Antcin A, a steroid-like compound from Antrodia camphorata, exerts anti-inflammatory effect via mimicking glucocorticoids  

作　　者：Yi-ching CHEN Ya-lin LIU Feng-yin LI Chi-I CHANG Sheng-yang WANG Kuo-yang LEE Shun-lai LI Yi-peng CHEN Tzyy-rong JINN Jason TC TZEN 

机构地区：[1]Graduate Institute of Biotechnology [2]Department of Chemistry [3]Graduate Institute of Biotechnology, National Pingtung University of Science and Technology,Pingtung 91201, Taiwan, China [4]Department of Forestry, National Chung Hsing University,Taichung 40227, Taiwan, China [5]Center for General Education, Southern Taiwan University of Technology, Tainan 71005, Taiwan,China [6]Department of Biotechnology, Southern Taiwan University of Technology, Tainan 71005, Taiwan, China [7]School of ChineseMedicine, China Medical University, Taichung 40402, Taiwan, China [8]Agricultural Biotechnology Research Center, Academia Sinica,Taipei 11529, Taiwan, China

出　　处：《Acta Pharmacologica Sinica》2011年第7期904-911,共8页中国药理学报（英文版）

摘　　要：Aim： To determine the active ingredient of Niuchangchih （Antrodia camphorata） responsible for its anti-inflammatory effects and the relevant molecular mechanisms. Methods： 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. Molecular docking was performed to model the tertiary structure of GR associated with antcins. Results： 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 glu- cocorticoid 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. Conclusion： 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.Aim： To determine the active ingredient of Niuchangchih （Antrodia camphorata） responsible for its anti-inflammatory effects and the relevant molecular mechanisms. Methods： 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. Molecular docking was performed to model the tertiary structure of GR associated with antcins. Results： 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 glu- cocorticoid 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. Conclusion： 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.

关 键 词：antcin A Antrodia camphorata CORTISONE DEXAMETHASONE glucocorticoid receptor ANTI-INFLAMMATION 

分 类 号：Q577[生物学—生物化学] TQ655[化学工程—精细化工]