Contribuição ao estudo botânico, químico e farmacológico de plantas medicinais da Amazônia contra Leishmania sp.

Abstract

The discovery of natural substances found in plants has been a target of several scientific studies, as urgency for drugs more selective and less toxic for the treatment of incurable diseases. Leishmaniasis is a major disease with priority for research according to the World Health Organization. This study selected three botanical species in the search for new chemical therapies against this disease. Vismia cayennensis (Clusiaceae), Piper duckei (Piperaceae) e P. demeraranum (Piperaceae) are medicinal native species of Brazil, used by people to treat skin diseases and healing of wounds. The phytochemical study of the barks and fruits of V. cayennensis was carried out resulting in four extracts ethanolic, hexanic, chloroformic of fruit and dichloromethane of barks. The study of hexane extract resulted in the isolation and identification a mixture of steroids (sytosterol and stygmasterol), and Fridelin, a Triterpene, already isolated from the specie. The leishmanicidal activity of the extracts and Fridelin were evaluated against promastigotes forms of L. amazonensis and L. guyanensis, the chloroform and hexane extracts showed strong activity leishmanicidal for the two species, showing DL 50 = 32,4 μg/mL (L. amazonensis), 9,1 μg/mL (L. guyannensis) e 8,9 μg/mL (L. amazonensis), 19,7 μg/mL (L. guyannensis), respectively. However the Fridelina showed moderate activity to promastigotes forms of L. amazonensis with LD50 = 231,21 μg /mL. The extract chloroform of the fruit was fractionated resulting in the isolation of two compounds, identified like the antranoid prenylated, Vismin and Ferruginin. The leishmanicidal activity this compounds were weak in relation to the crude extract with LD50 = 178,3 μg /mL and DL50 = 214,8 μg/mL, respectively. The extracts, fractions and phytochemicals isolates were also evaluated as antioxidant activity and toxicity front of the microcrustáceo Artemia salina. Essential oils of the leaves were obtained by hydrodestillation and analyzed by GC/MS. The major constituents identified in the leaf of Piper duckei oil were trans-caryophyllene (29,62%), Germacrene D (15,92%) e 1H-Cicloprop[e]azulen (19,20%) while in the P. demeraranum oil was observed β- elemene (34.50%), dl-limonene (20.56%), Germacrene B (9.11%), Germacrene D (5.36%) e β-Selinene (5.20%). It was evaluated the leishmanicidal activity of oils. The species P. duckei showed inhibition of 50% of the parasites in the concentration 70 μg/mL, while the species P. demeraranum presented LD50 = 91.51 μg/mL. To the strain of L. guyanensis strain the oils showed a pronounced leishmanicidal activity with LD50 = 15.2 μg/mL for P. duckei and 22.7 μg/mL for P. demeraranum. It was evaluated the toxicity of oils in macrophage cells removed from the intraperitoneal cavity of mice; oils showed low cytotoxicity, encouraging future tests in amastigotes forms of Leishmania. The irritant potential of oils was also evaluated by the method HET - CAM, the data were very promising featuring oils with moderate skin irritation.