Chen Congcong, Yin Qicai, Tian Junshen, Gao Xiaoxia, Qin Xuemei, Du Guanhua, Zhou Yuzhi
Modern Research Center for Traditional Chinese Medicine of Shanxi University, Taiyuan, China.
College of Chemistry and Chemical Engineering, Shanxi University, Taiyuan, China.
Front Pharmacol. 2021 Mar 8;12:630970. doi: 10.3389/fphar.2021.630970. eCollection 2021.
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 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 behaviors by combining multi-component pharmacokinetics with metabolomics, which was contributed to clarifying the scientific connotation of herb-herb compatibility.
柴胡-白芍药对（RB-RPA）是经典药对，临床常用于通过疏肝理气治疗抑郁症。然而，关于柴胡（RB）与白芍（RPA）的配伍机制、其生物活性形式以及对机体的调节作用，目前仍知之甚少。本研究旨在通过超高效液相色谱-高分辨质谱法的高分辨全扫描模式，阐明RB与RPA配伍后多成分药代动力学（PK）行为的变化（共获得38种成分的PK图谱，其中23种成分来自RB，15种成分来自RPA）。此外，采用代谢组学方法分析RB-RPA干预后内源性代谢物的动态响应，并通过Pearson相关性分析表征RB-RPA中38种成分的浓度-时间曲线与内源性代谢物动态响应图谱之间的相关性。结果表明，RB与RPA配伍可显著提高RB中5种成分和RPA中6种成分的生物利用度。此外，代谢组学结果表明，共有21种内源性代谢物在给予RB-RPA后呈现出时间依赖性变化，其中12种内源性代谢物显著增加，9种内源性代谢物显著减少。此外，相关性分析结果表明，配伍后生物利用度显著提高的成分，如柴胡皂苷F、柴胡皂苷G、芍药苷、没食子酸甲酯、芍药代谢物II与具有神经保护作用的代谢物吡啶甲酸显著正相关；柴胡皂苷F、柴胡皂苷G与具有抗炎活性的内源性代谢物衣康酸显著正相关；芍药苷、芍药代谢物II与对脑功能具有强大保护作用的代谢物α-亚麻酸显著正相关。这些结果表明，RB与RPA配伍可增强彼此的神经保护和抗炎活性。本研究通过多成分药代动力学与代谢组学相结合，开发了一种新颖高效的策略来分析RB与RPA配伍行为的影响，有助于阐明药-药配伍的科学内涵。
