Integrated network pharmacology and metabolomics to dissect the combination mechanisms of Bupleurum chinense DC-Paeonia lactiflora Pall herb pair for treating depression

Xiao, Li; Qin, Xuemei; Tian, Jun-Sheng; Gao, Xiaoxia; Du, Guanhua; Zhou, Yuzhi

doi:10.1016/j.jep.2020.113281

Cited by 54 publications

(38 citation statements)

References 40 publications

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“…In animal models, the antidepressant effects of Radix Paeoniae Rubra and Radix Paeoniae Rubra were significantly better than those of Radix Paeoniae Rubra or Radix Paeoniae Rubra, achieved by regulating the mitogen-activated protein kinase (MAPK) signaling pathway. This conduction pathway and arachidonic acid metabolism have a synergistic effect [ 108 ]. Pretreatment with Bupleurum and Radix Paeoniae Alba significantly increased the concentration of serotonin and epinephrine in the hippocampus and cortical tissue [ 109 ].…”

Section: The ‘Three Syndromes and Six Chinese Patent Medicines’ Projectmentioning

confidence: 99%

The three syndromes and six Chinese patent medicine study during the recovery phase of COVID-19

Duan

Zhang

et al. 2021

Chin Med

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The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), first broke out in Wuhan, China, in 2019. SARS-CoV-2 develops many types of mutations (such as B.1.1.7), making diagnosis and treatment challenging. Although we now have a preliminary understanding of COVID-19, including pathological changes, clinical manifestations, and treatment measures, we also face new difficulties. The biggest problem is that most COVID-19 patients might face sequelae (e.g., fatigue, sleep disturbance, pulmonary fibrosis) during the recovery phase. We aimed to test six Chinese patent medicines to treat three major abnormal symptoms in COVID-19 patients during the recovery phase, including cardiopulmonary function, sleep disturbance, and digestive function. We launched the “three syndromes and six Chinese patent medicines” randomized, double-blind, placebo-controlled, multicenter clinical trial on April 10, 2020. The results showed that Jinshuibao tablets and Shengmaiyin oral liquid significantly improved the cardiopulmonary function of recovering COVID-19 patients. Shumian capsules, but not Xiaoyao capsules, significantly improved patients’ sleep disorders. This might be because the indication of Xiaoyao capsules is liver qi stagnation rather than psychological or emotional problems. Xiangsha Liujun pills and Ludangshen oral liquid significantly improved digestive function. Our research provides a guideline for treating COVID-19 sequelae in patients during the recovery period based on high-quality evidence.

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Section: The ‘Three Syndromes and Six Chinese Patent Medicines’ Projectmentioning

confidence: 99%

The three syndromes and six Chinese patent medicine study during the recovery phase of COVID-19

Duan

Zhang

et al. 2021

Chin Med

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“…The "Sovereign" herb is the predominant medicine used for therapy disease and the "Minister" herb has synergistic effects with the "Sovereign" herb [18]. And, previous experimental studies have suggested that both Radix Bupleuri and Radix Paeoniae alba possess antidepressant effects respectively, and the combination can strengthen the anti-depressant effects [19][20][21][22]. Based on previous research, we hypothesis that the SSA and AF combination may display synergistic neuroprotective effects.…”

Section: Introductionmentioning

confidence: 86%

Synergistic Effect of Saikosaponin a and Albiflorin Against Corticosterone-Induced Neuro-Injury in PC12 Cells via Regulation of TCA Cycle, Purine Metabolism, and Glutamate Metabolism

