Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 14, 2020; 26(22): 3056-3075
Published online Jun 14, 2020. doi: 10.3748/wjg.v26.i22.3056
Optimal dosing time of Dachengqi decoction for protection of extrapancreatic organs in rats with experimental acute pancreatitis
Jia-Qi Yao, Lin Zhu, Yi-Fan Miao, Lv Zhu, Huan Chen, Ling Yuan, Jing Hu, Xiao-Lin Yi, Qiu-Ting Wu, Xi-Jing Yang, Mei-Hua Wan, Wen-Fu Tang
Jia-Qi Yao, Yi-Fan Miao, Lv Zhu, Huan Chen, Ling Yuan, Jing Hu, Xiao-Lin Yi, Qiu-Ting Wu, Mei-Hua Wan, Wen-Fu Tang, Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Lin Zhu, Digestive System Department, Sichuan Integrative Medicine Hospital, Chengdu 610041, Sichuan Province, China
Xi-Jing Yang, Animal Experiment Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Author contributions: Tang WF designed the research; Yao JQ, Zhu L, Miao YF, Chen H, Yuan L, Hu J, Yi XL, and Wu QT performed the research; Yao JQ, Zhu L, and Miao YF analyzed the data; Yang XJ were responsible for the drafting of the paper; Wan MH contributed new reagents or analytic tools; Tang WF and Wan MH obtained funding and provided study supervision.
Supported by the National Natural Science Foundation of China, No. 81603480 and No. 81573857.
Institutional animal care and use committee statement: This study was reviewed and approved by the Institutional Animal Care and Use Committee of West China Hospital of Sichuan University. All experiments were reviewed and approved by the Institution Animal Care and Use Committee of Sichuan University (Chengdu, China; protocol number: 2019003A).
Conflict-of-interest statement: None of the authors have any conflicts of interest to declare.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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/
Corresponding author: Wen-Fu Tang, PhD, Professor, Department of Integrative Medicine, West China Hospital, Sichuan University, No. 37, Guoxue Lane, Wuhou District, Chengdu 610041, Sichuan Province, China. tangwf@scu.edu.cn
Received: January 21, 2020
Peer-review started: January 21, 2020
First decision: February 27, 2020
Revised: March 26, 2020
Accepted: May 13, 2020
Article in press: May 13, 2020
Published online: June 14, 2020
Abstract
BACKGROUND

Acute pancreatitis (AP) is a pancreatic inflammatory disorder that is commonly complicated by extrapancreatic organ dysfunction. Dachengqi decoction (DCQD) has a potential role in protecting the extrapancreatic organs, but the optimal oral administration time remains unclear.

AIM

To screen the appropriate oral administration time of DCQD for the protection of extrapancreatic organs based on the pharmacokinetics and pharmacodynamics of AP rats.

METHODS

This study consisted of two parts. In the first part, 24 rats were divided into a sham-operated group and three model groups. The four groups were intragastrically administered with DCQD (10 g/kg) at 4 h, 4 h, 12 h, and 24 h postoperatively, respectively. Tail vein blood was taken at nine time points after administration, and then the rats were euthanized and the extrapancreatic organ tissues were immediately collected. Finally, the concentrations of the major DCQD components in all samples were detected. In the second part, 84 rats were divided into a sham-operated group, as well as 4 h, 12 h, and 24 h treatment groups and corresponding control groups (4 h, 12 h, and 24 h control groups). Rats in the treatment groups were intragastrically administered with DCQD (10 g/kg) at 4 h, 12 h, and 24 h postoperatively, respectively, and rats in the control groups were administered with normal saline at the same time points. Then, six rats from each group were euthanized at 4 h and 24 h after administration. Serum amylase and inflammatory mediators, and pathological scores of extrapancreatic organ tissues were evaluated.

RESULTS

For part one, the pharmacokinetic parameters (C max, T max, T 1/2, and AUC 0 → t) of the major DCQD components and the tissue distribution of most DCQD components were better when administering DCQD at the later (12 h and 24 h) time points. For part two, delayed administration of DCQD resulted in lower IL-6 and amylase levels and relatively higher IL-10 levels, and pathological injury of extrapancreatic organ tissues was slightly less at 4 h after administration, while the results were similar between the treatment and corresponding control groups at 24 h after administration.

CONCLUSION

Delayed administration of DCQD might reduce pancreatic exocrine secretions and ameliorate pathological injury in the extrapancreatic organs of AP rats, demonstrating that the late time is the optimal dosing time.

Keywords: Oral administration time, Dachengqi decoction, Pharmacokinetics, Pharmacodynamics, Acute pancreatitis, Extrapancreatic organs

Core tip: This study is the first to assess the optimal dosing time of Dachengqi decoction for protecting the extrapancreatic organs of acute pancreatitis rats. Based on the pharmacokinetic and pharmacodynamic experiments, we proved that delayed administration may be more appropriate in alleviating damage to multiple extrapancreatic organs in acute pancreatitis rats. In addition, this is the first time we have tried to compare the efficacy at different times after administration, and we found that a single-dose administration of the decoction leads to a rapid onset of relief but no steady-state effect, suggesting that multiple-dose administration should be considered.