Citation: LIU Hai-Bo, CUI Wei, XU Jun, PENG Yong, ZHOU Jia-Ju, XIAO Pei-Gen. Molecular Simulations of the Inhibition of Active Components in Traditional ChineseMedicine on the Thromboxane A2 Receptor[J]. Acta Physico-Chimica Sinica, ;2010, 26(09): 2549-2556. doi: 10.3866/PKU.WHXB20100844 shu

Molecular Simulations of the Inhibition of Active Components in Traditional ChineseMedicine on the Thromboxane A2 Receptor

LIU Hai-Bo ¹ ,
CUI Wei ² ,
XU Jun ^3, ,
PENG Yong ^1, ,
ZHOU Jia-Ju ⁴ ,
XIAO Pei-Gen ¹

1.
1. Institute of Medicinal Plant Development, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100193, P. R. China;
2. College of Chemistry and Chemical Engineering, Graduate University of Chinese Academy of Sciences, Beijing 100049, P. R. China;
3. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510275, P. R. China;
4. Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, P. R. China)

Received Date: 10 February 2010
Available Online: 7 July 2010
Fund Project: 国家自然科学基金重点项目(30530860)资助 (30530860)

Some natural products from traditional Chinese medicine (TCM) such as flavones and resveratrol have been reported to have thromboxane A2 receptor (TP) inhibiting activity.We investigated a possible inhibition mechanism by a homology model of TP, which was built based on the crystal structure of squid rhodopsin. After that, docking methods were used to investigate the binding modes of resveratrol and apigenin in the active pocket of TP. Furthermore, a three- dimensional pharmacophore model was generated for screening other potential natural TP inhibitors. The results indicate that resveratrol and apigenin bind to the active site of TP similar to the way that thromboxane A2 binds to Ser201, Leu198, Arg295, and Thr298. The former three key residues can form hydrogen bonds with the inhibitors. The pharmacophore model consisted of seven features and a set of volume spheres, which has been proven to be efficient in identifying compounds with high TP inhibition activity. In this way, a set of potential TP inhibitors were screened from a natural product database. Some of them were reported to have platelet aggregation inhibiting activities. This research indicates that TP could be an important target of TCMdrugs with blood circulation activation effects.
- Traditional Chinese medicine,
- Drug target,
- Thromboxane A2 receptor,
- Blood circulation activating
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