Chemometric guided isolation of new triterpenoid saponins as acetylcholinesterase inhibitors from Achyranthes bidentata Blume

Achyranthes bidentata Blume is an annual herb widely used as functional food and for ethnomedicinal purposes in Traditional Chinese medicine. Its seeds are widely used as cereal grain substitutes due to their excellent nutritional composition and health benefits. In current study, chemical profiling with chemometric guided approach was adopted for the tentative identification of fifty-six compounds based on UPLC-IM-Q-TOF-MS/MS analysis. Chemometric guided approach also led to the isolation of two previously undescribed triterpenoid saponins, named as, achyranosides A-B (1-2) along with three known compounds (3-5) from water fraction of A. bidentata seeds. The structure elucidation of isolated molecules was done by using NMR, HR-ESI-MS, FT-IR and GC-FID techniques. Chikusetsusaponin IVa (5) exhibited most promising inhibition (IC50 values of 63.72 µM) of acetylcholinesterase in vitro with mixed type of AChE inhibition in enzyme kinetic studies. Additionally, in-silico studies disclosed the underlying molecular interactions and binding free energy between ligands and the binding sites. The current study demonstrated the effectiveness of chemometric guided integrated approach for the phytochemical exploration and isolation of new oleanane-type triterpenoid saponins from A. bidentata seeds.