Aged Garlic Extract (AGE) and Its Constituent S-Allyl-Cysteine (SAC) Inhibit the Expression of Pro-Inflammatory Genes Induced in Bronchial Epithelial IB3-1 Cells by Exposure to the SARS-CoV-2 Spike Protein and the BNT162b2 Vaccine

Garlic (<i>Allium sativum</i> L.) is a species of the onion family (<i>Alliaceae</i>) widely used as a food and a folk medicine. The objective of this study was to determine the effects of AGE (aged garlic extract) on pro-inflammatory genes relevant to COVID-19. To this aim,...

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Main Authors: Jessica Gasparello, Chiara Papi, Giovanni Marzaro, Alberto Macone, Matteo Zurlo, Alessia Finotti, Enzo Agostinelli, Roberto Gambari
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/29/24/5938
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author Jessica Gasparello
Chiara Papi
Giovanni Marzaro
Alberto Macone
Matteo Zurlo
Alessia Finotti
Enzo Agostinelli
Roberto Gambari
author_facet Jessica Gasparello
Chiara Papi
Giovanni Marzaro
Alberto Macone
Matteo Zurlo
Alessia Finotti
Enzo Agostinelli
Roberto Gambari
author_sort Jessica Gasparello
collection DOAJ
description Garlic (<i>Allium sativum</i> L.) is a species of the onion family (<i>Alliaceae</i>) widely used as a food and a folk medicine. The objective of this study was to determine the effects of AGE (aged garlic extract) on pro-inflammatory genes relevant to COVID-19. To this aim, we treated bronchial epithelial IB3-1 cells with SARS-CoV-2 spike protein (S-protein) or with the COVID-19 BNT162b2 vaccine in the absence or in the presence of AGE. The results obtained demonstrated that AGE is a potent inhibitor of the S-protein-induced expression of the IL-1β, IL-6 and IL-8 genes. Bio-Plex analysis demonstrated that AGE reduced release of IL-6 and IL-8, which were highly induced by S-protein. No inhibition of cells’ growth, toxicity and pro-apoptotic effects were found in AGE-treated cells. The effects of one of the major AGE constituents (S-allyl cysteine, SAC) were studied on the same experimental model systems. SAC was able to inhibit the S-protein-induced expression of IL-1β, IL-6 and IL-8 genes and extracellular release of IL-6 and IL-8, confirming that S-allyl-cysteine is one of the constituents of AGE that is responsible for inhibiting S-protein-induced pro-inflammatory genes. Docking experiments suggest that a possible mechanism of action of SAC is an interference with the activity of Toll-like receptors (TLRs), particularly TLR4, thereby inhibiting NF-κB- and NF-κB-regulated genes, such as IL-1β, IL-6 and IL-8 genes. These results suggest that both AGE and SAC deserve further experimental efforts to verify their effects on pro-inflammatory genes in SARS-CoV-2-infected cells.
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spelling doaj-art-22dad3cbe4f348dc84ae5487250253e72025-08-20T02:01:20ZengMDPI AGMolecules1420-30492024-12-012924593810.3390/molecules29245938Aged Garlic Extract (AGE) and Its Constituent S-Allyl-Cysteine (SAC) Inhibit the Expression of Pro-Inflammatory Genes Induced in Bronchial Epithelial IB3-1 Cells by Exposure to the SARS-CoV-2 Spike Protein and the BNT162b2 VaccineJessica Gasparello0Chiara Papi1Giovanni Marzaro2Alberto Macone3Matteo Zurlo4Alessia Finotti5Enzo Agostinelli6Roberto Gambari7Department of Life Sciences and Biotechnology, Ferrara University, 44121 Ferrara, ItalyDepartment of Life Sciences and Biotechnology, Ferrara University, 44121 Ferrara, ItalyDepartment of Diagnostics and Public Health, University of Verona, 37134 Verona, ItalyDepartment of Biochemical Sciences ‘A. Rossi Fanelli’, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Life Sciences and Biotechnology, Ferrara University, 44121 Ferrara, ItalyDepartment of Life Sciences and Biotechnology, Ferrara University, 44121 Ferrara, ItalyDepartment of Sensory Organs, Sapienza University of Rome, Policlinico Umberto I, Viale del