Precursor ions-guided comprehensive profiling of triterpenoid saponins from the Eleutherococcus senticosus stems and their neuroprotective effect evaluation

Triterpenoid saponins (TS) are the main constituents of Eleutherococcus senticosus, also termed as Siberian ginseng or Ciwujia, a widely used herb in China, Japan, Korea, and Russia for its beneficial effects on memory enhancement, tonifying, heart-nourishing, and tranquilizing. Although the stems, rhizomes, and roots are used identically, a preliminary experiment found TS were specifically distributed in stems rather than the underground parts. However, a comprehensive profiling of the TS compounds in E. senticosus stems (ESS) is still absent. In this study, an MS/MS molecular networking (MN)-based precursor ions (PIs) discovery strategy was applied to fast track the TS compounds from ESS extract. A total of 80 TS were tracked and characterized, among which 78 ones were reported for the first time in ESS. Furthermore, the TS-rich fraction (ESS-TS) was prepared by a series of chromatography separation, and was found with significant neuralprotective effects on attenuating Aβ25-35-induced neurite atrophy, and promoting the outgrowth of damaged neurite in the Aβ25-35-induced primary cortical neuronal damage model. In conclusion, this study highlighted the existence of TS compounds in ESS, a major medicinal parts nowadays adopted as Ciwujia by the Chinese Pharmacopiea and market. In addition, the TS was found with determined roles in the outgrowth of neuritis, and was proposed as crucial constituent when the E. senticosus was used as the therapeutic agents for neural diseases. These results supplies scientific data for the quality control of E. senticosus and the further development of ESS-TS as memory enhancement agents.