Antiplatelet Effect and Selective Binding to Cyclooxygenase (COX) by Molecular Docking Analysis of Flavonoids and Lignans

International Journal of Molecular Sciences

Chien-Ming Wu⁵  Shu-Chun Wu²  Wan-Jung Chung¹  Hsien-Cheng Lin⁷  Kun-Tze Chen⁶  Yu-Chian Chen⁶  Mei-Feng Hsu⁴  Jwu-Maw Yang¹  Jih-Pyang Wang³ 

[1] Department of Biotechnology, Chia-Nan University of Pharmacy and Science, Tainan Hsien 717, Taiwan;School of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan;Department of Education and Research, Taichung Veterans General Hospital, Taiwan 407, Taiwan;Department of Biochemistry, China Medical University, Taichung 404, Taiwan;Department of Physical Medicine and Rehabilitation, Yuan’s General Hospital, Kaohsiung 802, Taiwan;Department of Biological Science and Technology, China Medical University, Taichung 404, Taiwan;School of Technology for Medical Science, Kaohsiung Medical University, Kaohsiung 807, Taiwan

关键词: Flavonoids;    lignans;    antiplatelet;    COX-1;    molecular docking;   

DOI  :  10.3390/i8080830

来源: mdpi

【 摘 要 】

The known flavonoids ginkgetin (1), taiwanhomoflavone A (2), taiwanhomoflavone B (3), and taiwanhomoflavone C (4) and eight known lignans: justicidin B (9), justicidin C (10), justicidin D (11), chinensinaphthol methyl ether (12), procumphthalide A (13), procumbenoside A (15), and ciliatosides A (16) and B (17) were isolated from Cephalotaxus wilsoniana and Justicia species, respectively. The antiplatelet effects of the above constituents on human platelet-rich plasma (PRP) were evaluated. Of the compounds tested on human PRP, compounds 1, 4, 9, and 11 showed inhibition of secondary aggregation induced by adrenaline. Compound 1 had an inhibitory effect on cyclooxygenase-1 (COX-1). Molecular docking studies revealed that 1 and the related compounds apigenin (5), cycloheterophyllin (6), broussoflavone F (7), and quercetin (8) were docked near the gate of active site of COX-1. It indicated that the antiplatelet effect of 1, 4, 9, and 11 is partially owed to suppression of COX-1 activity and reduced thromboxane formation. Flavonoids, 1, 5, 6, 7, and 8 may block the gate of the active site of COX-1 and interfere the conversion of arachidonic acid to prostaglandin (PG) H₂ in the COX-1 active site.

【 授权许可】

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