Studies on the Changes of Pharmacokinetics Behaviors of Phytochemicals and the Influence on Endogenous Metabolites After the Combination of Radix Bupleuri and Radix Paeoniae Alba Based on Multi-Component Pharmacokinetics and Metabolomics

Abstract

Radix Bupleuri-Radix Paeoniae Alba (RB-RPA) is a classic herb pair, which is commonly used to treat depression by soothing “liver qi stagnation” in the clinic. However, little is yet known concerning the combination mechanism of Radix Bupleuri (RB) and Radix Paeoniae Alba (RPA), their bioactive forms in vivo and the regulatory effects on the organism. The present study aimed to elucidate the changes in multi-component pharmacokinetics (PK) behavior after the combination of RB and RPA by a high-resolution full-scan mode of UPLC-HRMS method (a total of 38 components PK profiles were obtained, of which 23 components come from RB and 15 components come from RPA). Moreover, the metabolomics approach was used to analyze the dynamic response of endogenous metabolites intervened by RB-RPA, and the correlation between concentration-time curves of 38 components from RB-RPA and the dynamic response profiles of endogenous metabolites was characterized by Pearson correlation analysis. The results demonstrated that the combination of RB and RPA could significantly improve the bioavailability of five components in RB, and six components in RPA. Besides, metabolomics results indicated that a total of 21 endogenous metabolites exhibited time-dependent changes in response to the RB-RPA administration, of which 12 endogenous metabolites were significantly increased, and nine endogenous metabolites were significantly decreased. Furthermore, correlation analysis results indicated that the components with significantly improved bioavailability after combination such as saikogenin F, saikogenin G, albiflorin, methyl gallate, paeonimetabolin II were significantly positively correlated with picolinic acid, a metabolite with neuroprotective effect; saikogenin F, saikogenin G were significantly positively correlated with itaconic acid, a endogenous metabolite with anti-inflammatory activity; and albiflorin, paeonimetabolin II were significantly positively correlated with α-linolenic acid, a metabolite with strong protective actions on brain functions. These results indicated that the combination of RB and RPA can enhance each other’s neuroprotective and anti-inflammatory activities. In this study, A novel and efficient strategy has been developed to analyze the influence of the combination of RB and RPA in vivo behaviors by combining multi-component pharmacokinetics with metabolomics, which was contributed to clarifying the scientific connotation of herb–herb compatibility.

Comprehensive comparison on the anti-inflammation and GC-MS-based metabolomics discrimination between Bupleuri chinense DC. and B. scorzonerifolium Willd

“…In clinical applications, BR has been widely used for treatment of fever, pain, and inflammation associated with influenza or the common cold ( Yang et al, 2017 ). The modern pharmacological investigations reported that BR presented broad biological activities including anti-influenza ( Yan et al, 2022 ), anti-tumor ( Zhao et al, 2019 ; Zhou et al, 2021 ), anti-inflammation ( Jiang et al, 2020 ), anti-depression ( Guo et al, 2020 ; Chen et al, 2021 ), anti-stress ( Wang P. et al, 2021 ; Wang Z. et al, 2021 )and antipyretic ( Wang et al, 2019 ), antiviral ( Du et al, 2018 ), antimicrobial ( Liu et al, 2016 ), immunomodulatory ( Tang et al, 2021 ) and hepatoprotective effects ( Ren et al, 2019 ). Although different types of chemicals have been reported to contain in BCH (saponins, volatile oils, flavonoids and polysaccharides) ( Xing et al, 2015 ) and NCH (saponins, lignans, fatty acids, volatile oils and polysaccharides) ( Jiang et al, 2020 ), the saponins and volatile oils have been investigated to be the most important parts for both BR species which are associated to their antipyretic ( Xing et al, 2015 ; Li et al, 2018 ) and anti-inflammatory effects ( Kim et al, 2015 ; Ma et al, 2016 ).…”

Metabolomics Based on Peripheral Blood Mononuclear Cells to Dissect the Mechanisms of Chaigui Granules for Treating Depression

“…The CUMS program was performed as previously described, with some modifications. , With the exception of the control group, rats in the other groups were exposed to one of the following chronic unpredictable mild stressors in random order daily for four weeks: swimming in cold water (4 °C) (5 min), banning water (24 h), 50 °C exposure (10 min), tail clamping for 2 min, fasting (24 h), ultrasound stimulation (60 MHz) (3 h), restraint (3h), foot shock every 10s (2 min), and breaking circadian rhythms . At the same time, rats were kept separately under the same conditions except for the control rats, which were kept undisturbed in their cages.…”

Mass spectrometry-based metabolomics for discovering active ingredients and exploring action mechanism of herbal medicine

“…The results showed that sFF&sPF group had the best efficacy in the treatment of diarrhea and polyuria, and salt treatment would briefly affect the correlation between pharmacodynamic components and endogenous metabolites. Chen et al (2021) used pharmacokinetics and metabolomics, relying on UHPLC-Q Exactive Orbitrap-MS technology, to elucidate the compatibility mechanism of Radix Bupleuri-Radix Paeoniae Alba (RB-RPA). The results showed that the RB-RPA combination could dramatically enhance the bioavailability of 11 drug ingredients and raise neuroprotective and anti-inflammatory activity.…”