et al. 2021

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The combination of Radix Bupleuri - Radix Paeoniae alba is one of the most approbated herb pairs in traditional Chinese medicine (TCM) formula for curing depression. Saikosaponin A (SSA) and albiflorin (AF) are major bioactive compounds of Radix Bupleuri and Radix Paeoniae alba respectively, which possess antidepressant effects in pharmacological experiments. However, whether SSA and AF have synergistic neuroprotective effects and the synergistic mechanism is still unknown. The present study employed the corticosterone-induced PC12 cells neuro-injury model to assess the protective effect of SSA and AF, alone and in combination, and the synergistic effect was analyzed using three mathematical models. Meanwhile, the cell metabolomics was used to detect the effects on metabolite regulation of SSA and AF, alone and in combination. According to the results of cell metabolomics, the vital cell transduction pathway related to the crucial cell metabolic pathways were selected. Furthermore, the key metabolites, metabolic enzymes, and cellular markers were verified by ELISA and Western blotting. The results showed that the combination of SSA and AF has a synergistic neuroprotective effect. Besides, the combination could regulate more metabolites (16) than a single agent (12 & 10) and possessed a stronger adjustment effect on metabolites. Correspondingly, the combination regulated more metabolism pathways (7) than alone agents (3 & 5). Furthermore, the TCA cycle, purine metabolism, and glutamate metabolism were selected as crucial metabolism pathways. The results showed that the TCA cycle disorder was regulated by SSA and AF via improving mitochondrial function. The purine metabolism disorder was regulated by SSA via inhibition xanthine oxidase (XOD) activity and the glutamate metabolism disorder was regulated by AF via inhibition glutaminase (GLS) activity. Moreover, the oxidative stress induced by the purine metabolism disorder was attenuated by SSA via a reduction in the ROS level. Additionally, the inflammation induced by the oxidative stress was attenuated by the SSA and AF via inhibition of the NLRP3 protein expression. This study for the first time demonstrated the synergistic neuroprotective effect of SSA and AF, and the synergistic mechanism was involved in metabolic disorders regulation.

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“…As described in previous reports (Chen et al, 2020;Li et al, 2021), Radix Bupleuri (3 kg) or Radix Paeoniae Alba (3 kg) were soaked in 70% ethanol (2.4 L) for 1.5 h before extraction. Then Radix Bupleuri or Radix Paeoniae Alba were extracted twice with 70% ethanol under reflux, each time for 1.5 h. The extracts were filtrated and concentrated in vacuo and lyophilized into powders (15.15% yield for Radix Bupleuri, and 11.78% yield for Radix Paeoniae Alba), and then stored at 4°C until use and UPLC-MS analysis.…”

Section: Preparation Of Herb Extractsmentioning

confidence: 99%

“…Herb-herb compatibility is a common form of TCM, it can achieve an optimal effect by obtaining synergy or reducing possible adverse reactions (Zhao et al, 2010). Modern pharmacological studies have shown that the analgesic, antiinflammatory, and antidepressant effect was significantly improved after the combination of RB and RPA (Wang et al, 2016;Li et al, 2021). However, the scientific connotation of RB and RPA combination and the potential theoretical basis of increasing therapeutic effect after combination were unclear.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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Integrated network pharmacology and metabolomics to dissect the combination mechanisms of Bupleurum chinense DC-Paeonia lactiflora Pall herb pair for treating depression

Cited by 54 publications

References 40 publications

The three syndromes and six Chinese patent medicine study during the recovery phase of COVID-19

The three syndromes and six Chinese patent medicine study during the recovery phase of COVID-19

Synergistic Effect of Saikosaponin a and Albiflorin Against Corticosterone-Induced Neuro-Injury in PC12 Cells via Regulation of TCA Cycle, Purine Metabolism, and Glutamate Metabolism

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

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Integrated network pharmacology and metabolomics to dissect the combination mechanisms of Bupleurum chinense DC-Paeonia lactiflora Pall herb pair for treating depression

Cited by 54 publications

References 40 publications

The three syndromes and six Chinese patent medicine study during the recovery phase of COVID-19

The three syndromes and six Chinese patent medicine study during the recovery phase of COVID-19

Synergistic Effect of Saikosaponin a and Albiflorin Against Corticosterone-Induced Neuro-Injury in PC12&nbsp;Cells via Regulation of TCA&nbsp;Cycle, Purine Metabolism, and Glutamate Metabolism

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

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Synergistic Effect of Saikosaponin a and Albiflorin Against Corticosterone-Induced Neuro-Injury in PC12 Cells via Regulation of TCA Cycle, Purine Metabolism, and Glutamate Metabolism