Ellagic acid potentiates insulin sensitising activity of pioglitazone in L6 myotubes

• Ellagic acid is the major contributor to glucose uptake activity of pomegranate
• Interacts synergistically with pioglitazone to improve glucose uptake in myotubes
• Ellagic acid upregulates Glut-4 and PPAR-γ
• It enhances insulin sensitising activity of pioglitazone
• Activity of pioglitazone achieved at low doses by combining with ellagic acid

The methanol extract of pomegranate peels was re-extracted with ethyl acetate. It was then evaporated to dryness. It was found to have a profound effect on the glucose uptake in L6 myotubes. The major constituents of this extract were ellagic acid and its glycosides and so further studies were carried out with pure commercial ellagic acid. Its effect on glucose uptake and expression of genes involved in the insulin signalling were investigated individually and in combination with a commercial drug, pioglitazone. They interact synergistically to increase insulin stimulated glucose uptake. Ellagic acid increases the expression of glucose transporter type 4 (GLUT4) and peroxisome proliferator-activated receptor gamma (PPAR-γ). Activation of the latter by pioglitazone upregulates adiponectin, but when combined with pure ellagic acid, this upregulation is achieved at lower concentrations of the drug. The current study proves that insulin sensitising activity of pioglitazone can be enhanced at low doses by combining it with ellagic acid.