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pharmacology

Wide spectrum

The Guaco, a plant native to the Atlantic Rain Forest, has more therapeutic properties than previously supposed

There are lots of popular homemade medicines that recommend Guaco extract (Mikania glomerata and Mikania laevigata ) for respiratory problems. Back in 1942, the first Brazilian pharmacopoeia (a guide to medicinal plants) written by Pio Correa, recommended the plant for tea and cough mixtures, due to its richness in coumarin. Now it has been discovered that the phytotherapeutic properties of this plant, native to the Atlantic Rain Forest, go way beyond its popular use: in research coordinated by Vera Lúcia Garcia Rehder at the Pluri-disciplinary Center of Chemical, Biological and Agricultural Research (CPQBA) of the State University of Campinas (Unicamp), the effects of the guaco plant against cancer, ulcers and micro organism infections have been proved, as well as the prevention of cavities and bacterial plaque in teeth.

For example, it was verified that simple mouth washes with a guaco solution can avoid cavities and dental plaque. The results were obtained through experiments in vitro carried out during a year and a half by the group consisting of Jaime Cury and Pedro Rosalen, of the Odontology School of Unicamp in the town of Piracicaba, with the help of the researcher Hyun Koo, of Rochester University in New York.

The therapeutic action was efficient against streptococcus ofmutans groups, responsible for the development of the cavity process and also for dental plaque. The tests demonstrated that, besides the capacity to inhibit or even kill off the bacterium, the effect could be obtained in low concentrations – which motivated the group to search for a medical patent.

“The interest in the work with the two species of guaco – which is a plant of wide popular use, is because although they are very similar, they have different properties: the plant M. laevigata has more anti-ulcer activity due to a higher concentration of its main active ingredient coumarin, which was tested on its own. On the other hand, the plant M. glomerata presents better results in its anti-microbe activity on various tested micro organisms”. Vera adds that, in the case of anti-carcinogenic activity, no important differences were noted, since the main active ingredient – diterpenic acids – are present in the two species.

Against ulcers
The partnership of Vera with João Ernesto de Carvalho, pharmacology and toxicology coordinator at the CPQBA, began in 1998, during the study of the action of guaco on gastric ulcers. “Our surprise was to detect, in laboratory tests on mice, guaco being more active than the already known espinheira-santa- Maytenus ilicifolia, explains Carvalho. This means that, tested in the same experimental model for the induction of an ulcer in animals and in the same dosage or concentration of the extract, guaco brought about a more accentuated effect against the illness.

The laboratory for the carrying out of these studies doesn’t demand sophisticated equipment and, since 1994, has been researching extracts from various medicinal plants. Vera’s team carry out the necessary purification for the Pharmacology Division to conduct the studies and to determine what is the mechanism of anti-ulcer action carried out by the extracts and by the coumarin isolated from them. The studies show that the extracts and the coumarin exercise an anti-ulcer effect by lowering of the secretion of acid by the stomach. This lowering is a consequence of the blocking the receptors of the acetylcholine neurotransmitters.

These same receptors are also present in the respiratory system and their stimulation, through acetylcholine, produces bronchial constriction and increases the secretion. In this manner, the blocking of these receptors by guaco’s active ingredients brings on bronchial dilation and the decreasing of bronchial secretion. Consequently, the same mechanism involved in the anti-ulcer activity by guaco is considered responsible for the bronchial dilation and anti-secretion that it exercises over the respiratory system.

The study of the anti-ulcer activity of the guaco is the object of the pharmaceutical doctorate thesis of Aparecida Érica Bighetti, of the Medical Sciences School of Unicamp, overseen by Dr. Carvalho.

Against melanoma
The current phase is the study of other substances such as diterpenic acids, in the active ingredients of guaco that act against cancer. Carvalho has tested the guaco extract in vitro on five tumor kinds – breast, breast resistant to known remedies, melanoma, leukemia and lung. The results point to a strong inhibiting action on the growth and the death of human tumor cells. Its action was most efficient on melanoma, with 78% of the cells dead. On the other tumors, the rate is between 40% and 50%.

“Each type of cancer”, reminds Carvalho, “is an illness in itself with its own aetiology, evolution and treatment, and consequently it is practically impossible to discover a unique drug efficient on all types of cancer. For this reason, research in this area is looking for selective agents for each type of neoplasia”. Nonetheless, the researcher emphasized that the powerful action of guaco on the death of cancerous cells brings up concern regarding to its possible toxicity towards normal cell, which has yet to be evaluated.

