Research on Vegetable-derived Exosome

Plants have great potential for application as resources for human survival. With the growing interest in discovering new medicinal properties in plants, in recent years, researchers have turned attention to exploring the characterization and potential applications of plant-derived exosomes, especially vegetable-derived exosomes.

Exosomes are small nanoscale vesicles (30-150nm) secreted from most cells with a phospholipid bilayer structure containing DNA, RNA, proteins, and lipids involved in intercellular communication. Various evidence has shown that vegetable-derived exosomes exhibit antimicrobial, anticancer, antioxidant, and anti-inflammatory effects, thus providing potential advantages in cancer therapy, tissue protection, and repair.

What is Vegetable-derived Exosome?

It is well known that vegetables or their extracts are rich in valuable nutrients and have many benefits for the human body. Vegetable-derived exosomes have a similar ultrastructure to exosomes of animal origin. Still, its chemical composition of lipids, proteins, and nucleic acids is significantly different and has unique biological functions with broad application prospects. Research has found that exosomes isolated from ginger, ginseng, garlic, onion, broccoli, and carrot carry various active substances, which have significant regulatory roles in skin repair, immunomodulation, and regenerative medicine.

Figure 1. Formation and secretion of the vegetable-derived exosome. (Liu Y, et al., 2024)

Advantages:

1. Vegetable-derived exosomes have the advantages of small size and high tissue penetration.
2. Vegetable-derived exosomes maintain good physicochemical stability at different pH and temperature.
3. Vegetable-derived exosomes show significant advantages in biocompatibility, stability, in vivo distribution, prolonged half-life, and cell internalization.
4. Vegetable-derived exosomes are an ideal carrier option for transdermal delivery and have a promising future for medical and aesthetic applications.
5. Vegetable-derived exosomes are easy to mass produce.

How to Isolate Vegetable-derived Exosome?

Plant exosomes are highly productive, but current research on exosome isolation and purification lags far behind that of animal exosomes. Vegetable-derived exosomes are isolated from plasmalemma washes. After extraction from vegetables, the first step is isolation. Differential centrifugation is the basic isolation method. However, exosomes obtained by this method are usually mixed with nucleic acid aggregates, proteins, or other extracellular vesicles. Therefore, further purification using density gradient ultracentrifugation is required to separate contaminants. To improve separation efficiency, researchers have proposed a combination of centrifugation methods, i.e., differential centrifugation combined with sucrose density gradient centrifugation. This method has gained popularity due to its simplicity, affordability, and ability to improve separation purity. However, although several methods have been developed to extract vegetable-derived exosomes, obtaining pure exosomes remains challenging due to the complexity and heterogeneity of plant cell structures.

Figure 2. Isolation of vegetable-derived exosomes by ultracentrifugation combined with sucrose density gradient centrifugation. (Mu N, et al., 2023)

Vegetable-derived Exosome in Dermatology

• Promoting Transdermal Absorption

• Drug Slow Release System

• Anti Aging Benefits

• Promoting Skin Regeneration

Biomedical Applications of Vegetable-derived Exosome

• Rebuilding the Intestinal Microbiota

Because of its ability to resist digestion by pepsin and enteropancreatic enzymes, vegetable-derived exosomes can maintain stability in the digestive system and further exert therapeutic effects. Research has found that ginger-derived exosomes can alter the composition of the gut microbiome and positively impact host physiology. Ginger-derived exosomes prevent alcohol-induced liver injury by regulating the TLR4/TRIF pathway and activating nuclear factor erythroid 2-related factor 2 (Nrf2). Oral administration of ginger-derived exosomes reduced acute colitis, increased intestinal repair, and prevented chronic colitis. In particular, the research found that broccoli-derived exosomes activated dendritic cell AMP-activated protein kinase and protected mice against colitis.

Figure 3. Broccoli-derived exosomes may prevent intestinal inflammation. (Deng Z, et al., 2017)

• Tumor Suppression

Vegetable-derived exosome exerts inhibitory effects on human tumor cells. For example, bitter gourd-derived exosomes effectively inhibited the invasion and migration of the U251 human glioma cell line by modulating the P13K/AKT pathway. Ginger-derived exosomes have shown promising results in the treatment of colitis-associated cancer (CAC) by decreasing the levels of inflammatory cytokines and cytosolic protein D1 mRNA and inhibiting the proliferation of intestinal epithelial cells in mice. Ginseng-derived exosomes hindered the migration, invasion, and adhesion ability of lung cancer cell lines by down-regulating the expression of thymidine phosphorylase mRNA in the pentose phosphate pathway. Asparagus-derived exosomes are also found to inhibit hepatocellular carcinoma cell proliferation without toxicity.

Figure 4. Momordica charantia-derived exosomes inhibit the proliferation of U251 glioma cells. (Bin Wang, et al., 2022)

• Treatment of Respiratory Diseases

Vegetable-derived exosome has shown great potential in the treatment of respiratory diseases, including COVID-19 and pulmonary fibrosis. Exosomes isolated from vegetables such as soy, ginger, and tomato have been found to contain tiny RNAs (miRNAs) that can target human transcripts. These miRNAs have the potential to target multiple regions within SARS-CoV-2, making them a promising therapeutic option for the treatment of COVID-19. For example, the ginger-derived miRNA miR396a-5p effectively inhibited lung inflammation induced by Nsp12 and Nsp13, exosomes released from lung epithelial cells previously infected with SARS-CoV-2.

Figure 5. Ginger-derived exosomal miRNA inhibits cytopathic effect (CPE) in SARS-CoV-2-infected Vero E2 cells. (Teng Y, et al., 2021)

There is quite a bit of research on the application of vegetable-derived exosomes. On the one hand, it can promote the penetration of ingredients and act as a carrier of active molecules. On the other hand, it comes with its efficacy, which can achieve a variety of effects such as anti-inflammatory, anti-aging, anti-tumor, and promote skin tissue regeneration, which is an exciting research field.

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References

1. Liu Y, et al. Exploring the Potential of Plant-Derived Exosome-like Nanovesicle as Functional Food Components for Human Health: A Review. Foods. 2024. 13(5): 712.
2. Mu N, et al. Plant-Derived Exosome-Like Nanovesicles: Current Progress and Prospects. Int J Nanomedicine. 2023. 18: 4987-5009.
3. Deng Z, et al. Broccoli-Derived Nanoparticle Inhibits Mouse Colitis by Activating Dendritic Cell AMP-Activated Protein Kinase. Mol Ther. 2017. 25(7): 1641-1654.
4. Bin Wang, et al. Momordica charantia-derived extracellular vesicles-like nanovesicles inhibited glioma proliferation, migration, and invasion by regulating the PI3K/AKT signaling pathway. Journal of Functional Foods. 2022. 90: 104968
5. Teng Y, et al. Plant-derived exosomal microRNAs inhibit lung inflammation induced by exosomes SARS-CoV-2 Nsp12. Mol Ther. 2021. 29(8): 2424-2440.