Medicinal plants in Brazil: Pharmacological studies, drug discovery, challenges and perspectives.

This review article focuses on pre-clinical and clinical studies with some selected Brazilian medicinal plants in different areas of interest, conducted by research groups in Brazil and abroad. It also highlights the Brazilian market of herbal products and the efforts of Brazilian scientists to develop new phytomedicines. This review is divided into three sections. The section I describes the Brazilian large biodiversity and some attempts of Brazilian scientists to assess the pharmacological profile of most plant extracts or isolated active principles. Of note, Brazilian scientists have made a great effort to study the Brazilian biodiversity, especially among the higher plants. In fact, more than 10,000 papers were published on plants in international scientific journals between 2011 and 2013. This first part also discussed the main efforts to develop new medicines from plants, highlighting the Brazilian phytomedicines market. Despite the large Brazilian biodiversity, notably with the higher plants, which comprise over 45,000 species (20-22% of the total worldwide), and the substantial number of scientific publications on medicinal plants, only one phytomedicine is found in the top 20 market products. Indeed, this market is still only worth about 261 million American dollars. This represents less than 5% of the global Brazilian medicine market. The section II of this review focus on the use of Brazilian plant extract and/or active principles for some selected diseases, namely: central nervous systems disorders, pain, immune response and inflammation, respiratory diseases, gastrointestinal tract and metabolic diseases. Finally, section III discusses in more details some selected Brazilian medicinal plants including: Cordia verbenacea, Euphorbia tirucalli, Mandevilla velutina, Phyllanthus spp., Euterpe oleracea, Vitis labrusca, Hypericum caprifoliatum and Hypericum polyanthemum, Maytenus ilicifolia, Protium kleinii and Protium heptaphylium and Trichilia catigua. Most of these publications are preliminary and only report the effects of crude extracts, both in vitro and in vivo studies. Only very few studies have been dedicated to investigate the mechanisms of action of isolated compounds. Likewise, studies on safety (toxicology), pharmacokinetic, and especially on well-conducted clinical trials are rare. In conclusion, in spite of the abundant Brazilian biodiversity and the thousands of academic publications on plants in international peer-reviewed scientific journals, few patents and medicines have been derived from such studies. Undoubtedly, great efforts must be made to improve the development of plant-derived medicine market in Brazil, especially by involving the partnership between academia and pharmaceutical companies.

Experimental benznidazole treatment of Trypanosoma cruzi II strains isolated from children of the Jequitinhonha Valley, Minas Gerais, Brazil, with Chagas disease

Trypanosoma cruzi strains from distinct geographic areas show differences in drug resistance and association between parasites genetic and treatment response has been observed. Considering that benznidazole (BZ) can reduce the parasite burden and tissues damage, even in not cured animals and individuals, the goal is to assess the drug response to BZ of T. cruzi II strains isolated from children of the Jequitinhonha Valley, state of Minas Gerais, Brazil, before treatment. Mice infected and treated with BZ in both phases of infection were compared with the untreated and evaluated by fresh blood examination, haemoculture, polymerase chain reaction, conventional (ELISA) and non-conventional (FC-ALTA) serologies. In mice treated in the acute phase, a significant decrease in parasitaemia was observed for all strains. Positive parasitological and/or serological tests in animals treated during the acute and chronic (95.1-100%) phases showed that most of the strains were BZ resistant. However, beneficial effect was demonstrated because significant reduction (p < 0.05%) and/or suppression of parasitaemia was observed in mice infected with all strains (acute phase), associated to reduction/elimination of inflammation and fibrosis for two/eight strains. BZ offered some benefit, even in not cured animals, what suggest that BZ use may be recommended at least for recent chronic infection of the studied region.

BAY 41-2272 activates host defence against local and disseminated Candida albicans infections

In our previous study, we have found that 5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]-pyrimidin-4-ylamine (BAY 41-2272), a guanylate cyclase agonist, activates human monocytes and the THP-1 cell line to produce the superoxide anion, increasing in vitro microbicidal activity, suggesting that this drug can be used to modulate immune functioning in primary immunodeficiency patients. In the present work, we investigated the potential of the in vivo administration of BAY 41-2272 for the treatment of Candida albicans and Staphylococcus aureus infections introduced via intraperitoneal and subcutaneous inoculation. We found that intraperitoneal treatment with BAY 41-2272 markedly increased macrophage-dependent cell influx to the peritoneum in addition to macrophage functions, such as spreading, zymosan particle phagocytosis and nitric oxide and phorbol myristate acetate-stimulated hydrogen peroxide production. Treatment with BAY 41-2272 was highly effective in reducing the death rate due to intraperitoneal inoculation of C. albicans, but not S. aureus. However, we found that in vitro stimulation of peritoneal macrophages with BAY 41-2272 markedly increased microbicidal activities against both pathogens. Our results show that the prevention of death by the treatment of C. albicans-infected mice with BAY 41-2272 might occur primarily by the modulation of the host immune response through macrophage activation. .

The use of an integrated molecular-, chemical- and biological-based approach for promoting the better use and conservation of medicinal species: a case study of Brazilian quinas.

