Structurally diverse dammarane-type glycosides from Gynostemma longipes and their neuroprotective activity

Gynostemma longipes (family Cucurbitaceae) is a medicinal plant widely used in traditional medicine by various ethnic groups in northern Vietnam for anti-aging effect and prevention of memory impairment. In this study, seven previously undescribed dammarane-type triterpenoid saponins (1-7) with the diverse structural variations in the C-17 side chain, along with five known analogues (8-12) were isolated from the aerial parts of Gynostemma longipes. The structures of the compounds were established on the basis of HRESIMS, NMR data, and electronic circular dichroism (ECD) calculations. Compounds 6 and 7 represent the rare 21-nordammarane saponins. The ethanol extract and undescribed compounds were evaluated for their protective effects against glutamate-induced cytotoxicity in HT22 cells. The ethanol extract (1.56-50 μg/mL) demonstrated neuroprotective effects in a dose-dependent manner with an EC₅₀ value of 23.06 μg/mL. Compounds 4 and 5 attenuated glutamate-mediated neurotoxicity in HT22 cells, maintaining cell viability above 60% at all three tested concentrations (3.125, 12.5, and 50 μM).