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Pharmacology

A Plant against tuberculosis

In the laboratory, an extract of Physalis angulata exterminates six types of Mycobacterium

Three years ago the chemist Suzelei de Castro França launched a challenge to her colleagues at the University of Ribeirão Preto (Unaerp): “For ten years now we have been researching plants with therapeutic potential against the same organisms, with good but modest results. Why don’t we work with the bacillus of tuberculosis which is causing a world wide problem?” The result: they have discovered that a raw extract of an Amazonian plant, the Physalis angulata which is known in English as mullaca, wild tomato and in Porutuguese as camapu, inhibits the multiplication of mycobacteria (genre Mycobacterium) responsible for tuberculosis and of opportunist illnesses in patients with weakened organic defenses. The popular uses of Physalis angulata already indicated its pharmacological potential. Besides as a diuretic and a digestive, it is also considered to be good against inflammations, fever, rheumatism and even malaria.

The present test results of the Unaerp group, done directly on the bacteria, are the first step towards medicines that will be more efficient and less toxic. If all goes well on the tests, they will be on the shelves in a period of five to ten years as an alternative to the drugs currently in use: isoniazid, rifampicin and pyrazinamide, today with reduced efficiency when faced with the variety of multi-resistant bacteria. It is estimated that 2 billion people, one third of the world’s population, are infected by the bacillus of tuberculosis, which kills 2 million people a year throughout the world.

Mechanics of the action
At the Vegetable Biotechnological Center of Unaerp, directed by Dr. Suzelei, what they are actually looking for are smaller and smaller fractions of the extract of Physalis angulata, in which are concentrated the substances that probably exterminate the mycobacteria. They are the physalaemin, obtained from the roots and the leaves of the plant. The physalaemins are already seen as anti-tumors and killer of the Trypanosoma cruzi, the protozoa that causes Chagas’s disease. At the beginning of the 90’s, studies carried out in China testified that one of these physalaemins, type B, already purified by the Unaerp team, acts against leukemia in laboratory animals.

“Now we want to know if the physalaemins work in the same way together or in isolation” says Rosemeire Cristina Linhari Rodrigues Pietro, the project’s coordinator. When Suzelei put the challenge to the team, she had just come back from her post-doctorate work carried out in a laboratory of the São Paulo University (USP) in Ribeirão Preto in which they studied DNA vaccines against tuberculosis. It was there that she discovered the seriousness of the problem and the prospects for research.

A mixture of physalaemins identified by the code A12912 destroys cells of six types (varieties) of the genre Mycobacterium: two of the tuberculosis species, that cause tuberculosis; one of Mycobacterium avium, one of the opportunist bacteria most frequently found in patients with Aids and resistant to conventional treatment; one of Mycobacterium kansasii, one of Mycobacterium malmoense and one of intracellulare that causes diverse types of tuberculosis, mainly in sick people with debilitated immunological systems. It was also noted that there was a discrete action against Staphylococcus aureus, the bacterium associated with hospital infections with which the team was already working when beginning the research with Mycobacterium. The work was published in a paper in August of 2000 in the magazine Phytomedicine.

American partner
In the next phase, the toxicology tests on the physalaemins, initially on cells, may consolidate a partnership with Scott Gerald Franzblau, a specialist in antimicrobial activities of natural products, from the Chicago University in the United States. Dr. Franzblau offered in 1999 to test the efficiency of the extracts on animals.

As matter of fact, it was Dr. Franzblau who freely sent, as it the habit between researchers, the reagent called alamar blue, a blue liquid that he himself had tested against Mycobacterium. In contact with a solution containing live Mycobacterium, it becomes pink in color. It came in handy. No longer did the researchers need to wait almost a month to see if the bacteria had been killed. “The alamar blue works even on a single cell.” reports Daisy Nakamura Sato, responsible for the mycobacteria laboratory of the Adolfo Lutz Institute in Ribeirão Preto, who carried out the tests.

Other plants
The researchers have also analyzed other plants. With the espinheira-santa (Maytenus ilicifolia) and a shrub of the pepper family (Potomorphe umbelatta), the results were not very promising. However, an extract from the carqueja (Baccharis trimera), a shrub from the tropical forests of South America, and the mangaba (Hancornia speciosa), a plant from the uplands, have shown potential anti mycobacteria activity.

From another plant of the same family as the mangaba, the maria-sem-vergonha or vinca (Catharanthus roseus), substances have been extracted that act as anti tumors. Dr. Suzelei concluded: “If we really want to contribute to scientific advances in the exploration of the potential of medicinal plants, we will have to expand the biological activities to be tested.”

The Project
Analysis of Anti Mycobacterium Activity in Vegetal Extracts (nº 98/15950-2);  Modality Assistance to a research project; Coordinator Dr. Rosemeire Cristina LinhariRodrigues Pietro – Unaerp;
Investment R$ 23,503.61 and US$ 16,465.28

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