Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2017; 23(8): 1367-1374
Published online Feb 28, 2017. doi: 10.3748/wjg.v23.i8.1367
Pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction in the liver of rats with severe acute pancreatitis
Yu-Mei Zhang, Hong-Yu Ren, Xian-Lin Zhao, Juan Li, Jun-Yi Li, Fu-Sheng Wu, Hang Su, Wen-Fu Tang
Yu-Mei Zhang, Hong-Yu Ren, Juan Li, Jun-Yi Li, Wen-Fu Tang, Sichuan Provincial Pancreatitis Center, Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Fu-Sheng Wu, Hang Su, School of Acupuncture, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, Sichuan Province, China
Xian-Lin Zhao, Department of Integrative Medicine, Chengdu Integrated TCM and Western Medicine Hospital, Chengdu 610016, Sichuan Province, China
Author contributions: Zhang YM and Ren HY contributed equally to this work; Tang WF designed the research; Zhang YM, Ren HY, Zhao XL, Li J and Su H performed this study; Zhao XL, Li JY and Wu FS analyzed the data; Zhang YM and Ren HY wrote the paper; Tang WF was responsible for the critical revision of the paper.
Supported by National Natural Science Foundation of China, No. 81374042, No. 81370091 and No. 81573857.
Institutional review board statement: This study was approved by the Animal Ethics Committee of the Animal Facility of the West China Hospital (Chengdu, China).
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Animal Ethics Committee of the Animal Facility of the West China Hospital (protocol number: 2016001A, Chengdu, China) according to the Guide for the Care and Use of Laboratory Animals of Sichuan University.
Conflict-of-interest statement: The authors declared that they have no conflicts of interest to this work.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Wen-Fu Tang, Professor, Sichuan Provincial Pancreatitis Center, Department of Integrative Medicine, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu 610041, Sichuan Province, China. hxtangwenfu@126.com
Telephone: +86-28-85423546 Fax: +86-28-85423373
Received: October 5, 2016
Peer-review started: October 6, 2016
First decision: October 20, 2016
Revised: November 6, 2016
Accepted: January 11, 2017
Article in press: January 11, 2017
Published online: February 28, 2017
Processing time: 143 Days and 20.2 Hours
Abstract
AIM

To explore the pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction (DCQD) in the liver of rats with severe acute pancreatitis (SAP) based on an herbal recipe tissue pharmacology hypothesis.

METHODS

Healthy male Sprague-Dawley rats were randomly divided into a sham operation group (SOG); a model group (MG); and low-, median- and high-dose treatment groups (LDG, MDG, and HDG, respectively). Different dosages (6, 12 and 24 g/kg for the LDG, MDG, and HDG, respectively) of DCQD were administered to the rats with SAP. The tissue concentrations of aloe-emodin, rhein, emodin, chrysophanol, honokiol, rheo chrysophanol, magnolol, hesperidin, naringenin and naringin in the liver of the treated rats were detected by high-performance liquid chromatography tandem mass spectrometry. Alanine transaminase (ALT) and aspartate transaminase (AST) in serum, inflammatory mediators in the liver and pathological scores were evaluated.

RESULTS

The major components of DCQD were detected in the liver, and their concentrations increased dose-dependently. The high dose of DCQD showed a maximal effect in ameliorating the pathological damages, decreasing the pro-inflammatory mediators tumor necrosis factor-α and interleukin (IL)-6 and increasing anti-inflammatory mediators IL-4 and IL-10 in the liver. The pathological scores in the pancreas for the MG were significantly higher than those for the SOG (P < 0.05). DCQD could reduce the pathological scores in the pancreas and liver of the rats with SAP, especially in the HDG. Compared to the SOG, the ALT and AST levels in serum were higher in the MG (P < 0.05), while there was no statistical difference in the MG and HDG.

CONCLUSION

DCQD could alleviate liver damage by altering the inflammatory response in rats with SAP based on the liver distribution of its components.

Keywords: Pharmacokinetics; Pharmacodynamics; Da-Cheng-Qi decoction; Acute pancreatitis; Acute liver injury

Core tip: Our study group had raised the herbal recipe tissue pharmacology hypothesis, which assumed that the effect of herb formula is related to its target tissue distributions or concentrations of the effective components in target tissues. This study was to investigate the mechanism by which Da-Cheng-Qi decoction (DCQD) ameliorates acute liver injury complicated with severe acute pancreatitis in rats by detecting the tissue distributions of the components from DCQD in the liver and the inflammatory mediators as well as the pathological scores.