Anti‐inflammatory properties of lemon‐derived extracellular vesicles are achieved through the inhibition of ERK/NF‐κB signalling pathways

Abstract

Chronic inflammation is associated with the occurrence of several diseases. However, the side effects of anti‐inflammatory drugs prompt the identification of new therapeutic strategies. Plant‐derived extracellular vesicles (PDEVs) are gaining increasing interest in the scientific community for their biological properties. We isolated PDEVs from the juice of Citrus limon L. (LEVs) and characterized their flavonoid, limonoid and lipid contents through reversed‐phase high‐performance liquid chromatography coupled to electrospray ionization quadrupole time‐of‐flight mass spectrometry (RP‐HPLC–ESI‐Q‐TOF‐MS). To investigate whether LEVs have a protective role on the inflammatory process, murine and primary human macrophages were pre‐treated with LEVs for 24 h and then were stimulated with lipopolysaccharide (LPS). We found that pre‐treatment with LEVs decreased gene and protein expression of pro‐inflammatory cytokines, such as IL‐6, IL1‐β and TNF‐α, and reduced the nuclear translocation and phosphorylation of NF‐κB in LPS‐stimulated murine macrophages. The inhibition of NF‐κB activation was associated with the reduction in ERK1‐2 phosphorylation. Furthermore, the ability of LEVs to decrease pro‐inflammatory cytokines and increase anti‐inflammatory molecules was confirmed ex vivo in human primary T lymphocytes. In conclusion, we demonstrated that LEVs exert anti‐inflammatory effects both in vitro and ex vivo by inhibiting the ERK1‐2/NF‐κB signalling pathway.

Protein Biocargo and Anti-Inflammatory Effect of Tomato Fruit-Derived Nanovesicles Separated by Density Gradient Ultracentrifugation and Loaded with Curcumin

“…Interestingly, PDNVs from different plant species, e.g., ginger rhizome [ 12 , 15 , 17 ], grapefruit [ 15 , 16 , 18 ], blueberries [ 13 ], broccoli [ 19 ], lemon [ 20 ] and cabbage [ 11 ] were shown to have anti-inflammatory activities in vitro and in vivo. The mechanisms underlying the anti-inflammatory effects of PDNVs include the induction of anti-inflammatory cytokines (IL-10, IL-22), suppression of pro-inflammatory cytokines (IL-6, IL-1β and TNF-α), induction of heme oxygenase-1 (HO-1), activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) or the inhibition of ERK/NF-κB signaling pathways [ 15 , 20 ]. The molecules in pristine PDNVs with anti-inflammatory activities could be diverse including miRNAs, secondary metabolites, fatty acids, peptides and proteins.…”

Celery (Apium graveolens L.) Exosome-like Nanovesicles as a New-Generation Chemotherapy Drug Delivery Platform against Tumor Proliferation

“…Lipid is an integral part of the bilayer membrane structure of PELNs, which affects the stability, uptake, and other biological functions of PELNs . Through the analysis of the lipid composition of CELNs, we found that DG accounted for 45%, which was much higher than the other three PELNs (lemon, grape, and ginger). ,,, Therefore, we speculate that DG may play a significant role in the fusion of cells and CELNs. As early as 1973, DG was found to promote membrane fusion .…”

Bioactive Metabolite Survey of Actinobacteria Showing Plant Growth Promoting Traits to Develop Novel Biofertilizers

“…HPLC/MS analysis was performed by adapting previously reported methods [ 21 , 22 ]. Samples for HPLC (Agilent 1260 Infinity) were prepared by collecting spent media from cultures (1 mL).…”