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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2018.01493

Identification of Pharmacokinetic Markers for Guanxin Danshen Drop Pills in Rats by Combination of Pharmacokinetics, Systems Pharmacology and Pharmacodynamic Assays

 Hong Yao1*, Xiaomei Huang1, Yuanjiao Xie1, Xuliang Huang1, Yijun Ruan1, Liying Huang1, Xinhua Lin1 and  Peiying Shi2*
  • 1Fujian Medical University, China
  • 2Fujian Agriculture and Forestry University, China

This paper reported a feasibility study strategy of identifying pharmacokinetic (PK) markers for a cardiovascular herbal medicines, Guanxin Danshen drop pill (GDDP). First, quantification analysis revealed the constituent composition in the preparation by high-performance liquid chromatography (HPLC). Subsequently, physiochemical property calculation predicted the solubility and intestinal permeability of the constituents in the preparation. Furthermore, HPLC-MS analysis ascertained the absorbable ingredients and their PK properties in rat plasma. The main effective substances from the ingredients absorbed into blood and their cardiovascular effects were also predicted by systems pharmacology study, and were further confirmed by in vivo protective effects on isoprenaline-induced myocardial injury in mice. Finally, the ingredients with high content, representative structure feature, favorable PK properties, high relevant degree to myocardial ischemia issues, and validated therapeutic effects were considered as the PK markers for the preparation. Ginsenosides Rg1, Rb1, and tanshinone IIA were identified originally as PK markers for representing PK properties of GDDP. In addition, integrated PK studies were carried out according to previous reports, viz. drug concentration sum method and the AUC weighting method, to understand the in vivo process of GDDP comprehensively. The present study maybe provide a reference approach to identify PK markers for cardiovascular herbal medicines.

Keywords: Tratditional Chinese Medicine, cardiovascular herbal medicines, Pharmacokinetic markers, Systems Pharmacology, Guanxin Danshen drop pills

Received: 02 Sep 2018; Accepted: 06 Dec 2018.

Edited by:

Marcello Locatelli, Università degli Studi G. d'Annunzio Chieti e Pescara, Italy

Reviewed by:

Gokhan Zengin, Selçuk University, Turkey
Rufeng Wang, Beijing University of Chinese Medicine, China  

Copyright: © 2018 Yao, Huang, Xie, Huang, Ruan, Huang, Lin and Shi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Dr. Hong Yao, Fujian Medical University, Fuzhou, China, yauhung@126.com
Dr. Peiying Shi, Fujian Agriculture and Forestry University, Fuzhou, 350002, Fujian Province, China, Peiyshi@126.com