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
Department of Medical Sciences, Section of Experimental Medicine, University of Ferrara, 44121, Ferrara, Italy.
Laboratory of Technologies for Advanced Therapy (LTTA), Technopole of Ferrara, 44121, Ferrara, Italy.
J Inflamm (Lond). 2023 Nov 20;20(1):40. doi: 10.1186/s12950-023-00364-9.
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.
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.
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.
近期由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引发的大流行疫情再次凸显了炎症过程在病毒感染传播中的核心作用。2019冠状病毒病（COVID-19）的主要后果是引发弥漫性促炎状态，也被定义为细胞因子风暴，它会影响不同器官，但主要是肺部。我们旨在证明肉桂中的活性化合物肉桂醛作为一种抗炎化合物，能够减轻SARS-CoV-2引发的细胞因子风暴。
我们纳入了53名因呼吸衰竭住院的COVID-19患者。该队列由39名男性和13名女性组成，年龄为65.0±9.8岁。我们报告称，与非COVID-19肺炎患者相比，COVID-19患者的白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）血浆水平显著更高。此外，从感染SARS-CoV-2的患者中分离出的人单核细胞（外周血单核细胞，PBMCs）在受到刺激后显著更易释放促炎细胞因子。我们使用体外细胞模型证明，巨噬细胞介导促炎细胞因子风暴，而肺细胞在病毒感染时支持SARS-CoV-2复制。在此背景下，给予肉桂醛可通过抑制PBMCs和THP-1巨噬细胞中NLRP3介导的IL-1β释放以及CaLu-3上皮细胞中的病毒复制，显著减轻与SARS-CoV-2相关的炎症。最后，雾化吸入肉桂醛能够在体内肺部炎症模型中显著减少IL-1β释放。
所得结果表明，肉桂醛有可能作为COVID-19疾病与疫苗接种联合的辅助预防性治疗药物，也有可能作为一种有前景的膳食补充剂，更广泛地减轻病毒引发的炎症。
