Eijitsu, the fruits of Rosa multiflora Thunberg, is a traditional Japanese natural medicine and used as purgatives. The active constituents were identified as flavonol glycosides, multiflorin A (MF), and multinoside A (MSA), but mechanism of the purgative action is still unknown. We hypothesized that the flavonol glycosides 1 and 2 may exhibit the purgative actions through modulating intestinal epithelial barrier function. Then, this study aimed to investigate their effects on intestinal epithelial barrier function and possible molecular mechanisms in human intestinal Caco-2 cells. MF and MSA decreased transepithelial electrical resistance and increased paracellular permeability of Caco-2 cell monolayers. Expression of claudins (CLDNs) involved in paracellular permeability of ions and low-molecular substances was significantly decreased by the treatment with MF or MSA. The compounds increased the ratio of N-cadherin/E-cadherin, expression of transforming growth factor-β and Slug, and phosphorylation level of Smad3, suggesting epithelial-mesenchymal transition activation, and epithelial-mesenchymal transition inhibition by transforming growth factor-β receptor kinase inhibitors completely recovered the decreased CLDNs expression caused by MF and MSA. Moreover, the increased paracellular permeability and the decreased CLDNs expression by the treatment with MF or MSA for 24 hours recovered to the same extent as the untreated group with the compounds by continuous culture in the growth medium alone for 48 hours. These results suggest that Eijitsu may be effective in preventing or relieving constipation symptoms, unless used chronically.

中文翻译：

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蔷薇黄酮醇苷通过抑制分化的 Caco-2 细胞中的密蛋白表达调节肠道屏障功能

Eijitsu 是野蔷薇的果实，是一种传统的日本天然药物，用作泻药。活性成分被确定为黄酮醇苷、多花苷 A (MF) 和多糖苷 A (MSA)，但其通便作用机制尚不清楚。我们假设黄酮醇糖苷 1 和 2 可能通过调节肠上皮屏障功能表现出通便作用。然后，本研究旨在研究它们对人肠道 Caco-2 细胞中肠上皮屏障功能的影响和可能的分子机制。MF 和 MSA 降低跨上皮电阻并增加 Caco-2 细胞单层的细胞旁通透性。通过用MF或MSA处理，与离子和低分子物质的细胞旁通透性有关的密蛋白(CLDN)的表达显着降低。这些化合物增加了 N-cadherin/E-cadherin 的比率、转化生长因子-β 和 Slug 的表达以及 Smad3 的磷酸化水平，表明上皮-间充质转化激活和转化生长因子-β 受体抑制上皮-间充质转化激酶抑制剂完全恢复了由 MF 和 MSA 引起的 CLDNs 表达降低。此外，通过用 MF 或 MSA 处理 24 小时增加的细胞旁通透性和降低的 CLDN 表达恢复到与未处理组相同的程度，通过单独在生长培养基中连续培养 48 小时。