Material basis and molecular mechanisms of Chaihuang Qingyi Huoxue Granule in the treatment of acute pancreatitis based on network pharmacology and molecular docking-based strategy

Front Immunol. 2024 May 3:15:1353695. doi: 10.3389/fimmu.2024.1353695. eCollection 2024.

Abstract

Objectives: This study aimed to analyze active compounds and signaling pathways of CH applying network pharmacology methods, and to additionally verify the molecular mechanism of CH in treating AP.

Materials and methods: Network pharmacology and molecular docking were firstly used to identify the active components of CH and its potential targets in the treatment of AP. The pancreaticobiliary duct was retrogradely injected with sodium taurocholate (3.5%) to create an acute pancreatitis (AP) model in rats. Histological examination, enzyme-linked immunosorbent assay, Western blot and TUNEL staining were used to determine the pathway and mechanism of action of CH in AP.

Results: Network pharmacological analysis identified 168 active compounds and 276 target proteins. In addition, there were 2060 targets associated with AP, and CH had 177 targets in common with AP. These shared targets, including STAT3, IL6, MYC, CDKN1A, AKT1, MAPK1, MAPK3, MAPK14, HSP90AA1, HIF1A, ESR1, TP53, FOS, and RELA, were recognized as core targets. Furthermore, we filtered out 5252 entries from the Gene Ontology(GO) and 186 signaling pathways from the Kyoto Encyclopedia of Genes and Genomes(KEGG). Enrichment and network analyses of protein-protein interactions predicted that CH significantly affected the PI3K/AKT signaling pathway, which played a critical role in programmed cell death. The core components and key targets showed strong binding activity based on molecular docking results. Subsequently, experimental validation demonstrated that CH inhibited the phosphorylation of PI3K and AKT in pancreatic tissues, promoted the apoptosis of pancreatic acinar cells, and further alleviated inflammation and histopathological damage to the pancreas in AP rats.

Conclusion: Apoptosis of pancreatic acinar cells can be enhanced and the inflammatory response can be reduced through the modulation of the PI3K/AKT signaling pathway, resulting in the amelioration of pancreatic disease.

Keywords: Chaihuang Qingyi Huoxue Granule; Traditional Chinese; acute pancreatitis; molecular docking; network pharmacology; pancreatic acinar cells.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Disease Models, Animal
  • Drugs, Chinese Herbal* / chemistry
  • Drugs, Chinese Herbal* / pharmacology
  • Drugs, Chinese Herbal* / therapeutic use
  • Male
  • Molecular Docking Simulation*
  • Network Pharmacology*
  • Pancreatitis* / drug therapy
  • Pancreatitis* / metabolism
  • Pancreatitis* / pathology
  • Protein Interaction Maps
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction* / drug effects

Substances

  • qingyi

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the grants from the Foundation of Chinese Medicine Hospital Affiliated to Southwest Medical University (No. 2022-CXTD-01), National Natural Science Foundation of China (No. 82174264), the Strategic Cooperation Program, the Fundamental Research Funds for Central Universities, the Sichuan University (No. 2020CDLZ-18), the Sichuan Provincial Administration of Traditional Chinese Medicine Science and Technology Program (No. 2023MS416), Sichuan Science and Technology Program (2023NSFSC1808) and Science and Technology Program of Southwest Medical University Chinese and Western Medicine (2023ZYYQ13).