Euterpe oleracea Mart.: BIOPROSPECÇÃO FITOQUÍMICA, POTENCIAL LEISHMANICIDA E CICATRIZANTE DE LESÕES CUTÂNEAS.

Abstract

Leishmaniasis is a complex of diseases with epidemiological diversity and varied clinical spectrum. The main clinical forms are visceral leishmaniasis (VT) and cutaneous leishmaniasis (LT). There are limitations in relation to treatment, since the systemic leishmanicidal agents used, cause various adverse effects and the increase in resistance, driving the emergence of new treatment perspectives such as alternative protocols and growing interest in new substances obtained from natural products. Açaí, the fruit of Euterpe oleracea MARTIUS is a plant species, whose studies already describe its antioxidant, anti-inflammatory and leishmanicidal potential, prompting more comprehensive research on the same. Thus, the objective of this research was to carry out a bioprospecting study with an emphasis on investigating the chemical composition, leishmanicidal, immunomodulatory activity, healing of Euterpe oleracea seed extracts and / or pulp, as well as its bioproduct. For this purpose, the preparation of the hydroethanolic extract of the pulp and ethanol of the seed of E. oleracea was carried out, with subsequent chemical characterization of the extracts by mass spectrometry, antioxidant and leishmanicidal activity of promastigost forms of L. amazonensis by MTT and antioxidant activity by the methods DPPH and ABTS. Thus, the extract with the best leishmanicidal and antioxidant activity was selected for the development of the cream type formulation (CLA 15%) and an analysis of its stability, physical-chemical and microbiological, was carried out. For biological assays, 65 Balb/c mice were used, divided into four groups of 15 animals that were infected with L. amazonensis in the right ear, and a healthy group of 5 animals, which were named: Base Group treated with 0, 1mL of the excipient of the base cream for 21 days topically, CLA Group 15% treated with 0.1mL of E. oleracea cream for 21 days topically, Group Sb + 5 treated with the pentavalent antimonial (Sb + 5) ( 28 mg / kg / day) for 15 days intraperitoneally and the Group that received an association of the compounds (CLA 15% + Sb + 5) was treated simultaneously with E. oleracea cream for 21 days topically and pentavalent antimonial (Sb + 5) (28 mg / kg / day) intraperitoneally for 15 days. The lesion was monitored weekly by measuring the lesions using digital planimetry, considering the vertical and horizontal measures. The parasitic load was quantified by the Limiting Dilution assay, in samples of the cervical lymph node from all groups that received treatment. In addition, immunophenotyping of the lymph node, spleen and lesion cells was performed, and the cytokine dosage (CBA technique) in the peritoneal cell culture supernatant. Histopathological analysis of the infected ears was also performed. The results showed that E.oleracea seed and pulp extracts are mainly composed of flavonoids, the seed extract being made up of catechins and procyanidins. The seed extract was selected for the formulation because it showed better leishmanicidal activity, in the forms of L. amazonensis with IC 50 of 0.44 mg / mL, in addition to having antioxidant activity. The 15% CLA formulation showed no organoleptic changes, with a slightly acid pH of 4.5, as well as no growth of colonies of bacteria and fungi, being considered suitable for use in in vivo tests. There was a reduction in the lesion area after the second week of treatment in the Sb + 5, CLA15% and Sb + 5 + CLA15% groups, as well as a reduction in the weight of the ears. There was no effect on the parasite load in the treatment groups, demonstrating that the cream formulation CLA15% has no direct effect on the parasite, at least under these conditions of concentration and treatment time, but the association of the treatment (Sb + 5 + CLA15%) demonstrated to modulate the immune system with increased expression of lymphocytes and macrophages, as well as treatment with CLA15%, increased the expression of MCP-1, the main chemokine that regulates migration and infiltration of monocytes / macrophages. These data indicate that the formulation with E. oleracea extract is a promising combination therapy for meglumine antimoniate.