Epalrestat suppresses inflammatory response in lipopolysaccharide-stimulated RAW264.7 cells

Allergol Immunopathol (Madr). 2021 Sep 1;49(5):1-8. doi: 10.15586/aei.v49i5.102. eCollection 2021.

Abstract

Introduction and objectives: Lipopolysaccharide (LPS) is a potent inducer of inflammatory response. Inflammation is a major risk factor for many diseases. Regulation of inflammatory mediator and pro-inflammatory cytokine levels could be a potential therapeutic approach to treat inflammatory injury. The purpose of the present study was to determine whether epalrestat (EPS), which is used for the treatment of diabetic neuropathy, suppresses inflammatory response in LPS-stimulated RAW264.7 cells.

Material and methods: The effects of EPS at near-plasma concentration on the levels of pro-inflammatory cytokines and inflammatory mediators was examined using by MTS assay, quantitative RT-PCR analysis, and western blotting in LPS-stimulated RAW264.7 cells.

Results: EPS suppressed mRNA and protein expression levels of pro-inflammatory cytokines, including IL-1β, IL-6, and TNFα, in RAW264.7 cells stimulated with LPS. EPS also affected inflammatory mediators such as iNOS and NF-κB in LPS-stimulated RAW264.7 cells.

Conclusions: In this study, we demonstrated for the first time that EPS suppresses inflammatory response in LPS-stimulated RAW264.7 cells. From these results, we propose that targeting the regulation of pro-inflammatory cytokine levels and inflammatory mediators by EPS is a promising therapeutic approach to treat inflammatory injury. It is expected that EPS, whose safety and pharmacokinetics have been confirmed clinically, would be useful for the treatment of inflammatory diseases.

Keywords: epalrestat; inflammatory cytokine; inflammatory mediator; inflammatory response; pro-inflammatory cytokine.

MeSH terms

  • Animals
  • Cytokines
  • Inflammation / drug therapy
  • Inflammation Mediators*
  • Lipopolysaccharides*
  • Mice
  • Nitric Oxide
  • RAW 264.7 Cells
  • Rhodanine / analogs & derivatives
  • Thiazolidines

Substances

  • Cytokines
  • Inflammation Mediators
  • Lipopolysaccharides
  • Thiazolidines
  • Nitric Oxide
  • epalrestat
  • Rhodanine