Búsqueda de inhibidores de enzimas digestivas a partir del extracto hidroalcohólico de hojas de Neurolaena Lobata (Asteraceae)

Abstract

The present research contributes to the ethnopharmacological study of Colombian medicinal plants used in the treatment of diabetes and obesity, combining phytochemical studies and biological experimentation as a strategy for the search of new natural substances able to inhibit the catalytic activity of some digestive enzymes related to the lipid and carbohydrate metabolism, such as α-glucosidase and pancreatic lipase. It also contributes considerably to the worldwide efforts that have been launched in the search for new natural sources of bioactive molecules with antidiabetic and anti-obesity properties. This thesis includes the isolation and characterization of secondary metabolites present in the hydroalcoholic leaf extract of Neuroalena lobata (Asteraceae) by chromatographic and spectroscopic techniques, respectively, and the evaluation of its potential inhibitory effect in vitro against α-glucosidase and lipase pancreatic. As a result of the biodirected fractionation it was found that the CH2Cl2 fraction presented the best activity on the enzymes, significantly inhibiting (P <0.001) the catalytic activity of α-glucosidase with IC50 = 4.65 ± 2.01 μg / mL and of pancreatic lipase with IC50 = 8.13 ± 0.97 μg / mL. Taking into account the activity profile of the fractions obtained, the CH2Cl2 fraction was selected to continue with the biodirected chemical study, leading the isolation of a sterol called stigmasterol (NL-2) and a germacranolide sesquiterpenlactone called neurolenin B (NL- 1), the latter being a bioactive compound capable of inhibiting the two enzymes under study. The results of the evaluation of antidiabetic and anti-obesity potential of NL-1 showed that said substance has the capacity to inhibit the catalytic activity of pancreatic lipase with a competitive inhibition profile, with IC50 = 27.04 ± 2.78 μM and inhibition constant (Ki) of 1.68 μM; and to inhibit the catalytic activity of α-glucosidase with a mixed inhibition profile, with IC50 = 1.49 ± 0.30 μM and inhibition constant (Ki) of 0.69 μM.