Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025
The three dicaffeoylquinic acids of Erigeron breviscapus strengthen anticoagulation of warfarin in rats: Implications in pharmacokinetics and pharmacodynamics.
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Zhao Yue, Qin Mengnan, Wei Lin, Shi Xuepeng, Xu Shiwei, Shao Bing, Yang Chunjuan, Liu Gaofeng
Аннотация
OBJECTIVES: Three dicaffeoylquinic acids, isochlorogenic acid A (ICAA), isochlorogenic acid B (ICAB) and 1,5-O-dicaffeoylquinic acid (1,5-DCQA), existing in Erigeron breviscapus and other herbal medicine, were investigated the effect on warfarin anticoagulation, to assess risk of concurrent use and mechanisms.
METHODS: Rats were randomly grouped and treated with single dose of warfarin with or without one dicaffeoylquinic acid. UHPLC-MS/MS combined with chiral column was applied to examine plasma concentrations of S/R-warfarin. Pharmacokinetic parameters were analyzed using DAS2.0 software. The plasma protein binding rate (PPBR) of warfarin was measured by ultrafiltration method. A blood coagulation analyzer was used to measure prothrombin time (PT) and activated partial thromboplastin time (APTT), and international normalized ratio (INR) values were calculated accordingly. Pharmacokinetic data were further ananlyzed by multivariate statistical analysis including principal component analysis (PCA) and orthogonal partial least squares discriminate analysis (OPLS-DA).
RESULTS: The pharmacokinetic parameters Cmax, AUC0-t, AUC0-∞ and t1/2 of both warfarin enantiomers increased while CL/F decreased upon warfarin co-administrated with ICAA, ICAB or 1,5-DCQA (P < 0.05 or 0.01). All the three components could reduce the PPBR of warfarin. Consistently, PT/INR increased significantly when any of the three components administrated with warfarin while APTT wasn't significantly changed. Besides, ICAA alone prolonged PT/INR (P < 0.01) markedly while ICAB and 1,5-DCQA showed no significant anticoagulant effect. Among pharmacokinetic parameters, AUC0-∞ of S-warfarin had the biggest variable importance in the projection (VIP) score.
CONCLUSIONS: The three components of Erigeron breviscapus, ICAA, ICAB, and 1,5-DCQA can enhance anticoagulation of warfarin by altering its pharmacokinetic and pharmacodynamic characteristics.
METHODS: Rats were randomly grouped and treated with single dose of warfarin with or without one dicaffeoylquinic acid. UHPLC-MS/MS combined with chiral column was applied to examine plasma concentrations of S/R-warfarin. Pharmacokinetic parameters were analyzed using DAS2.0 software. The plasma protein binding rate (PPBR) of warfarin was measured by ultrafiltration method. A blood coagulation analyzer was used to measure prothrombin time (PT) and activated partial thromboplastin time (APTT), and international normalized ratio (INR) values were calculated accordingly. Pharmacokinetic data were further ananlyzed by multivariate statistical analysis including principal component analysis (PCA) and orthogonal partial least squares discriminate analysis (OPLS-DA).
RESULTS: The pharmacokinetic parameters Cmax, AUC0-t, AUC0-∞ and t1/2 of both warfarin enantiomers increased while CL/F decreased upon warfarin co-administrated with ICAA, ICAB or 1,5-DCQA (P < 0.05 or 0.01). All the three components could reduce the PPBR of warfarin. Consistently, PT/INR increased significantly when any of the three components administrated with warfarin while APTT wasn't significantly changed. Besides, ICAA alone prolonged PT/INR (P < 0.01) markedly while ICAB and 1,5-DCQA showed no significant anticoagulant effect. Among pharmacokinetic parameters, AUC0-∞ of S-warfarin had the biggest variable importance in the projection (VIP) score.
CONCLUSIONS: The three components of Erigeron breviscapus, ICAA, ICAB, and 1,5-DCQA can enhance anticoagulation of warfarin by altering its pharmacokinetic and pharmacodynamic characteristics.