Fig. 1

Summary of previous findings. Effect of ultramicronized(um)-PEA on SP-challenged murine alveolar macrophages. Anti-inflammatory effect of um-PEA in SARS-CoV-2 spike protein challenged murine alveolar macrophages depends upon PPARα-mediated control of NF-κB and NLRP3 inflammasome signaling pathways. Schematic representation of SARS-CoV-2 spike protein-induced inflammasome activation and relative proposed anti-inflammatory mechanism of um-PEA in mice alveolar macrophages. Spike protein interacts at TLR4 and ACE-2 receptor sites, activating phosphorylation of p38MAPK and consequent NF-κB activation. This is accompanied by cytokine release (IL-6 and TNF-α) and inflammasome pathway activation, featured by NLRP3 and Caspase-1/IL-1β upregulation. Um-PEA acting at PPAR-α receptor site inhibits NF-κB transcription and NLRP-3 inflammasome signaling leading to a significant anti-inflammatory effect in spike protein-challenged alveolar macrophages