This program will assess effectiveness and safety of plants used by traditional medicine practitioners in in vitro systems and animal models for three conditions: tumors, leishmaniasis and diarrheal diseases. In vitro effectiveness will be determined with traditionally prepared extracts. Toxicity tests will guide ranges assayed in animal model effectiveness tests. Promising plants will be fractionated to purify active principles. In vitro bioassays will guide purification at every step, until isolation is achieved or the activity is dissipated (by dilution or by separation of synergistic compounds). Principles will be tested in progressively more complex assays, as follows. Antitumor principles will be assayed in non-transformed cell lines and tumor- derived cell lines comparing the GI50 (50% Growth Inhibitory dose) in each case. Plants will be matched to bioassays with cell lines showing greatest effects. Animal studies will be performed with mouse tumors in ascitic and solid forms using doses below the LD50. Tumor inhibitory effects will be measured by increases in life span, smaller tumor size, better appearance, etc., as compared to control groups. Anti-Leishmania effects will be measured first in vitro against promastigote cultures and later in a mastigote-infected macrophage (mouse and human) cultures, using the two main Leishmania found in Peru: L. braziliensis and L. peruviana. Animal models: infected BALB/c mice first, and hamsters, which show pathology similar to humans, later. Secretory antidiarrheal effects will be explored in Chinese Hamster Ovary cells which elongate with Vibrio cholerae and Escherichia coli toxins. Infant suckling mice and rabbit ileal loops will be the animal models. In each case, principles should inhibit toxic effects. This procedure should select the most effective plants and active principles, as new presents from the New World, against the conditions chosen, true Public Health priorities, regionally and world-wide.
