Canna~Fangled Abstracts

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

By October 12, 2021October 14th, 2021No Comments

doi: 10.1002/ptr.7302.

Online ahead of print.
Affiliations 

Abstract

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.

 

Keywords: Caco-2, Cannabidiol, NLRP3, SARS-CoV-2 spike (S) protein

References

REFERENCES

    1. Ahlawat, S. A., & Sharma, K. K. (2020). Immunological co-ordination between gut and lungs in SARS-CoV-2 infection. Virus Research, 286, 198103. https://doi.org/10.1016/j.virusres.2020.198103
    1. Alhamoruni, A., Lee, A. C., Wright, K. L., Larvin, M., & O’Sullivan, S. E. (2010). Pharmacological effects of cannabinoids on the Caco-2 cell culture model of intestinal permeability. The Journal of Pharmacology and Experimental Therapeutics, 335(1), 92-102. https://doi.org/10.1124/jpet.110.168237
    1. Anil, S. M., Shalev, N., Vinayaka, A. C., Nadarajan, S., Namdar, D., Belausov, E., … Koltai, H. (2021). Cannabis compounds exhibit anti-inflammatory activity in vitro in COVID-19-related inflammation in lung epithelial cells and pro-inflammatory activity in macrophages. Scientific Reports, 11(1), 1462. https://doi.org/10.1038/s41598-021-81049-2
    1. Berg, B. B., Soares, J. S., Paiva, I. R., Rezende, B. M., Rachid, M. A., Cau, S. B. A., … Castor, M. (2021). Cannabidiol enhances intestinal cannabinoid receptor type 2 receptor expression and activation increasing regulatory T cells and reduces murine acute graft-versus-host disease without interfering with the graft-versus-leukemia response. The Journal of Pharmacology and Experimental Therapeutics, 377(2), 273-283. https://doi.org/10.1124/jpet.120.000479
    1. Bifulco, M., Fiore, D., Piscopo, C., Gazzerro, P., & Proto, M. C. (2021). Commentary: Use of cannabinoids to treat acute respiratory distress syndrome and cytokine storm associated with coronavirus disease-2019. Frontiers in Pharmacology, 12, 631646. https://doi.org/10.3389/fphar.2021.631646

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