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.
Chiara CorpettiAlessandro Del ReLuisa SeguellaIrene PalencaSara RurgoBarbara De ConnoMarcella PesceGiovanni SarnelliGiuseppe EspositoPublished in: Phytotherapy research : PTR (2021)
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-1β), 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.
Keyphrases
- sars cov
- angiotensin converting enzyme
- respiratory syndrome coronavirus
- coronavirus disease
- induced apoptosis
- angiotensin ii
- oxidative stress
- binding protein
- rheumatoid arthritis
- high throughput
- anti inflammatory
- toll like receptor
- protein protein
- inflammatory response
- cell death
- immune response
- insulin resistance
- cell cycle arrest
- endoplasmic reticulum stress
- nuclear factor
- type diabetes
- blood brain barrier
- diabetic rats
- nlrp inflammasome
- skeletal muscle
- endothelial cells
- electronic health record
- long non coding rna
- deep learning
- depressive symptoms
- pi k akt
- combination therapy