Metabolômica e fitoquímica de espécies de Lauraceae e avaliação da inibição das principais vias inflamatórias por seus extratos e substâncias purificadas

Abstract

In this work, 19 species of the Lauraceae family were submitted to high-resolution masses (UHPLC-UV-HRMS-ESI-Orbitrap), aiming to obtain a model capable of predicting the activity -inflammatory for species of this family not yet investigated in vivo and, thus, to choose a promising species for the metabolomic and phytochemical studies. The species Ocotea odorifera (Vellozo) Rohwer, which is already a plant with an ethnopharmacological history for the anti-inflammatory activity, has shown to be promising in the statistical model used, being predicted by this as possibly active in the dual inhibition of cyclooxygenase (COX) and lipoxygenase (LOX). In this sense, we sought to evaluate for the first time this dual anti-inflammatory potential, in addition to using classic phytochemistry techniques to isolate a biomarker of the studied activity. Thus, the evaluation of the raw leaf extract and the Ocotea odorifera fractions were evaluated first, as well as the dual inhibition of COX and LOX through an in vivo model. And with these results a new metabolic model was developed specific for the O. odorifera, to guide the isolation of a biomarker. Therefore, the essential oils of O. odorifera leaves and branches were evaluated in 0.5 and 2.5% concentrations, in addition to leaf decoction, simulating the traditional method used by the population to treat rheumatism. Afterwards, the chromatographic steps were performed together with the statistical analyzes aiming the isolation of the biomarker present in the alkaloid rich fraction. From the chloroform fraction, the substance reticulin was isolated, an alkaloid very common in the genus Ocotea sp. Reticulin was also submitted to bioassays. The alkaloid, ethyl acetate and hydroethanolic fractions, as well as reticulin and essential oils showed anti-edematogenic activity and inhibition of neutrophil recruitment, that is, dual inhibition of the COX and LOX pathways. The decoction, however, demonstrated only the anti-edematogenic effect like the nonsteroidal drugs available in the market. This result corroborates the popular use of this species as anti-inflammatory and the use of metabolomic strategies to guide the isolation of substances with high pharmacological potential, as well as to provide a guide in the selection of an already promising species for a given property.