Pomegranate flower : a unique traditional antidiabetic medicine with dual PPAR-α/-γ activator properties

PPARs are transcription factors belonging to the superfamily of nuclear receptors. PPAR-α is involved in the regulation of fatty acid (FA) uptake and oxidation, inflammation and vascular function, while PPAR-γ participates in FA uptake and storage, glucose homeostasis and inflammation. The PPARs are thus major regulators of lipid and glucose metabolism. Synthetic PPAR-α or PPAR-γ agonists have been widely used in the treatment of dyslipidaemia, hyperglycaemia and their complications. However, they are associated with an incidence of adverse events. Given the favourable metabolic effects of both PPAR-α and PPAR-γ activators, as well as their potential to modulate vascular disease, combined PPAR-α/-γ activation has recently emerged as a promising concept, leading to the development of mixed PPAR-α/-γ activators. However, some major side effects associated with the synthetic dual activators have been reported. It is unclear whether this is a specific effect of the particular synthetic compounds or a class effect. To date, a medication that may combine the beneficial metabolic effects of PPAR-α and PPAR-γ activation with fewer undesirable side effects has not been successfully developed. Pomegranate plant parts are used traditionally for the treatment of various disorders. However, only pomegranate flower has been prescribed in Unani and Ayurvedic medicines for the treatment of diabetes. This review provides a new understanding of the dual PPAR-α/-γ activator properties of pomegranate flower in the potential treatment of diabetes and its associated complications.