Anti-thrombotic effect of W007B, a newly synthesized compound, in vitro and in vivo

doi:10.5246/jcps.2014.11.096

Journal of Chinese Pharmaceutical Sciences ›› 2014, Vol. 23 ›› Issue (11): 760-764.DOI: 10.5246/jcps.2014.11.096

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Anti-thrombotic effect of W007B, a newly synthesized compound, in vitro and in vivo

Kun Hu¹, Xiaoyan Liu¹, Yuanjun Zhu¹, Jingliang Zhang¹, Ye Liu², Yinye Wang^1*

1. Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
2. Beijing Honghui New Medical Technology Co. Ltd., Beijing 102600, China

Received:2014-05-12 Revised:2014-05-27 Online:2014-11-24 Published:2014-06-06
Contact: Tel.: 86-10-82802652, Fax: 86-10-62015584
Supported by:
Natural Science Foundation of China (Grant No. 81302763) and Beijing Natural Science Foundation (Grant No. 7144218).

Abstract

Abstract:

In the present study, we investigated anti-thrombotic effects of W007B, a water-soluble derivative of honokiol, with different models both in vitro and in vivo. Rat platelet aggregation was induced by adenosine diphosphate (ADP), thrombin, arachidonic acid (AA) and collagen in vitro. The anti-thrombotic effects were evaluated with the arterio-venous shunt model, electrode-stimulated carotid thrombosis model in rats and ADP-induced acute pulmonary embolic model in mice. The bleeding time in vivo was examined with tail incision in mice. W007B inhibited ADP-, thrombin-, collagen- and AA-induced platelet aggregation in a concentration-dependent manner, with an IC₅₀ value of899.5 μM, 212.9 μM, 266.0 μM and 52.5 μM, respectively. In vivo, W007B (2–10 mg/kg, ig) significantly reduced the thrombus weight in the model of arterio-venous shunt. Besides, W007B could effectively prolong the occlusion time in the electrode-stimulated carotid thrombosis model. Moreover, in the ADP-induced acute pulmonary embolism model in mice, 2.8–14 mg/kg of W007B significantly reduced the death of mice. In conclusion, W007B is effective on platelet aggregation, and it is most sensitive on AA-induced aggregation. W007B has potent anti-thrombotic effect on different arterial thrombosis models. It may be an orally active candidate of anti-thrombotic agents.

Key words: Antiplatelet, Antithrombosis, W007B

CLC Number:

R962

Supporting:

Kun Hu, Xiaoyan Liu, Yuanjun Zhu, Jingliang Zhang, Ye Liu, Yinye Wang. Anti-thrombotic effect of W007B, a newly synthesized compound, in vitro and in vivo[J]. Journal of Chinese Pharmaceutical Sciences, 2014, 23(11): 760-764.

References

[1] Mathers, C.D.; Loncar, D. PLoS Med. 2006, 3, e442.

[2] Packham, M.A.; Mustard, J.F. Semin. Hematol. 1986, 23, 8-26.

[3] Ruggeri, Z.M. Thromb. Haemost. 1997, 78, 611-616.

[4] Fuster, V.; Steele, P.M.; Chesebro, J.H. Am. Coll. Cardiol. 1985, 175, B-84B SV.

[5] Banno, H.; Kawazura, H.; Yutaka, T.; Sakuma, N.; Kitamori, T.; Hosoya, J. Eur. J. Pharmacol. 1999, 367, 275-282.

[6] Organización Panamericana de la Salud. BMJ. 2002, 324, 71-86.

[7] De Meyer, S.F.; Vanbooelbeke, K.; Broos, K.; Salles, I.I.; Deckmyn, H. Brit. J. Haematol. 2008, 142, 515-528.

[8] Yun-Choi, H.S.; Pyo, M.K.; Park, K.M.; Chang, K.C.; Lee, D.H. Thromb. Res. 2001, 104, 249-255.

[9] Yoshioka, M.; Tamada, T. Biogenic. Amines. 2005,19, 89-96.

[10] Lo, Y.C.; Teng, C.M.; Chen, C.F.; Chen, C.C.; Hong, C.Y. Biochem. Pharmacol. 1994, 47, 549-553.

[11] Liou, K.T.; Shen, Y.C.; Chen, C.F.; Tsao, C.M.; Tsai, S.K. Eur. J. Pharmacol. 2003, 475, 19-27.

[12] Teng, C.M.; Chen, C.C.; KoF, N. Thromb. Res. 1988, 50, 757-765.

[13] Chen, F.; Wang, T.; Wu, Y.F. World J. Gastroenterol. 2004, 10, 3459-3463.

[14] Bu, Q.X.; Liu, X.Y.; Zhu, Y.J.; Liu, Y.; Wang, Y.Y. Brain Res. 2014, 16, 100-108.

[15] Adams, H.P.; Adams, R.J.; Brott, T. Stroke. 2003, 34, 1056-1083.

[16] Umar, A.; Boisseau, M.; Yusup, A.; Upur, H.; Begaud, B.; Moore, N. Fund Clin. Pharmacol. 2004,18, 559-563.

[17] Umar, A.; Guerin, V.; Renard, M.; Boisseau, M.; Garreau, C.; Begaud, B. Thromb. Res. 2003, 110, 135-140.

[18] Tang, Z.Y.; Wang, Y.Y.; Xiao, Y.L.; Zhao, M.; Peng, S.Q. Thromb. Res. 2003, 110, 127-133.

[19] Sheu, J.R.; Chao, S.H.; Yen, M.H.; Huang, T.F. Thromb. Haemost. 1994,72, 617-621.

[20] Dogne, J.M.; de Leval, X.; Hanson, J.; Frederich, M.; Lambermont, B.; Ghuysen, A. Curr. Med. Chem. 2004,11, 1223-1229.

[21] Zhang, X.X.; Chen, S.Z.; Wang, Y.Y. Eur. J. Pharmacol. 2007, 554, 1-7.

Anti-thrombotic effect of W007B, a newly synthesized compound, in vitro and in vivo

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