Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 21, 2017; 23(39): 7098-7109
Published online Oct 21, 2017. doi: 10.3748/wjg.v23.i39.7098
Optimal timing for the oral administration of Da-Cheng-Qi decoction based on the pharmacokinetic and pharmacodynamic targeting of the pancreas in rats with acute pancreatitis
Yu-Mei Zhang, Lin Zhu, Xian-Lin Zhao, Huan Chen, Hong-Xin Kang, Jian-Lei Zhao, Mei-Hua Wan, Juan Li, Lv Zhu, Wen-Fu Tang
Yu-Mei Zhang, Huan Chen, Hong-Xin Kang, Mei-Hua Wan, Juan Li, Lv Zhu, 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
Xian-Lin Zhao, Department of Integrative Medicine, Chengdu Integrated TCM and Western Medicine Hospital, Chengdu 610016, Sichuan Province, China
Jian-Lei Zhao, Department of Pharmacology, School of Preclinical and Forensic Medicine, West China Medical Center, Sichuan University, Chengdu, 610041, Sichuan Province, China
Author contributions: Zhang YM and Zhu L contributed equally to this paper; Tang WF designed the study; Zhang YM, Zhu L, Chen H, Kang HX and L Zhu performed this study; Zhao XL, Zhao JL, Wan MH and Li J analyzed the data; Zhang YM and Zhu L wrote the paper; Tang WF was responsible for the critical revision of the paper.
Supported by the National Natural Science Foundation of China, No. 81374042, No. 81370091 and No. 81603480.
Institutional review board statement: The study was approved by the Animal Ethics Committee Guidelines of the Animal Facility of the West China Hospital (Chengdu, China).
Institutional animal care and use committee statement: All procedure involving animals were reviewed and approved by the Guide for the Care and Use of Laboratory Animals of Sichuan University and the Animal Ethics Committee Guidelines of the Animal Facility of the West China Hospital (Chengdu, China) (Protocol No. 2016001A).
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
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, Department of Integrative Medicine, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu 610041, Sichuan Province, China. tangwf@scu.edu.cn
Telephone: +86-28-85423546 Fax: +86-28-85423373
Received: July 21, 2017
Peer-review started: July 24, 2017
First decision: August 15, 2017
Revised: August 27, 2017
Accepted: September 13, 2017
Article in press: September 13, 2017
Published online: October 21, 2017
Abstract
AIM

To identify the optimal oral dosing time of Da-Cheng-Qi decoction (DCQD) in rats with acute pancreatitis (AP) based on the pharmacokinetic and pharmacodynamic parameters.

METHODS

First, 24 male Sprague-Dawley rats were divided into a sham-operated group [NG(a)] and three model groups [4hG(a), 12hG(a) and 24hG(a)]. The NG(a) and model groups were administered DCQD (10 g/kg.BW) intragastrically at 4 h, 4 h, 12 h and 24 h, respectively, after AP models induced by 3% sodium taurocholate. Plasma samples were collected from the tails at 10 min, 20 min, 40 min, 1 h, 2 h, 4 h, 8 h, 12 h and 24 h after a single dosing with DCQD. Plasma and pancreatic tissue concentrations of the major components of DCQD were determined by high-performance liquid chromatography tandem mass spectroscopy. The pharmacokinetic parameters and serum amylase were detected and compared. Second, rats were divided into a sham-operated group [NG(b)] and three treatment groups [4hG(b), 12hG(b) and 24hG(b)] with three corresponding control groups [MG(b)s]. Blood and pancreatic tissues were collected 24 h after a single dosing with DCQD. Serum amylase, inflammatory cytokines and pathological scores of pancreatic tissues were detected and compared.

RESULTS

The concentrations of emodin, naringin, honokiol, naringenin, aloe-emodin, chrysophanol and rheochrysidin in the 12hG(a) group were higher than those in the 4hG(a) group in the pancreatic tissues (P < 0.05). The area under the plasma concentration-time curve from time 0 to the time of the last measurable concentration values (AUC0→t) for rhein, chrysophanol, magnolol and naringin in the 12hG(a) group were larger than those in the 4hG(a) or 24hG(a) groups. The 12hG(a) group had a higher Cmax than the other two model groups. The IL-10 levels in the 12hG(b) and 24hG(b) groups were higher than in the MG(b)s (96.55 ± 7.84 vs 77.46 ± 7.42, 251.22 ± 16.15 vs 99.72 ± 4.7 respectively, P < 0.05), while in the 24hG(b) group, the IL-10 level was higher than in the other two treatment groups (251.22 ± 16.15 vs 154.41 ± 12.09/96.55 ± 7.84, P < 0.05). The IL-6 levels displayed a decrease in the 4hG(b) and 12hG(b) groups compared to the MG(b)s (89.99 ± 4.61 vs 147.91 ± 4.36, 90.82 ± 5.34 vs 171.44 ± 13.43, P < 0.05).

CONCLUSION

Late-time dosing may have higher concentrations of the most major components of DCQD, with better pharmacokinetics and pharmacodynamics of anti-inflammation than early-time dosing, which showed the late time to be the optimal dosing time of DCQD for AP.

Keywords: Da-Cheng-Qi decoction, Acute pancreatitis, Pharmacokinetics, Oral dosing time, Pharmacodynamics

Core tip: Our study group had raised the hypothesis of tissue pharmacology of an herbal recipe, which assumed the effect of an herb formula is related to its target tissue distribution or concentration of effective components in target tissues. This study was then designed to screen the optimal oral dosing time of Da-Cheng-Qi decoction (DCQD) in rats with acute pancreatitis based on the pharmacokinetics of the main absorbed components and the pharmacodynamics of DCQD targeting of the pancreas.