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<p>Intestinal tight junction disruption is considered as one of key pathogenic factors of several diseases including inflammatory bowel diseases. At present, there is no FDA-approved drug targeting intestinal tight junction recovery. <i>Coffea arabica</i> pulp is an agricultural waste but its aqueous extract contains a number of polyphenol-rich, bioactive compounds. The main aim of this study was to elucidate the pharmacological effects of <i>Coffea arabica</i> pulp aqueous extract (CPE) on intestinal tight junction re-assembly. Transepithelial electrical resistance (TER) measurement indicated that CPE significantly enhanced TER across the intestinal epithelial-like T84 cell monolayers in a time- and dose-dependent manner with a maximal effect being observed at 1,000&#xa0;µg/ml. MTT assay and nuclear staining indicated that CPE had no cytotoxic effect on T84 cells. Fluorescein isothiocyanate (FITC)-dextran permeability assay demonstrated that CPE suppressed intestinal tight junction-dependent leak pathway permeability. In addition, the effect of CPE on enhancing intestinal tight junction assembly was not affected by inhibitors of calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ), AMP-activated protein kinase (AMPK), and extracellular signal-regulated kinase (ERK). Surprisingly, sirtuin-1 (SIRT-1) inhibitors abrogated CPE-induced tight junction assembly in T84 cell monolayers. Furthermore, immunostaining indicated that CPE enhanced re-distribution of occludin and zonula occludens-1 (ZO-1) to cell junction region via SIRT-1-dependent mechanism. Collectively, CPE may be useful in the treatment of diseases related to intestinal tight junction disruption.</p>

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Enhancement of intestinal tight junction assembly by Coffea arabica pulp aqueous extract: mechanism of action and role of SIRT-1

  • 期刊论文

  • 发表日期：

    2025年1月20日

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  • Pichayapa Sukmak,
  • Laongdao Thongnak,
  • Wanapas Wachiradejkul,
  • Jakkapong Inchai,
  • Nichapa Chindaduangratn,
  • Natnicha Kitti-udom,
  • Thaam Limwattananon,
  • Nuttakritta Choksukchalalai,
  • Wilasinee Satianrapapong,
  • Sunisa Hankan,
  • Doungporn Amornlerdpison,
  • Atcharaporn Ontawong,
  • Nattaphong Akrimajirachoote,
  • Chanat Aonbangkhen,
  • Chatchai Muanprasat,
  • Chutima S. Vaddhanaphuti,
  • Pawin Pongkorpsakol

摘要

Intestinal tight junction disruption is considered as one of key pathogenic factors of several diseases including inflammatory bowel diseases. At present, there is no FDA-approved drug targeting intestinal tight junction recovery. Coffea arabica pulp is an agricultural waste but its aqueous extract contains a number of polyphenol-rich, bioactive compounds. The main aim of this study was to elucidate the pharmacological effects of Coffea arabica pulp aqueous extract (CPE) on intestinal tight junction re-assembly. Transepithelial electrical resistance (TER) measurement indicated that CPE significantly enhanced TER across the intestinal epithelial-like T84 cell monolayers in a time- and dose-dependent manner with a maximal effect being observed at 1,000 µg/ml. MTT assay and nuclear staining indicated that CPE had no cytotoxic effect on T84 cells. Fluorescein isothiocyanate (FITC)-dextran permeability assay demonstrated that CPE suppressed intestinal tight junction-dependent leak pathway permeability. In addition, the effect of CPE on enhancing intestinal tight junction assembly was not affected by inhibitors of calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ), AMP-activated protein kinase (AMPK), and extracellular signal-regulated kinase (ERK). Surprisingly, sirtuin-1 (SIRT-1) inhibitors abrogated CPE-induced tight junction assembly in T84 cell monolayers. Furthermore, immunostaining indicated that CPE enhanced re-distribution of occludin and zonula occludens-1 (ZO-1) to cell junction region via SIRT-1-dependent mechanism. Collectively, CPE may be useful in the treatment of diseases related to intestinal tight junction disruption.