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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

  • role： First author第一作者
  • Affiliation：

    School of Life Sciences，Beijing University of Chinese Medicine，Beijing 102488，China

  • Email：20240941121@bucm.edu.cn
  • Introduction：孙晶，在读博士，从事中药药剂学研究，E-mail：20240941121@bucm.edu.cn
SUN Jing,  
  • Affiliation：

    School of Life Sciences，Beijing University of Chinese Medicine，Beijing 102488，China

QI Yunpeng,  
  • Affiliation：

    School of Life Sciences，Beijing University of Chinese Medicine，Beijing 102488，China

LI Siyuan,  
  • Affiliation：

    School of Life Sciences，Beijing University of Chinese Medicine，Beijing 102488，China

HU Yingbo,  
  • Affiliation：

    School of Life Sciences，Beijing University of Chinese Medicine，Beijing 102488，China

ZHONG Linying,  
  • role： Corresponding author通信作者
  • Affiliation：

    School of Life Sciences，Beijing University of Chinese Medicine，Beijing 102488，China

  • Email：chenjianbo@bucm.edu.cn
  • Introduction：陈建波，博士，副研究员，从事中药分析与质量评价方法研究，E-mail：chenjianbo@bucm.edu.cn；
CHEN Jianbo*,  
  • role： Corresponding author通信作者
  • Affiliation：

    School of Life Sciences，Beijing University of Chinese Medicine，Beijing 102488，China

  • Email：dongling@bucm.edu.cn
  • Introduction：董玲，博士，研究员，从事中药标准化、中药生物药剂学、中药制剂新技术研究，E-mail：dongling@bucm.edu.cn
DONG Ling*

resumen

ObjectiveTo 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.MethodsA 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 chromatography-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.ResultsPharmacokinetic results indicated that compared with RRR， the time to peak concentration（tmax） of the six components in RRRC was significantly shortened， with statistically significant differences specifically observed for chrysophanol and gallic acid （P<0.05， P<0.01）， and the area under the concentration-time curve（AUC）， the peak concentration（Cmax） and elimination half-life（t1/2z） 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.ConclusionThe 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.

palabra clave

Rhei Radix et Rhizoma;charring;ulcerative colitis;pharmacokinetics;tissue distribution;free anthraquinones;gallic acid

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