Profiling and activity screening of Dammarane-type triterpen saponins from Gynostemma pentaphyllum with glucose-dependent insulin secretory activity

The global prevalence of type 2 diabetes is increasing rapidly; consequently there is great need for new and novel therapeutic options. Gynostemma pentaphyllum (GP) is a traditional medicinal plant, mainly present in Southeast Asian countries, that has been reported to exert antidiabetic effects, by stimulating insulin secretion. The specific compound responsible for this effect is however as yet unidentified. Screening for discovery and identification of bioactive compounds of an herbal GP extract, was performed in isolated pancreatic islets from spontaneously diabetic Goto-Kakizaki (GK) rats, a model of type 2 diabetes, and from non-diabetic control Wistar rats. From this herbal extract 27 dammarane-type saponins, including two novel compounds, were isolated and their structure was elucidated by mass spectrometry and NMR spectroscopy. One of the dammarane-type triterpenoid showed a glucose-dependent insulin secretion activity. This compound, gylongiposide I, displays unique abilities to stimulate insulin release at high glucose levels (16.7 mM), but limited effects at a low glucose concentration (3.3 mM). Further studies on this compound, also in vivo, are warranted with the aim of developing a novel anti-diabetic therapeutic with glucose-dependent insulinogenic effect.