Extracellular Vesicles Derived From Citrus sinensis Modulate Inflammatory Genes and Tight Junctions in a Human Model of Intestinal Epithelium

Abstract

It is widely acknowledged that mammalian exosomes (or extracellular vesicles), have a key role in intercellular communication, owing to the presence of various bioactive molecules such as lipids, proteins, and microRNAs within their inner compartment. Most recently, the discovery of extracellular vesicles isolated from edible plants (such as vegetables and fruits) and their similarity in terms of size and content with exosomes has opened new perspectives on possible intercellular communication and regulation of important biological processes in which these vesicles are involved. It is also well-known that a balanced diet rich of fruits and vegetables (i.e., the Mediterranean diet) can contribute to maintain a “healthy gut” by preserving the intestinal epithelial barrier integrity and avoid that inflammatory stimuli that can alter homeostasis. In our study, we optimized a method to isolate extracellular vesicles from the orange juice (Citrus sinensis) (CS-EVs), and we characterized their morphology and behavior when in contact with the intestinal epithelium. We showed that CS-EVs are stable in a simulated gastrointestinal environment and are absorbed by intestinal cells without toxic effects, as expected. Furthermore, we demonstrated that CS-EVs can alter the gene expression of several genes involved in inflammation (i.e., ICAM1 and HMOX-1) and tight junctions (i.e., OCLN, CLDN1, and MLCK), contributing to limit inflammatory stimuli and restore a functional barrier by increasing the tight junction OCLN protein. Therefore, our study emphasizes the relevant role of fruit-derived extracellular vesicles in modulating important biological processes and maintaining a healthy intestinal epithelium, ultimately promoting human health and well-being.

Plant extracellular vesicles: A novel bioactive nanoparticle for tumor therapy

“…Compared with delivery vehicles such as liposomes, silver nanoparticles and animal extracellular vesicles, plant extracellular vesicles are regarded as a natural source, biocompatibility, non-immunogenicity and non-toxicity to normal cells, an ideal nanosphere to hold and transport cargo ( De Jong and Borm, 2008 ). It is also relatively easy to obtain plant extracellular vesicles, which can be obtained directly from plant stems and leaves, plant seeds and fruit juices ( Rutter and Innes, 2017 ; Potesta et al, 2020 ; Bruno et al, 2021 ; Karimi et al, 2022 ). Although the application of plant extracellular vesicles seems to be easier and faster than that of animal extracellular vesicles, many efforts are still required.…”

Emergence of Edible Plant-Derived Nanovesicles as Functional Food Components and Nanocarriers for Therapeutics Delivery: Potentials in Human Health and Disease

“…Pre-processing steps for PDNVs are largely the same with a slight modification depending on the type of fruits or the structure of vegetables. For example, fleshy fruits, such as apple [ 18 , 19 ], blueberry [ 20 , 21 ], orange [ 22 , 23 ], lemon [ 24 ], and grapefruit [ 25 , 26 ], having high water content, were crushed/smashed and then homogenized using a blender or squeezed manually or pressed using a juicer. The collected juice was then processed to isolate nanoparticles.…”

The Emerging Role of Plant-Derived Exosomes-Like Nanoparticles in Immune Regulation and Periodontitis Treatment

“…Cabbage and red cabbage-derived ELNs decrease the levels of IL-6, IL-1b, and COX-2 expression in LPS-treated macrophages, showing clear anti-inflammatory effects (55). Orange (Citrus sinensis)-derived ELNs limit inflammation and restore the functional intestinal barrier by altering the expression of HMOX-1, ICAM1, OCLN, CLDN1, and MLCK (91). The anti-inflammatory properties of PELNs could be possibly attributed to the micro-RNA in PELNs.…”