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.
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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基于多成分药动学和代谢组学研究柴胡与白芍合用后植物化学物质药动学行为的变化及对内源代谢物的影响
DOI：
10.3389/fphar.2021.630970
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发表时间：
2021
影响因子：
5.6
通讯作者：
Zhou Y
中科院分区：
文献类型：
--
作者：
Chen C;Yin Q;Tian J;Gao X;Qin X;Du G;Zhou Y
柴胡-白芍（RB-RPA）是一对经典的中药组合，临床上常用于疏通“肝郁”治疗抑郁症。然而，柴胡（RB）和白芍（RPA）的联合作用机制、体内生物活性形式以及对机体的调节作用尚不清楚。本研究旨在通过UPLC-HRMS方法的高分辨率全扫描模式，阐明RB与RPA联用后多组分药代动力学（PK）行为的变化（共获得38个组分的PK谱，其中RB 23个组分，RPA 15个组分）。此外，利用代谢组学方法分析了RB-RPA干预内源代谢物的动态响应，并通过Pearson相关分析表征了RB-RPA中38种成分的浓度-时间曲线与内源代谢物动态响应谱的相关性。结果表明，RB与RPA联合使用可显著提高RB中5种组分和RPA中6种组分的生物利用度。此外，代谢组学结果显示，共有21种内源代谢物在RB-RPA给药后表现出时间依赖性变化，其中12种内源代谢物显著升高，9种内源代谢物显著降低。此外，相关分析结果表明，联合用药后生物利用度显著提高的芍药苷F、芍药苷G、芍药苷、没食子酸甲酯、芍药苷II与具有神经保护作用的代谢物吡啶酸呈显著正相关；柴草素F、柴草素G与衣康酸呈显著正相关，衣康酸是一种具有抗炎活性的内源性代谢物；芍药苷、芍药代谢苷II与α-亚麻酸呈显著正相关，α-亚麻酸是一种对脑功能具有较强保护作用的代谢物。上述结果表明，RB和RPA联合使用可增强彼此的神经保护和抗炎活性。本研究将多组分药代动力学与代谢组学相结合，建立了一种新颖有效的方法来分析RB和RPA联合使用对体内行为的影响，有助于阐明中草药配型的科学内涵。
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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影响因子：
4.7
作者：
Jia, Rui;Gu, Zhengyan;Yin, Guojun
通讯作者：
Yin, Guojun
DOI：
10.1016/j.jtemb.2014.06.014
发表时间：
2015-01-01
影响因子：
3.5
作者：
Dubey, Vivek Kumar;Ansari, Faraha;Khanam, Razia
通讯作者：
Khanam, Razia
影响因子：
10.6
作者：
Davidson, JRT;Abraham, K;McLeod, MN
通讯作者：
McLeod, MN
影响因子：
10.6
作者：
Oh, Hyunjung;Piantadosi, Sean C.;Sibille, Etienne
通讯作者：
Sibille, Etienne
白芍总苷对马钱子引起的大鼠神经毒性的预防性神经保护作用：抑制氧化应激并减少有毒成分的吸收
影响因子：
5.9
作者：
Li S;Chu Y;Zhang R;Sun L;Chen X
通讯作者：
Chen X