Oleanane- and Ursane-Type Triterpene Saponins from Centella asiatica Exhibit Neuroprotective Effects.

Six new pentacyclic triterpenoid saponins, centelloside F ( 1 ), centelloside G ( 2 ), 11- oxo -asiaticoside B ( 3 ), 11- oxo -madecassoside ( 4 ), 11(β)-methoxy asiaticoside B ( 5 ), and 11(β)-methoxy madecassoside ( 6 ), along with seven known ones, asiaticoside ( 7 ), asiaticoside B ( 8 ), madecassoside ( 9 ), centellasaponin A ( 10 ), isoasiaticoside ( 11 ), scheffoleoside A ( 12 ), and centelloside E ( 13 ), were separated from the 80% MeOH extract of the whole plant of Centella asiatica , which has been used as a medicinal plant and is now commercially available as a diatery supplement in many countries. Compounds 1 and 2 , 3 and 4 , and 5 and 6 are three pairs of isomers with oleanane- or ursane-type triterpenes as aglycones. The chemical structures of the new triterpene saponins were fully characterized by extensive analysis of their nuclear magnetic resonance and high-resolution electrospray ionization mass spectrometry data. The protective effects of compounds 1 - 13 on PC12 cells induced by 6-OHDA were screened, and compound 3 displayed the best neuroprotective effect, with 91.75% cell viability at the concentration of 100 μM. Moreover, compound 3 also attenuated cell apoptosis and increased the mRNA expression of antioxidant enzymes, including superoxide dismutase and catalase. Additionally, compound 3 activated the phosphatidylinositol 3-kinase/Akt pathway, including PDK1, Akt, and GSK-3β. These findings suggested that triterpene saponins from C. asiatica were worthy of further biological research to develop new neuroprotective agents.