Suppression of inflammatory responses in macrophages by onion-derived extracellular vesicles

Chronic inflammation is closely associated with several serious diseases that affect millions of individuals. Although researchers have focused on drug discovery toward regulating inflammation, developing novel biomaterials with high efficacy, productivity, and low cytotoxicity remains an essential priority. In this context, extracellular vesicles (EVs) were directly isolated from onions and investigated for their anti-inflammatory activity in RAW 264.7 macrophages. As EVs are nano-sized vesicles containing bioactive components enclosed by a lipid bilayer, onion-derived EVs (Onex) most likely would contain onion-derived anti-inflammatory components for delivery to macrophages. A high concentration of Onex was isolated by size-exclusion chromatography combined with ultrafiltration. No significant cytotoxicity was observed, even at a high Onex concentration. Moreover, Onex showed a dose-dependent suppression of secretion and expression of pro-inflammatory factors, including interleukin 6, interleukin 1β, cyclooxygenase 2, and inducible nitric oxide synthase in RAW 264.7 cells after lipopolysaccharide treatment. Western blot analysis showed that Onex modulates the phosphorylation of NF-κB, a transcription factor that regulates the expression of other pro-inflammatory factors. Interestingly, it was determined that Onex contains components other than quercetin derivatives, which are well-known anti-inflammatory constituents of onion extract that significantly suppressed LPS-induced inflammation in RAW 264.7 macrophages. Considering its low cytotoxicity and robust anti-inflammatory activity, Onex is a potentially promising biomaterial for treating diseases accompanying severe inflammation.