Immunomodulatory Properties of Masticadienonic Acid and 3 alpha-Hydroxy Masticadienoic Acid in Dendritic Cells

Dendritic cells are antigen-presenting cells, which identify and process pathogens to subsequently activate specific T lymphocytes. To regulate the immune responses, DCs have to mature by the recognition of TLR ligands, TNF alpha or IFN gamma. These ligands have been used as adjuvants to activate DCs in situ or in vitro, with toxic effects. It has been shown that some molecules affect the immune system, e.g., Masticadienonic acid (MDA) and 3 alpha-hydroxy masticadienoic acid (3 alpha-OH MDA) triterpenes naturally occurring in several medicinal plants, since they activate the nitric oxide synthase in macrophages and induce T lymphocyte proliferation. The DCs maturation induced by MDA or 3a-OH MDA was determined by incubating these cells with MDA or 3 alpha-OH MDA, and their phenotype was afterwards analyzed. The results showed that only 3 alpha-OH MDA was able to induce DCs maturation. When mice with melanoma were inoculated with DCs/3 alpha-OH MDA, a decreased tumor growth rate was observed along with an extended cell death area within tumors compared to mice treated with DCs incubated with MDA. In conclusion, it is proposed that 3 alpha-OH MDA may be an immunostimulant molecule. Conversely, it is proposed that MDA may be a molecule with anti-inflammatory properties.