Anti-Inflammatory Effects and Molecular Mechanisms of Shenmai Injection in Treating Acute Pancreatitis: Network Pharmacology Analysis and Experimental Verification

Yanqiu He; Cheng Hu; Shiyu Liu; Mingjie Xu; Ge Liang; Dan Du; Tingting Liu; Fei Cai; Zhiyao Chen; Qingyuan Tan; Lihui Deng; Qing Xia

doi:10.2147/DDDT.S364352

Anti-Inflammatory Effects and Molecular Mechanisms of Shenmai Injection in Treating Acute Pancreatitis: Network Pharmacology Analysis and Experimental Verification

Drug Des Devel Ther. 2022 Aug 2:16:2479-2495. doi: 10.2147/DDDT.S364352. eCollection 2022.

Authors

Yanqiu He^#¹, Cheng Hu^#¹, Shiyu Liu¹, Mingjie Xu¹, Ge Liang², Dan Du³, Tingting Liu¹, Fei Cai¹, Zhiyao Chen¹, Qingyuan Tan¹, Lihui Deng¹, Qing Xia¹

Affiliations

¹ Pancreatitis Centre, Department and Laboratory of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
² Laboratory of Clinical Proteomics and Metabolomics, Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
³ Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, People's Republic of China.

^# Contributed equally.

Abstract

Background: Acute pancreatitis (AP) is an inflammatory disorder of the exocrine pancreas without specific treatment. Shenmai injection (SMI) was reported to eliminate the severity of experimental AP. This study aimed to explore the mechanisms underlying the synergistic protective effects of SMI on AP based on network pharmacology and experimental validation.

Methods: Network pharmacology analysis and molecular docking based on identified components were performed to construct the potential therapeutic targets and pathways. The principal components of SMI were detected via ultra-high-performance liquid chromatography-coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS). Effect of SMI and the identified components on cellular injury and IL6/STAT3 signaling was assessed on mouse pancreatic acinar cell line 266-6 cells. Finally, 4% sodium taurocholate (NaT) was used to induce AP model to assess the effects of SMI in treating AP and validate the potential molecular mechanisms.

Results: By searching the TCMSP and ETCM databases, 119 candidate components of SMI were obtained. UHPLC-QTOF/MS analysis successfully determined the representative components of SMI: ginsenoside Rb1, ginsenoside Rg1, ginsenoside Re, and ophiopogonin D. Fifteen hub targets and eight related pathways were obtained to establish the main pharmacology network. Subnetwork analysis and molecular docking indicated that the effects of these four main SMI components were mostly related to the interleukin (IL) 6/STAT3 pathway. In vitro, SMI, ginsenoside Rb1, ginsenoside Rg1, ginsenoside Re, and ophiopogonin D increased the cell viability of NaT-stimulated mouse pancreatic acinar 266-6 cells and decreased IL6 and STAT3 expression. In vivo, 10 mL/kg SMI significantly alleviated the pancreatic histopathological changes and the expression of IL6 and STAT3 in the AP mice.

Conclusion: This study demonstrated SMI may exert anti-inflammatory effects against AP by suppressing IL6/STAT3 activation, thus providing a basis for its potential use in clinical practice and further study in treating AP.

Keywords: IL6/STAT3 signaling pathway; Shenmai injection; acute pancreatitis; molecular docking; network pharmacology.

MeSH terms

Acute Disease
Animals
Anti-Inflammatory Agents / pharmacology
Anti-Inflammatory Agents / therapeutic use
Drug Combinations
Drugs, Chinese Herbal*
Interleukin-6
Mice
Molecular Docking Simulation
Network Pharmacology
Pancreatitis* / metabolism

Substances

Anti-Inflammatory Agents
Drug Combinations
Drugs, Chinese Herbal
Interleukin-6
fructus schizandrae, radix ginseng, radix ophiopogonis drug combination

Grants and funding

This study was supported by the National Natural Science Foundation of China (No. 82104715, CH; No. 82074230, LD); Sichuan Province Science and Technology Support Program (No. 2020YJ0235, CH).