{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:11:13Z","timestamp":1792098673802,"version":"4.4.0"},"reference-count":45,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T00:00:00Z","timestamp":1633996800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:p>\n                    Given the abundancy of angiotensin converting enzyme 2 (ACE\u20102) receptors density, beyond the lung, the intestine is considered as an alternative site of infection and replication for severe acute respiratory syndrome by coronavirus type 2 (SARS\u2010CoV\u20102). Cannabidiol (CBD) has recently been proposed in the management of coronavirus disease 2019 (COVID\u201019) respiratory symptoms because of its anti\u2010inflammatory and immunomodulatory activity exerted in the lung. In this study, we demonstrated the in vitro PPAR\u2010\u03b3\u2010dependent efficacy of CBD (10\n                    <jats:sup>\u22129<\/jats:sup>\n                    \u201010\n                    <jats:sup>\u22127<\/jats:sup>\n                    \u00a0M) in preventing epithelial damage and hyperinflammatory response triggered by SARS\u2010CoV\u20102 spike protein (SP) in a Caco\u20102 cells. Immunoblot analysis revealed that CBD was able to reduce all the analyzed proinflammatory markers triggered by SP incubation, such as tool\u2010like receptor 4 (TLR\u20104), ACE\u20102, family members of Ras homologues A\u2010GTPase (RhoA\u2010GTPase), inflammasome complex (NLRP3), and Caspase\u20101. CBD caused a parallel inhibition of interleukin 1 beta (IL\u20101\u03b2), IL\u20106, tumor necrosis factor alpha (TNF\u2010\u03b1), and IL\u201018 by enzyme\u2010linked immunosorbent assay (ELISA) assay. By immunofluorescence analysis, we observed increased expression of tight\u2010junction proteins and restoration of transepithelial electrical resistance (TEER) following CBD treatment, as well as the rescue of fluorescein isothiocyanate (FITC)\u2013dextran permeability induced by SP. Our data indicate, in conclusion, that CBD is a powerful inhibitor of SP protein enterotoxicity in vitro.\n                  <\/jats:p>","DOI":"10.1002\/ptr.7302","type":"journal-article","created":{"date-parts":[[2021,10,16]],"date-time":"2021-10-16T11:33:43Z","timestamp":1634384023000},"page":"6893-6903","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Cannabidiol inhibits\n                    <scp>SARS\u2010Cov<\/scp>\n                    \u20102 spike (S) protein\u2010induced cytotoxicity and inflammation through a\n                    <scp>PPAR\u03b3<\/scp>\n                    \u2010dependent\n                    <scp>TLR4<\/scp>\n                    \/\n                    <scp>NLRP3<\/scp>\n                    \/Caspase\u20101 signaling suppression in Caco\u20102 cell line"],"prefix":"10.1002","volume":"35","author":[{"given":"Chiara","family":"Corpetti","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Del Re","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Seguella","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Sapienza University of Rome  Rome Italy"},{"name":"Department of Physiology Michigan State University  East Lansing Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Palenca","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Rurgo","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery University of Naples \u201cFederico II\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"De Conno","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery University of Naples \u201cFederico II\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5996-4259","authenticated-orcid":false,"given":"Marcella","family":"Pesce","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery University of Naples \u201cFederico II\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Sarnelli","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine and Surgery University of Naples \u201cFederico II\u201d  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8080-8218","authenticated-orcid":false,"given":"Giuseppe","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology Sapienza University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2020.198103"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.110.168237"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-81049-2"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.120.000479"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.631646"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.26119"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2020.12.011"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.641210"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0028159"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo11090592"},{"key":"e_1_2_10_12_1","doi-asserted-by":"crossref","unstructured":"Dickson 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