Paeoniflorin Inhibits Pancreatitis-Induced Oxidative Stress and Endoplasmic Reticulum Stress through NF-κB/MAPK Pathway

Xin-lian WU

Article ID: 7256
Vol 37, Issue 4, 2023
DOI: https://doi.org/10.23812/j.biol.regul.homeost.agents.20233704.202
Received: 9 May 2023; Accepted: 9 May 2023; Available online: 9 May 2023; Issue release: 9 May 2023

Abstract

Background: Affluent studies have confirmed the spectrum anti-oxidant and anti-inflammatory effects of paeoniflorin (PF). Therefore, the present work deliberates PF-mediated protection against pancreatitis. Gene expression data set GSE41418 was analyzed. Methods: A cells-based pancreatitis model was generated by lipopolysaccharide and cerulein, and the stimulated mouse pancreas cancer (MPC-83) cell line and human pancreatic cancer (HPAC) cell line were subjected to treatment with 0, 5, 10, and 20 μM of PF. A mouse model of pancreatitis was established using cerulein, and the mice were treated by intraperitoneal injection of PF (50 and 100 mg/kg). Bioinformatics analysis was performed to uncover the main biological processes related to pancreatitis. For MPC-83 and HPAC cells, cell viability, apoptosis and oxidative stress, endoplasmic reticulum (ER) stress, autophagy, and nuclear factor-κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathway activation were evaluated. For mice, inflammatory factor, pancreatic pathological injury, ER stress, oxidative stress and NF-κB/MAPK activation were particularly analyzed. Results: GO (Gene Ontology)-BP (biological process) enrichment analysis presented that the up-regulated genes in pancreatitis mice model were related to MAPK activity, NF-κB pathway and apoptotic pathway. PF concentration-dependently promoted viability and autophagy and inhibited apoptosis, oxidative stress and ER stress of MPC-83 and HPAC cells. PF weakened pancreatitis-induced inflammatory injury, as well as oxidative stress and ER stress in mice. Either in the cell model or the animal model of pancreatitis, PF suppressed NF-κB/MAPK pathway activation. Conclusions: PF inhibits pancreatitis-induced oxidative stress and ER stress through blocking NF-κB/MAPK pathway activation, serving a clinical promising direction for the disease control.


Keywords

pancreatitis;paeoniflorin;oxidative stress;endoplasmic reticulum stress;inflammation;NF-κB/MAPK pathway


References

Supporting Agencies



Copyright (c) 2023 Xin-lian WU




This site is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).