Pharmacokinetic analysis on compatibility of Atractylodes macrocephala and Paeoniae radix herb pair ameliorates functional constipation model rats using microdialysis with ultra-performance liquid chromatography

Q1 Health Professions

Animal models and experimental medicine Pub Date : 2025-01-27 DOI:10.1002/ame2.12550

Xiaoting Wang, Xiaojun Li, Rui Zhang, Yin Hong, Jiaqi Guan

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Abstract

Background

In a previous study, we found that Atractylodes macrocephala and Paeoniae radix (AM-PR) was useful for the alleviation of functional constipation (FC). However, the precise mechanism underlying the compatibility between AM and PR in the treatment of FC remains uncertain. This study aims to analyze the pharmacokinetic differences in the active ingredients in the blood of rat models with FC when applied individually and in combination with AM-PR. It also seeks to compare the changes in the content of the active ingredient when applied individually and in combination with in vitro AM-PR, further in-depth investigation into its material foundation in terms of pharmacokinetics, as well as the composition of the substance.

Methods

Blood microdialysis samples were collected using microdialysis technology. These samples from rats with FC were compared after administration of AM, PR, and AM-PR. The concentration of the main active ingredients was determined using the Ultra Performance Liquid Chromatography-Tunable Ultraviolet (UPLC-TUV) method. The concentration of the main active ingredients of the decoction compatibility before and after combining AM-PR was also determined using the UPLC-TUV method.

Results

Our findings reveal that upon combination, the time to maximum concentration (T_max) of isochlorogenic acid A (ICA-A) and ataridolide II (ATR-II) T_max was prolonged, terminal elimination half-life (T_1/2) was reduced, and maximum plasma concentrations (C_max) increased. The T_max of ataridolide III (ATR-III) remained consistent, whereas its T_1/2 and C_max were significantly reduced. Conversely, for peoniflorin (PAE), T_max occurred sooner, T_1/2 was shortened, and C_max increased. The T_max for albiflorin (ALB) remained consistent, whereas T_1/2 and C_max witnessed significant increases. The area under the moment curve (AUMC) (0–t) and AUMC (0–∞) of PAE, ALB, ICA-A, ATR-II experienced an increase after AM-PR administration in rats, attributable to the heightened C_max. In comparison to individual herb administration, the T_max of ALB was advanced in combination, the T_max of PAE remained unchanged, and the T_max of ICA-A and ART-II was delayed, with an increased area under the concentration–time curve (AUC) (0–t), indicating enhanced C_max and bioavailability. Furthermore, the dissolution rates of PAE, ICA-A, and ATR-II significantly improved after compatibility.

Conclusions

This study partially clarifies the rationale and compatibility of AM-PR in treating FC and offers a new perspective on the pharmacokinetic interactions of AM-PR in FC treatment.

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用超高效液相色谱微透析法分析白术与芍药对改善功能性便秘模型大鼠的配伍性。

背景：在之前的研究中，我们发现苍术和芍药（AM-PR）对缓解功能性便秘（FC）有一定的作用。然而，AM和PR在治疗FC中的相容性的确切机制仍不确定。本研究旨在分析单独应用FC大鼠模型和与AM-PR联合应用FC大鼠模型血液中有效成分的药动学差异。比较单独使用和与体外AM-PR联合使用时活性成分含量的变化，进一步深入研究其药代动力学的物质基础，以及物质的组成。方法：采用微透析技术采集血液微透析标本。在给药AM、PR和AM-PR后比较FC大鼠的这些样本。采用超高效液相色谱-可调紫外（UPLC-TUV）法测定其主要有效成分的浓度。采用UPLC-TUV法测定复方AM-PR前后汤剂配伍主要有效成分的浓度。结果：本研究发现，异绿原酸A （ICA-A）和阿达他啶酯II （ATR-II）联合使用后，达到最大浓度的时间（Tmax）延长，终末消除半衰期（T1/2）缩短，最大血浆浓度（Cmax）增加。阿他度胺III （ATR-III）的Tmax保持不变，而其T1/2和Cmax显著降低。相反，芍药苷（PAE）的Tmax发生更快，T1/2缩短，Cmax增加。albiflorin （ALB）的Tmax保持不变，而T1/2和Cmax显著增加。AM-PR给药后大鼠PAE、ALB、ICA-A、ATR-II的瞬间曲线下面积（AUMC）（0-t）和AUMC（0-∞）增加，是由于Cmax升高所致。与单药给药相比，联合给药时ALB的Tmax提前，PAE的Tmax不变，ICA-A和ART-II的Tmax延迟，浓度-时间曲线下面积（0-t）增大，表明Cmax和生物利用度提高。此外，配型后PAE、ICA-A、ATR-II的溶出率显著提高。结论：本研究部分阐明了AM-PR治疗FC的原理和相容性，为AM-PR治疗FC的药动学相互作用提供了新的视角。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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