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      Comparative pharmacodynamic, pharmacokinetic and tissue distribution of Dahuang-Gancao decoction in normal and experimental constipation mice

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          Abstract

          Dahuang-Gancao decoction (DGD) is a classical formula, which is commonly used for reliving constipation in Chinese clinic. The aim of this study was to investigate the pharmacodynamic, pharmacokinetic and tissue distribution alternations of DGD in normal and constipation mice. DGD exhibited stronger purgative effect in constipation mice by the increased fecal excretion and reduced first defection time compared with normal mice. The C max, AUC 0-t and MRT 0-t of rhein, aloe-emodin, rhein-8- O- β-D-glucoside, sennoside A, and glycyrrhizic acid as main bio-active components in DGD were markedly increased in constipation mice. The tissue distribution of the analytes in constipation mice were higher than those in normal mice with rhein > rhein-8- O- β-D-glucoside > aloe-emodin > glycyrrhizic acid > emodin in liver, and glycyrrhizic acid > rhein-8- O- β-D-glucoside > liquitin > sennoside A > rhein > aloe-emodin > emodin in colon. The kidney concentrations of the analytes showed a descending order of rhein > rhein-8- O- β- D-glucoside > sennoside A > glycyrrhizic acid > aloe-emodin > emodin, most of them were higher while rhein was lower in constipation mice than normal mice. The higher exposure of the anthraquinones in plasma, liver and colon may result in the stronger purgative effect in the constipation mice than normal mice. Rhein is mainly excreted through the kidney, the decreased level of rhein in constipation mice may explain the alleviated side effects. Accumulation of glycyrrhizic acid in colon may related with the moderate property of licorice. These results provided the experimental basis for understanding the therapeutic effects and metabolite profile of DGD.

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          Author and article information

          Journal
          CJNM
          Chinese Journal of Natural Medicines
          Elsevier BV
          1875-5364
          20 November 2019
          : 17
          : 11
          : 871-880
          Affiliations
          1 Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility, and State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi’an 712046, China
          2 Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, Nanjing 210023, China
          Author notes
          *Corresponding author: TANG Yu-Ping, E-mail: yupingtang@ 123456sntcm.edu.cn

          These authors have no conflict of interest to declare.

          Article
          S1875-5364(19)30104-9
          10.1016/S1875-5364(19)30104-9
          Copyright © 2019 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.
          Funding
          Funded by: National Natural Science Foundation of China
          Award ID: 81603258
          Funded by: Youth Talent Project Funded by Shaanxi Higher Education Association for Science and Technology
          Award ID: 20180307
          Funded by: Subject Innovation Team of Shaanxi University of Chinese Medicine
          Award ID: 2019-YL10
          Funded by: Key Research and Development Program of Shaanxi
          Award ID: 2019-SF-300
          This work was supported by the National Natural Science Foundation of China (No. 81603258), Youth Talent Project Funded by Shaanxi Higher Education Association for Science and Technology (No. 20180307), Subject Innovation Team of Shaanxi University of Chinese Medicine (No. 2019-YL10), and Key Research and Development Program of Shaanxi (No. 2019-SF-300).
          Categories
          Research article

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