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首页> 外文期刊>RSC Advances >Combination of icariin and oleanolic acid attenuates in vivo and in vitro glucocorticoid resistance through protecting dexamethasone-induced glucocorticoid receptor impairment
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Combination of icariin and oleanolic acid attenuates in vivo and in vitro glucocorticoid resistance through protecting dexamethasone-induced glucocorticoid receptor impairment

机译：通过保护地塞米松诱导的糖皮质激素受体损伤，鞘翅蛋白和葡聚糖酸的组合衰减和体外糖皮质激素抗性

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摘要

Glucocorticoid resistance (GCR) remains a significant problem and is the most important reason for treatment failure of glucocorticoids (GCs). How to increase the sensitivity to GCs and exploring new agents to overcome GCR is of great significance. Herein, we report for the first time that the effects of combination of icariin and oleanolic acid (OA) on dexamethasone (Dex)-induced glucocorticoid receptor (GR) impairment in vivo and in vitro. Compared with the use of Dex or combination of icariin and OA alone, co-administration resulted in a significant increase in apoptosis, GR protein, GR binding and GR alpha protein both in GC-sensitive CEM-C7 and GC-resistant CEM-C1 cells and a decrease in GR beta protein and GR beta/GR alpha only in CEM-C1 cells. Furthermore, an ovalbumin-induced rat asthma model was chosen to evaluate the effects of co-administration of Dex and combination of icariin and OA in vivo. Compared with the use of Dex alone, co-administration could protect blood lymphocyte from excessive apoptosis, significantly increasing GR binding, GR protein and mRNA of GR alpha while decreasing GR beta protein and mRNA of GR beta. The results suggested that combination of icariin and OA could increase sensitivity to GCs through attenuating in vivo and in vitro Dex-induced GR impairment.
机译：糖皮质激素抗性（GCR）仍然是一个重要问题，是糖皮质激素治疗失败的最重要原因（GCS）。如何增加对GCS的敏感性，并探索新代理商克服GCR具有重要意义。在此，我们首次报告了赤素蛋白和甲醛酸（OA）组合对地塞米松（DEX）诱导的糖皮质激素受体（GR）损伤在体内和体外损伤的影响。与单独使用乙素和OA的使用相比，共同给药导致GC敏感CEM-C7和GC抗性CEM-C1细胞中的细胞凋亡，GR蛋白，GR结合和GRα蛋白显着增加并且仅在CEM-C1细胞中降低GRβ蛋白和GRβ/GRα.此外，选择卵泡诱导的大鼠哮喘模型来评估乙烯和OA在体内共同施用和组合的影响。与单独使用DEX相比，共同施用可以保护血液淋巴细胞过量凋亡，显着增加GRα谷物GR蛋白和MRNA的GRα的同时降低GRβ蛋白和GRβ的mRNA。结果表明，通过体内和体外DEX诱导的GR损伤，ICARIIN和OA的组合可以通过衰减和体外诱导的GR损伤来增加对GCS的敏感性。

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  • 来源
    《RSC Advances》 |2018年第1期|共13页
  • 作者

    Tang Xiu-Feng; Li Xiao-Xi; Chen Yu-Heng; Gao Ying-Ying; Yu Ping; Xu Li-Ping; Liu Ren-Hui;

  • 作者单位

    Capital Med Univ Sch Tradit Chinese Med Room 283 Bldg Jie Ping 10 Xitoutiao Beijing 100069 Peoples R China;

    Capital Med Univ Sch Tradit Chinese Med Room 283 Bldg Jie Ping 10 Xitoutiao Beijing 100069 Peoples R China;

    Capital Med Univ Sch Tradit Chinese Med Room 283 Bldg Jie Ping 10 Xitoutiao Beijing 100069 Peoples R China;

    Capital Med Univ Sch Tradit Chinese Med Room 283 Bldg Jie Ping 10 Xitoutiao Beijing 100069 Peoples R China;

    Capital Med Univ Sch Tradit Chinese Med Room 283 Bldg Jie Ping 10 Xitoutiao Beijing 100069 Peoples R China;

    Capital Med Univ Sch Tradit Chinese Med Room 283 Bldg Jie Ping 10 Xitoutiao Beijing 100069 Peoples R China;

    Capital Med Univ Sch Tradit Chinese Med Room 283 Bldg Jie Ping 10 Xitoutiao Beijing 100069 Peoples R China;

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  • 正文语种 eng
  • 中图分类 化学;
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