SARS-CoV-2 infection as a model to study the effect of cinnamaldehyde as adjuvant therapy for viral pneumonia

以SARS-CoV-2感染为模型研究肉桂醛对病毒性肺炎的辅助治疗效果

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作者:Bianca Vezzani #, Mariasole Perrone #, Marianna Carinci #, Laura Palumbo, Alberto Tombolato, Denis Tombolato, Claudio Daminato, Valentina Gentili, Roberta Rizzo, Gianluca Campo, Luca Morandi, Alberto Papi, Savino Spadaro, Paolo Casolari, Marco Contoli, Paolo Pinton, Carlotta Giorgi

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.

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.

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.

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