Rikkunshito, a traditional Japanese medicine, may relieve abdominal symptoms in rats with experimental esophagitis by improving the barrier function of epithelial cells in esophageal mucosa

J Gastroenterol. 2010 May;45(5):478-87. doi: 10.1007/s00535-009-0180-1. Epub 2009 Dec 18.

Abstract

Background: A traditional Japanese medicine, rikkunshito, has been reported to relieve dyspepsia symptoms. We investigated the effect of rikkunshito on RE-induced abdominal dyspepsia, and performed experiments to elucidate the mechanism of that effect.

Methods: RE model rats were prepared using 8-week-old male Wistar rats, and rikkunshito was administered in drinking water. Voluntary movement was used as an index of RE-induced abdominal dyspepsia, which was monitored by an infrared sensor. On the tenth day after surgery, the total area of esophageal erosion was measured, and samples of nonerosive mucosa were collected. Using those samples, intercellular spaces of epithelial mucosa were examined by transmission electron microscopy, and the NP-40-soluble and -insoluble levels of the tight junction proteins claudin-1, -3 and -4 and their mRNAs were determined.

Results: Rikkunshito did not reduce the average total area of erosive lesions in the esophageal mucosa of RE model rats. On day 10, voluntary movement was significantly decreased in the RE model rats and rikkunshito significantly increased it. Nonerosive esophageal mucosa from RE rats showed dilation of intercellular spaces in epithelium, and significantly decreased claudin-3 mRNA and protein levels. Rikkunshito significantly suppressed intercellular space dilation and significantly increased the level of NP-40-insoluble claudin-3, but it did not affect the mRNA level, suggesting that it promoted tight junction formation by facilitating the translocation of proteins.

Conclusion: Rikkunshito increased voluntary movement in RE model rats. This may have been because rikkunshito ameliorated the symptoms of RE by improving the barrier function of esophageal mucosa.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Claudin-3
  • Disease Models, Animal
  • Drugs, Chinese Herbal / pharmacology*
  • Drugs, Chinese Herbal / therapeutic use
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Epithelial Cells / ultrastructure
  • Esophagitis, Peptic / drug therapy
  • Esophagitis, Peptic / metabolism
  • Esophagitis, Peptic / pathology*
  • Extracellular Space / drug effects
  • Extracellular Space / metabolism
  • Japan
  • Male
  • Membrane Proteins / metabolism
  • Motor Activity / drug effects
  • Mucous Membrane / drug effects
  • Mucous Membrane / metabolism
  • Mucous Membrane / pathology
  • Rats
  • Rats, Wistar
  • Tight Junctions / drug effects*
  • Tight Junctions / metabolism
  • Tight Junctions / ultrastructure

Substances

  • Claudin-3
  • Cldn3 protein, rat
  • Drugs, Chinese Herbal
  • Membrane Proteins
  • liu-jun-zi-tang