Simultaneous Quantification of Four Ginsenosides in Rat Plasma and Its Application to a Comparative Pharmacokinetic Study in Normal and Depression Rats Using UHPLC-MS/MS.

Lian-Yun Du,Hui-E Zhang,Shuang Zhu,En-Peng Wang,Kun Wei,Chang-Bao Chen,Ping Ye,Yan-Long Shen,Tao Jiang,Antony C Calokerinos

doi:10.1155/2021/4488822

Lian-Yun Du, Hui-E Zhang + Show 8 more

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https://doi.org/10.1155/2021/4488822

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Abstract

A sensitive method has been developed for simultaneous determination of ginsenoside Rh1 (G-Rh1), ginsenoside Rb1 (G-Rb1), ginsenoside Rc (G-Rc), and ginsenoside Rd (G-Rd) in rat plasma of normal and depression model group after oral administration of their solutions by using Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-QQQ-MS). The biological samples were prepared by protein precipitation. Ginsenoside Rg3 (G-Rg3) was used as an internal standard (IS). MS analysis was performed under the multiple reaction monitoring (MRM) with electron spray ionization (ESI) operated in the negative mode. The method showed good linearity over a wide concentration range (R2 > 0.999) and obtained lower limits of quantification (LLOQ) of 5 ng/mL. The whole analysis procedure could be completed in as short as 16.5 min. The intraday precisions, interday precisions, and stabilities were less than 10%. The extraction recoveries from rat plasma were exceeded 86.0%. The results indicated that there were significant differences between the two groups on pharmacokinetics parameters; the absorptions of four analytes in the depression group were higher than those in the normal group because the liver metabolism and internal environment of the model rats had been affected.

Highlights

Depression is a sort of chronic mental disorder characterized by persistent black mood, which seriously affects the physical and mental health of human race [1]
A natural stressful stimulus such as ultraviolet radiation B (UVB) radiation can trigger the activation of the HPA axis [6], no matter what acute or chronic dose irradiation may both individually reduce neurogenesis and synaptic protein expression, which lead to a depression-like behavior [7, 8]
In order to confirm whether the rat depression model was successfully established or not, we verified a series of indicators, such as the sucrose preference test, forced swimming test, and the open-field test

Summary

Introduction

Depression is a sort of chronic mental disorder characterized by persistent black mood, which seriously affects the physical and mental health of human race [1]. A large number of studies illustrated that a certain relationship was observed between the incidence of depression and the maladjustment of Hypothalamus-Pituitary-Adrenal (HPA), and excessive stress stimulation was considered to be the major cause of depression occurrence [2,3,4,5]. A natural stressful stimulus such as UVB radiation can trigger the activation of the HPA axis [6], no matter what acute or chronic dose irradiation may both individually reduce neurogenesis and synaptic protein expression, which lead to a depression-like behavior [7, 8]. Conventional chemical medicines on depression usually have various limitations or side effects, such as sleep disorders, cognitive dysfunction, high recurrence rate, and even much more severe effects [9,10,11]. Ginsenosides, widely considered as the main active ingredients, show a variety of pharmacological activities including increasing the ability to resist pressure, stimulating immune function, and protecting the nervous system and were responsible for the anti-

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