{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T12:09:19Z","timestamp":1782821359645,"version":"3.54.5"},"reference-count":98,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["58514_DIPECC_23_27"],"award-info":[{"award-number":["58514_DIPECC_23_27"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Visceral pain is a major symptom of inflammatory bowel diseases (IBDs), requiring effective treatment strategies. Gut epithelium, beyond maintaining barrier integrity and microbiota homeostasis, modulates neurosensorial circuitries, influencing visceral sensitivity.\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Moringa oleifera<\/jats:italic>\n                    <\/jats:styled-content>\n                    constituents show beneficial properties that may counteract inflammation\u2010induced epithelial dysfunction and visceral hypersensitivity. Among these, we investigated moringin (MOR), the isothiocyanate derived from the myrosinase (MYR)\u2010mediated hydrolysis of glucomoringin (GMG). A three\u2010stage experimental strategy was applied. First, murine colon organoids were exposed to a pro\u2010inflammatory cytokine cocktail (CKs; TNF\u2010\u03b1, IL\u20101\u03b2, IL\u20106; 10\u2009ng\u2009mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    , 6\u2009h) to model epithelial inflammatory stress and treated with MOR (2\u201330\u2009\u03bcM). Second, epithelial\u2013neuronal communication was assessed by exposing primary dorsal root ganglion (DRG) neurons to conditioned media from inflamed organoids, with (CM\n                    <jats:sup>CKs\u2009+\u2009MOR 30\u2009\u03bcM<\/jats:sup>\n                    ) or without (CM\n                    <jats:sup>CKs<\/jats:sup>\n                    ) MOR treatment. Third, the therapeutic relevance of these findings was validated in\u00a0vivo using a dextran sulfate sodium (DSS)\u2013induced colitis model, in which mice received oral administration of MYR\u2010bioactivated GMG (GMG\u2009+\u2009MYR) at different doses (30\u2013100\u2009mg\u2009kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    ), followed by behavioral and histological assessments. CKs\u2010treated organoids showed cytotoxicity, increased superoxide dismutase activity, and upregulation of\n                    <jats:italic>Ccl2<\/jats:italic>\n                    ,\n                    <jats:italic>Ccnd1<\/jats:italic>\n                    ,\n                    <jats:italic>Mki67,<\/jats:italic>\n                    and\n                    <jats:italic>Pyy<\/jats:italic>\n                    . MOR 30\u2009\u03bcM co\u2010treatment normalized oxidative stress and gene expression, although cytotoxicity remained unaffected. CM\n                    <jats:sup>CKs<\/jats:sup>\n                    increased c\u2010Fos and CGRP expression in DRG neurons, while CM\n                    <jats:sup>CKs\u2009+\u2009MOR 30\u2009\u03bcM<\/jats:sup>\n                    prevented this response, indicating MOR modulation of epithelial inflammation\u2010driven neuronal activation. In DSS\u2010treated mice, oral GMG (30\u2013100\u2009mg\u2009kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    )\u2009+\u2009MYR dose\u2010dependently reduced visceral hypersensitivity, pain\u2010associated behavioral alterations, and colonic damage. Overall, MOR\/GMG\u2009+\u2009MYR showed gut\u2010protective and analgesic effects under intestinal inflammation. Intestinal organoids effectively model inflammation and therapeutic responses, potentially reducing animal use in IBD research.\n                  <\/jats:p>","DOI":"10.1002\/ptr.70303","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T01:01:28Z","timestamp":1774314088000},"page":"3250-3266","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Combined Colon Organoid\u2010Sensory Neuron Model Reveals Epithelial Contribution to Moringin Efficacy Against Painful Inflammatory Bowel Disease"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4172-2478","authenticated-orcid":false,"given":"Francesco","family":"Margiotta","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Psychology, Drug Research and Child Health\u2014NEUROFARBA\u2014Pharmacology and Toxicology Section University of Florence  Florence Italy"},{"name":"European Biomedical Research Institute of Salerno (EBRIS)  Salerno Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3459-2660","authenticated-orcid":false,"given":"Elena","family":"Lucarini","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Psychology, Drug Research and Child Health\u2014NEUROFARBA\u2014Pharmacology and Toxicology Section University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8435-6017","authenticated-orcid":false,"given":"Alessandra","family":"Toti","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Psychology, Drug Research and Child Health\u2014NEUROFARBA\u2014Pharmacology and Toxicology Section University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Giovanna","family":"Cataldi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Psychology, Drug Research and Child Health\u2014NEUROFARBA\u2014Pharmacology and Toxicology Section University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3299-9263","authenticated-orcid":false,"given":"Clara","family":"Ciampi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Psychology, Drug Research and Child Health\u2014NEUROFARBA\u2014Pharmacology and Toxicology Section University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2916-8662","authenticated-orcid":false,"given":"Gina Rosalinda","family":"De Nicola","sequence":"additional","affiliation":[{"name":"Research Centre for Vegetable and Ornamental Crops, Council for Agricultural Research and Economics (CREA)  Pescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8374-4432","authenticated-orcid":false,"given":"Lorenzo","family":"Di Cesare Mannelli","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Psychology, Drug Research and Child Health\u2014NEUROFARBA\u2014Pharmacology and Toxicology Section University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9856-8144","authenticated-orcid":false,"given":"Carla","family":"Ghelardini","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Psychology, Drug Research and Child Health\u2014NEUROFARBA\u2014Pharmacology and Toxicology Section