Forsythia Fruit Prevents Fulminant Hepatitis in Mice and Ameliorates Inflammation in Murine Macrophages

Nutrients. 2021 Aug 23;13(8):2901. doi: 10.3390/nu13082901.

Abstract

Forsythia Fruit (FF), the fruit of Forsythia suspensa, has been used since ancient times as an herbal medication in East Asia to treat inflammation, gonorrhea, and pharyngitis. However, the efficacy of FF against liver damage due to inflammation has not been studied. Here, we explored the protective effects of FF in a mouse hepatitis model induced by lipopolysaccharide (LPS)/D-galactosamine (GalN) treatment. We measured inflammatory cytokine and aminotransferase levels in mouse blood and analyzed the effects of FF on inflammatory gene and protein expression levels in liver tissue. Our results show that FF treatment effectively lowers inflammatory cytokine and serum aminotransferase levels in mice and inhibits the expression of hepatic cytokine mRNA and inflammatory proteins. Furthermore, treatment with FF activated the antioxidant pathway HO-1/Nrf-2 and suppressed severe histological alteration in the livers of LPS/D-GalN-treated mice. Further investigation of the effects of FF on inflammatory reactions in LPS-stimulated macrophages showed that pretreatment with FF inhibits inflammatory mediator secretion and activation of inflammatory mechanisms both in a mouse macrophage RAW 264.7 cells and in primary peritoneal macrophages. These results show that FF has potential worth as a candidate for the treatment of fulminant inflammatory reactions and subsequent liver injury.

Keywords: D-galactosamine; Forsythia Fruit; antioxidant; inflammation; lipopolysaccharide; liver injury.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / isolation & purification
  • Antioxidants / pharmacology
  • Cytokines / genetics
  • Cytokines / metabolism
  • Disease Models, Animal
  • Forsythia* / chemistry
  • Fruit* / chemistry
  • Galactosamine
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Male
  • Massive Hepatic Necrosis / chemically induced
  • Massive Hepatic Necrosis / metabolism
  • Massive Hepatic Necrosis / pathology
  • Massive Hepatic Necrosis / prevention & control*
  • Mice
  • Mice, Inbred ICR
  • Oxidative Stress / drug effects
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • RAW 264.7 Cells

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Cytokines
  • Inflammation Mediators
  • Lipopolysaccharides
  • Plant Extracts
  • lipopolysaccharide, E coli O55-B5
  • Galactosamine