Journal Article

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

Agostinelli, Enzo, Zurlo, Matteo, Papi, Chiara, Macone, Alberto, Finotti, Alessia, Marzaro, Giovanni, Gasparello, Jessica, Gambari, Roberto

2024

Overview

Garlic (Allium sativum L.) is a species of the onion family (Alliaceae) 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.

• Publisher: MDPI AG
• Subject: Age / Anti-Inflammatory Agents - chemistry / Anti-Inflammatory Agents - pharmacology / Anti-Inflammatory Agents - therapeutic use / BNT162 Vaccine - immunology / Bronchi - cytology / Cell Line / Chemokines / COVID-19 - complications / COVID-19 - immunology / COVID-19 - metabolism / COVID-19 - virology / COVID-19 Drug Treatment - methods / COVID-19 vaccines / Cysteine - analogs & derivatives / Cysteine - pharmacology / Cysteine - therapeutic use / Cytokine Release Syndrome - drug therapy / Cytokine Release Syndrome - immunology / Cytokine Release Syndrome - metabolism / Cytokine Release Syndrome - virology / Cytokine storm / Epithelial Cells - drug effects / Epithelial Cells - immunology / Epithelial Cells - metabolism / Garlic / Garlic - chemistry / Gene Expression Regulation - drug effects / Gene Expression Regulation - immunology / Humans / Interleukins - immunology / Interleukins - metabolism / natural products / NF-κB / Pandemics / Plant Extracts - chemistry / Plant Extracts - pharmacology / Plant Extracts - therapeutic use / pro-inflammatory genes / Proteins / Respiratory Mucosa - cytology / Severe acute respiratory syndrome coronavirus 2 / Spike Glycoprotein, Coronavirus - metabolism / Toll-like receptor 4 / Traditional medicine