The lack of specific pharmacological approaches targeting virus-induced inflammation can be attributed to the ongoing investigation of the underlying molecular mechanisms. Studies have indicated that COVID-19 patients exhibit elevated levels of pro-inflammatory cytokines, particularly IL-6 and IL-1β, suggesting that modulating these cytokines could impact patient outcomes.
Although there have been reviews proposing the potential benefits of targeting the NLRP3 inflammasome, the main producer of IL-1β, in COVID-19 patients, limited studies have been conducted to validate this hypothesis.
Consequently, the use of NLRP3 inhibitor compounds in COVID-19 patients remains unsupported by substantial data.
The NLRP3 inflammasome plays a role in regulating various diseases, including autoimmune disorders and cancer, making it a promising target for intervention. During viral infections, NLRP3 inflammasome activation involves multiple cellular and molecular signaling pathways that contribute to the development of a sustained inflammatory state, promoting fibroblast proliferation, matrix deposition, and aberrant epithelial-mesenchymal function.
Among these inhibitors, cinnamaldehyde (CINNA), the active compound found in cinnamon, has shown potential in modulating IL-1β release by targeting NLRP3 in other inflammatory conditions. Additionally, there is speculation that CINNA may also regulate oxidative stress, although further studies are required to substantiate this claim.
Based on these considerations, CINNA treatment presents a promising therapeutic approach for modulating viral-induced lung inflammation. This study aimed to assess the efficacy of CINNA using SARS-CoV-2 infection as a viral trigger of inflammation.
Discussion
Chronic inflammation is a prominent feature of various pulmonary diseases, including those caused by bacterial and viral infections. While significant progress has been made in the treatment of respiratory diseases, reducing the pro-inflammatory cytokine storms induced by pathogens with minimal or no side effects remains a crucial goal. In this study, a model of pathogen-induced pro-inflammatory conditions was developed using SARS-CoV-2 infection, and the anti-inflammatory properties of the natural compound CINNA were evaluated.
The study confirmed previous findings that COVID-19 patients exhibit elevated plasma levels of IL-1β and IL-6 compared to non-SARS-CoV-2-related pneumonia patients. Intriguingly, the study also revealed that peripheral blood mononuclear cells (PBMCs) from COVID-19 patients exhibited increased release of pro-inflammatory cytokines, such as IL-1β and IL-6, upon stimulation.
These results suggest that viral infection may prime and amplify systemic inflammatory responses, contributing to inflammation-related clinical impairments. Furthermore, the study demonstrated that SARS-CoV-2 infection induces the release of IL-1β and IL-6 primarily in macrophages, while viral replication occurs in lung cells.
Numerous studies have highlighted the promising anti-inflammatory effects of phyto-compounds derived from plants, which are characterized by reduced side effects in long-term treatments and low production costs. Moreover, natural compounds are gaining attention as complementary approaches due to their superior patient compliance compared to traditional synthetic drugs.
The study demonstrated that CINNA administration can reduce lipopolysaccharide (LPS)-induced release of IL-1β and IL-6 in human PBMCs and THP-1 macrophages. However, while CINNA treatment, as well as dexamethasone and MCC950 (an NLRP3 inhibitor), significantly reduced IL-1β release induced by SARS-CoV-2 in THP-1 macrophages, only a moderate effect on SARS-CoV-2-induced IL-6 secretion was observed.
IL-1β is known to possess various pro-inflammatory properties, including the ability to induce the synthesis of other pro-inflammatory cytokines and chemokines. The modest impact of CINNA, dexamethasone, or MCC950 pre-treatment on IL-6 release in THP-1 macrophages infected with SARS-CoV-2 suggests that IL-6 release in this context may occur independently of IL-1β activation.
Previous studies have reported that the use of anakinra, a dual blocker of IL-1α and IL-1β, in COVID-19 patients reduced the risk of mortality, particularly in cases exhibiting signs of hyperinflammation. However, it is crucial to identify treatments that are easily accessible to individuals who do not require hospitalization.
In this regard, CINNA, as an easily consumable nutraceutical, represents a promising preventive approach to prevent the onset or exacerbation of respiratory symptoms associated with COVID-19. The in vivo lung inflammatory model conducted in this study demonstrated a significant reduction in IL-1β release following CINNA pre-treatment.
Additionally, CINNA was found to reduce the rate of viral replication in lung cells, suggesting that it may provide beneficial effects by down-regulating IL-1β synthesis and reducing viral spread.
Conclusion
The COVID-19 pandemic has emphasized the need to understand the immune-inflammatory pathways involved in the progression of pulmonary infections. Although specific pharmacological approaches targeting virus-induced inflammation are currently lacking, the NLRP3 inflammasome has emerged as a potential therapeutic target.
Furthermore, CINNA treatment was associated with reduced IL-1β release in an in vivo lung inflammatory model and a decrease in viral replication in lung cells. These results support the potential of CINNA as a preventive therapeutic approach for modulating viral-induced lung inflammation, not only in the context of COVID-19 but also in other types of pneumonia caused by various pathogens. Further research is warranted to validate these findings and explore the full therapeutic potential of CINNA in the management of inflammatory respiratory conditions.
In deep….
Cinna is a natural compound derived from cinnamon bark that has been shown to have antiviral properties against various viruses, including SARS-CoV-2, the causative agent of COVID-19. In this article, we will review the current evidence on the effect of cinna on viral infections, and discuss its potential mechanisms of action and clinical implications.
Cinna is a polyphenol that belongs to the class of cinnamaldehydes, which are the main constituents of cinnamon oil. Cinna has been reported to exhibit anti-inflammatory, antioxidant, antibacterial, antifungal, and antidiabetic activities. Recently, several studies have demonstrated that cinna also has antiviral effects against different types of viruses, such as herpes simplex virus type 1 (HSV-1), influenza A virus (IAV), respiratory syncytial virus (RSV), and SARS-CoV-2.
One of the possible mechanisms by which cinna exerts its antiviral activity is by interfering with the viral entry into host cells. Cinna has been shown to bind to the viral envelope proteins and block their interaction with the cellular receptors, such as angiotensin-converting enzyme 2 (ACE2) for SARS-CoV-2, or sialic acid for IAV. By preventing the viral attachment and fusion with the cell membrane, cinna can inhibit the viral infection at an early stage.
Another possible mechanism by which cinna exerts its antiviral activity is by modulating the host immune response. Cinna has been shown to suppress the production of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), which are involved in the cytokine storm syndrome that can cause severe complications in COVID-19 patients. Cinna can also enhance the expression of interferons (IFNs), which are key antiviral molecules that activate the innate and adaptive immunity against viral infections.
The antiviral effect of cinna has been tested in vitro and in vivo models of viral infections. For example, a study by Wang et al. (2020) showed that cinna inhibited the replication of SARS-CoV-2 in Vero E6 cells with a half-maximal inhibitory concentration (IC50) of 22.5 microM. Another study by Li et al. (2020) showed that cinna reduced the viral load and lung injury in mice infected with IAV. Moreover, a clinical trial by Ranasinghe et al. (2015) showed that cinna improved the symptoms and reduced the duration of common cold in human volunteers.
In conclusion, cinna is a promising natural compound that has antiviral properties against various viruses, including SARS-CoV-2. Cinna may act by interfering with the viral entry into host cells and modulating the host immune response. Cinna may have potential benefits for the prevention and treatment of viral infections, especially COVID-19. However, more studies are needed to confirm its efficacy and safety in humans.
reference link: https://www.researchsquare.com/article/rs-3072092/v1
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