New AKT-dependent mechanisms of anti-COVID-19 action of high-CBD Cannabis sativa extracts.
Journal
Cell death discovery
ISSN: 2058-7716
Titre abrégé: Cell Death Discov
Pays: United States
ID NLM: 101665035
Informations de publication
Date de publication:
11 Mar 2022
11 Mar 2022
Historique:
received:
28
07
2021
accepted:
10
02
2022
revised:
05
02
2022
entrez:
12
3
2022
pubmed:
13
3
2022
medline:
13
3
2022
Statut:
epublish
Résumé
COVID-19 is caused by the SARS-CoV-2 virus, which enters target cells via interactions with ACE2 and TMPRSS2. Here, we show AKT serine/threonine kinase-dependent epigenetic control of ACE2 and TMPRSS2 expression by high-cannabidiol (CBD) cannabis extracts and their individual components. CBD alone and extracts #1, #5, #7, and #129 downregulated ACE2 and TMPRSS2 in lung fibroblast WI-38 cells through AKT-mediated inhibition. miR-200c-3p and let-7a-5p were two contributing miRNAs in CBD-mediated suppression of ACE2 and TMPRSS2. CBD and terpene PTWT2.2 profoundly inhibited ACE2 and TMPRSS2 expression, both individually and in combination. Extracts #1, #5, #7, and #169 suppressed COX2 expression and remarkably attenuated TNFα/IFNγ-triggered induction of proinflammatory factors IL-6 and IL-8 by AKT pathway. The most abundant molecules present in extracts #1 and #7 modulated the expression of COX2, IL-6, and IL-8 both individually and in combination. These results reveal that high-CBD cannabis extracts attenuated ACE2 and TMPRSS2 expression and the induction of inflammatory mediators COX2, IL-6, and IL-8 via the AKT pathway, highlighting their potential anti-COVID-19 features.
Identifiants
pubmed: 35277472
doi: 10.1038/s41420-022-00876-y
pii: 10.1038/s41420-022-00876-y
pmc: PMC8913855
doi:
Types de publication
Journal Article
Langues
eng
Pagination
110Informations de copyright
© 2022. The Author(s).
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