Shengxian Decotion (SXT), a well-known
Traditional Chinese Medicine (TCM) formula composed of Astragali
Radix, Bupleuri Radix,
Cimicifugae Rhizoma, Anemarrhenae Rhizoma and Platycodonis Radix, is clinically considered as an effective formula against
cardiovascular diseases. However, the exact effective substance of SXT in treating chronic
heart failure (CHF) still remains unclear. In the current study, we investigated the benefit of SXT in
doxorubicin (DOX)-induced CHF rats and established a UHPLC-MS/MS method to simultaneously determine 18 key compounds in a subsequent comparative pharmacokinetic study in normal and CHF rats. Histopathological studies, transmission electron microscopy, and echocardiography were applied to assess the
therapeutic effect of SXT on DOX-induced CHF rats, which indicated that SXT significantly ameliorated DOX-induced CHF, similar to
enalapril. In addition, we successfully established a UHPLC-MS/MS method to determine the pharmacokinetics of the components in rat plasma, which was validated with good linearity, inter-day and intra-day precisions and accuracies, matrix effects, extraction recovery, and stability values. Our results showed that only
astragaloside IV showed increased plasma exposure in the CHF rats, while
saikosaponin A,
quercetin,
timosaponin B-II,
ferulic acid,
isoferulic acid and
formononetin decreased compared to their pharmacokinetic characteristics in the normal and CHF rats. This study demonstrates that SXT enjoys obvious
therapeutic effect on DOX-induced CHF rats, and the altered metabolism of some compounds in SXT is affected by the pathological state of CHF rats. Our findings provide a better understanding of the in vivo exposure to complex compounds of SXT, supporting effective substance screening and further investigation of the therapeutic mechanism.