To search for potential candidate anti-AD agents, the gypenosideson the aerial parts of Gynostemma pentaphyllum were phytochemically investigated, yielding two undescribed (1-2) and five known (3-7) dammarane saponins. Their molecular structures were unambiguously elucidated via spectroscopic analyses (1D and 2D NMR, HR-ESI-MS, IR, and optical rotation) chemical transformations. All of the compounds possessed a 21-O-n-butyl-20,21-dihydroxy-21,23-epoxydammar-24-ene moiety in their structures.

The short-term memory assay on a transgenic fly Alzheimer’s disease (AD) model revealed that all of the compounds displayed potential anti-AD activity. Of the compounds, 1 and 6 at 10 μM showed comparable short-term memory rescue ability to memantine, the positive control, at 100 μM. This study revealed the potent antagonistic effect of dammarane-type saponins 1 and 6 against Alzheimer’s disease.