Sete espécies de Connaraceae : composição química e potencial efeito biológico para o tratamento do diabetes

Abstract

Connaraceae is a family of plants with high pharmacological potential, worldwide we found that 39 taxa are associated with traditional use or have scientific reports about their use in research on pharmacological activities. Worldwide, about 200 species of Connaraceae have been described and among these only 10 have their chemical composition known. In Brazil, this family of plants can be found in the Caatinga, Cerrado, Amazon Rainforest and Atlantic Forest biomes. The Cerrado and the Atlantic Forest are considered biomes highly impacted (hotspots) by anthropic action and in these, about half of the taxa have their habitat. Therefore, Connaraceae species endemic to these areas are more susceptible to extinction. Among all Connaraceae species, Agelaea pentagyna, Cnestis ferruginea, Connarus suberosus and Roura minor have the most advanced stage of research development and, therefore, are closest to giving rise to useful medicines for mankind. In ethnobotanical use, the various forms of preparation include, among other methods, decoction, infusion and maceration. Thus, we propose to study the chemical composition under qualitative optics in four species of the genus Connarus, including C. blanchetii, C. nodosus, C. regnellii and C. suberosus. We used liquid chromatography associated with mass spectrometry (LC/MS) and by studying the data produced using bioinformatics platforms, we identified 23 compounds from these species in this phase. From a qualitative point of view, most metabolites can be identified using the three methods. Among the main compounds associated with these species are quercetin, myricetin, guaijaverin, hyperin, myricetrin and querciturone, on which we conducted a brief review of their pharmacological potential. Then, using only the extracts obtained by maceration of C. blanchetii, C. regnellii, C. suberosus and R. glazioui, we conducted an organic fractionation and showed that the more polar fractions, ethyl acetate and n-butanol, have the best quantitative profile of secondary metabolites of interest to the activities we propose.Thus, we sought to study the antioxidant potential in the ethyl acetate and n-butyl acetate fractions. Plant-derived compounds have been studied as alternatives to minimize oxidative stress in patients with diabetes, as this is one of the events associated with complications from this disease. In addition to the antioxidant potential, we studied the inhibitory effect of compounds associated with these extracts in reducing protein glycation through oxidative and non-oxidative pathways. Secondary metabolites were studied via LC/MS and identified through bioinformatics platforms. The results of this phase pointed to a better antioxidant performance for the n-butanol fractions of C. blanchetii, C. regnellii and C. suberosus and ethyl acetate/n-butanol fractions of R. glazioui. In evaluating the antiglycant activity for the oxidative pathway, R. glazioui ethyl acetate fraction and C. suberosus n-butanolic fraction showed the best performance. For the non-oxidative pathway R. glazioui ethyl acetate fraction C. blanchetii n-butanolic fraction were the most promising. Among C. blanchetii, C. regnellii, C. suberosus and R. glazioui 29 were identified. The antioxidant and antiglycant activities observed can be related to several of the compounds present in these species, including the flavonoids apigenin, quercetin, myricetin and their derivatives. Thus, we propose that these species have the potential to give rise to drugs that are useful in controlling the complications of diabetes. Sequentially, we conducted an analysis of the inhibitory activity of C. blanchetii, C. nodosus, C. regnellii, C. suberosus, R. cuspidata, R. glazioui and R. induta extracts against (alfa)-amylase and (alfa)-glucosidase enzymes.The results obtained show that all these species are not very active against these two enzymes related to carbohydrate metabolism. Against these seven species 34 secondary metabolites were identified. Finally, we propose to study the toxic effects of the n-butanolic fractions of C. suberosus and R. cuspidata and the ethyl acetate and n-butanolic fractions of R. glazioui, as well as the ability of these fractions to reverse cell cytotoxicity in endothelial cells. We observed that none of the species is toxic to these cells and that when tested at concentrations of 10 and 25 µg/mL, they are able to reverse the cell damage caused by the high concentration of glucose. Therefore, we conclude that these Connaraceae species may be useful in controlling many of the complications of diabetes. We added 4 new species among them C. blanchetii, C. nodosus, C. regnellii and R. glazioui to the list of Connaraceae taxa with established chemical constitution and revealed the pharmacological potential of these species as promising in the control of diabetes complications to the scientific community. [resumo fornecido pelo autor]