Effect of <i>Ginkgo biloba</i> extract on anticoagulation of 4 new oral anticoagulants

LIU Zhishuang; ZHENG Yufen; SUN Hongna; YU Feng

doi:10.11665/j.issn.1000-5048.20200310

Journal of China Pharmaceutical University > 2020 > 51(3): 327-332. > DOI: 10.11665/j.issn.1000-5048.20200310

LIU Zhishuang, ZHENG Yufen, SUN Hongna, YU Feng. Effect of Ginkgo biloba extract on anticoagulation of 4 new oral anticoagulants[J]. Journal of China Pharmaceutical University, 2020, 51(3): 327-332. DOI: 10.11665/j.issn.1000-5048.20200310

Citation:

PDF (517 KB)

Effect of Ginkgo biloba extract on anticoagulation of 4 new oral anticoagulants

Funds: This study was supported by the Basic Research Foundation of China Pharmaceutical University (No. 2632019PY05)

More Information

Received Date: February 18, 2020
Revised Date: April 29, 2020

Graphical Abstract

Abstract

Abstract

To explore the effect of Ginkgo biloba extract (GBE) on anticoagulation of 4 new oral anticoagulants (NOACs), dabigatran, apixaban, rivaroxaban and edoxaban in vitro, thrombin time (TT), prothrombin time (PT), activated partial thrombin time (APTT) and the activity of coagulation factor Xa (FXa) of rat plasma were measured at different concentrations of NOACs, GBE or NOACs combined with GBE, respectively. The results showed that TT, PT and APTT were prolonged with the increase of NOACs concentration in the range of 0-500 ng/mL; that except for TT of rivaroxaban, other results showed a good linear correlation with NOACs concentration (r²= 0.78-0.98); and that FXa activity decreased with increased concentration of FXa inhibitors (apixaban, rivaroxaban and edoxaban), with a good linear correlation with concentration of FXa inhibitors in the range of 0-250 ng/mL (r²= 0.85-0.94). GBE had no significant effect on TT, PT and APTT (P>0.05) in the concentration range of 0-500 μg/mL, but FXa activity had a positive linear correlation with GBE concentration (r²= 0.840 4). TT was prolonged with increasing GBE concentration when dabigatran was combined with GBE. When the above FXa inhibitors were combined with GBE, TT shortened and FXa activity increased with rising GBE concentration. There were no significant changes in PT and APTT (P>0.05) when NOACs were combined with GBE. The study results suggest that GBE may synergize with the anticoagulant activity of dabigatran and antagonize the anticoagulant activity of FXa inhibitors, possibly due to its role in increasing FXa activity.
- Ginkgo biloba extract,
- anticoagulants,
- drug interaction,
- thrombin time,
- prothrombin time,
- factor Xa activity

FullText(HTML)

References (19)

References

[1]	. Eur Heart J， 2018， 39（16）： 1330-1393.
[2]	Tran HA， Gibbs H， Merriman E， et al. New guidelines from the Thrombosis and Haemostasis Society of Australia and New Zealand for the diagnosis and management of venous thromboembolism［J］. Med J Aust， 2019， 210（5）： 227-235.
[3]	Saar JA， Maack C， European Society of Cardiology. Diagnosis and management of acute pulmonary embolism. ESC guidelines 2014［J］. Herz， 2015， 40（8）： 1048-1054.
[4]	Wang GX， Cao FL， Chen J. Progress in researches on the pharmaceutical mechanism and clinical application of Ginkgo Biloba extract on various kinds of diseases［J］. Chin J Integr Med， 2006， 12（3）： 234-239.
[5]	Tian JF， Liu Y， Chen KJ. Ginkgo biloba extract in vascular protection： molecular mechanisms and clinical applications［J］. Curr Vasc Pharmacol， 2017， 15（6）： 532-548.
[6]	Li JY， Fang J， Zhong FY， et al. Development and validation of a liquid chromatography/tandem mass spectrometry assay for the simultaneous determination of dabigatran etexilate， intermediate metabolite and dabigatran in 50 μL rat plasma and its application to pharmacokinetic study［J］. J Chromatogr B Analyt Technol Biomed Life Sci， 2014， 973C： 110-119.
[7]	Gai SC， Huang AL， Feng T， et al. LC-MS/MS method for simultaneous determination of rivaroxaban and metformin in rat plasma： application to pharmacokinetic interaction study［J］. Bioanalysis， 2019， 11（24）： 2269-2281.
[8]	He K， Luettgen JM， Zhang DL， et al. Preclinical pharmacokinetics and pharmacodynamics of apixaban， a potent and selective factor Xa inhibitor［J］. Eur J Drug Metab Pharmacokinet， 2011， 36（3）： 129-139.
[9]	Ude C， Schubert-Zsilavecz M， Wurglics M. Ginkgo biloba extracts： a review of the pharmacokinetics of the active ingredients［J］. Clin Pharmacokinet， 2013， 52（9）： 727-749.
[10]	Chen TR， Wei LH， Guan XQ， et al. Biflavones from Ginkgo biloba as inhibitors of human thrombin［J］. Bioorg Chem， 2019， 92： 103199.
[11]	Hirsch GE， Viecili PRN， de Almeida AS， et al. Natural products with antiplatelet action［J］. Curr Pharm Des， 2017， 23（8）： 1228-1246.
[12]	Diamond BJ， Bailey MR. Ginkgo biloba： indications， mechanisms， and safety［J］. Psychiatr Clin North Am， 2013， 36（1）： 73-83.
[13]	Peng YR， Jiang J， Shen H， et al. Pharmacodynamic study of Ginkgo leaf extract on promoting blood circulation［J］. J China Pharm Univ （中国药科大学学报）， 2003， 34（6）： 77-79.
[14]	Parasrampuria DA， Truitt KE. Pharmacokinetics and pharmacodynamics of edoxaban， a non-vitamin K antagonist oral anticoagulant that inhibits clotting factor xa［J］. Clin Pharmacokinet， 2016， 55（6）： 641-655.
[15]	Gouin-Thibault I， Flaujac C， Delavenne X， et al. Assessment of apixaban plasma levels by laboratory tests： suitability of three anti-Xa assays. A multicentre French GEHT study［J］. Thromb Haemost， 2014， 111（2）： 240-248.
[16]	Bookstaver DA， Sparks K， Pybus BS， et al. Comparison of anti-Xa activity in patients receiving apixaban or rivaroxaban［J］. Ann Pharmacother， 2018， 52（3）： 251-256.
[17]	Wolzt M， Samama MM， Kapiotis S， et al. Effect of edoxaban on markers of coagulation in venous and shed blood compared with fondaparinux［J］. Thromb Haemost， 2011， 105（6）： 1080-1090.
[18]	Katsuura Y， Mochizuki T， Tamura M， et al. Species specificity of anticoagulant activity of activated human protein C： involvement of factor V as well as protein S［J］. Thromb Res， 1996， 82（2）： 147-157.
[19]	Fernández JA， Heeb MJ， Xu X， et al. Species-specific anticoagulant and mitogenic activities of murine protein S［J］. Haematologica， 2009， 94（12）： 1721-1731.

Cited By

Get Citation

PDF

XML

Article views (313) PDF downloads (449)

Turn off MathJax

Article Contents

Abstract

References

Effect of Ginkgo biloba extract on anticoagulation of 4 new oral anticoagulants

Abstract

References

Catalog

Export File

Citation

Format

Content