Sukmak P.Thongnak L.Wachiradejkul W.Inchai J.Chindaduangratn N.Kitti-udom N.Limwattananon T.Choksukchalalai N.Satianrapapong W.Hankan S.Amornlerdpison D.Ontawong A.Akrimajirachoote N.Aonbangkhen C.Muanprasat C.Vaddhanaphuti C.S.Pongkorpsakol P.Mahidol University2025-02-122025-02-122025-01-01Advances in Traditional Medicine (2025)26624052https://repository.li.mahidol.ac.th/handle/20.500.14594/104260Intestinal 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.MedicineArticleSCOPUS10.1007/s13596-025-00817-x2-s2.0-8521661356526624060