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.
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.


CONCLUSIONS
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.
Miwa
Hiroto
H
Division of Upper Gastroenterology, Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo, Japan. miwahgi@hyo-med.ac.jp
Koseki
Junichi
J
Oshima
Tadayuki
T
Kondo
Takashi
T
Tomita
Toshihiko
T
Watari
Jiro
J
Matsumoto
Takayuki
T
Hattori
Tomohisa
T
Kubota
Kunitsugu
K
Iizuka
Seiichi
S
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D062465:Claudin-3; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D004942:Esophagitis, Peptic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D007564:Japan; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
D062465:Claudin-3; C568124:Cldn3 protein, rat; D004365:Drugs, Chinese Herbal; D008565:Membrane Proteins; C084136:liu-jun-zi-tang