Paeonol protects against acute pancreatitis by Nrf2 and NF-κB pathways in mice

J Pharm Pharmacol. 2022 Nov 4;74(11):1618-1628. doi: 10.1093/jpp/rgac065.

Abstract

Objectives: Paeonol (PAE) is an active ingredient with anti-inflammatory and antioxidant properties. This study was designed to investigate the effect of PAE on acute pancreatitis (AP).

Methods: AP was induced by the intraperitoneal injection of 20% l-arginine (4 g/kg) for 6 h. Mice were pretreated with PAE (25, 50 or 100 mg/kg) intragastrically for 5 days. The histological damage and alterations of biochemical indicators, inflammatory cytokines and oxidative stress factors in AP mice were detected. The Nrf2 and NF-κB pathways were examined to illustrate the potential mechanism.

Key findings: In AP model, we found that PAE attenuated histological injury of pancreatic tissues, reduced the serum levels of α-amylase and increased Ca2+ contents in a dose-dependent manner. The white blood cell content, and IL-1β, IL-6 and TNF-α levels in the serum of AP mice were reduced by PAE. Furthermore, PAE caused a reduction of MPO and MDA levels, accompanied by an increase in SOD activity in the pancreas of AP mice. We also demonstrated that the alterations of Nrf2 and NF-κB pathways in AP mice were reversed by PAE.

Conclusions: PAE attenuates inflammation and oxidative stress in the development of AP by the regulation of Nrf2 and NF-κB pathways.

Keywords: NF-κB; Nrf2; acute pancreatitis; l-arginine; paeonol.

MeSH terms

  • Acute Disease
  • Animals
  • Mice
  • NF-E2-Related Factor 2 / metabolism
  • NF-kappa B* / metabolism
  • Pancreatitis* / chemically induced
  • Pancreatitis* / drug therapy
  • Pancreatitis* / prevention & control

Substances

  • NF-kappa B
  • NF-E2-Related Factor 2
  • paeonol