RESUMEN
Policosanol is a well-defined nutraceutical for the management of blood cholesterol levels. The present study examined (i) the effect of policosanol supplementation on blood cholesterol and glucose levels and (ii) changes in hepatic cholesterol biosynthesis using 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) activity in Wistar rats fed high cholesterol diets. The Wistar rats were assigned randomly to high-cholesterol diets (1.25% cholesterol) with or without policosanol (8.0 mg/kg body weight) for 6 weeks. Compared with the control group, dietary treatment with policosanol resulted in a significant decrease of blood cholesterol (p<0.01), blood glucose (p<0.01), triglyceride (p<0.001), and low density lipoprotein-cholesterol levels (p<0.01) and HMG-CoA reductase activity (p<0.001) in the liver. These results indicate that policosanol decreases blood cholesterol levels by suppressing cholesterol biosynthesis via decrease of HMG-CoA activity. Policosanol has the potential to be developed into an effective dietary strategy for both postprandial hyperglycemia and hypercholesterolemia.
RESUMEN
New alpha-glucosidase inhibitors, CKD-711 and CKD-711a were produced from the fermentation broth of Streptomyces sp. CK-4416 which was isolated from a forest soil of Jeju Island, South Korea. CKD-711 and CKD-711a were purified by Dowex 50W-2X and Sephadex G-10 column chromatography. In in vitro studies, CKD-711 showed a potent inhibitory activity against a-glucosidase from mammalian, but less inhibition against a-amylase from microorganism and mammalian. CKD-711a showed a lower inhibitory activity than CKD-711.
Asunto(s)
Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores de Glicósido Hidrolasas , Streptomyces/clasificación , Streptomyces/metabolismo , Animales , Medios de Cultivo , Inhibidores Enzimáticos/metabolismo , Fermentación , Microscopía Electrónica de Rastreo , Ratas , Microbiología del Suelo , Streptomyces/crecimiento & desarrollo , alfa-Amilasas/antagonistas & inhibidoresRESUMEN
CKD-711 and CKD-711a are aminooligosaccharide alpha-glucosidase inhibitors discovered during the bioactive material screening for antibacterial agent. Their inhibitory activities were studied and compared with those of acarbose in vitro and in vivo with animals. In in vitro study, CKD-711 showed similar effects to acarbose on porcine intestinal maltase and sucrase, IC50s of 2.5 and 0.5 microg/ml, respectively, whereas it had about 2 fold lower alpha-amylase inhibitory activity (IC50, 78.0 microg/ml) than acarbose (IC50, 36 microg/ml). CKD-711a showed less inhibitory activity than CKD-711 against all the enzymes tested. In rat fed on starch and sucrose meals, the dose of CKD-711 which reduced the postprandial blood glucose increment by 50 percent in comparison to control rats (ED50) were 3.07 and 1.15 mg/kg, respectively, and acarbose had ED50s of 1.94 and 1.15 mg/kg, respectively. CKD-711 and CKD-711a also showed antibacterial activity against Comamonas terrigena.
Asunto(s)
Comamonas/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Inhibidores de Glicósido Hidrolasas , Hiperglucemia/tratamiento farmacológico , Streptomyces/metabolismo , Acarbosa/farmacología , Animales , Bacterias/efectos de los fármacos , Inhibidores Enzimáticos/metabolismo , Hongos/efectos de los fármacos , Intestinos/efectos de los fármacos , Intestinos/enzimología , Masculino , Pruebas de Sensibilidad Microbiana , Páncreas/efectos de los fármacos , Páncreas/enzimología , Ratas , Ratas Wistar , Sacarasa/efectos de los fármacos , Porcinos , alfa-Amilasas/efectos de los fármacos , alfa-Glucosidasas/efectos de los fármacosRESUMEN
We have isolated two novel a-glucosidase inhibitors, O-[4-deoxy-4-(2,3-epoxy-3-hydroxymethyl-4,5,6-trihydroxycyclohexane-1-yl-amino)-alpha-D-glucopyranosyl]-(1-->4)-O-alpha-D-glucopyranosyl-(1-->4)-alpha-D-glucopyranose (named CKD-711) and its hexameric analog CKD-711a, from the fermentation broth of Streptomyces sp. CK-4416. HRFAB-MS and NMR analyses reveal that molecular formulae of CKD-711 and CKD-711a are C25H43NO20 and C37H63NO30, respectively with the latter containing two more glucose moieties than the former. Detailed chemical structures of both compounds have been characterized by high-resolution two-dimensional NMR methods.