Comparison of Pharmacokinetics and Tissue Distribution of Free Anthraquinones and Gallic Acid in Mice with Ulcerative Colitis Before and After Processing of Rhei Radix et Rhizoma Carbonisata

SUN Jing; QI Yunpeng; LI Siyuan; HU Yingbo; ZHONG Linying; CHEN Jianbo; DONG Ling

doi:10.13422/j.cnki.syfjx.20250861

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Comparison of Pharmacokinetics and Tissue Distribution of Free Anthraquinones and Gallic Acid in Mice with Ulcerative Colitis Before and After Processing of Rhei Radix et Rhizoma Carbonisata

更新时间：2025-06-13

- Comparison of Pharmacokinetics and Tissue Distribution of Free Anthraquinones and Gallic Acid in Mice with Ulcerative Colitis Before and After Processing of Rhei Radix et Rhizoma Carbonisata
  增强出版
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 31, Issue 14, Pages: 198-205(2025)
- 作者机构：
  
  北京中医药大学生命科学学院，北京 102488
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20250861
  CLC： R943.1;O657;R969.1
- Received：03 September 2024，
  
  Accepted：24 October 2024，
  
  Published Online：24 October 2024，
  
  Published：20 July 2025
- 稿件说明：
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孙晶,亓云鹏,李思远等.大黄炒炭前后游离蒽醌与没食子酸在溃疡性结肠炎小鼠体内药代动力学及组织分布比较[J].中国实验方剂学杂志,2025,31(14):198-205.

SUN Jing,QI Yunpeng,LI Siyuan,et al.Comparison of Pharmacokinetics and Tissue Distribution of Free Anthraquinones and Gallic Acid in Mice with Ulcerative Colitis Before and After Processing of Rhei Radix et Rhizoma Carbonisata[J].Chinese Journal of Experimental Traditional Medical Formulae,2025,31(14):198-205.
孙晶,亓云鹏,李思远等.大黄炒炭前后游离蒽醌与没食子酸在溃疡性结肠炎小鼠体内药代动力学及组织分布比较[J].中国实验方剂学杂志,2025,31(14):198-205. DOI： 10.13422/j.cnki.syfjx.20250861.

SUN Jing,QI Yunpeng,LI Siyuan,et al.Comparison of Pharmacokinetics and Tissue Distribution of Free Anthraquinones and Gallic Acid in Mice with Ulcerative Colitis Before and After Processing of Rhei Radix et Rhizoma Carbonisata[J].Chinese Journal of Experimental Traditional Medical Formulae,2025,31(14):198-205. DOI： 10.13422/j.cnki.syfjx.20250861.

摘要

目的

研究生大黄与大黄炭中游离蒽醌与没食子酸在溃疡性结肠炎（UC）小鼠体内的药代动力学及组织分布的情况，从体内过程角度探索大黄炒炭前后治疗UC的药效差异机制。

方法

126只雄性C57BL/6JNifdc小鼠，随机分为21组，其中1组为空白组，1

0组为生大黄组，10组为大黄炭组，每组6只。除空白组外，其他组使用3.5%葡聚糖硫酸钠（DSS）自由饮用诱导UC小鼠模型，按6.5 g·kg

-1

（以生药量计算）灌胃生大黄或大黄炭水提浸膏后收集不同时间点的血浆及肝、小肠、结肠样品，采用超高效液相色谱-四极杆/静电场轨道阱高分辨质谱法（UPLC-Q-Exactive Orbitrap MS）检测小鼠血浆和组织中大黄酸、大黄素、芦荟大黄素、大黄素甲醚、大黄酚、没食子酸在不同时间点的浓度，通过DAS 2.0软件应用非房室模型计算各成分的药代动力学参数，采用IBM SPSS Statistics 20对实验数据进行统计学分析。

结果

药代动力学结果表明，与生大黄比较，大黄炭中6种成分的达峰时间（

max

）均缩短，其中大黄酚和没食子酸的差异有统计学意义（

0.05，

0.01）；5种游离蒽醌的药-时曲线下面积（AUC）、达峰浓度（

max

）及半衰期（

1/2

）增加。组织分布结果表明，生大黄及大黄炭中没食子酸及游离蒽醌的分布模式存在明显差异，生大黄在4~6 h组织药物浓度达最大值，大黄炭则在0.25~1 h组织药物含量相对较高。

结论

炒炭炮制明显改变了大黄中5种游离蒽醌与没食子酸的药代动力学及组织分布行为，增加了活性成分的体内暴露，加快了吸收速度，这可能是大黄炭治疗UC的作用优于生大黄的原因之一。

Abstract

Objective

To investigate the pharmacokinetics and tissue distribution of free anthraquinones and gallic acid from Rhei Radix et Rhizoma Carbonisata（RRRC） and its raw products in mice with ulcerative colitis（UC）， and to explore the mechanism of the pharmacodynamic difference in the treatment of UC before and after processing of RRRC from the perspective of

in vivo

process.

Methods

A total of 126 male C57BL/6JNifdc mice were randomly divided into 21 groups， of which 1 group was the blank group， 10 groups were RRR group， and 10 groups were RRRC group， with 6 mice per group. Except for the blank group， other groups were given 3.5% dextran sulfate sodium（DSS） in drinking water to induce a mouse model of UC. After intragastric administration of RRR or RRRC water extracts at a crude drug dose of 6.5 g·kg

-1

， plasma and liver， small intestine， and colon samples were collected at different time points， and the concentrations of rhein， emodin， aloe-emodin， physcion， chrysophanol and gallic acid in plasma and tissues of mice were determined by ultra-performance liquid chromatogra

phy-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）. Pharmacokinetic parameters of the components were calculated using the non-compartmental model with DAS 2.0 software， and the data were statistically analyzed by IBM SPSS Statistics 20.

Results

Pharmacokinetic results indicated that compared with RRR， the time to peak concentration（

max

） of the six components in RRRC was significantly shortened， with statistically significant differences specifically observed for chrysophanol and gallic acid （

0.05，

0.01）， and the area under the concentration-time curve（AUC）， the peak concentration（

max

） and elimination half-life（

1/2z

） of five free anthraquinones exhibited increases. Tissue distribution results showed that there were significant differences in the distribution patterns of gallic acid and free anthraquinones between RRR and RRRC， the RRR group reached the maximum drug concentration in tissues at 4-6 h， while the RRRC group had relatively higher tissue drug content at 0.25-1 h.

Conclusion

The carbonization significantly alters the pharmacokinetic and tissue distribution behaviors of five free anthraquinones and gallic acid in RRR， increases the

in vivo

exposure of the active components， and accelerates the absorption rate， which may be one of the reasons why RRRC is superior to the raw products in the treatment of UC.

关键词

Keywords

references

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