Eleusenticosides A–O: Neuroprotective Triterpenoid Saponins from the Leaves of Eleutherococcus senticosus Using a Building-Block-Based Molecular Networking Strategy

Twenty-two oleanane-type triterpenoid saponins were isolated from the ethanol-extract of Eleutherococcus senticosus leaves through building-block-based molecular-networking-guided strategy, among which 15 new compounds, eleusenticosides A–O (1–15), were isolated and identified. Notably, eleusenticosides A and B (1, 2) containing eight sugar units were the largest saponins that have been discovered from E. senticosus so far. The structural elucidation was achieved using comprehensive spectroscopic techniques, including 1D/2D NMR and HRESIMS, complemented by acid hydrolysis. Furthermore, the neuroprotective potential of these saponins was evaluated in an Aβ25–35-induced neurite degeneration primary neuron model. The results revealed that saponins 3, 5, 17 and 19 can significantly restrain the axonal damage and promote neuronal network regeneration, suggesting their potential as therapeutic candidates for neurodegenerative diseases. A structure–activity relationship analysis mainly revealed that the neuroprotectivity of saponins might be affected mainly by the noroleanane-type aglycone and specific sugar units.