Qing-Yi Decoction in the Treatment of Acute Pancreatitis: An Integrated Approach Based on Chemical Profile, Network Pharmacology, Molecular Docking and Experimental Evaluation.

Tian-Fu Wei,Ju-Ying Jiao,Peng Huang,Liang Zhao,Feng-Lin Hu,Zhi-Zhou Wang,Jia-Lin Qu,Dong Shang,Kai-Lai Xiang

doi:10.3389/fphar.2021.590994

Abstract

Background: Qing-Yi Decoction (QYD) is a classic precompounded prescription with satisfactory clinical efficacy on acute pancreatitis (AP). However, the chemical profile and overall molecular mechanism of QYD in treating AP have not been clarified. Methods: In the present study, a rapid, simple, sensitive and reliable ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS)-based chemical profile was first established. An integration strategy of network pharmacology analysis and molecular docking based identified ingredients was further performed to screen out the potential targets and pathways involved in the treatment of QYD on AP. Finally, SD rats with acute pancreatitis were constructed to verify the predicted results through a western blot experiment. Results: A total of 110 compounds, including flavonoids, phenolic acids, alkaloids, monoterpenes, iridoids, triterpenes, phenylethanoid glycosides, anthraquinones and other miscellaneous compounds were identified, respectively. Eleven important components, 47 key targets and 15 related pathways based on network pharmacology analysis were obtained. Molecular docking simulation indicated that ERK1/2, c-Fos and p65 might play an essential role in QYD against AP. Finally, the western blot experiments showed that QYD could up-regulate the expression level of ERK1/2 and c-Fos, while down-regulate the expression level of p65. Conclusion: This study predicted and validated that QYD may treat AP by inhibiting inflammation and promoting apoptosis, which provides directions for further experimental studies.

Highlights

Molecular docking simulation indicated that ERK1/2, c-Fos and p65 might play an essential role in Qing-Yi Decoction (QYD) against acute pancreatitis (AP)
The western blot experiments showed that QYD could up-regulate the expression level of ERK1/2 and c-Fos, while down-regulate the expression level of p65
Qing-Yi Decoction Component Targets Network and Acute Pancreatitis Related Therapeutic Targets Based on the chemical profile of QYD characterized by UHPLC/ QTOF-MS, 541 targets associated with the 110 constituents were predicted as potential targets of QYD (Supplementary Table S2, Supplementary Figure S1)

Summary

Introduction

Acute pancreatitis (AP) is a common clinical disease caused by a variety of factors, including cholelithiasis, excessive drinking, obesity, smoking, etc (Sadr-Azodi et al, 2012; Yadav and Lowenfels, 2013; Lankisch et al, 2015; Forsmark et al, 2016), which is manifested by acute epigastric pain, nausea, vomiting and fever (Lankisch et al, 2015). The overall incidence rate of AP is 13–45 per 100,000 persons and is increasing year by year (Yadav and Lowenfels, 2013; Lankisch et al, 2015). It is imperative to develop safer and more effective drugs to treat AP. Traditional Chinese medicine (TCM), which has a history of clinical application for thousands of years in China, has been gradually accepted in the treatment of AP in view of its characteristics of holism concept and pattern differentiation (Wang and Zhang, 2017) as well as advantages of less side effects and systemic regulation. The chemical profile and overall molecular mechanism of QYD in treating AP have not been clarified

Methods

Results

Discussion

Conclusion