Identifying the active components of Baihe-Zhimu decoction that ameliorate depressive disease by an effective integrated strategy: a systemic pharmacokinetics study combined with classical depression model tests

Abstract

Background: Modern pharmacological studies have demonstrated that Baihe-Zhimu decoction (BZD) has antidepressant effects. However, the complex composition and lack of clear evaluation standards for BZD make it less likely to be understood and accepted than evidence-based active natural compounds.

Methods: In this study, an effective method for the identification of antidepressant components was demonstrated and applied to BZD. The first step was to evaluate the efficacy of BZD by the forced swimming test (FST) and the tail suspension test (TST), followed by successive quantitative analyses of the absorbed constituents at different stages, such as before hepatic disposition, liver distribution, after hepatic disposition and brain distribution after the oral administration of BZD. Finally, the compounds detected in the brain were confirmed by activity testing.

Results: Our investigation observed that timosaponin BII and timosaponin BIII were accurately determined in the brain after oral administration of BZD, and they were further confirmed to reduce the immobility time in the FST and TST. As described above, timosaponin BII and timosaponin BIII were used to scientifically and reasonably explain the effective chemical basis of the effect of BZD on depression.

Conclusions: This research affords an effective method to discover lead molecules for antidepressants from traditional Chinese medicine.

Keywords: Antidepressant; Baihe–Zhimu decoction; Drug discovery; Timosaponin BII; Timosaponin BIII.

Fig. 1

Procedure for the discovery of antidepressant components in BZD

Fig. 2

Mean concentration–time curves of the major chemical constituents in the portal vein plasma after the oral administration of BZD at 15 g/kg in rats (n = 5)

Fig. 3

Mean concentration–time curves of the major chemical constituents in the liver tissue after the oral administration of BZD at 15 g/kg in rats (n = 5)

Fig. 4

Mean concentration–time curves of the major chemical constituents in the systemic plasma after the oral administration of BZD at 15 g/kg in rats (n = 5)

Fig. 5

Mean concentration–time curves of timosaponin BII (a) and timosaponin BIII (b) in the hippocampus tissue and of timosaponin BII (c) and timosaponin BIII (d) in the cerebellum tissue after the oral administration of BZD at 15 g/kg in rats (n = 5)