RESUMO
Given worldwide increases in the incidence of obesity and type 2 diabetes, new strategies for preventing and treating metabolic diseases are needed. The nuclear receptor PPARγ (peroxisome proliferator-activated receptor gamma) plays a central role in lipid and glucose metabolism; however, current PPARγ-targeting drugs are characterized by undesirable side effects. Natural products from edible biomaterial provide a structurally diverse resource to alleviate complex disorders via tailored nutritional intervention. We identified a family of natural products, the amorfrutins, from edible parts of two legumes, Glycyrrhiza foetida and Amorpha fruticosa, as structurally new and powerful antidiabetics with unprecedented effects for a dietary molecule. Amorfrutins bind to and activate PPARγ, which results in selective gene expression and physiological profiles markedly different from activation by current synthetic PPARγ drugs. In diet-induced obese and db/db mice, amorfrutin treatment strongly improves insulin resistance and other metabolic and inflammatory parameters without concomitant increase of fat storage or other unwanted side effects such as hepatoxicity. These results show that selective PPARγ-activation by diet-derived ligands may constitute a promising approach to combat metabolic disease.
Assuntos
Produtos Biológicos/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fabaceae/química , Hipoglicemiantes/farmacologia , Salicilatos/farmacologia , Células 3T3-L1 , Animais , Produtos Biológicos/química , Produtos Biológicos/metabolismo , Western Blotting , Células CHO , Cricetinae , Cricetulus , Cristalografia por Raios X , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/etiologia , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Expressão Gênica/efeitos dos fármacos , Glycyrrhiza/química , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Obesidade/complicações , Obesidade/tratamento farmacológico , Obesidade/etiologia , PPAR gama/genética , PPAR gama/metabolismo , Ligação Proteica , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Salicilatos/química , Salicilatos/metabolismoRESUMO
A fast HPLC method for the analysis of eight selected sulfonamides (SA) and trimethoprim has been developed with the use of high temperature HPLC. The separation could be achieved in less than 1.5 min on a 50 mm sub 2 microm column with simultaneous solvent and temperature gradient programming. Due to the lower viscosity of the mobile phase and the increased mass transfer at higher temperatures, the separation could be performed on a conventional HPLC system obtaining peak widths at half height between 0.6 and 1.3 s.
Assuntos
Anti-Infecciosos Urinários/análise , Cromatografia Líquida de Alta Pressão/métodos , Solventes , Sulfonamidas/análise , Temperatura , Trimetoprima/análise , Animais , Cromatografia Líquida de Alta Pressão/instrumentação , Espectrometria de Massas/instrumentação , Espectrometria de Massas/métodosRESUMO
In this paper, three different HPLC methods for the quantification of thalidomide in tablets were developed and compared. The comparison of a conventional method at 30 degrees C with two high-temperature methods at 180 degrees C showed equal results. Using high-temperature HPLC (HT-HPLC), faster analysis times could be achieved. We have also focused on analyte stability and could show that the stationary phase has a pronounced effect on the on-column degradation of thalidomide at high temperatures. Virtually no degradation occurs if a polystyrene divinylbenzene column is used, whereas thalidomide is completely degraded at 180 degrees C when a carbon clad zirconium dioxide column is used.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Talidomida/análise , Talidomida/química , Estabilidade de Medicamentos , ComprimidosRESUMO
In this study the temperature stability of several normal phase and RP columns was investigated using a water-only mobile phase. The temperature was adjusted to 120 degrees C for the bare silica stationary phases and to 185 degrees C for the metal oxide and carbon stationary phases. It could be shown that metal oxide stationary phases exhibited excellent thermal stability over the duration of the test period and are therefore suitable for high temperature LC applications.