In recent years, Tumor Necrosis Factor-alpha (TNF-α) has been at the centre of immunological research, often referred to as both a saviour and saboteur in inflammatory conditions. While crucial in defending the body against pathogens, chronic TNF-α overexpression is linked to a host of disorders, including autoimmune diseases, cancer, neurodegeneration, and sepsis.

A rising star in natural therapeutics, plant-derived exosome-like nanovesicles (PDELNs), is showing immense potential in modulating TNF-α activity. These nano-sized biological messengers, harvested from fruits, vegetables, and herbs, offer a biocompatible, non-toxic alternative for regulating inflammation.

In this post, we explore the dual role of TNF-α, the cutting-edge science behind PDELNs, and how plant exosomes may revolutionize the future of anti-inflammatory therapy.

What is TNF-α and Why Is It a Double-Edged Sword?

TNF-α is a pro-inflammatory cytokine produced primarily by macrophages and monocytes. It plays a vital role in:

• Activating immune cells
• Promoting fever and inflammation
• Initiating apoptosis in infected cells

However, persistent activation of TNF-α is associated with:

• Rheumatoid arthritis
• Inflammatory bowel disease
• Neuroinflammation
• Cancer progression

As Sochocka et al. (2017) describe, TNF-α has a context-dependent role, being neuroprotective in acute responses but neurotoxic when chronically elevated.

The Rise of Plant-Derived Exosomes in Inflammatory Disease

Recent breakthroughs suggest that plant-derived exosomes, tiny lipid vesicles similar to those secreted by mammalian cells, can carry microRNAs, lipids, and bioactive compounds that regulate immune responses.

Benefits of Plant-Derived Exosome-Like Nanovesicles:

• Suppress TNF-α, IL-6, and IL-1β expression
• Promote tissue repair
• Reduce oxidative stress
• Biocompatible and non-toxic

According to Wei et al. (2023), exosomes derived from blueberries and shiitake mushrooms significantly reduced TNF-α levels in liver injury models.

Plant Exosomes in Action: Research Highlights

1. Blueberry and Shiitake Exosomes Suppress Liver Inflammation

In mouse models, these exosomes decreased TNF-α and IL-6 expression, reducing hepatocyte damage (Wei et al., 2023).

2. Catharanthus roseus Nanovesicles Activate TNF-α/NF-κB Pathway for Immune Tuning

Plant vesicles were shown to trigger controlled TNF-α signalling, enhancing immunity without chronic inflammation (Ou et al., 2023).

3. Pueraria lobata Vesicles Downregulate Cytokine Storm

These vesicles lowered pro-inflammatory cytokines (TNF-α, IL-6) in gut inflammation models, restoring epithelial integrity (Lv et al., 2024).

4. Nanovesicles for Cancer and Lung Fibrosis

Rhodiola rosea-derived exosomes reduced fibrotic markers and inflammatory cytokines in lung models (Sha et al., 2024).

Conclusion

The debate over TNF-α being a friend or foe lies in its dose, duration, and context. While essential for immune defence, its dysregulation fuels inflammatory diseases.

Plant-derived exosomes, with their natural origin and precise immune-modulating properties, represent a promising therapeutic strategy. By targeting inflammatory pathways like TNF-α without the side effects of synthetic drugs, they may soon become a cornerstone of future personalised medicine.

References

Ou, X., Wang, H., Tie, H., Liao, J., Luo, Y. & Huang, W. (2023). Novel plant-derived exosome-like nanovesicles from Catharanthus roseus: preparation, characterization, and immunostimulatory effect via TNF-α/NF-κB/PU.1 axis. Journal of Nanobiotechnology, 21(1). Available at: https://link.springer.com/article/10.1186/s12951-023-01919-x

Wei, X., Li, X., Zhang, Y., Wang, J. & Shen, S. (2023). Advances in the therapeutic applications of plant-derived exosomes in the treatment of inflammatory diseases. Biomedicines, 11(6), 1554. Available at: https://www.mdpi.com/2227-9059/11/6/1554

Mu, N., Li, J., Zeng, L., You, J., Li, R., Qin, A. & Liu, X. (2023). Plant-derived exosome-like nanovesicles: current progress and prospects. International Journal of Nanomedicine, 18, 4075–4091. Available at: https://www.tandfonline.com/doi/abs/10.2147/IJN.S420748

Lv, L., Li, Z., Liu, X., Zhang, W., Zhang, Y., Liang, Y. & Zhang, Z. (2024). Harnessing plant-derived vesicles for therapy and drug transport. Heliyon, 10(5). Available at: https://www.cell.com/heliyon/fulltext/S2405-8440(24)16158-0

Sha, A., Luo, Y., Xiao, W., He, J., Chen, X. & Xiong, Z. (2024). Plant-derived exosome-like nanoparticles: composition, biogenesis, and biological applications. International Journal of Molecular Sciences, 25(22), 12092. Available at: https://www.mdpi.com/1422-0067/25/22/12092

Nemati, M., Singh, B., Mir, R. A., Nemati, M. & Babaei, A. (2022). Plant-derived extracellular vesicles: a novel nanomedicine approach with advantages and challenges. Cell Communication and Signaling, 20(1), 112. Available at: https://link.springer.com/article/10.1186/s12964-022-00889-1

Sochocka, M., Diniz, B. S. & Leszek, J. (2017). Inflammatory response in the CNS: friend or foe? Molecular Neurobiology, 54(9), 8071–8089. Available at: https://link.springer.com/article/10.1007/s12035-016-0297-1