Pharmacokinetics-pharmacodynamics and tissue distribution analysis of Low Polar extract of Xiaoyao Powder combined with rat model of chronic unpredictable mild stress

Abstract

Xiaoyao powder (XYP) is a valuable traditional Chinese Medicine (TCM) prescription developed for depression. Previous findings have suggested that the low polar extract of XYP (XYP-A) was more effect than other parts and its main ingredients included ligustilide, (2Z,8Z,10E)-pentadecatriene-4,6-diyn-1-ol (RB-1), (2Z,8E,10E)-pentadecatriene-4,6-diyn-1-ol (RB-2), (2Z,8Z,10E)-heptadecatriene-4,6-diyn-1-ol (RB-3), and bupleurynol (RB-4). However, the correlation between concentration of main ingredients and effects is still indeterminate. This study developed an ultra performance lipid chromatography combined with photo-diode array detector (UPLC-PDA) method to determine the contents of main ingredients in serum and tissues for pharmacokinetics and tissue distribution analysis. And, norepinephrine (NE) and 5-hydroxytryptamine (5-HT) were selected as the pharmacodynamic index and determined using the method of high performance lipid chromatography combined with fluorescence detector (HPLC-FD) in the serum for pharmacodynamics analysis. The DAS3.0 software was used to fit the pharmacokinetics-pharmacodynamics (PK-PD) model. The pharmacokinetic assay revealed that the absorption of polyacetylene compound was more favorable under pathological status. And, the result of tissue distribution showed that RB-2 and RB-4 were rapidly and widely distributed in tissues, and easy to cross the blood-brain barrier. The comparison of the value of NE and 5-HT in chronic unpredictable mild stress (CUMS) and control group rats suggested that 5-HT might be the main targets for the four polyacetylene compounds. The present study demonstrated that XYP-A showed the certain therapeutic effect of for depression safely and that polyacetylene compounds might be active ingredient for depression.

Graphical Abstract

Keywords:

• Pharmacokinetics-pharmacodynamics (PK-PD)
• low polar extract of Xiaoyao powder (XYP-A)
• polyacetylene
• Chronic Unpredictable Mild Stress (CUMS)
• monoamine neurotransmitters

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was supported by National Science Foundation of China (No. 81473415), Outstanding youth foundation project of applied basic research project of Shanxi Province (201701D211009), International Science & Technology Cooperation Program (2011DFA32630), and Program for the Outstanding Innovative Teams of Higher Learning Institutions of Shanxi.