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: http://creativecommons.org/licenses/by-nc/4.0/
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. tangwf@scu.edu.cn
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
Abstract
AIM

To explore the pharmacokinetics and pharmacodynamics of Shengjiang decoction (SJD) in rats with acute pancreatitis (AP) for protecting against multiple organ injury.

METHODS

An AP model was established by retrograde perfusion of 3.5% sodium taurocholate into the biliopancreatic duct, and a control group (CG) received 0.9% sodium chloride instead. Twelve male Sprague-Dawley rats were randomly divided into a CG treated with SJD (CG + SJD) and a model group treated with SJD (MG + SJD), both of which were orally administered with SJD (5 g/kg) 2 h after surgery. Blood samples were collected via the tail vein at 10, 20, and 40 min and 1, 2, 3, 4, 6, 8, and 12 h after a single dose of SJD to detect its main components using high-performance liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters were compared. In the pharmacodynamic experiment, 18 male Sprague-Dawley rats were randomly divided into a CG, an AP model group (MG), and an SJD treated AP group (SJDG). Serum amylase, lipase, and inflammatory cytokines were measured, and heart, lung, liver, spleen, pancreas, kidney, and intestine tissues were collected for pathological examination.

RESULTS

The MG + SJD displayed significantly shorter mean residence time (MRT) and higher clearance (CL) for emodin and aloe-emodin; significantly shorter time of maximum concentration and T1/2 and a lower area under curve (AUC) for aloe-emodin; a significantly 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, interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-α levels in the 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).

CONCLUSION

AP may have varying effects on the pharmacokinetics of the major SJD components in rats. SJD might alleviate pathological injuries of the lung, pancreas, kidney, and intestine in rats with AP via regulating pro- and anti- inflammatory responses, which might guide the clinical application of SJD for AP treatment.

Keywords: Pancreatic distribution, Pharmacodynamics, Shengjiang decoction, Pharmacokinetics, Acute pancreatitis

Core tip: Shengjiang decoction (SJD) has been identified to be effective in treating acute pancreatitis (AP) in both in vivo and in vitro tests. We report the metabolic processes of major components of SJD in vivo and the pharmacodynamic mechanism of SJD in relieving AP. This study demonstrated 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 based on the hypothesis of tissue pharmacology of herbal recipe. SJD may attenuate AP by regulating inflammatory responses to protect against multiple organ injury.