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Cannabidiol inhibits SARS-Cov-2 spike (S) protein-induced cytotoxicity and inflammation through a PPARγ-dependent TLR4/NLRP3/Caspase-1 signaling suppression in Caco-2 cell line.
Corpetti, Chiara; Del Re, Alessandro; Seguella, Luisa; Palenca, Irene; Rurgo, Sara; De Conno, Barbara; Pesce, Marcella; Sarnelli, Giovanni; Esposito, Giuseppe.
Afiliación
  • Corpetti C; Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
  • Del Re A; Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
  • Seguella L; Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
  • Palenca I; Department of Physiology, Michigan State University, East Lansing, Michigan, USA.
  • Rurgo S; Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy.
  • De Conno B; Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy.
  • Pesce M; Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy.
  • Sarnelli G; Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy.
  • Esposito G; Department of Clinical Medicine and Surgery, University of Naples "Federico II", Naples, Italy.
Phytother Res ; 35(12): 6893-6903, 2021 Dec.
Article en En | MEDLINE | ID: mdl-34643000
Given the abundancy of angiotensin converting enzyme 2 (ACE-2) 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-CoV-2). Cannabidiol (CBD) has recently been proposed in the management of coronavirus disease 2019 (COVID-19) respiratory symptoms because of its anti-inflammatory and immunomodulatory activity exerted in the lung. In this study, we demonstrated the in vitro PPAR-γ-dependent efficacy of CBD (10-9 -10-7  M) in preventing epithelial damage and hyperinflammatory response triggered by SARS-CoV-2 spike protein (SP) in a Caco-2 cells. Immunoblot analysis revealed that CBD was able to reduce all the analyzed proinflammatory markers triggered by SP incubation, such as tool-like receptor 4 (TLR-4), ACE-2, family members of Ras homologues A-GTPase (RhoA-GTPase), inflammasome complex (NLRP3), and Caspase-1. CBD caused a parallel inhibition of interleukin 1 beta (IL-1ß), IL-6, tumor necrosis factor alpha (TNF-α), and IL-18 by enzyme-linked immunosorbent assay (ELISA) assay. By immunofluorescence analysis, we observed increased expression of tight-junction proteins and restoration of transepithelial electrical resistance (TEER) following CBD treatment, as well as the rescue of fluorescein isothiocyanate (FITC)-dextran permeability induced by SP. Our data indicate, in conclusion, that CBD is a powerful inhibitor of SP protein enterotoxicity in vitro.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cannabidiol / Transducción de Señal / Glicoproteína de la Espiga del Coronavirus / SARS-CoV-2 Límite: Humans Idioma: En Revista: Phytother Res Asunto de la revista: TERAPIAS COMPLEMENTARES Año: 2021 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido
Texto completo
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cannabidiol / Transducción de Señal / Glicoproteína de la Espiga del Coronavirus / SARS-CoV-2 Límite: Humans Idioma: En Revista: Phytother Res Asunto de la revista: TERAPIAS COMPLEMENTARES Año: 2021 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Reino Unido