Abstract: Objective To investigate the effect of clopidogrel on the binding rate of ginsenosides with rat serum proteins (RSA).
Methods Equilibrium dialysis and liquid chromatography-mass spectrometry were employed to quantify the concentration of
ginsenoside Rg1 and Rb1. The protein-binding rates of Rg1 and Rb1 in the presence or absence of clopidogrel (1.0 mg/L) were
determined. A molecular simulation model (consisting of homology modeling and molecular docking interaction) was used to
reveal the target protein-compound interactions. Results The binding rates of ginsenosides Rg1 (0.4, 1.0, and 2.0 mg/L) with
RSAwere (30.16±2.82)%, (33.42±4.21)%, and (34.61±3.42)%, and those of and Rb1 were (50.13±2.34)%, (51.23±3.23)%, and (53.11±
3.26)%, respectively. In the presence of clopidogrel, the binding rates of Rg1 decreased to (22.13±2.72)%, (21.42±3.22)%, and
(25.45 ± 3.52)% , and those of Rb1 to (40.13 ± 3.24)% , (41.25 ± 4.15)% , and (43.11 ± 3.31)% , receptively. The molecular docking
suggested that these compounds competed to bind with RSA. Conclusion Clopidogrel can competitively bind to RSA with
ginsenosides to lower the plasma protein binding rates of ginsenosides.