Ponciretin attenuates ethanol-induced gastric damage in mice by inhibiting inflammatory responses

Int Immunopharmacol. 2017 Feb;43:179-186. doi: 10.1016/j.intimp.2016.12.021. Epub 2016 Dec 22.

Abstract

Background: Poncirin (PO) and isosakuranetin (or ponciretin [PT]) are compounds found in fruits of the genus Citrus. They are frequently used in traditional Chinese medicine for the treatment of inflammation and asthma. Therefore, we examined their anti-gastritis effects in vitro and in vivo.

Methods: The anti-inflammatory effects of PO and PT were examined using ethanol- or LPS-stimulated KATO III cells. Gastritis was induced in ICR mice via intragastric injection of absolute ethanol. Levels of inflammatory markers were measured by enzyme-linked immunosorbent assay, immunoblotting, and quantitative polymerase chain reaction.

Results: Treatment with PT or PO inhibited the secretion of interleukin (IL)-8 and tumor necrosis factor (TNF) in ethanol- or LPS-stimulated KATO III cells. They also reduced the activation of nuclear factor kappa B (NF-κB). Pre-treatment with PT or PO significantly protected against ethanol-induced hemorrhagic gastritis, characterized by edema, tissue erosions, and mucosal friability in mice. Treatment with PT or PO suppressed ethanol-induced NF-κB activation and the release of TNF, IL-8, and IFN-γ. The protective effect of PT was greater than that of PO and comparable to ranitidine, a positive control.

Conclusion: PT may attenuate ethanol-induced gastritis by inhibiting the infiltration of immune cells, including neutrophils, via the regulation of CXCL4 (or IL-8) secretion and the activation NF-κB.

Keywords: Alcohol; Gastritis; Neutrophil; Ponciretin; Poncirin.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / therapeutic use*
  • Cell Line
  • Cell Movement / drug effects
  • Citrus / immunology*
  • Ethanol / toxicity
  • Flavonoids / therapeutic use*
  • Gastric Mucosa / drug effects*
  • Gastric Mucosa / immunology
  • Gastritis / chemically induced
  • Gastritis / drug therapy*
  • Interleukin-8 / metabolism*
  • Male
  • Medicine, Chinese Traditional
  • Mice
  • Mice, Inbred ICR
  • NF-kappa B / metabolism
  • Neutrophils / drug effects*
  • Neutrophils / immunology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Flavonoids
  • Interleukin-8
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Ethanol
  • poncirin
  • isosakuranetin