基于微透析和液相色谱-串联质谱的药代动力学-药效学分析黄芪红花主要有效部位治疗脑缺血/再灌注的最佳配伍

摘要(中文译文)

为研究黄芪-红花(ARSA)主要有效部位对脑缺血/再灌注损伤(CI/RI)的治疗作用及配伍机制，特别是药代动力学和药效学研究，按L(3)正交设计将ARSA的三种主要有效部位(黄芪总黄酮、黄芪总皂苷和红花黄色素)配制成9个配方。通过血脑双通道微透析进行样品采集，结合LC-MS/MS定量测定ARSA的六种成分(羟基红花黄色素A、黄芪甲苷、毛蕊异黄酮-7-O-β-D-葡萄糖苷、芒柄花苷、毛蕊异黄酮和芒柄花素)以及与CI/RI相关的五种神经递质(天冬氨酸、5-羟色胺、γ-氨基丁酸、多巴胺和谷氨酸)。采用熵权法和偏最小二乘法分析数据。ARSA主要有效部位的最佳配伍处方为黄芪总黄酮600 mg/kg、黄芪总皂苷140 mg/kg和红花黄色素840 mg/kg，该配方较其他配方具有更好的治疗效果和最大的总曲线下面积。在CI/RI状态下，五种神经递质中谷氨酸受到主要调控，对神经递质调节影响较大的成分为羟基红花黄色素A和黄芪甲苷。中药有效部位的不同配伍会影响CI/RI大鼠中各活性成分的药代动力学参数。正交配伍和总统计矩法为寻找最佳配伍提供了途径。本研究为中药配伍探索提供了一种模式。

Abstract

To research the therapeutic effect and compatibility mechanism of Astragali Radix-Safflower (ARSA) main effective parts in cerebral ischemia/reperfusion injury (CI/RI), especially pharmacokinetics and pharmacodynamics study. Nine formulas of three main effective parts (total flavonoids of Astragali Radix, total saponins of Astragali Radix and safflower yellow pigment) of ARSA were formulated according to L (3) orthogonal design. The sample collection was performed via blood-brain dual-channel microdialysis, combined with LC-MS/MS to quantify six components (hydroxysafflor yellow A, astragaloside IV, calycosin-7-O-β-D-glucopyranoside, ononin, calycosin, and formononetin) of ARSA and five neurotransmitters (aspartic acid, 5-hydroxytryptamine, γ-aminobutyric acid, dopamine, and glutamate) associated with CI/RI. The entropy weight method and the partial least square method were applied to analyze data. The best compatibility prescription of the main effective parts of ARSA was total flavonoids of Astragali Radix 600 mg/kg, total saponins of Astragali Radix 140 mg/kg, and safflower yellow pigment 840 mg/kg, which had a better therapeutic effect and the largest total area under the curve than other formulas. Undergoing CI/RI, glutamate was primarily regulated among the five neurotransmitters, and the components with the greater impact on neurotransmitter modulation were hydroxysafflor yellow A and astragaloside IV. The different compatibility of effective parts of traditional Chinese medicine would influence the pharmacokinetics parameters of each active component in CI/RI rats. Orthogonal compatibility and total statistical moment method provided a way to find the best compatibility. This study provided a pattern for the exploration of traditional Chinese medicine compatibility.

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