# Plant Exosomal Vesicles: Perspective Information Nanocarriers in Biomedicine
## 10 Therapeutic Effects of Plant Nanovesicles  
In the last decade, the attention of researchers has been attracted by the possibility of using plant exosomes as a drug delivery system. The plant origin and high biocompatibility, as well as the universal therapeutic potential of the exosomes, make them advantageous over synthetic liposomes used as nanocarriers. It was found that the plant exosomes participate in the regulation of the immune response and have a pronounced anti-inflammatory effect. Due to the interspecies translocation ability of exosomes, the molecules they contain can regulate the interaction between the intestinal microbiota and the host immune system, resulting in a homeostatic balance [113]. In a recurrent inflammatory bowel disease, such as colitis, the intestinal macrophages lose their tolerogenic abilities. [PERSON] and co-authors showed that graprefruit-derived exosomes have a beneficial effect on the gut immune homeostasis by enhancing the anti-inflammatory capacity of intestinal macrophages, ultimately alleviating colitis in mice. After exosome capture by the intestinal macrophages, these nanocarriers increased the expression of heme oxygenase-1 and interleukin (IL)-10, but at the same time suppressed IL-6, IL-1b, and tumor necrosis factor (TNF) [45]. In addition, the nanovesicles delivered naringin, a key flavanone in graprefruit. Upon release, naringin is hydrolyzed by the gut microbiota to its active metabolite naringenin. The exosomes have been shown to exhibit antitumor activity in a mouse model of dextran sodium sulfate-induced colitis [101]. It has also been reported that miRNAs of the exosomes isolated from ginger and graprefruit specifically downregulated some genes of the intestinal probiotic _Lactobacillus rhamnosus_ in mice [67]. A great number of studies are devoted to the nanovesicles isolated from ginger [74; 82; 102; 104; 110]. When ginger nanovesicles are loaded with doxorubicin for delivery to colon tumor cells, they effectively invade colon tumors and suppress their growth [82]. Probably, the nanovesicles release doxorubicin at the acidic pH of the tumor extracellular microenvironment, reducing the side effects of the drug [82]. Moreover, the ginger exosomes have shown promising results in reducing colorectal tumorigenesis in mice by decreasing the level of pro-inflammatory cytokines, as well as suppressing the intestinal epithelial cells proliferation and apoptosis by reducing the cyclin D1 expression,which is a marker in the early stages of cancer development [102]. Along with the above effects of ginger exosomes, successful suppression of tumor growth has been shown by reducing the level of survival genes expression using intravenous nanovesicular microRNA delivery [104]. The grape nanovesicles also exhibited an antitumor activity. The effect was achieved by increasing the expression of the _Lgr5_ and _BMI1_ genes, which serve as the intestinal stem cell markers and are the genes that regulate the growth and proliferation of stem cells [106]. Other researchers have found that the lemon juice nanovesicles are able to inhibit the proliferation of the A549 (human lung carcinoma), LAMA84 (chronic myeloid leukemia), and human colorectal adenocarcinoma cell lines. The inhibition of proliferation occurred due to the activation of apoptotic cell death mediated by an apoptosis-inducing ligand associated with TNF [108]. It should be noted that in addition to the antitumor effects, the plant exosomes are known to be used in regenerative medicine. It was shown that the grape nanovesicles are able to penetrate into intestinal stem cells, induce their proliferation by regulating the expression of genes responsible for pluripotency (_Oct4_, _SOX2_, and _Klf4_), and thereby regenerate epithelial tissue [110]. At the same time, the ginger nanovesicles exhibited the hepatotoxicity activity by reducing the generation of reactive oxygen species in alcohol-damaged mouse livers. Due to their bioactive components, the exosomes can influence the nuclear factor NRF2.