Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 21, 2018; 24(39): 4448-4461
Published online Oct 21, 2018. doi: 10.3748/wjg.v24.i39.4448
Sheng-jiang powder ameliorates obesity-induced pancreatic inflammatory injury via stimulating activation of the AMPK signalling pathway in rats
Yi-Fan Miao, Juan Li, Yu-Mei Zhang, Lv Zhu, Huan Chen, Ling Yuan, Jing Hu, Xiao-Lin Yi, Qiu-Ting Wu, Mei-Hua Wan, Wen-Fu Tang
Yi-Fan Miao, Juan Li, Yu-Mei Zhang, 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
Author contributions: Tang WF designed the study; Miao YF, Li J, Zhang YM, Zhu L, Chen H, Yuan L, Hu J, Yi XL, Wu QT, and Wan MH were responsible for the acquisition of data; Miao YF, Li J, and Zhang YM were responsible for the analysis and interpretation of data; Miao YF and Li J were responsible for the drafting of the paper; Tang WF was responsible for critical revisions of the paper; Tang WF and Li J obtained funding and provided study supervision; all authors read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 81603519 and No. 81573857.
Institutional review board statement: This study was reviewed and approved by the Institutional Animal Care and Use Committee of West China Hospital of Sichuan University.
Institutional animal care and use committee statement: All rats were handled according to the University Guidelines and the Animal Care Committee Guidelines of West China Hospital (Chengdu, China) (protocol number, 2017052A).
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 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, Department of Integrative Medicine, West China Hospital, Sichuan University, No. 37, Guoxue Lane, Wuhou District, Chengdu 610041, Sichuan Province, China. tangwf@scu.edu.cn
Telephone: +86-28-85423546 Fax: +86-28-85423373
Received: July 9, 2018
Peer-review started: July 9, 2018
First decision: August 25, 2018
Revised: September 12, 2018
Accepted: October 5, 2018
Article in press: October 5, 2018
Published online: October 21, 2018
Processing time: 103 Days and 19.9 Hours
ARTICLE HIGHLIGHTS
Research background

Obesity is a risk factor for non-alcoholic fatty pancreas disease and induces pancreatic inflammatory injury. Sheng-jiang powder (SJP) can ameliorate obesity-induced pancreatic inflammatory injury, but the specific mechanisms remain unclear. Therefore, the investigation of the specific mechanisms underlying the SJP amelioration of obesity-induced pancreatic inflammatory injury is urgently required.

Research motivation

Our previous studies have demonstrated that SJP can ameliorate the inflammatory response and histopathological lesions in the pancreas of obese rats. However, the specific mechanisms underlying ameliorating effects of SJP on obesity-induced pancreatic inflammatory injury are far from sufficiently understood. Therefore, this study aimed to further explore the specific mechanisms of SJP on obesity-induced pancreatic inflammatory injury, to provide evidence for its clinical application in the future.

Research objectives

This study aimed to investigate the specific mechanisms by which SJP can ameliorate obesity-induced pancreatic inflammatory injury.

Research methods

In the in vivo study, an obese rat model was induced by high-fat diet feeding, which is widely accepted and used for the induction of obesity in rats. The serum adiponectin levels were measured by enzyme-linked immunosorbent assay (ELISA), which is a simple, rapid, accurate, and sensitive method. The expression levels of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and transforming growth factor beta (TGF-β) in pancreatic tissues were measured by immunohistochemistry. The levels of apoptotic cells in pancreatic tissue samples were analysed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL) assay.

In the in vitro study, a high-fat AR42J acinar cell injury model was established with very low-density lipoprotein (VLDL), and the AR42J acinar cell culture supernatants, treated with different interventions, were applied to pancreatic stellate cells (PSCs). The proliferation of PSCs and the expression of fibronectin and type I collagenase were measured by immunofluorescence analysis.

All statistical analyses were performed with GraphPad Prism 6.01 software. Quantitative data are expressed as the mean ± standard deviation when normally distributed. One-way analysis of variance followed by multiple pair-wise comparisons using Dunnett-t test was used to detect differences among the above parameters.

Research results

In the in vivo study, compared to the obese group (HLG), we found reduced body weight, Lee’s index scores, serum triglyceride levels, and pathological scores of pancreatic tissues; higher serum adiponectin levels; and lower expression levels of NF-κB in pancreatic tissue and TGF-β in the inflammatory cells of the pancreas in the SJP treatment group (HSG) (P < 0.05). In the in vitro study, PSC activation was enhanced after SJP treatment, and the expression levels of fibronectin and type I collagenase were increased after SJP treatment. An adenosine 5‘-monophosphate-activated protein kinase (AMPK) inhibitor inhibited the PSC activation process described above.

What remains to be determined is the relationship between dose or dose frequency and the concentration effect. Furthermore, the specific effective monomer components of SJP should be taken under consideration to provide more systematic and comprehensive evidence for the clinical application of this Chinese decoction.

Research conclusions

This study demonstrates, for the first time, that obesity exacerbates pancreatic inflammatory injury in rats and promotes apoptosis in pancreatic acinar cells. In addition, SJP can inhibit the inflammatory response, prevent pancreatic fibrosis, promote pancreatic acinar cell repair, through the regulation of key molecules of the adiponectin-AMPK signalling pathway, and eventually ameliorate obesity-induced pancreatic inflammatory injury in rats. Therefore, our study provides molecular mechanisms as evidence for the clinical application of SJP.

Research perspectives

As we have found that SJP may ameliorate obesity-induced pancreatic inflammatory injury in rats by regulating key molecules of the adiponectin-AMPK signalling pathway, further investigation regarding the potential active components of SJP and the interactions among these components is urgently required to provide evidence for wider clinical usage and to optimize and simplify the formula.