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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.

Timosaponin BIII, as one of the steroid saponins isolated from Anemarrhena asphodeloides Bge., was proved to have many pharmacological activities in recent years and became a natural active compound with good development prospect. In the present study, a simple and rapid method using high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry was developed for the determination of the structures of timosaponin BIII and its metabolites in rats after administrating intragastrically at 300 mg kg−1. By comparing their changes in molecular masses (ΔM), retention times and spectral patterns with those of the parent compound, nine metabolites were detected and identified in urine, and eight in plasma as well as four in brain. It is also indicated that the deglycosylation and oxidation reactions were the main metabolic pathways in the biotransformation of timosaponin BIII in vivo and the structures of the nine metabolites were identified and proposed to be timosaponin BII(M1), the hydroxylated metabolite of TBII(M2), the hydroxylated metabolites of TBIII(M3 and M4), deglycosylation and monooxygenation product of TBIII(M5), the deglycosylation product of TBII(M6), timosaponin AIII(M8), the isomers of timosaponin AIII(M7 and M9).

Background: Anemarrhenae rhizoma (AR) is widely used for the treatment of febrile diseases, cough, and diabetes in traditional Chinese medicines. AR mainly contains flavonoids and steroidal saponins, such as neomangiferin, mangiferin, timosaponin BII, timosaponin BIII, and timosaponin AIII, which showed various biological activities. Objective: The main objective of the study is to establish an ultra-high-performance liquid chromatography-tandem mass spectrometry (MS/MS) method to determine the concentrations of five bioactive constituents in rats' plasma and various tissues. Materials and Methods: The analytes were separated on a C18reversed-phase column. A triple-quadrupole MS/MS equipped with an electrospray ionization source was used as a detector. The main pharmacokinetic parameters were estimated with Drug and Statistics 2.0 Software Package. Results: Neomangiferin and mangiferin exhibit poor oral absorption and slow clearance from the body. Timosaponin BII and timosaponin BIII could be quickly absorbed into the blood circulation and showed double plasma concentration peaks. Timosaponin AIII exhibited a single peak in the plasma concentration-time plot and pharmacokinetic parameters of timosaponin AIII indicated slower absorption, longer body residence time, and slower elimination than timosaponin BII and timosaponin BIII. The five analytes were widely distributed to most of the tissues. Neomangiferin and mangiferin exhibited the maximum concentration in the lung at 6 h after oral administration, the highest levels of timosaponin BII and timosaponin BIII were also observed in the lung at 1 h after oral administration, and the maximum concentration of timosaponin AIII was observed in the liver. Conclusion: The findings of the present study might be helpful to better understand the pharmacokinetics and distribution of AR bioactive constituents in vivo, which would facilitate the clinical application of AR.

Two novel steroidal saponins (timosaponin BIII-a, timosaponin BIII-b) together with a known steroidal saponin (timosaponin BII-b) were prepared by the dilute acid hydrolysis of timosaponin BIII. Their structures were elucidated by means of 1D, 2D NMR and TOF-MS spectral analysis.