV-2 cells. A blank control group, a model group (with LPS added), an administration group (with both LPS and the compound added), and a positive control group (with LPS and dexamethasone added) were set up for the test. Results Six butenolide derivatives (1-6) were isolated and identified, including one novel compound (1). Compared with the blank control group, the NO content in LPS-activated BV-2 cells of the model group was significantly increased (P < 0.001); In comparison to the model group, the NO content in the cell culture medium of the compounds 2, 3, 4, 6 were significantly decreased (P < 0.001 or P < 0.005). However. no significant difference was observed in the NO content in the compound 5 group. Conclusions A novel butenolide derivative (compound 1) was isolated from the marine-derived fungus Aspergillus terreus, while compounds 2-4 and 6 exhibited weak anti-neuroinflammatory activities.