Industrial-produced lemon nanovesicles ameliorate experimental colitis-associated damages in rats via the activation of anti-inflammatory and antioxidant responses and microbiota modification.

Plant-derived nanovesicles (PDNVs) have recently emerged as natural delivery systems of biofunctional compounds toward mammalian cells. Considering their already described composition, anti-inflammatory properties, stability, and low toxicity, PDNVs offer a promising path for developing new preventive strategies for several inflammatory diseases, among which the inflammatory bowel disease (IBD). In this study, we explore the protective effects of industrially produced lemon vesicles (iLNVs) in a rat model of IBD. Characterization of iLNVs reveals the presence of small particles less than 200 nm in size and a profile of bioactive compounds enriched in flavonoids and organic acids with known beneficial properties. In vitro studies on human macrophages confirm the safety and anti-inflammatory effects of iLNVs, as evidenced by the reduced expression of pro-inflammatory cytokines and increased levels of anti-inflammatory markers. As evidenced by in vivo experiments, pre-treatment with iLNVs significantly alleviates symptoms and histological features in 2,4 dinitrobenzensulfuric acid (DNBS)-induced colitis in rats. Molecular pathway analysis reveals modulation of NF-κB and Nrf2, indicating anti-inflammatory and antioxidant effects. Finally, iLNVs affects gut microbiota composition, improving the consistent colitis-related alterations. Overall, we demonstrated the protective role of industrially produced lemon nanovesicles against colitis and emphasized their potential in managing IBD through multifaceted mechanisms.

Lemon-derived nanovesicles achieve antioxidant and anti-inflammatory effects activating the AhR/Nrf2 signaling pathway.

In the last years, extracellular vesicles (EVs) from different plant matrices have been isolated and gained the interest of the scientific community for their intriguing biological properties. In this study, we isolated and characterized nanovesicles from lemon juice (LNVs) and evaluated their antioxidant effects. We tested LNV antioxidant activity using human dermal fibroblasts that were pre-treated with LNVs for 24 h and then stimulated with hydrogen peroxide (H2O2) and UVB irradiation. We found that LNV pre-treatment reduced ROS levels in fibroblasts stimulated with H2O2 and UVB. This reduction was associated with the activation of the AhR/Nrf2 signaling pathway, whose protein expression and nuclear localization was increased in fibroblasts treated with LNVs. By using zebrafish embryos as in vivo model, we confirmed the antioxidant effects of LNVs. We found that LNVs reduced ROS levels and neutrophil migration in zebrafish embryos stimulated with LPS.

Plant-RNA in Extracellular Vesicles: The Secret of Cross-Kingdom Communication.

The release of extracellular vesicles (EVs) is a common language, used by living organisms from different kingdoms as a means of communication between them. Extracellular vesicles are lipoproteic particles that contain many biomolecules, such as proteins, nucleic acids, and lipids. The primary role of EVs is to convey information to the recipient cells, affecting their function. Plant-derived extracellular vesicles (PDEVs) can be isolated from several plant species, and the study of their biological properties is becoming an essential starting point to study cross-kingdom communication, especially between plants and mammalians. Furthermore, the presence of microRNAs (miRNAs) in PDEVs represents an interesting aspect for understanding how PDEVs can target the mammalian genes involved in pathological conditions such as cancer, inflammation, and oxidative stress. In particular, this review focuses on the history of PDEVs, from their discovery, to purification from various matrices, and on the functional role of PDEV-RNAs in cross-kingdom interactions. It is worth noting that miRNAs packaged in PDEVs can be key modulators of human gene expression, representing potential therapeutic agents.