Punicatannins A and B: α-glucosidase inhibitory ellagitannins from pomegranate (Punica granatum) flowers

The fruit of Punica granatum L., commonly known as pomegranate, has been extensively studied but there is paucity of data on compounds in its flowers. Interestingly, pomegranate flowers have been utilized for treating diabetes in traditional medicine systems including Unani and Ayurveda. Moreover, a pomegranate flower extract was reported to lower blood glucose levels in the Zucker rat diabetes model. However, to date, the bioactive compounds responsible for these effects remain unidentified. Herein, α-glucosidase inhibitory bioassay guided isolation of pomegranate flowers yielded nine hydrolysable tannins including two new ellagitannins named punicatannins A and B. The punicatannins contained an unprecedented oxidized hexahydroxydiphenoyl moiety not previously observed in ellagitannins. Their structures and absolute configurations were determined by extensive spectroscopic analyses (including NMR, HRMS, and ECD) and chemical methods. Punicatannin A was 30 times more potent than the clinical α-glucosidase inhibitory drug, acarbose. These results suggest that ellagitannins are the bioactive constituents in pomegranate flowers responsible for its blood glucose lowering effects.