Oleanane- and Ursane-Type Triterpene Saponins from <i>Centella asiatica</i> Exhibit Neuroprotective Effects

Abstract

Six new pentacyclic triterpenoid saponins, centelloside F (<b>1</b>), centelloside G (<b>2</b>), 11-<i>oxo</i>-asiaticoside B (<b>3</b>), 11-<i>oxo</i>-madecassoside (<b>4</b>), 11(β)-methoxy asiaticoside B (<b>5</b>), and 11(β)-methoxy madecassoside (<b>6</b>), along with seven known ones, asiaticoside (<b>7</b>), asiaticoside B (<b>8</b>), madecassoside (<b>9</b>), centellasaponin A (<b>10</b>), isoasiaticoside (<b>11</b>), scheffoleoside A (<b>12</b>), and centelloside E (<b>13</b>), were separated from the 80% MeOH extract of the whole plant of <i>Centella asiatica</i>, which has been used as a medicinal plant and is now commercially available as a diatery supplement in many countries. Compounds <b>1</b> and <b>2</b>, <b>3</b> and <b>4</b>, and <b>5</b> and <b>6</b> 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 <b>1</b>-<b>13</b> on PC12 cells induced by 6-OHDA were screened, and compound <b>3</b> displayed the best neuroprotective effect, with 91.75% cell viability at the concentration of 100 μM. Moreover, compound <b>3</b> also attenuated cell apoptosis and increased the mRNA expression of antioxidant enzymes, including superoxide dismutase and catalase. Additionally, compound <b>3</b> activated the phosphatidylinositol 3-kinase/Akt pathway, including PDK1, Akt, and GSK-3β. These findings suggested that triterpene saponins from <i>C. asiatica</i> were worthy of further biological research to develop new neuroprotective agents.