Obtenção da mistura triterpênica de A, B amirenona e avaliação de seus efeitos hipolipemiante, hipoglicemiante e antiobesidade

Abstract

α-Amyrenone and β-amyrenone are triterpenoid isomers that occur naturally in various oleoresins of the Brazilian Amazon species Protium (Burseraceae). The mixture of α- and β-amyrenone can also be synthesised by oxidation from the principal components α and β- amyrins, obtained from the same oleoresins. However, information about its physicochemical properties and biological activity is poor in the scientifical literature. The main objectives of this study were to obtain the triterpenic mixture α,β-amyrenone and to evaluate its hypolipemiant, hypoglicemiant and anti-obesity effects via in vivo tests. Using a simple, high-yield process and a commercially available mix (comercial resin) rich in α,β amyrins as a substrate, the binary mix α,β-amyrenone was synthesised and submitted to physio-chemical analysis using different techniques, including liquid cromatography and nuclear magnetic resonance (1H and 13C), mass spectrometry, scanning electron microscopy, differential scanning calorimetry, thermogravimetry and derived thermogravimetry, and Fourier transform infrared spectroscopy. The in vitro effects of α,β-amyrenone were evaluated in relation to the inhibition of the enzymes α-amylase, α-glucosidase, lipase, and of an antioxidant enzyme, xanthine oxidase. Anti-hyperglicemic, hypolipemiant and anti-obesity effects on male adult mice of the BALB/c and C57BL/6 strains were evaluated. Bloodbiochemical and histopathological analysis were carried out on animals from obesity test. The mixture of α, β-amyrenone was obtained by optimization of semi-sinthesys of its precursor α, β- amyrin, in a direct way from resin, using hexan as solvent. The mixture inhibited α-glucosidase enzyme at a concentration of 1.6 μg/mL, reaching an inhibition index of 96.59% (SD ± 0.52) (p<0.05). For lipase, at a concentration of 100 μg/mL, an inhibition index of 82.99 ± 1.51 was achieved, with a CI50 (mg/mL) value of 1.193  0.41 μg/mL (p<0.05). The tests of α-amilase, α-glucosidase and of xanthine oxidase presented values less than 50% of inhibiting activity at a concentration of 100μg/mL. In the evaluation of the profile of acute or episodic hyperglycemia induced by maltose and sucrose, a 25mg/kg mixture of α,β-amyrenone achieved a greater reduction of the post-prandial glycemic peak in animals than acarbose at 50mg/kg (p<0.05). In the test for induced diabetes, animals presented reduced levels of plasmatic glycose with α,β-amyrenone at a concentration of 50mg/kg in comparison with animals from the standard (acarbose) group (p<0.05). In 50 and 100mg/kg concentrations, α,β-amyrenone reduced the plasmatic levels of triglycerides to a more marked degree than the standard orlistat in animals submitted to oral lipid-based emulsion. In chronic tests for the induction of obesity, a reduction in weight was seen in animals treated with α,β-amyrenone in 25 and 50mg/kg concentrations respectively. This study brought evidences of lowering action of α,β-amyrenone on post prandial glicemia, induced diabetes and body weight. In its anti-obesity action, α,β-amyrenone mainly affects the carbohydrates and the lipid metabolism via mechanisms that include the inhibition of digestive enzymes. Mixture of α,β-amyrenone seemed a potential chemical for treatment or prevention of metabolic syndromes, but further studies are necessary in order to clarify some aspects of its activity.