# Plant Extracellular Vesicles: Investigating Their Utilization as Beneficial Nutrients in Diet
## 4 P-EV Biological Properties and Therapeutic Applications
#### Antioxidant Functions
investigated the use of natural antioxidants in the treatment of [PERSON]'s disease. In particular, hydroxytyrosol, a phenolic compound extracted from olive oil and leaves, and curcumin showed neuroprotective effects on SH-SYSY cells, which were associated with a reduction in neurotoxin-induced ROS production and modulation of apoptosis pathways [76]. A separate study demonstrated the potential antitumor effects of green-synthesized nanoparticles containing berberine, an alkaloid molecule derived from various medicinal plants, whose pharmacological effects are widely recognized. Berberine treatment significantly increased the survival rate of mice injected with Ehrlich ascites tumor cells and reduced tumor growth, showing antioxidant and proapoptotic activities [81]. Taking into account that plants are rich in antioxidant compounds, research is therefore increasingly focusing on the isolation of vesicles that enclose and transport these molecules, not only for medicinal purposes but also for anti-aging formulations and food preservation. One of the antioxidant metabolites present in P-EVs is vitamin C, a powerful free radical scavenger, possessing a significant protective effect against oxidative damage, and it is also a cofactor for important enzymatic reactions. Its high molecular instability under physiological conditions reduces the bioavailability; thus, the vitamin C packaged in P-EVs can be considered very important [82]. Exosomal vesicles from citrus fruits and berries have been shown to resist in the gastric environment before being absorbed in the intestine [38]. The vesicles extracted from these fruits contain elevated concentrations of vitamin C (e.g., 50 \(\upmu\)g/mL of lemon exosomes contain about 7 \(\upmu\)M vitamin C); therefore, the ability to effectively deliver high doses to target cells may explain the antioxidant properties of these vesicles [25]. In support of this finding, mesenchymal stem cells pretreated with H\({}_{2}\)O\({}_{2}\) showed a significantly increased survival after the internalization of lemon EVs, in a dose-dependent manner and reduced ROS production [83]. The high contents of vitamin C and other active metabolites, including anthocyanins, folic acid, and flavonoids, have been detected in EVs isolated from _Fragaria_ x _ananassa_ strawberry juice. The adipose-derived mesenchymal stem cells internalize _Fragaria_-derived vesicles that do not negatively affect cell viability; moreover, the pretreatment of cells with _Fragaria_-derived vesicles prevents oxidative damage in a dose-dependent manner. This is mainly due to the presence of vitamin C in the nanovesicle membrane, indicating the potential health-promoting activity of _Fragaria_-derived vesicles [40]. In addition, carrot-derived vesicles were shown to have antioxidant properties in H9C2 cardiomyocytes and the human neuroblastoma SH-SYSY cell line. Carrot EVs show low cytotoxicity in both cell lines and a high uptake ratio. The treatment significantly inhibited ROS formation and apoptosis in vitro in myocardial infarction and Parkinson's disease models by inhibiting the reduction of antioxidant molecules expression, including Nrf-2 nuclear factor erythroid 2-related factor 2, HO-1, and NQO-1, in both models [84]. Another study confirmed that carrot-derived EVs have antioxidant properties by increasing nuclear translocation of Nrf2, a key regulator of the HO1 gene involved in anti-inflammation and anti-oxidation activity, in Raw 264.7 macrophages [58]. An effect on the Nrf expression increment leading to the expression of detoxifying/antioxidant genes has been demonstrated in mice alcoholic liver model. In particular, ginger-derived EVs protect the liver against alcohol-induced damage. Specifically, the researchers have identified in the compound 6-shogaol the active molecule acting on Nrf2 expression and contributing to hepatoprotection [73]. Berry fruits have been reported to exhibit the highest total antioxidant capacity among fruits, mainly due to their elevated content of phytochemicals and polyphenols [85].