Published online Dec 14, 2017. doi: 10.3748/wjg.v23.i46.8169
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
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.
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.
This study aimed to explore the pharmacokinetics and pharmacodynamics of SJD in rats with AP for protecting against multiple organ injury.
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.
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.
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.
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.