Goreisan regulates AQP3 expression and improves diarrhea

Aim: Goreisan (GRS) is often used for gastrointestinal symptoms associated with bacterial and viral infections, to cure diarrhea and to prevent general dehydration. Although several clinical reports have shown the effectiveness of GRS, the pharmacological properties and underlining mechanism of GRS have not been clarified. Methods: Lipopolysaccharide (LPS, 10 mg/kg, i.p.) was administered to ICR mice and the diarrhea score was measured every 15 min. Goreisan (GRS; 1 g/kg) was administered 30 min before LPS administration, and the tissues were collected 90 min later. Caco-2 cells were treated with tumor necrosis factor-alpha (TNF-alpha, 10 ng/mL) and GRS (0.1 mg/mL) for 24h, and the aquaporin-3 (AQP3) expression level was examined by qPCR. Results: In this in vivo study, GRS did not affect cytokine production, but markedly improved tissue injury and diarrhea scores. On the other hand, AQP3 mRNA and protein expression in the intestinal epithelium in the LPS-treated group were significantly reduced, and GRS inhibited this decrease in AQP3. In a similar experiment performed on AQP3-deficient mice, the diarrhea-improving and tissue-improving effects of GRS disappeared. Furthermore, in this in vitro study, GRS suppressed the decrease in AQP3 expression by TNF-a stimulation, and the mechanism was due to extracellular signal-regulated kinase (ERK) inhibition. Conclusion: GRS has both an antidiarrhea effect and an intestinal tissue-protective effect, which it exerts through the inhibition of an inflammation-induced decrease in intestinal AQP3 expression. Our data strongly support the clinical usefulness of GRS to prevent dehydration in infectious gastroenteritis as well as the pharmacological rationale for using GRS to treat this disease.