Galangin ameliorates severe acute pancreatitis in mice by activating the nuclear factor E2-related factor 2/heme oxygenase 1 pathway

Biomed Pharmacother. 2021 Dec:144:112293. doi: 10.1016/j.biopha.2021.112293. Epub 2021 Oct 8.

Abstract

Acute pancreatitis (AP) is a common serious acute condition of the digestive system that remains a clinical challenge. Severe acute pancreatitis (SAP) in particular is characterized by high morbidity and mortality. The present study was designed to investigate the protective effect of Galangin (Gal), a natural flavonol obtained from lesser galangal, on L-arginine-induced SAP in mice and in AR42J cells. Amylase and lipase activities were measured and the histopathology of the pancreas, lung, and kidney was evaluated. Inflammation and oxidative stress were assessed using ELISA, western blotting, RT-PCR, and immunohistochemistry. Gal was shown to reduce proinflammatory cytokine production and reactive oxygen species (ROS) generation in vivo and in vitro. L-arginine treatment reduced the expression of components of the nuclear factor E2-related factor 2 (Nrf2) signaling pathway and the downstream protein heme oxygenase-1 (HO-1) in mice, whereas Gal increased their expression. Furthermore, the Nrf2/HO-1 pathway inhibitor brusatol prevented the anti-inflammatory and antioxidant effects of Gal in mice with SAP. Taken together, our results imply that Gal has protective effects in L-arginine-induced SAP that are induced by the upregulation of the Nrf2/HO-1 pathway, which has anti-inflammatory and antioxidant effects. Thus, Gal may represent a promising treatment for SAP.

Keywords: Acute pancreatitis; Galangin; Inflammation; Nuclear factor E2-related factor 2; Oxidative stress.

MeSH terms

  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / prevention & control
  • Acute Lung Injury / metabolism
  • Acute Lung Injury / pathology
  • Acute Lung Injury / prevention & control
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Cell Line
  • Disease Models, Animal
  • Flavonoids / pharmacology*
  • Heme Oxygenase (Decyclizing) / metabolism*
  • Heme Oxygenase-1 / metabolism*
  • Inflammation Mediators / metabolism
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Lung / drug effects
  • Lung / metabolism
  • Lung / pathology
  • Male
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • NF-E2-Related Factor 2 / metabolism*
  • Oxidative Stress
  • Pancreas / drug effects*
  • Pancreas / enzymology
  • Pancreas / pathology
  • Pancreatitis / enzymology
  • Pancreatitis / pathology
  • Pancreatitis / prevention & control*
  • Rats
  • Severity of Illness Index
  • Signal Transduction

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Flavonoids
  • Inflammation Mediators
  • Membrane Proteins
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Nfe2l2 protein, rat
  • galangin
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • Hmox1 protein, rat