Betulinic Acid — Structure, Health Benefits, Supplements, & Food Sources

Inflammation

Significant anti-inflammatory effects of betulinic acid are demonstrated in a number of ways. Its principal mechanism of action involves inhibiting nuclear factor-kappa B (NF-κB), a protein complex that is essential for controlling the immune system's reaction to inflammation. Tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) are two examples of pro-inflammatory mediators and cytokines that are produced less when betulinic acid inhibits NF-κB (8). Moreover, betulinic acid prevents the signaling pathways that cause inflammation by blocking the activation of mitogen-activated protein kinases (MAPKs). Moreover, it lowers the expression of the enzyme cyclooxygenase-2 (COX-2), which is in charge of producing prostaglandins that promote inflammation. Moreover, betulinic acid's antioxidant qualities lower oxidative stress, which frequently plays a role in the development of chronic inflammation.

Cancer

One of the main ways that betulinic acid works is by activating apoptosis, which is a type of controlled cell death that kills cancer cells without damaging the healthy tissue around them. By altering the mitochondrial membrane potential, betulinic acid triggers intrinsic apoptotic pathways. This results in the release of cytochrome C and the activation of caspases, two essential proteins in the apoptosis cascade. Furthermore, betulinic acid inhibits the growth and multiplication of cancer cells, exhibiting anti-proliferative effects. It interferes with multiple signaling pathways, such as the MAPK and NF-κB pathways, which are important for inflammation, cell survival, and proliferation. Additionally, betulinic acid possesses anti-angiogenic qualities. It may stop new blood vessels from growing, which is necessary for tumors to grow and metastasize. It deprives cancers of vital nutrition and oxygen by inhibiting angiogenesis (9). 

It has been discovered that betulinic acid is very effective in the treatment of melanoma because it selectively promotes apoptosis in cancer cells while keeping healthy cells (10). Furthermore, inducing pathways leading to cell death has demonstrated promise in treating neuroblastoma, a kind of cancer originating from nerve tissues (11). 

Betulinic acid has shown promise in preventing cell division and metastasis in prostate cancer. Research has also shown that it can prevent breast cancer by causing apoptosis and inhibiting the cancer cell cycle (12). 

Moreover, betulinic acid is a broad-spectrum anticancer drug since it acts against lung and colon tumors (13) (14). 

Malaria

Betulinic acid has drawn interest due to its possible antimalarial effects. These qualities work through a variety of mechanisms. Betulinic acid exhibits potential as a versatile antimalarial drug due to its ability to impact several stages of the parasite life cycle, such as the liver and blood stages (15). The parasite's ability to produce energy and survive depends on the potential of its mitochondrial membrane, which is disrupted by one of its main mechanisms. The depolarization of this membrane brought on by betulinic acid causes a drop in ATP synthesis, cellular stress, and the Plasmodium parasite's programmed cell death, or apoptosis. Its selective toxicity further enhances the compound's therapeutic potential, which targets the parasite while sparing the host cells.

Anti-HIV Properties

Betulinic acid, a compound found in nature, and its modified versions are showing a lot of promise in fighting HIV. These derivatives block critical steps in the virus's life cycle: they inhibit the virus's protease enzyme, prevent it from entering host cells, and stop it from replicating (16). One standout derivative, Bevirimat (PA-457), prevents the virus from maturing properly, making it non-infectious, and has shown good results in clinical trials (17). Other derivatives, like RPR103611 and IC9564, also demonstrate strong anti-HIV activity through various mechanisms. These modified versions of betulinic acid are designed to be more effective, easier for the body to absorb, and less toxic (18). However, there's always a risk of the virus developing resistance, and researchers need to fine-tune how these drugs work in the body. Despite these challenges, betulinic acid derivatives are a promising area of research in the quest to treat HIV effectively.