Acta Chimica Sinica ›› 2012, Vol. 70 ›› Issue (06): 796-802.DOI: 10.6023/A1109071 Previous Articles     Next Articles

Special Topic

AT1 受体的中药活性成分筛选模型及其作用机理研究

吴琼a, 康宏b, 王欢欢a, 高军b,c, 朱瑞新a,b, 康廷国a   

  1. a 辽宁中医药大学药学院 大连 116600;
    b 同济大学生命科学与技术学院 上海 200092;
    c 上海海事大学信息工程学院 上海 201306
  • 投稿日期:2011-09-07 修回日期:2011-11-28 发布日期:2011-12-19
  • 通讯作者: 朱瑞新
  • 基金资助:

    国家自然科学基金(No. 30976611)、高等学校博士学科点专项科研基金(No. 2010-0072120050)资助项目.

AT1R-based Virtual Screening Model for Bioactive Components from Traditional Chinese Medicines and Its Mechanism Study

Wu Qionga, Kang Hongb, Wang Huanhuana, Gao Junb,c, Zhu Ruixina,b, Kang Tingguoa   

  1. a School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China;
    b School of Life Sciences and Technology, Tongji University, Shanghai 200092, China;
    c School of Information Engineering, Shanghai Maritime University, Shanghai 201306, China
  • Received:2011-09-07 Revised:2011-11-28 Published:2011-12-19
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 30976611), the Specialized Research Fund for the Doctoral Program of Higher Education of China (No. 2010-0072120050).

The traditional Chinese medicine (TCM) has a significant effect on the treatment of cardiovascular diseases and some has been widely used in clinical therapy, such as Uncaria, Astragalus and Motherwort. The previous research found that Rhy could lower blood pressure; Calycosin in Astragalus could relax vascular smooth muscle, protect cardiovascular and cerebrovascular; and Leonurine could increase telangiectasia, improve abnormity of hemorheology; however, the mechanism of these was not clear. Here, the structure of receptor AT1, which was the main target of cardiovascular diseases, has been modeled based on the crystal structure of bovine rhodopsin; meanwhile, the interaction of receptor AT1 antagonists to receptor AT1 was compared with that of the active compounds in TCMs. The results indicated that Calycosin and Leonurine could bind the residues Try113, Lys199, Gln257, Ser105 by hydrogen bonds, and the mechanism was similar with receptor AT1 antagonists which bound with the residues His183, Lys199, His256, Gln257,Ser105, Ser109, Tyr113, Asn200. In this study, the mechanism of some TCM active compounds was explained on molecular level, which provided a foundation for further screening and rational design of AT1R antagonists from traditional Chinese medicine.

Key words: angiotensin Ⅱ type 1 receptor, active components in traditional Chinese medicine, homology model, molecular docking, molecular mechanism