ETHNOPHARMACOLOGICAL RELEVANCE: Quina is a popular name originally attributed to Cinchona pubescens Vahl (=Cinchona succirubra) and Cinchona. calisaya Wedd., species native from Peru that have the antimalarial alkaloid quinine. In Brazil, bitter barks substitutes for the Peruvian species began to be used centuries ago, and they still are sold in popular markets. To assess the authenticity and the conditions on which samples of quinas have been commercialized, using the DNA barcode, chemical and biological assays. MATERIALS AND METHODS: Starting with 28 samples of barks acquired on a popular market, 23 had their DNA extracted successfully. The regions matK and rbcL were amplified and sequenced for 15 and 23 samples, respectively. Phytochemical analyses were performed by chromatographic methods, and biological essays were done by antimalarial tests in vitro. RESULTS: The identified species belonged to six different families, many of them endangered or with no correlation with use in traditional medicine as a Brazilian quina. The absence of typical bitter chemical substances indicated that barks have been collected from other species or from very young trees. The results of biological essays confirm the lack of standardization of the sold materials. CONCLUSION: The integrated approaches proved to be efficient to evaluate medicinal plants sold in popular markets and can be useful for promoting their better use and conservation.

Socioeconomic interest and valorization of medicinal plants from the Rissani oasis (SE of Morocco) / Interés socioeconómico y valorización de plantas medicinales del oasis de Rissani (SE de Marruecos)

The survival and sustenance of man depends largely on plants which generate directly 87 percent of its food needs and constitute a source of basic health care in developing countries. Based on socio-economic surveys and field observations led in the Rissani oasis (SE of Morocco), we have identified 109 species belonging to 45 botanical families and 102 genera. The distribution in families is: Lamiaceae (15.2 percent, Asteraceae (11.5 percent), Fabaceae (8.46 percent, Poaceae (8.12 percent) and Apiaceae (6.75 percent). The species used in traditional medicine correspond to 57.8 percent, for food 10.1 percent and for other uses 28.4 percent. Of these species, 10.1 percent are cultivated, naturalized, introduced and/or weeds. Byproducts of 46.8 percent of these species are imported from other regions of Morocco and locally marketed. Many medicinal species from this area are not recognized by the inhabitants, and their sensitization towards the use and conservation of local plant diversity is needed.

La supervivencia y sustentabilidad de la humanidad depende en gran medida de las plantas. Estas satisfacen directamente el 87 por ciento de sus necesidades alimenticias y constituyen, en países en desarrollo, una fuente para el cuidado de salud. Basados en estudios y observaciones de campo realizadas en el oasis de Rissani (SE de Marruecos), hemos identificado las 109 especies de plantas más utilizadas que pertenecen a 45 familias y 102 géneros. La distribución por familia es: Lamiaceae (15.2 por ciento), Asteraceae (11.5 por ciento), Fabaceae (8.46 por ciento), Proaceae (8.12 por ciento) y Apiaceae (6.75 por ciento). Las especies utilizadas en medicina tradicional corresponden al 57.8 por ciento, en alimentación 28.5 por ciento y para usos múltiples 28.4 por ciento. De estas especies el 10.1 por ciento son cultivadas, naturalizadas, introducidas y/o corresponden a malezas. Subproductos del 48.8 por ciento de estas especies son importados de otras regiones de Marrueco para su comercialización. Muchas de las especies medicinales no son reconocidas por los habitantes del oasis y es necesario sensibilizarlos en relación a su utilización y conservación.

Actividad molusquicida del Paraiso (Melia azedarach L.) (Meliaceae) sobre Lymnaea cubensis, molusco vector de Fasciolosis / Molluscicidal activity of Paraiso (Melia azedarach L.) (Meliaceae) on Lymnaea cubensis, host snail of Fasciolosis

A Fasciolosis constitui em diversas regiöes fonte importante de perdas econômicas, e quando näo se adotam medidas de controle de seus hospedeiros (moluscos), junto a condiçöes ecológicas favoráveis, pode ocorrer o aparecimento de casos isolados de Fasciolosis humana. Dentro dos métodos alternativos para o seu controle está o uso de extratos vegetais e se tem pretendido avaliar o provável emprego do suco extraíso do fruto e sementes do Paraiso (Melia azedarach L.), no controle de Lymnaea cubensis, principal vetor da Fasciolosis em Cuba. Diferentes concentraçöes do suco extraído do fruto e semente do Paraiso (Melia azedarach L.) foram testadas para determinar as doses médias letais (DL50) e máxima (DL90) usando um programa computadorizado PROBIT-LOG. Sete séries experimentais foram realizadas, usando 72 moluscos em cada uma. Para determinar a influência sobre a freqüência cardíaca foram testados três grupos de 10 moluscos, dois foram tratados com as CL50=0,88627 e CL90=1,7641, respectivamente, enquanto que o terceiro foi considerado como controle. Observou-se uma marcada influência de ambas as doses sobre a freqüência cardíaca do molusco estudado. Os resultados foram alentadores, pois demonstraram um potencial uso dessa planta no controle de moluscos näo desejados