Betulinic Acid

What is Betulinic Acid?

Betulinic Acid is a naturally occurring pentacyclic triterpene compound that various plant species – particularly the bark of birch trees (Betula spp.) – contain. Chemically, it belongs to the group of lupane triterpenes and is closely related to the equally well-known betulin, from which it can be derived through oxidation. The name "Betulinic Acid" is derived directly from the Latin name for the birch. As a secondary plant compound, Betulinic Acid primarily serves protective functions in nature: it helps the plant defend itself against microorganisms, UV radiation, and herbivores. It became increasingly interesting for pharmaceutical research from the 1990s onward – initially because of its observed cytotoxic effect against certain tumor cells in vitro. Many potential mechanisms of action are now known, making Betulinic Acid a highly interesting candidate for a wide variety of therapeutic applications. Although Betulinic Acid is not yet an approved drug, it is being intensively investigated in preclinical research and is also an increasingly discussed ingredient in natural cosmetics and dietary supplements.

What benefits does Betulinic Acid offer for health?

Betulinic Acid possesses a broad spectrum of biological activities, which has been documented in various laboratory and animal studies. Here is an overview of some of its promising properties:

  • Antitumor activity: In preclinical studies, Betulinic Acid showed growth-inhibiting effects on various cancer cells, particularly through the targeted induction of apoptosis (programmed cell death) (1,2).
  • Anti-inflammatory effects: According to studies, the substance can regulate inflammatory processes, for example by inhibiting prostaglandins and certain cytokines (4,5).
  • Antimicrobial properties: Initial investigations suggest antiviral potential, including against HIV-1, as well as antimicrobial and antifungal effects (6,7,8).
  • Wound healing and skin protection: In dermatology, Betulinic Acid is being tested as a possible active ingredient in ointments and creams to support skin regeneration in certain health problems (9,10).

How does Betulinic Acid work in the body?

The molecular action of Betulinic Acid is complex and has not yet been fully elucidated. It interacts with various cellular signaling pathways, influences inflammation-related enzymes (e.g., COX-2), and activates mechanisms of apoptosis – above all in cancer cells, without affecting healthy cells to the same extent (1–10).

Are there any risks or side effects?

  • No long-term studies yet: Despite many positive in vitro and animal studies, there is currently a lack of sufficient clinical data on safety and efficacy in humans.
  • Limited bioavailability: Pure Betulinic Acid powder has low water solubility, which can limit absorption in the body. Modified forms or combinations with carrier substances are being tested here.
  • Potential interactions: Caution is advised when taken at the same time as other medications, as effects on cellular enzyme systems cannot be ruled out.

Conclusion

Betulinic Acid is a promising secondary plant compound with a broad spectrum of biological activity – particularly in the field of cancer and inflammation research. Even though initial results are promising, its therapeutic use in humans is still in the experimental phase. Further studies are needed to reliably assess its potential and risks.

Sources:

  1. Xiu, Z., Zhu, Y., Li, S., Li, Y., Yang, X., Li, Y., Song, G., Jin, N., Fang, J., Han, J., Li, Y., & Li, X. (2023). Betulinic acid inhibits growth of hepatoma cells through activating the NCOA4-mediated ferritinophagy pathway. Journal of Functional Foods, 102, 105441. https://doi.org/10.1016/j.jff.2023.105441
  2. Jiang, W., Li, X., Dong, S., & Zhou, W. (2021). Betulinic acid in the treatment of tumour diseases: Application and research progress. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 142, 111990. https://doi.org/10.1016/j.biopha.2021.111990
  3. Fulda S. (2008). Betulinic Acid for cancer treatment and prevention. International journal of molecular sciences, 9(6), 1096–1107. https://doi.org/10.3390/ijms9061096
  4. Lingaraju, M. C., Pathak, N. N., Begum, J., Balaganur, V., Bhat, R. A., Ramachandra, H. D., Ayanur, A., Ram, M., Singh, V., Kumar, D., Kumar, D., & Tandan, S. K. (2015). Betulinic acid attenuates lung injury by modulation of inflammatory cytokine response in experimentally-induced polymicrobial sepsis in mice. Cytokine, 71(1), 101–108. https://doi.org/10.1016/j.cyto.2014.09.004
  5. Oliveira-Costa, J. F., Meira, C. S., Neves, M. V. G. D., Dos Reis, B. P. Z. C., & Soares, M. B. P. (2022). Anti-Inflammatory Activities of Betulinic Acid: A Review. Frontiers in pharmacology, 13, 883857. https://doi.org/10.3389/fphar.2022.883857
  6. Lin, C.-K., Tseng, C.-K., Chen, K.-H., Wu, S.-H., Liaw, C.-C. and Lee, J.-C. (2015), Anti-HCV activity of betulinic acid. Br J Pharmacol, 172: 4481-4492. https://doi.org/10.1111/bph.13233
  7. Oloyede, H. O. B., Ajiboye, H. O., Salawu, M. O., & Ajiboye, T. O. (2017). Influence of oxidative stress on the antibacterial activity of betulin, betulinic acid and ursolic acid. Microbial Pathogenesis, 111, 338–344. https://doi.org/10.1016/j.micpath.2017.08.012
  8. Rodrigues, G. C. S., Dos Santos Maia, M., de Souza, T. A., de Oliveira Lima, E., Dos Santos, L. E. C. G., Silva, S. L., da Silva, M. S., Filho, J. M. B., da Silva Rodrigues Junior, V., Scotti, L., & Scotti, M. T. (2023). Antimicrobial Potential of Betulinic Acid and Investigation of the Mechanism of Action against Nuclear and Metabolic Enzymes with Molecular Modeling. Pathogens (Basel, Switzerland), 12(3), 449. https://doi.org/10.3390/pathogens12030449
  9. Xie, W., Hu, W., Huang, Z., Li, M., Zhang, H., Huang, X., & Yao, P. (2022). Betulinic acid accelerates diabetic wound healing by modulating hyperglycemia-induced oxidative stress, inflammation and glucose intolerance. Burns & trauma, 10, tkac007. https://doi.org/10.1093/burnst/tkac007
  10. Frew, Q., Rennekampff, H.-O., Dziewulski, P., Moiemen, N., Zahn, T., & Hartmann, B. (2019). Betulin wound gel accelerated healing of superficial partial thickness burns: Results of a randomized, intra‐individually controlled, phase III trial with 12‐months follow‐up. Burns, 45(4), 876–890. https://doi.org/10.1016/j.burns.2018.10.019