Author:
Vezzani Bianca,Perrone Mariasole,Carinci Marianna,Palumbo Laura,Tombolato Alberto,Tombolato Denis,Daminato Claudio,Gentili Valentina,Rizzo Roberta,Campo Gianluca,Morandi Luca,Papi Alberto,Spadaro Savino,Casolari Paolo,Contoli Marco,Pinton Paolo,Giorgi Carlotta
Abstract
Abstract
Background
The recent pandemic outbursts, due to SARS-CoV-2, have highlighted once more the central role of the inflammatory process in the propagation of viral infection. The main consequence of COVID-19 is the induction of a diffuse pro-inflammatory state, also defined as a cytokine storm, which affects different organs, but mostly the lungs. We aimed to prove the efficacy of cinnamaldehyde, the active compound of cinnamon, as an anti-inflammatory compound, able to reduce SARS-CoV-2 induced cytokine storm.
Results
We enrolled 53 COVID-19 patients hospitalized for respiratory failure. The cohort was composed by 39 males and 13 females, aged 65.0 ± 9.8 years. We reported that COVID-19 patients have significantly higher IL-1β and IL-6 plasma levels compared to non-COVID-19 pneumonia patients. In addition, human mononuclear cells (PBMCs) isolated from SARS-CoV-2 infected patients are significantly more prone to release pro-inflammatory cytokines upon stimuli. We demonstrated, using in vitro cell models, that macrophages are responsible for mediating the pro-inflammatory cytokine storm while lung cells support SARS-CoV-2 replication upon viral infection. In this context, cinnamaldehyde administration significantly reduces SARS-CoV-2-related inflammation by inhibiting NLRP3 mediated IL-1β release in both PBMCs and THP-1 macrophages, as well as viral replication in CaLu-3 epithelial cells. Lastly, aerosol-administered cinnamaldehyde was able to significantly reduce IL-1β release in an in vivo lung-inflammatory model.
Conclusion
The obtained results suggest the possible use of cinnamaldehyde as a co-adjuvant preventive treatment for COVID-19 disease together with vaccination, but also as a promising dietary supplement to reduce, more broadly, viral induced inflammation.
Funder
Ministero della Salute
Associazione Italiana per la Ricerca sul Cancro
Ministero dell'Università e della Ricerca
European Research Council
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Clinical Biochemistry
Reference41 articles.
1. Chavda VP, Patel AB, Vaghasiya DD. SARS-CoV-2 variants and vulnerability at the global level. J Med Virol. 2022;94:2986–3005. Available from: http://www.ncbi.nlm.nih.gov/pubmed/35277864.
2. Hillary VE, Ceasar SA. An update on COVID-19: SARS-CoV-2 variants, antiviral drugs, and vaccines. Heliyon. 2023;9:e13952. Available from: http://www.ncbi.nlm.nih.gov/pubmed/36855648.
3. Bell LCK, Meydan C, Kim J, Foox J, Butler D, Mason CE, et al. Transcriptional response modules characterize IL-1β and IL-6 activity in COVID-19. iScience. 2021;24:101896. Available from: http://www.ncbi.nlm.nih.gov/pubmed/33319166.
4. Tripathy AS, Vishwakarma S, Trimbake D, Gurav YK, Potdar VA, Mokashi ND, et al. Pro-inflammatory CXCL-10, TNF-α, IL-1β, and IL-6: biomarkers of SARS-CoV-2 infection. Arch Virol. 2021;166:3301–10. Available from: http://www.ncbi.nlm.nih.gov/pubmed/34554303.
5. Conti P, Ronconi G, Caraffa A, Gallenga C, Ross R, Frydas I, et al. Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies. J Biol Regul Homeost Agents. 34:327–31. Available from: http://www.ncbi.nlm.nih.gov/pubmed/32171193.