Another stage, already happening, is expanding the research to four other types of tumor – prostate, ovary, kidney and colon – and is also involving the use of test models in vivo with laboratory animals.

Anti-microbe action
Marta Cristina Teixeira Duarte, the coordinator of the Microbiology Division of the Center, got into this research three years ago to investigate the anti-microbe activity of guaco on eight strains of pathogenic bacteria, as well as the yeast Candida albicans, which causes candidiasis in the female genital region or in a baby’s mouth.

A preliminary evaluation proved the effective action of the extracts – especially M. glomerata – against various bacteria. In this case, the chemical fraction of the extract, enriched in acids that act on the cancer, was also efficient against the bacteria. “At the moment, the tests are seeking to determine the minimum inhibiting concentration for these fractions and the substances isolated from the plants”, says Marta.

The evaluation included the tea made from the dry leaves of M. laevigata , which is the most popular form of consumption of guaco, and observed the presence of active coumarin not only for expectorant action but also for combating gastric ulcers.

In the evaluation made with twenty distinct vegetable extracts, the two species of guaco showed the best performance as potential anti-cavity and anti bacterial plaque agents. “Other studies are being developed, with various models (in vitro, in vivo and in situ), in such a manner as to throw light on the mechanism of the action of Mikania on mouth pathogens, and the initial results are promising”, says Rosalen.

Predatory extraction
Guaco is a plant of the family of compositae of creeping plants climbing such as lianas, which spirals. It is a vine without tendrils, but with a very flexible stalk. Its small flowers, united in inflorescence, attract bees and have an agreeable smell, which is enhanced after rain. The leaves are large and those of the Mikania laevigata , when crushed together, exhale a light aroma of vanilla. As well, the leaves of this species are thicker and have more rounded edges than those of the Mikania glomerata . The guaco leaves have been widely collected in the Atlantic Rain Forest for use in phytotherapeutic medicines. Today there is commercial growing, mainly in the state of Paraná.

The research carried out through the Unicamp Center began with the agricultural part. The intention was to attain a growing system that would avoid native extraction and would allow quality control. The concern about this particular plant has a strong conservation motive: other native species of phytotherapeutic value such as the espinheira-santa (Maytenus ilicifolia ), the jaborandi (Pilocarpus jaborandi ) and the ipecacuanha (Cephaelis ipecacuanha ) have already almost been made extinct through predatory extraction Pedro Melillo de Magalhães reminds.

As the coordinator of theagro-technology division of the Center, Magalhães has managed to solve this problem, at least for the guaco, and is supporting the production on a large scale: “From the point of view of the production of raw material, there is a prepared technological package”, he asserted after ten years of work.

Without drying
The domestic cultivation of the species was carried out using examples of M. laevigata and M. glomerata brought from various regions of the country. The growing area, developed over an area of 630 square meters and with 310 plants, was supported by wooden poles, done in the plain light of day and with the use of irrigation.

Experiments with drying revealed that with the heat, even at the moderate temperature of 40° Celsius, a plant loses up to 50% of its level of the active ingredient, coumarin. The conclusion was that the ideal situation is to use the freshly cut plant. “The coumarin molecule has a simple structure and the heat brings on the reduction of its level in the plant”, explains Vera, who coordinates the organic chemical division at the Center. It so happens that the boiling point of the substance is low – between 68°C and 70°C: consequently, it volatilizes easily with heating and therefore there are losses.

Vera’s team also worked with hydroalcoholic extracts, for the easy manipulation and reproduction of the experiments. From the extracts, they obtained fractions for the evaluation of microbiological and pharmacological activities. “We isolated as many as ten substances that are being individually evaluated for their anti-carcinogenic, anti-ulcer and anti-microbe functions.”

The measuring of the level of coumarin was carried out on fresh plants, on dried plants and on extracts, through liquid chromatography technique of high efficiency. For the fresh plants it was verified that the average level of coumarin was 1.30% for M. laevigata and 0.0082% for M. glomerata . In the dried plants there was a reduction in level of 50%. The levels present in extracts were 2.88% for M. laevigata and 0.033% for M. glomerata .

The Project
Pharmacological, Microbiological and Chemical Study of Mikania laevigata and Mikania glomerata (nº 99/03610-5); Modality Regular Line of Research Assistance; Coordinator Vera Lúcia Garcia Rehder – Multi-disciplinary Center of Chemical,Biological and Agricultural Research of Unicamp; Investment R$ 51,349.26 and US$ 16,566.91

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