Goreisan regulates AQP3 expression and improves diarrhea
Goreisan regulates AQP3 expression and improves diarrhea
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DOI：
10.1002/tkm2.1276
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发表时间：
2021-04-01
期刊：
影响因子：
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通讯作者：
Isohama, Yoichiro
中科院分区：
文献类型：
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作者：
Murakami, Kazuhito;Horie, Ichiro;Isohama, Yoichiro
目的：Goreisan (GRS) 通常用于治疗与细菌和病毒感染相关的胃肠道症状、治疗腹泻和预防一般脱水。尽管一些临床报告显示了 GRS 的有效性，但 GRS 的药理特性和潜在机制尚未阐明。 方法：给 ICR 小鼠注射脂多糖（LPS，10 mg/kg，腹腔注射），每 15 分钟测量一次腹泻评分。在LPS给药前30分钟给予Goreisan（GRS；1g/kg），并在90分钟后收集组织。用肿瘤坏死因子-α（TNF-α，10 ng/mL）和GRS（0.1 mg/mL）处理Caco-2细胞24小时，通过qPCR检测水通道蛋白-3（AQP3）表达水平。结果：在这项体内研究中，GRS不影响细胞因子的产生，但显着改善组织损伤和腹泻评分。另一方面，LPS处理组肠上皮中AQP3 mRNA和蛋白表达显着降低，GRS抑制了AQP3的这种降低。在对 AQP3 缺陷小鼠进行的类似实验中，GRS 的腹泻改善和组织改善作用消失了。此外，在这项体外研究中，GRS抑制了TNF-a刺激引起的AQP3表达下降，其机制是由于细胞外信号调节激酶（ERK）抑制。结论：GRS具有止泻作用和肠道组织保护作用，其通过抑制炎症诱导的肠道AQP3表达下降来发挥作用。我们的数据有力地支持了 GRS 在预防传染性胃肠炎脱水方面的临床用途，以及使用 GRS 治疗这种疾病的药理学原理。
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.