Published online Oct 21, 2018. doi: 10.3748/wjg.v24.i39.4448
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
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.
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.
This study aimed to investigate the specific mechanisms by which SJP can ameliorate obesity-induced pancreatic inflammatory injury.
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.
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.
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.
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.