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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

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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.

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Acknowledgments

We deeply thank Ms. M. Togawa and N. Kamiya for their technical assistance and Y. Okano for her dedicated secretarial assistance.

Conflict of interest statement

H. Miwa is a consultant to AstraZeneca (Japan) Co. Ltd., Takeda Pharmaceutical Co. Ltd., Eisai Co. Ltd., Tsumura & Co., and Dainippon Sumitomo Pharmaceutical Co. Ltd. T. Matsumoto is a consultant to Tanabe-Mitsubishi Pharmaceutical Co. Ltd., Otsuka Pharmaceuticals Co. Ltd., and Ajinomoto Pharma Co. Ltd. J. Koseki, T. Hattori, K. Kubota and S. Iizuka are employees of Tsumura & Co.

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Authors and Affiliations

  1. Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan

    Hiroto Miwa, Junichi Koseki, Tadayuki Oshima, Takashi Kondo, Toshihiko Tomita & Jiro Watari

  2. Division of Lower Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan

    Takayuki Matsumoto

  3. Tsumura Research Laboratories, Tsumura & Co., Ibaraki, Japan

    Junichi Koseki, Tomohisa Hattori, Kunitsugu Kubota & Seiichi Iizuka

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  1. Hiroto Miwa
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  2. Junichi Koseki
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  3. Tadayuki Oshima
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Correspondence to Hiroto Miwa.

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Miwa, H., Koseki, J., Oshima, T. et al. 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 45, 478–487 (2010). https://doi.org/10.1007/s00535-009-0180-1

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  • DOI: https://doi.org/10.1007/s00535-009-0180-1

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