University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-018-2943-4"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1515\/jbcpp-2014-0105"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26010121"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-024-01574-0"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/7275309"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.00363"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2021.718356"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2022-328052"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-05829-8"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.117177"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25040976"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3516"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471142735.im1525s104"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.12717\/DR.2015.19.2.061"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70640"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-020-00914-w"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000003056"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2023.2256045"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.2174\/2772270817666221121143853"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000411"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.npep.2019.101973"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2012.1222"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu11071489"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu11071547"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/7651_2016_8"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202250248"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2024.01.045"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2024.06.050"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/259417"},{"key":"e_1_2_12_31_1","first-page":"343","article-title":"4(\u03b1\u2010l\u2010Rhamnosyloxy)\u2010Benzyl Isothiocyanate, a Bioactive Phytochemical That Defends Cerebral Tissue and Prevents Severe Damage Induced by Focal Ischemia\/Reperfusion","volume":"29","author":"Galuppo M.","year":"2015","journal-title":"Journal of Biological Regulators and Homeostatic Agents"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules181114340"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1177\/1744806917724318"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10400"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01757-9"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-99412-8"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2023.11.303"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2024.1409026"},{"key":"e_1_2_12_39_1","unstructured":"ISO.2019.\u201cISO 9167:2019.\u201d"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000000831"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu10050580"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0182658"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2024.03.034"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.865131"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19072025"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxrep.2018.02.012"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0184709"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-024-08716-y"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2021.08.055"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1312"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.4161\/chan.5.6.18016"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.2174\/0113892010261502231102040149"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2022.2064147"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11101-022-09809-0"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu14153137"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26062519"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9081772"},{"key":"e_1_2_12_58_1","first-page":"1671","article-title":"Role of Enteric Glia as Bridging Element Between Gut Inflammation and Visceral Pain Consolidation During Acute Colitis in Rats","volume":"9","author":"Lucarini E.","year":"2021","journal-title":"Biomedicine"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.386403"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2025.2547029"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2016.12.107"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2017.03.007"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-024-02130-x"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-021-01069-8"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1357690"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112158"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2019.12.007"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002110"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1093\/ilar.40.3.119"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.121.000731"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-024-01136-9"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.14202\/vetworld.2024.1449-1458"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24032098"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14191"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xpro.2021.100333"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fitote.2016.05.008"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.1017\/jns.2025.10035"},{"key":"e_1_2_12_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(95)90006-3"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0248691"},{"key":"e_1_2_12_80_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10616-021-00487-y"},{"key":"e_1_2_12_81_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2089"},{"key":"e_1_2_12_82_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-017-0741-2"},{"key":"e_1_2_12_83_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-023-01224-4"},{"key":"e_1_2_12_84_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13637"},{"key":"e_1_2_12_85_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.107598"},{"key":"e_1_2_12_86_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-75702-5"},{"key":"e_1_2_12_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2015.10.008"},{"key":"e_1_2_12_88_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2011.02.016"},{"key":"e_1_2_12_89_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1328324"},{"key":"e_1_2_12_90_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-023-01556-1"},{"key":"e_1_2_12_91_1","doi-asserted-by":"publisher","DOI":"10.1093\/ecco-jcc\/jjae190.1589"},{"key":"e_1_2_12_92_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.18344"},{"key":"e_1_2_12_93_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2970"},{"key":"e_1_2_12_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2015.01.004"},{"key":"e_1_2_12_95_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2024.177396"},{"key":"e_1_2_12_96_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1FO03888E"},{"key":"e_1_2_12_97_1","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/3328655"},{"key":"e_1_2_12_98_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.116929"},{"key":"e_1_2_12_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112241"}],"container-title":["Phytotherapy Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.70303","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ptr.70303","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.70303","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T14:32:38Z","timestamp":1782311558000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.70303"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,23]]},"references-count":98,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,6]]}},"alternative-id":["10.1002\/ptr.70303"],"URL":"https:\/\/doi.org\/10.1002\/ptr.70303","archive":["Portico"],"relation":{},"ISSN":["0951-418X","1099-1573"],"issn-type":[{"value":"0951-418X","type":"print"},{"value":"1099-1573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,23]]},"assertion":[{"value":"2025-12-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-09","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}