{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T15:24:54Z","timestamp":1766503494625,"version":"3.40.5"},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,9,10]],"date-time":"2020-09-10T00:00:00Z","timestamp":1599696000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p><jats:italic>Clostridium difficile<\/jats:italic> toxin A (TcdA) impairs the intestinal epithelial barrier, increasing the mucosa permeability and triggering a robust inflammatory response. <jats:italic>Lathyrus sativus<\/jats:italic> diamino oxidase (LSAO) is a nutraceutical compound successfully used in various gastrointestinal dysfunctions. Here, we evaluated the LSAO (0.004\u20130.4 \u03bcM) ability to counter TcdA\u2010induced (30\u2009ng\/mL) toxicity and damage in Caco\u20102 cells, investigating its possible mechanism of action. LSAO has improved the transepithelial electrical resistance (TEER) score and increased cell viability in TcdA\u2010treated cells, significantly rescuing the protein expression of Ras homolog family members, A\u2010GTPase (RhoA\u2010GTPase), occludin, and zonula occludens\u20101 (ZO\u20101). LSAO has also exhibited an anti\u2010apoptotic effect by inhibiting the TcdA\u2010induced expression of Bcl\u20102\u2010associated X protein (Bax), p50 nuclear factor\u2010kappa\u2010B (p50), p65nuclear factor\u2010kappa\u2010B (p65), and hypoxia\u2010inducible transcription factor\u20101 alpha (HIF\u20101\u03b1), and the release of tumor necrosis factor\u2010alpha (TNF\u2010\u03b1), interleukin\u20106 (IL\u20106), and vascular endothelial growth factor (VEGF) in the cell milieu. Our data showed that LSAO exerts a protective effect on TcdA\u2010induced toxicity in Caco\u20102 cells, placing itself as an interesting nutraceutical to supplement the current treatment of the <jats:italic>Clostridium difficile<\/jats:italic> infections.<\/jats:p>","DOI":"10.1002\/ptr.6814","type":"journal-article","created":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T13:57:38Z","timestamp":1600955858000},"page":"415-423","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<scp><i>Lathyrus sativus<\/i><\/scp> diamine oxidase reduces <scp><i>Clostridium difficile<\/i><\/scp> toxin A\u2010induced toxicity in Caco\u20102 cells by rescuing <scp>RhoA\u2010GTPase<\/scp> and inhibiting <scp>pp38\u2010MAPK<\/scp>\/<scp>NF\u2010\u03baB<\/scp>\/<scp>HIF<\/scp>\u20101\u03b1 activation"],"prefix":"10.1002","volume":"35","author":[{"given":"Paola","family":"Pietrangeli","sequence":"first","affiliation":[{"name":"Department of Biochemical Sciences \u201cA. Rossi Fanelli\u201d, Faculty of Pharmacy and Medicine Sapienza University of Rome  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Corpetti","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology \u201cV. Erspamer\u201d Sapienza University of Rome  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Seguella","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology \u201cV. Erspamer\u201d Sapienza University of Rome  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Del Re","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology \u201cV. Erspamer\u201d Sapienza University of Rome  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcella","family":"Pesce","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, section of Gastroenterology University Federico II  Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Vincenzi","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology \u201cV. Erspamer\u201d Sapienza University of Rome  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Lori","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology \u201cV. Erspamer\u201d Sapienza University of Rome  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1922-662X","authenticated-orcid":false,"given":"Giuseppe","family":"Annunziata","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University Federico II  Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mircea A.","family":"Mateescu","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Centre CERMO\u2010FC Universit\u00e9 du Qu\u00e9bec \u00e0 Montreal, CP8888 Branch A, Montreal (Qu\u00e9bec)  Montreal Qu\u00e9bec Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni","family":"Sarnelli","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery, section of Gastroenterology University Federico II  Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology \u201cV. Erspamer\u201d Sapienza University of Rome  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Marcocci","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences \u201cA. Rossi Fanelli\u201d, Faculty of Pharmacy and Medicine Sapienza University of Rome  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,9,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2012.02.032"},{"issue":"2","key":"e_1_2_8_3_1","first-page":"G333","article-title":"IL\u201011 inhibits Clostridium difficile toxin a enterotoxicity in rat ileum","volume":"273","author":"Castagliuolo I.","year":"1997","journal-title":"The American Journal of Physiology"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fux048"},{"issue":"120","key":"e_1_2_8_5_1","first-page":"1","article-title":"Rifaximin improves Clostridium difficile toxin A\u2010induced toxicity in Caco\u20102 cells by the PXR\u2010dependent TLR4\/MyD88\/NF\u2010\u03baB pathway","volume":"7","author":"Esposito G.","year":"2016","journal-title":"Frontiers in Pharmacology"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.45.29745"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02786955"},{"issue":"2","key":"e_1_2_8_8_1","first-page":"S237\u2013244","article-title":"Quercetin suppresses the migration and invasion in human colon cancer Caco\u20102 cells through regulating toll\u2010like receptor 4\/nuclear factor\u2010kappa B pathway","volume":"12","author":"Han M.","year":"2016","journal-title":"Pharmacognosy Magazine"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113760"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-018-0300-x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2004.08.003"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.23.13932"},{"issue":"24","key":"e_1_2_8_13_1","first-page":"2369","article-title":"Burden of Clostridium difficile infection in the United States","volume":"372","author":"Lessa F. 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