Graduate Institute of Biotechnology, National Chung Hsing University, Taichung 40227, Taiwan, China.
Acta Pharmacol Sin. 2011 Jul;32(7):904-11. doi: 10.1038/aps.2011.36. Epub 2011 May 23.
To determine the active ingredient of Niuchangchih (Antrodia camphorata) responsible for its anti-inflammatory effects and the relevant molecular mechanisms.
Five major antcins (A, B, C, H, and K) were isolated from fruiting bodies of Niuchangchih. Structural similarity between the antcins and 2 glucocorticoids (cortisone and dexamethasone) was compared. After incubation with each compound, the cytosolic glucocorticoid receptor (GR) was examined for its migration into the nucleus. Mo lecular docking was performed to model the tertiary structure of GR associated with antcins.
Incubation with cortisone, dexamethasone or antcin A (but not antcins B, C, H, and K) led to the migration of glucocorticoid receptor into the nucleus. The minimal concentration of antcin A, cortisone and dexamethasone to induce nuclear migration of glucocorticoid receptor was 10, 1, and 0.1 mol/L, respectively. The results are in agreement with the simulated binding affinity scores of these three ligands docking to the glucocorticoid receptor. Molecular modeling indicates that C-7 of antcin A or glucocorticoids is exposed to a hydrophobic region in the binding cavity of the glucocorticoid receptor, and the attachment of a hydrophilic group to C-7 of the other four antcins presumably results in their being expelled when docking to the cavity.
The anti-inflammatory effect of Niuchangchih is, at least, partly attributed to antcin A that mimics glucocorticoids and triggers translocation of glucocorticoid receptor into nucleus to initiate the suppressing inflammation.
确定牛樟芝（樟芝）中具有抗炎作用的活性成分及其相关的分子机制。
从牛樟芝的子实体中分离出五种主要的安特辛（A、B、C、H 和 K）。比较了安特辛与两种糖皮质激素（可的松和地塞米松）之间的结构相似性。在与每种化合物孵育后，检查细胞溶质糖皮质激素受体（GR）是否进入细胞核。进行分子对接以模拟与安特辛相关的 GR 的三级结构。
与可的松、地塞米松或安特辛 A（而非安特辛 B、C、H 和 K）孵育会导致糖皮质激素受体向核内迁移。诱导糖皮质激素受体核内迁移的最小安特辛 A、可的松和地塞米松浓度分别为 10、1 和 0.1 mol/L。这些结果与这三种配体对接至糖皮质激素受体的模拟结合亲和力评分一致。分子建模表明，安特辛 A 或糖皮质激素的 C-7 暴露于糖皮质激素受体结合腔中的疏水区，而其他四种安特辛的 C-7 上连接亲水基团可能导致它们在对接至腔时被排出。
牛樟芝的抗炎作用至少部分归因于安特辛 A，它模拟糖皮质激素并触发糖皮质激素受体向核内易位，从而启动抑制炎症。
