RESUMEN
In continuation of our drug discovery programme on Indian medicinal plants, we isolated an unusual amino acid, i.e. 2-amino-5-hydroxyhexanoic acid (1) from the seeds of Crotalaria juncea. The 2-amino-5-hydroxyhexanoic acid (1) showed dose dependent lipid lowering activity in the in vivo experiments and also showed good in vitro antioxidant activity. The cyclized compound, 3-amino-6-methyltetrahydro-2H-pyran-2-one (2) showed better lipid lowering and antioxidant profile than the parent compound 1.
Asunto(s)
Antioxidantes/uso terapéutico , Caproatos/uso terapéutico , Crotalaria/química , Hiperlipidemias/tratamiento farmacológico , Hipolipemiantes/uso terapéutico , Lípidos/sangre , Extractos Vegetales/uso terapéutico , Animales , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Caproatos/aislamiento & purificación , Caproatos/farmacología , Relación Dosis-Respuesta a Droga , Hiperlipidemias/sangre , Hiperlipidemias/inducido químicamente , Hipolipemiantes/aislamiento & purificación , Hipolipemiantes/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Ratas , Semillas/químicaRESUMEN
The diastereomeric mixture of calophyllic acid and isocalophyllic acid (F015) isolated from the leaves of Calophyllum inophyllum was investigated for the metabolic effect on glucose transport in skeletal muscle cells. In L6 myotubes, F015 dose-dependently stimulated glucose uptake by increasing translocation of glucose transporter4 (GLUT4) to plasma membrane without affecting their gene expression. The effects on glucose uptake were additive to insulin. Inhibitors analyses revealed that F015-induced glucose uptake was dependent on the activation of phosphatidylinositol-3-kinase (PI-3-K) and extracellular signal-regulated kinases 1 and 2 (ERK1/2), while independent to the activation of 5'AMP-activated kinase (AMPK). F015 significantly increased the phosphorylation of AKT, AS160 and ERK1/2, account for the augmented glucose transport capacity in L6 myotubes. Furthermore, F015 improved glucose tolerance and enhanced insulin sensitivity in skeletal muscle of dexamethasone-induced insulin resistant mice. Our findings demonstrate that F015 activates glucose uptake in skeletal muscle cells through PI-3-K- and EKR1/2-dependent mechanisms and can be a potential lead for the management of diabetes and obesity.
Asunto(s)
Cromonas/farmacología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Glucosa/metabolismo , Músculo Esquelético/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Transporte Biológico/efectos de los fármacos , Calophyllum/metabolismo , Línea Celular , Membrana Celular/metabolismo , Dexametasona , Diabetes Mellitus/metabolismo , Proteínas Activadoras de GTPasa/metabolismo , Transportador de Glucosa de Tipo 4/metabolismo , Humanos , Insulina/metabolismo , Resistencia a la Insulina , Sistema de Señalización de MAP Quinasas , Ratones , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/citología , Músculo Esquelético/efectos de los fármacos , Fosforilación/efectos de los fármacos , Extractos Vegetales/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
In continuation of our drug discovery program on Indian medicinal plants, we isolated bioactive compounds (1-5) from the leaves of Calophyllum inophyllum and evaluated their antidyslipidemic activity in triton induced hyperlipidemia model. The calophyllic acid (1A) and isocalophyllic acid (1B) mixture, canophyllic acid (4) and amentoflavone (5) showed dose dependent lipid lowering activity in in vivo experiments. The compounds 1A+1B mixture and 3 also showed good in vitro antioxidant activity.
