Diosgenin suppresses COX-2 and mPGES-1 via GR and improves LPS-induced liver injury in mouse

Prostaglandins Other Lipid Mediat. 2021 Oct:156:106580. doi: 10.1016/j.prostaglandins.2021.106580. Epub 2021 Jul 9.

Abstract

Using a wild yam (Dioscorea japonica), we previously found novel anti-inflammatory and anti-carcinogenic effects via the downregulation of cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase (mPGES)-1. One of the substances in wild yam is a steroidal saponin, diosgenin. We demonstrated that diosgenin suppressed COX-2 in human non-small-cell lung carcinoma A549 cells via nuclear factor-kappa B (NF-κB) translocation and the effects were reversed by a glucocorticoid receptor antagonist, RU486. In lipopolysaccharide (LPS)-induced mouse liver injury, COX-2 and mPGES-1 were induced and localized in sinusoidal macrophages and endothelial cells; however, diosgenin administration significantly suppressed Ptgs2 and Ptges expression and decreased COX-2 and mPGES-1 immunopositive cells in the sinusoids. Multiple immunohistochemical analyses showed that diosgenin had an effect on COX-2 and mPGES-1, particularly in the macrophages. Thus, we showed that diosgenin downregulated COX-2 and mPGES-1 via the glucocorticoid receptor and suppressed COX-2 and mPGES-1 in the macrophages of LPS-induced acute mouse liver injury.

Keywords: Cyclooxygenase-2; Liver injury; Microsomal prostaglandin E synthase-1; Steroidal saponin.

MeSH terms

  • A549 Cells
  • Animals
  • Chemical and Drug Induced Liver Injury / drug therapy
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Cyclooxygenase 2* / metabolism
  • Diosgenin* / pharmacology
  • Humans
  • Lipopolysaccharides* / pharmacology
  • Male
  • Mice
  • NF-kappa B / metabolism
  • Prostaglandin-E Synthases* / metabolism
  • Receptors, Glucocorticoid* / metabolism

Substances

  • Diosgenin
  • Prostaglandin-E Synthases
  • Lipopolysaccharides
  • Cyclooxygenase 2
  • Receptors, Glucocorticoid
  • Ptges protein, mouse
  • NF-kappa B