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Lathyrus sativus diamine oxidase reduces Clostridium difficile toxin A‐induced toxicity in Caco‐2 cells by rescuing RhoA‐GTPase and inhibiting pp38‐MAPK / NF‐κB / HIF ‐1α activation
Author(s) -
Pietrangeli Paola,
Corpetti Chiara,
Seguella Luisa,
Del Re Alessandro,
Pesce Marcella,
Vincenzi Martina,
Lori Chiara,
Annunziata Giuseppe,
Mateescu Mircea A.,
Sarnelli Giovanni,
Esposito Giuseppe,
Marcocci Lucia
Publication year - 2021
Publication title -
phytotherapy research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.019
H-Index - 129
eISSN - 1099-1573
pISSN - 0951-418X
DOI - 10.1002/ptr.6814
Subject(s) - clostridium difficile toxin a , rhoa , clostridium perfringens , occludin , caco 2 , clostridium difficile toxin b , diamine oxidase , microbiology and biotechnology , biology , viability assay , tumor necrosis factor alpha , clostridium difficile , pharmacology , chemistry , apoptosis , biochemistry , signal transduction , immunology , tight junction , cell , antibiotics , genetics , bacteria , enzyme
Clostridium difficile toxin A (TcdA) impairs the intestinal epithelial barrier, increasing the mucosa permeability and triggering a robust inflammatory response. Lathyrus sativus diamino oxidase (LSAO) is a nutraceutical compound successfully used in various gastrointestinal dysfunctions. Here, we evaluated the LSAO (0.004–0.4 μM) ability to counter TcdA‐induced (30 ng/mL) toxicity and damage in Caco‐2 cells, investigating its possible mechanism of action. LSAO has improved the transepithelial electrical resistance (TEER) score and increased cell viability in TcdA‐treated cells, significantly rescuing the protein expression of Ras homolog family members, A‐GTPase (RhoA‐GTPase), occludin, and zonula occludens‐1 (ZO‐1). LSAO has also exhibited an anti‐apoptotic effect by inhibiting the TcdA‐induced expression of Bcl‐2‐associated X protein (Bax), p50 nuclear factor‐kappa‐B (p50), p65nuclear factor‐kappa‐B (p65), and hypoxia‐inducible transcription factor‐1 alpha (HIF‐1α), and the release of tumor necrosis factor‐alpha (TNF‐α), interleukin‐6 (IL‐6), and vascular endothelial growth factor (VEGF) in the cell milieu. Our data showed that LSAO exerts a protective effect on TcdA‐induced toxicity in Caco‐2 cells, placing itself as an interesting nutraceutical to supplement the current treatment of the Clostridium difficile infections.