JTP-109192, a novel G protein-coupled receptor 119 agonist, prevents atherosclerosis by improving hypercholesterolaemia in congenic spontaneously hyperlipidaemic mice
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
Authors: Tadaki, Hironobu; Ogawa, Naoto; Yamanaka, Masao; Motohashi, Yu; Sasase, Tomohiko; Kawai, Takashi; Toriniwa, Yasufumi; Fukuda, Sumiaki; Ogawa, Nobuya; Harada, Kazuhito; Ohta, Takeshi; Yamada, Takahisa
Abstract
G protein-coupled receptor 119 (GPR119) expression in pancreatic beta-cells and intestinal L-cells is a potential therapeutic target for the treatment of type 2 diabetes. Previously, we have reported that the GPR119 agonist JTP-109192 improves glucose metabolism with single and repeated administration. Conversely, overexpression of the Gpr119 gene reportedly regulates cholesterol transporter expression in animal models, and a natural GPR119 agonist, oleoylethanolamide (OEA), improves atherosclerosis. Therefore, improving dyslipidaemia is considered a possible feature of GPR119 agonists. In the present study, the lipid-lowering effect of JTP-109192 was examined in BALB/c background spontaneously hyperlipidaemic (SHL) mice with repeated administration, once daily for 12 weeks. On repeated administration, JTP-109192 revealed a cholesterol-lowering effect and improved atherosclerosis following histopathological examination. With further investigation, the cholesterol-lowering effect and subsequent antiatherosclerotic effect of JTP-109192 was attributed to changes in intestinal cholesterol metabolism gene expression. Based on these results, JTP-109192 represents a new potential antihypercholesterolaemic agent for the treatment of dyslipidaemia.
Elderberry (Sambucus nigra L.) as potential source of antioxidants. Characterization, optimization of extraction parameters and bioactive properties
FOOD CHEMISTRY
Authors: Dominguez, Ruben; Zhang, Leilei; Rocchetti, Gabriele; Lucini, Luigi; Pateiro, Mirian; Munekata, Paulo E. S.; Lorenzo, Jose M.
Abstract
The present study aimed to characterize the nutritional value and potential use of elderberries as a source of antioxidant compounds. The chemical composition, fatty acids and phenolic compounds were determined for elderberries. The optimization of extraction parameters was designed with a Box-Behnken design coupled with response surface methodology (RSM) and desirability function analysis. The process parameters tested included extraction temperature, % of ethanol and pH, while response variables were global extraction yield, total phenolic and anthocyanins content (TAC), carotenoids and antioxidant activity. Analyses revealed that elder-berry was a rich source of total soluble solids, proteins and polyunsaturated fatty acids (omega-3: 38.12 g/100 g and omega-6: 39.54 g/100 g fatty acids). Regarding phenolic compounds, elderberries were found abundant in flavonoids (rutin and quercetin), and phenolic acids (i.e. gallic acid and gentisic acid). Finally, numerical optimization indicated that the best extraction parameters were the following: temperature 60 degrees C, 50% of ethanol and pH 2.