RESUMO
OBJECTIVE: Diabetes, obesity, and their associated metabolic disorders are public health problems that require prevention and new efficient drugs for treatment. We evaluated the anti-hyperglycemic, lipid-lowering, and anti-obesity effects of semisynthetic α, ß-amyrenones (ABA). MATERIALS AND METHODS: BALB/c mice were used for performing an acute model of oral carbohydrate and triglyceride tolerance, and in a streptozotocin-induced diabetes model, where glycemia and body weight changes were measured during ten days. C57BL/6 strain mice were used in the diet-induced obesity model, where lipidemia and body weight were measured during four weeks, and biochemical and histological parameters were analyzed after euthanasia. The doses considered in this study were 25, 50, and 100 mg/kg of ABA, used following some criteria for each experiment. RESULTS: ABA 25 mg/kg reduced the postprandial glycemia peak higher than acarbose 50 mg/kg (p<0.05). ABA 50 mg/kg significantly reduced glycemia in diabetic mice compared to acarbose 50 mg/kg (p<0.05). There was a reduction in the weight of the obese animals treated with ABA 25 and 50 mg/kg (p<0.05). ABA 50 mg/kg also significantly reduced lipidemia in these animals compared to orlistat 50 mg/kg. CONCLUSION: This study presents evidence of ABA's action in reducing postprandial glycemia and obesity in mice.
RESUMO
α,ß-amyrenone (ABAME) is a triterpene derivative with many biological activities; however, its potential pharmacological use is hindered by its low solubility in water. In this context, the present work aimed to develop inclusion complexes (ICs) of ABAME with γ- and ß-cyclodextrins (CD), which were systematically characterized through molecular modeling studies as well as FTIR, XRD, DSC, TGA, and SEM analyses. In vitro analyses of lipase activity were performed to evaluate possible anti-obesity properties. Molecular modeling studies indicated that the CD:ABAME ICs prepared at a 2:1 molar ratio would be more stable to the complexation process than those prepared at a 1:1 molar ratio. The physicochemical characterization showed strong evidence that corroborates with the in silico results, and the formation of ICs with CD was capable of inducing changes in ABAME physicochemical properties. ICs was shown to be a stronger inhibitor of lipase activity than Orlistat and to potentiate the inhibitory effects of ABAME on porcine pancreatic enzymes. In conclusion, a new pharmaceutical preparation with potentially improved physicochemical characteristics and inhibitory activity toward lipases was developed in this study, which could prove to be a promising ingredient for future formulations.
Assuntos
Inibidores Enzimáticos/farmacologia , Lipase/antagonistas & inibidores , Triterpenos/farmacologia , beta-Ciclodextrinas/farmacologia , Animais , Varredura Diferencial de Calorimetria , Simulação por Computador , Inibidores Enzimáticos/química , Lipase/química , Orlistate/farmacologia , Solubilidade/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier , Suínos , Triterpenos/síntese química , Triterpenos/química , Difração de Raios X , beta-Ciclodextrinas/químicaRESUMO
α-Amyrenone and ß-amyrenone are triterpenoid isomers that occur naturally in very low concentrations in several oleoresins from Brazilian Amazon species of Protium (Burseraceae). This mixture can also be synthesized by oxidation of α,ß-amyrins, obtained as major compounds from the same oleoresins. Using a very simple, high yield procedure, and using a readily commercially available mixture of α,ß-amyrins as substrate, the binary compound α,ß-amyrenone was synthesized and submitted to physico-chemical characterization using different techniques such as high-performance liquid chromatography, nuclear magnetic resonance (¹H and 13C), mass spectrometry, scanning electron microscopy, differential scanning calorimetry, thermogravimetry and derivative thermogravimetry, and Fourier transform infrared spectroscopy (FTIR). Biological effects were also evaluated by studying the inhibition of enzymes involved in the carbohydrate and lipid absorption process, such as α-amylase, α-glucosidase, lipase, and their inhibitory concentration values of 50% of activity (IC50) were also determined. α,ß-Amyrenone significantly inhibited α-glucosidase (96.5% ± 0.52%) at a concentration of 1.6 g/mL. α,ß-Amyrenone, at a concentration of 100 µg/mL, showed an inhibition rate on lipase with an IC50 value of 82.99% ± 1.51%. The substances have thus shown in vitro inhibitory effects on the enzymes lipase, α-glucosidase, and α-amylase. These findings demonstrate the potential of α,ß-amyrenone for the development of drugs in the treatment of chronic metabolic diseases.