Policlinico 155, 00161 Rome, ItalyDepartment of Life Sciences and Biotechnology, Ferrara University, 44121 Ferrara, ItalyGarlic (<i>Allium sativum</i> L.) is a species of the onion family (<i>Alliaceae</i>) widely used as a food and a folk medicine. The objective of this study was to determine the effects of AGE (aged garlic extract) on pro-inflammatory genes relevant to COVID-19. To this aim, we treated bronchial epithelial IB3-1 cells with SARS-CoV-2 spike protein (S-protein) or with the COVID-19 BNT162b2 vaccine in the absence or in the presence of AGE. The results obtained demonstrated that AGE is a potent inhibitor of the S-protein-induced expression of the IL-1β, IL-6 and IL-8 genes. Bio-Plex analysis demonstrated that AGE reduced release of IL-6 and IL-8, which were highly induced by S-protein. No inhibition of cells’ growth, toxicity and pro-apoptotic effects were found in AGE-treated cells. The effects of one of the major AGE constituents (S-allyl cysteine, SAC) were studied on the same experimental model systems. SAC was able to inhibit the S-protein-induced expression of IL-1β, IL-6 and IL-8 genes and extracellular release of IL-6 and IL-8, confirming that S-allyl-cysteine is one of the constituents of AGE that is responsible for inhibiting S-protein-induced pro-inflammatory genes. Docking experiments suggest that a possible mechanism of action of SAC is an interference with the activity of Toll-like receptors (TLRs), particularly TLR4, thereby inhibiting NF-κB- and NF-κB-regulated genes, such as IL-1β, IL-6 and IL-8 genes. These results suggest that both AGE and SAC deserve further experimental efforts to verify their effects on pro-inflammatory genes in SARS-CoV-2-infected cells.https://www.mdpi.com/1420-3049/29/24/5938garlicnatural productsToll-like receptor 4NF-κBpro-inflammatory genes
spellingShingle Jessica Gasparello
Chiara Papi
Giovanni Marzaro
Alberto Macone
Matteo Zurlo
Alessia Finotti
Enzo Agostinelli
Roberto Gambari
Aged Garlic Extract (AGE) and Its Constituent S-Allyl-Cysteine (SAC) Inhibit the Expression of Pro-Inflammatory Genes Induced in Bronchial Epithelial IB3-1 Cells by Exposure to the SARS-CoV-2 Spike Protein and the BNT162b2 Vaccine
Molecules
garlic
natural products
Toll-like receptor 4
NF-κB
pro-inflammatory genes
title Aged Garlic Extract (AGE) and Its Constituent S-Allyl-Cysteine (SAC) Inhibit the Expression of Pro-Inflammatory Genes Induced in Bronchial Epithelial IB3-1 Cells by Exposure to the SARS-CoV-2 Spike Protein and the BNT162b2 Vaccine
title_full Aged Garlic Extract (AGE) and Its Constituent S-Allyl-Cysteine (SAC) Inhibit the Expression of Pro-Inflammatory Genes Induced in Bronchial Epithelial IB3-1 Cells by Exposure to the SARS-CoV-2 Spike Protein and the BNT162b2 Vaccine
title_fullStr Aged Garlic Extract (AGE) and Its Constituent S-Allyl-Cysteine (SAC) Inhibit the Expression of Pro-Inflammatory Genes Induced in Bronchial Epithelial IB3-1 Cells by Exposure to the SARS-CoV-2 Spike Protein and the BNT162b2 Vaccine
title_full_unstemmed Aged Garlic Extract (AGE) and Its Constituent S-Allyl-Cysteine (SAC) Inhibit the Expression of Pro-Inflammatory Genes Induced in Bronchial Epithelial IB3-1 Cells by Exposure to the SARS-CoV-2 Spike Protein and the BNT162b2 Vaccine
title_short Aged Garlic Extract (AGE) and Its Constituent S-Allyl-Cysteine (SAC) Inhibit the Expression of Pro-Inflammatory Genes Induced in Bronchial Epithelial IB3-1 Cells by Exposure to the SARS-CoV-2 Spike Protein and the BNT162b2 Vaccine
title_sort aged garlic extract age and its constituent s allyl cysteine sac inhibit the expression of pro inflammatory genes induced in bronchial epithelial ib3 1 cells by exposure to the sars cov 2 spike protein and the bnt162b2 vaccine
topic garlic
natural products
Toll-like receptor 4
NF-κB
pro-inflammatory genes
url https://www.mdpi.com/1420-3049/29/24/5938
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