Brazilian medicinal plants: A rich source of immunomodulatory substances

RESUMO

Novel immunosuppressive and immunostimulatory substances are strongly needed to replace the existing toxic drugs currently used in the treatment of cancer, transplant rejection and autoimmune diseases or viral infections. We have tested the immunomodulatory activity of the crude extract of several plant species used in the Brazilian popular medicine. We found that two Kalanchoe species - K. pinnata and K. brasiliensis - were very potent in inhibiting both T cell proliferation and the expression of surface IL-2Ralpha. The inhibitory effect may be selective as it did not affect the activity of natural killer (NK) cells. The immunosuppressive effect of K. pinnata was tested in mice, and it proved to inhibit T cell-mediated responses, such as the mixed leukocyte reaction and the delayed-type hypersensitivity reaction. Other effects were also observed, such as protection against cutaneous leishmaniasis and increased nitric oxide production, two situations in which immunosuppression may be involved. In the search for the active substance, we found that quercetin 3-O-alpha-arabinopyranosyl (1r2)-alpha-L-rhamnopyranoside, a major flavonoid present in the crude extract of K. pinnata did not affect T cell proliferation. It is possible, however, that other minor flavonoids, such as quercitrin, afzelin and a flavone are the active substance(s). Contrary to the suppressive effect of Kalanchoe, we observed that the crude extract of Chenopodium ambrosioides was strongly stimulatory to murine but not human lymphocytes, and that the stimulatory substance was present in a protein-enriched fraction. These findings which were only attained due to the collaboration between interdisciplinary groups, strongly emphasize that the Brazilian flora may serve as a rich source of known and novel immunomodulatory substances.