Italian Study Finds That Aged Garlic Extract Reduces Inflammatory Genes Induced by COVID-19 Infections or Vaccines

Medical News: Garlic, a common culinary ingredient, has been used for centuries not only for its flavor but also for its medicinal properties. Aged garlic extract (AGE), a concentrated form of garlic obtained through an aging process, is believed to have health benefits that include immune support, anti-cancer effects, and particularly anti-inflammatory properties. Researchers are increasingly interested in AGE as a potential therapy for various inflammatory conditions, including the “cytokine storm” associated with COVID-19.


Aged Garlic Extract Reduces Inflammatory Genes Induced by COVID-19 Infections or Vaccines
 
A new study conducted by a team of researchers from Ferrara University-Italy, University of Verona-Italy, and Sapienza University of Rome has taken a closer look at AGE’s effects on inflammation, especially inflammation caused by the SARS-CoV-2 virus that leads to COVID-19. Given the significant inflammatory response seen in COVID-19 patients, often described as a “cytokine storm,” the research team wanted to investigate whether AGE could play a role in suppressing this reaction at the cellular level. This Medical News report examines how AGE and its active compound, S-allyl-cysteine (SAC), impact inflammatory gene expression in human cells exposed to COVID-19 proteins.
 
What the Study Examined: A Cellular Approach
To explore the potential of AGE in controlling inflammation, the research team conducted tests on a type of human cell called IB3-1, a bronchial epithelial cell line. These cells, often used in respiratory research, were exposed to the SARS-CoV-2 spike protein and the BNT162b2 vaccine (the vaccine created by Pfizer-BioNTech for COVID-19). Both the spike protein and the vaccine have been shown to induce an inflammatory response, especially in the form of elevated levels of cytokines like IL-6 and IL-8. Cytokines are small proteins that help regulate immune responses, but excessive production of cytokines, especially IL-6 and IL-8, is associated with severe inflammation in COVID-19 cases.
 
The researchers treated these cells with varying amounts of AGE to determine whether it could reduce the expression of pro-inflammatory genes. This study focused on the genes coding for interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8), three cytokines known to play significant roles in COVID-19’s inflammatory process. By measuring the cytokine levels in the cell environment, the research team could determine if AGE had a tangible effect on reducing inflammation.
 
How AGE and SAC Impacted Inflammatory Responses
The study findings showed a clear reduction in inflammation when cells were treated with AGE. Specifically, AGE was found to decrease the expression of IL-1β, IL-6, and IL-8 genes after exposure to the SARS-CoV-2 spike protein. In simple terms, AGE appears to interfere with the cellular pathways that lead to increased cytokine production, effectively “turning down” the inflammatory response that is commonly seen in COVID-19 infections. Researchers observed similar effects when cells were exposed to the BNT162b2 vaccine, suggesting that AGE’s anti-inflammatory effects could extend to vaccine-induced inflammation.
 
S-allyl-cysteine (SAC), a major compound within AGE, was also tested separately. The findings indicated that SAC alone could reduce the expression of IL-6 and IL-8 genes, underscoring SAC’s role as a key active component responsible for AGE’s anti-inflammatory properties. SAC appears to interact with specific cellular receptors, dampening the processes that lead to cytokine production. This interaction is believed to take place through Toll-like receptors (TLRs), particularly TLR4. TLRs are a family of receptors that recognize foreign substances and help kickstart immune responses, including inflammation.
 
The Mechanism Behind AGE’s Anti-Inflammatory Effects
One of the most significant aspects of this study was the exploration of how AGE and SAC reduce inflammation at a molecular level. The study suggests that SAC may prevent inflammatory gene activation by interfering with the NF-κB pathway. NF-κB, short for Nuclear Factor kappa-light-chain-enhancer of activated B cells, is a protein complex that plays a central role in controlling inflammation. NF-κB becomes activated in response to stress signals and subsequently initiates the transcription of various inflammatory genes, including IL-1β, IL-6, and IL-8.
 
When SARS-CoV-2 enters a cell, the spike protein binds to receptors on the cell surface, leading to the activation of NF-κB, among other cellular responses. This, in turn, causes the overproduction of cytokines and can trigger a cytokine storm, which can be fatal if not controlled. AGE’s ability to reduce cytokine levels may be linked to SAC’s potential to inhibit Toll-like receptor 4 (TLR4), which is involved in the activation of NF-κB. By interfering with TLR4, SAC essentially prevents NF-κB from triggering inflammation, reducing the production of pro-inflammatory cytokines.
 
Key Findings on AGE's Effects on Inflammatory Markers
The study produced several notable findings:

-Reduction in Inflammatory Gene Expression: AGE was shown to significantly reduce the expression of IL-1β, IL-6, and IL-8 in cells exposed to the SARS-CoV-2 spike protein. This finding is critical because IL-6 and IL-8 are major contributors to COVID-19’s inflammatory symptoms. The decrease in these cytokines suggests that AGE might help alleviate the severity of inflammatory responses associated with COVID-19.
 
-SAC’s Independent Effects: When SAC was tested independently of AGE, it still demonstrated a strong ability to inhibit IL-6 and IL-8 gene expression. This finding underscores SAC’s role as an essential active ingredient in AGE’s anti-inflammatory effects and hints at its potential use as a stand-alone supplement for managing inflammation.
 
-No Cytotoxicity Observed: Importantly, the study noted that AGE and SAC did not harm the cells or affect their growth at the concentrations tested. This aspect is significant because it supports the potential safety of AGE as a therapeutic agent. Higher doses of AGE are known to have pro-apoptotic (cell-killing) effects, but the doses used in this study were below those levels, indicating a safe threshold for use in therapeutic applications.
 
-Inhibition of Vaccine-Induced Inflammation: The study also examined AGE’s effects on cells treated with the BNT162b2 vaccine. Researchers found that AGE reduced IL-8 levels in cells exposed to the vaccine, a promising result suggesting that AGE could be helpful in managing inflammation resulting from vaccination.
 
Conclusions and Implications for Future Research
In conclusion, this study provides valuable insights into AGE’s anti-inflammatory properties, especially in the context of COVID-19. The data indicate that AGE, and specifically its component SAC, could help reduce the expression of inflammatory cytokines that contribute to COVID-19’s more severe symptoms. As a natural product with minimal toxicity at therapeutic doses, AGE could offer a complementary approach to managing COVID-19’s inflammatory aspects. The study’s findings point toward further exploration of AGE as a potential adjunct therapy, particularly for patients experiencing cytokine storms or severe inflammatory symptoms.
 
Looking forward, researchers plan to explore additional AGE components beyond SAC, as garlic contains numerous bioactive compounds that may also contribute to its effects. Future studies may also investigate AGE’s impact on other inflammatory markers associated with COVID-19, including IL-2, IL-7, and TNF-α. A more comprehensive analysis of these inflammatory pathways could solidify AGE’s role in COVID-19 treatment.
 
As research continues, AGE’s therapeutic applications could potentially extend beyond COVID-19 to other conditions characterized by excessive inflammation. However, more clinical trials and studies are needed to determine the efficacy and safety of AGE for broader use. Given the ongoing search for effective COVID-19 treatments, the study findings offer a hopeful step toward using natural products to combat this challenging disease.
 
The study findings were published on a preprint server and are currently being peer reviewed.
https://www.preprints.org/manuscript/202411.0635/v1
 
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