Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2017; 23(46): 8169-8181
Published online Dec 14, 2017. doi: 10.3748/wjg.v23.i46.8169
Pharmacokinetics and pharmacodynamics of Shengjiang decoction in rats with acute pancreatitis for protecting against multiple organ injury
Lv Zhu, Jun-Yi Li, Yu-Mei Zhang, Hong-Xin Kang, Huan Chen, Hang Su, Juan Li, Wen-Fu Tang
Lv Zhu, Yu-Mei Zhang, Hong-Xin Kang, Huan Chen, Hang Su, Juan Li, Wen-Fu Tang, Sichuan Provincial Pancreatitis Center, Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
Jun-Yi Li, Department of Traditional Chinese Medicine, Wuhan Union Hospital, Wuhan 430000, Hubei Province, China
Author contributions: Zhu L and Li JY contributed equally to this work; Tang WF designed the research; Zhu L, Li JY, Zhang YM, Kang HX and Chen H performed the study; Su H and Li J analyzed the data; Zhu L and Li JY wrote the paper; Tang WF was responsible for the critical revision of the paper.
Supported by the National Natural Science Foundation of China, No. 81603519, No. 81573857, and No. 81374042.
Institutional review board statement: The study was approved by the Animal Ethics Committee of the Animal Facility of West China Hospital (Chengdu, China).
Institutional animal care and use committee statement: All procedure involving animals were reviewed and approved by the Animal Ethics Committee of the Animal Facility of the West China Hospital (protocol number: 2017052A, Chengdu, China), and performed according to the Guide for the Care and Use of Laboratory Animals of Sichuan University.
Conflict-of-interest statement: The authors declare 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:
Correspondence to: Wen-Fu Tang, PhD, Professor, Sichuan Provincial Pancreatitis Center, Department of Integrative Medicine, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Chengdu 610041, Sichuan Province, China.
Telephone: +86-28-85423546 Fax: +86-28-85423373
Received: September 19, 2017
Peer-review started: September 20, 2017
First decision: October 10, 2017
Revised: October 24, 2017
Accepted: November 14, 2017
Article in press: November 14, 2017
Published online: December 14, 2017
Research background

Acute pancreatitis (AP) is one of the most common gastrointestinal disorders associated with a mortality rate up to 30%-56% among severe cases with systemic inflammatory response syndrome. Shengjiang decoction (SJD) is an effective prescription for the treatment of AP, but the exact active components are not clear. Little is known about the in vivo metabolic process of SJD. Therefore, full elucidation of the pharmacokinetic and pharmacodynamic mechanisms of SJD associated with the amelioration of AP is urgently needed.

Research motivation

This study aimed to explore the pharmacokinetics, pharmacodynamics, and pancreatic distribution of the main components of SJD in rats with AP to provide pharmacokinetic and pharmacodynamic evidence for its clinical application for the treatment of AP in the future.

Research objectives

This study aimed to explore the pharmacokinetics and pharmacodynamics of SJD in rats with AP for protecting against multiple organ injury.

Research methods

The AP model was established by retrograde perfusion of 3.5% sodium taurocholate into the biliopancreatic duct, which was widely accepted and used in the induction of AP in rats.

The concentrations of the main components of SJD in serum were measured by HPLC-MS/MS, which is a simple, rapid, accurate, and sensitive way to detect the components in serum and tissues of SJD. Analyst 1.4.2 software for HPLC-MS/MS was used for data collection.

All statistical analyses were performed with PEMS3.1 statistical software for windows. Quantitative data are expressed as the mean ± standard deviation when normally distributed. Comparisons of the pharmacokinetic parameters were performed by Student’s t-test. One-way repeated-measures ANOVA followed by multiple pair-wise comparisons using the Student-Newman-Keuls test was used to detect differences of the pharmacodynamic parameters.

Research results

In the pharmacokinetic experiment, the MG + SJD displayed significantly shorter mean residence time (MRT) and higher clearance (CL) for emodin and aloe-emodin; significantly shorter Tmax and T1/2 and a lower area under curve (AUC) for aloe-emodin; an apparently higher AUC and lower CL for rhein; and longer MRT and lower CL for chrysophanol than the CG + SJD. In the pharmacodynamic experiment, the amylase, IL-6, IL-10, and TNF-α levels in MG were higher than those in the CG (P < 0.05). After the herbal decoction treatment, the SJDG had higher IL-10 and lower TNF-α levels than the MG (P < 0.05). The MG had the highest pathological scores, and the pathological scores of the lung, pancreas, kidney, and intestine in the SJDG were significantly lower than those in the MG (P < 0.05). The results revealed metabolic process of the major components of SJD absorbed in serum and pancreas as well as the possible mechanism of SJD in alleviating AP.

What remains to be solved is that the distribution of the effective components to other target tissues to provide more systematic and comprehensive evidence for the clinical application of Chinese decoction. Furthermore, the specific molecular mechanism of how the potential active components alleviate the disease needs to be investigated to optimize herbal formulations and therapies.

Research conclusions

In the study, we found that AP may have varying effects on the pharmacokinetics of the major SJD components in rats, rhein and bisdemethoxycurcumin may be potential active components for the treatment of AP, and SJD might alleviate pathological injuries of the lung, pancreas, kidney, and intestine in rats with AP via regulating pro- and anti- inflammatory responses. The conclusions are based on our previous theory of ‘tissue pharmacology of recipe’, and are in accordance with the clinical and experiment results available that SJD is an effective way to alleviate AP.

We report the metabolic processes of major components of SJD in vivo and the pharmacodynamic mechanism of SJD in relieving AP. The study indicated that diseased condition of the body as well as formula composition may have certain effect on the metabolic process of different components in decoctions. As AP involves systemic inflammatory responses, based on the findings above, the mechanism for SJD to attenuate AP may be through the regulation of inflammatory responses to protect against multiple organ injury.

Research perspectives

As we have found the potential components of SJD in alleviating AP, further investigation about the interaction of these components is urgently needed to provide evidence for optimizing and simplifying the formula. Moreover, more in-depth studies about the molecular mechanism of SJD in alleviating AP should be explored to have a deeper and more comprehensive understanding of SJD in treating AP.