1 research outputs found
Naturally Occurring Carbazole Alkaloids from <i>Murraya koenigii</i> as Potential Antidiabetic Agents
This study identified koenidine (<b>4</b>) as a metabolically
stable antidiabetic compound, when evaluated in a rodent type 2 model
(leptin receptor-deficient <i>db/db</i> mice), and showed
a considerable reduction in the postprandial blood glucose profile
with an improvement in insulin sensitivity. Biological studies were
directed from the preliminary in vitro evaluation of the effects of
isolated carbazole alkaloids (<b>1</b>–<b>6</b>) on glucose uptake and GLUT4 translocation in L6-GLUT4<i>myc</i> myotubes, followed by an investigation of their activity (<b>2</b>–<b>5</b>) in streptozotocin-induced diabetic
rats. The effect of koenidine (<b>4</b>) on GLUT4 translocation
was mediated by the AKT-dependent signaling pathway in L6-GLUT4<i>myc</i> myotubes. Moreover, in vivo pharmacokinetic studies
of compounds <b>2</b> and <b>4</b> clearly showed that
compound <b>4</b> was 2.7 times more bioavailable than compound <b>2</b>, resulting in a superior in vivo efficacy. Therefore, these
studies suggested that koenidine (<b>4</b>) may serve as a promising
lead natural scaffold for managing insulin resistance and diabetes