Abstract

BackgroundModern 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.MethodsIn 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.ResultsOur 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.ConclusionsThis research affords an effective method to discover lead molecules for antidepressants from traditional Chinese medicine.

Highlights

  • Modern pharmacological studies have demonstrated that Baihe–Zhimu decoction (BZD) has antidepressant effects

  • The results showed that the Zhimu decoction (ZD) caused a significant reduction in immobility time in both tests compared with that of control mice (P < 0.05), indicating that the individual herbal medicine Zhimu could ameliorate depressive-like behavior

  • Based on the analysis of the components of BZD, the extract of Zhimu was further separated into different fractions by microporous resin, including the polysaccharides of Zhimu (PZ), xanthones of Zhimu (XZ) and saponins of Zhimu (SZ), for screening for antidepressant activity

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Summary

Introduction

Modern pharmacological studies have demonstrated that Baihe–Zhimu decoction (BZD) has antidepressant effects. Zhong et al Chin Med (2019) 14:37 cannot be regarded as the main effective components of Chinese medicine formulae, because efficacy is considered to rely on bioactive compounds with sufficient exposure in the plasma or target organs [5, 6]. Our group used an effective method combining classical tests for specific activity and pharmacokinetics studies based on high-performance liquid chromatography coupled to triple quadrupole mass spectrometry (HPLCQQQ MS) to screen for the main effective compounds in traditional Chinese medicine (TCM) [7,8,9]. The first step was to evaluate the efficacy of crude extracts and perform quantitative analysis of their major chemical constituents. The compounds detected in the target organ were confirmed by activity testing and further mechanistic research

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