Optimal Compatibility of Main Effective Parts of Astragali Radix‐Safflower for the Treatment of Cerebral Ischemia/Reperfusion by Pharmacokinetics‐Pharmacodynamics Analysis Based on Microdialysis and Liquid Chromatography–Tandem Mass Spectrometry

PURPOSE: 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. METHOD: ) 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. RESULTS: 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. CONCLUSION: 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.