Exosome-like nanoparticles from Arbutus unedo L. mitigate LPS-induced inflammation via JAK-STAT inactivation

Exosomes have garnered attention as a potential cell-free therapy for inflammatory diseases due to their immunomodulatory and anti-inflammatory properties. Exosome-like nanoparticles isolated from Arbutus unedo were characterized and analyzed for their anti-inflammatory potential. The results revealed that the isolated exosomes exhibited a spheroid morphology, with an approximate modal size of 190 nm. Exposure to these exosomes significantly reduced the mRNA expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), the glycoprotein CD80, the transcription factor STAT1, and pro-inflammatory cytokine genes like IL-1b and IL-6, in lipopolysaccharide (LPS)-induced protein RAW264.7 cells. In addition, exosomes reduced the LPS-induced protein levels of PSTAT1 and STAT1, IRF1 and RelB, which are key transcription factors in the control of proinflammatory gene expression. LC-MS analysis identified the presence of carotenoids, mainly β-carotene, with known anti-inflammatory activity, related to its ROS-scavenging activity, suggesting its potential contribution to the anti-inflammatory activity of the exosomes isolated from A. unedo fruits.