Selagintriflavonoids with BACE1 inhibitory activity from the fern Selaginella doederleinii

Eight triflavonoids, selagintriflavonoids A-H, were isolated from whole herbs of Selaginella doederleinii. The structures of compounds selagintriflavonoids A-C consisted of three naringenin units, whereas those of selagintriflavonoids D-H consisted of apigenin and two naringenin moieties. The structures and absolute configurations of the compounds were determined based on NMR, HRESIMS, and experimental and calculated electronic circular dichroism (ECD) data. The ability of the compounds to inhibit β-secretase (BACE1) was also evaluated. All compounds exhibited BACE1 inhibition with IC₅₀ values ranging from 0.75 to 46.99 μM. Selagintriflavonoid A exhibited the strongest inhibition (0.75 μM) and is thus a promising compound for treating Alzheimer's disease.