Ferrari Sara, Ferulli Federica, Galla Rebecca, Vicini Riccardo, Cattaneo Veronica, Mulè Simone, Uberti Francesca
Laboratory of Physiology, Department for Sustainable Development and Ecological Transition, University of Piemonte Orientale, UPO, 13100 Vercelli, Italy.
Bio Basic Europe Srl, 20146 Milan, Italy.
Int J Mol Sci. 2025 May 6;26(9):4409. doi: 10.3390/ijms26094409.
Esophageal barrier dysfunction is a crucial pathophysiological mechanism of gastroesophageal reflux disease (GERD). However, treatments mainly aim to reduce gastric acidity rather than improve tissue integrity. This study evaluated the protective and mucoadhesive properties of a formulation containing xyloglucan, pea proteins, and polyacrylic acid (XPPA) in gastric and esophageal cells. Cells were exposed to hydrochloric acid (HCl) and subsequently treated with the test compound. Trans-epithelial electrical resistance (TEER), tight junction (TJ) expression, and mucoadhesion of XPPA on gastric and esophageal cells were evaluated. To further confirm the protective ability of XPPA, a Lucifer Yellow assay was performed on a human reconstructed esophageal epithelium to assess the ability of XPPA to prevent HCl-induced hyperpermeability. XPPA possesses noteworthy mucoadhesive properties, ensuring an extended contact time between the product and the damaged mucosa to allow sustained mucosal protection. Furthermore, XPPA effectively restored gastroesophageal barrier integrity after HCl-induced damage, as assessed with TEER, after 1 h ( < 0.05). Finally, XPPA helped to restore TJ expression ( < 0.05) and protected the tissues from hyperpermeability for at least 2 h ( < 0.05). These results pave the way for using XPPA as a promising treatment to ameliorate gastroesophageal barrier properties in GERD patients.
食管屏障功能障碍是胃食管反流病（GERD）的关键病理生理机制。然而，目前的治疗主要旨在降低胃酸度，而非改善组织完整性。本研究评估了一种含有木葡聚糖、豌豆蛋白和聚丙烯酸（XPPA）的制剂在胃和食管细胞中的保护及黏膜黏附特性。将细胞暴露于盐酸（HCl）中，随后用受试化合物进行处理。评估了XPPA对胃和食管细胞的跨上皮电阻（TEER）、紧密连接（TJ）表达及黏膜黏附情况。为进一步证实XPPA的保护能力，在人重建食管上皮上进行了荧光黄试验，以评估XPPA预防HCl诱导的高通透性的能力。XPPA具有显著的黏膜黏附特性，可确保产品与受损黏膜之间有更长的接触时间，从而实现持续的黏膜保护。此外，用TEER评估发现，XPPA在HCl诱导损伤后1小时能有效恢复胃食管屏障完整性（P<0.05）。最后，XPPA有助于恢复TJ表达（P<0.05），并在至少2小时内保护组织免受高通透性影响（P<0.05）。这些结果为将XPPA用作改善GERD患者胃食管屏障特性的有前景的治疗方法铺平了道路。
