Isolation, bioactivity and molecular docking of stilbene acetylcholinesterase inhibitors from Arundina graminifolia (D. Don) Hochr.

Abstract

Twelve stilbenes were isolated and characterized from Arundina graminifolia (D. Don) Hochr (A. graminifolia.), including arundin (1), isoarundinin II (2), batatasin III (3), blestriarene A (4), densiflorol B (5), shancidin (6), coeloin (7), ephemeranthoquinone (8), isoshancidin (9), lusianthridin (10), orchinol (11), and arundinan (12). Notably, compounds 1 and 2 are reported here for the first time from this species, thereby expanding the chemical profile of A. graminifolia. Among these, compounds 4, 7, and 8 exhibited significant acetylcholinesterase (AChE) inhibitory activity, with IC₅₀ values ranging from 0.116 to 0.402 mM. Kinetic assays revealed a mixed-type inhibition mechanism for these compounds, with inhibition constants (K_i) against free AChE ranging from 0.193 to 0.542 mM, and K_i’ values for enzyme-substrate complexes between 0.157 and 0.387 mM.

Structure-activity relationship analysis indicated that bibenzyl compounds did not significantly affect AChE activity, while phenanthrenes exhibited more pronounced effects. Molecular dynamics simulations suggested that compound 8 interacts with the AChE binding pocket through conformational changes, stabilizing the structure via hydrogen bonds and π-stacking interactions with key residues, including Asn84, Thr154, His480, Tyr370, and Trp83. Molecular docking studies confirmed that these stilbenes effectively inhibit AChE activity, with predicted IC₅₀ values closely aligning with experimental data. These findings highlight the potent AChE inhibitory effects of the active stilbene compounds from A. graminifolia, providing valuable insights into their potential as therapeutic agents for Alzheimer's disease.