Abstract: Five new polycyclic polyprenylated acylphloroglucinols ( 1 − 5 ), ascyrones A−E, and four known compounds ( 6 − 9 ) were isolated from the aerial parts of Hypericum ascyron. All of the isolates containing a bicyclo3.3.1nonane-2,4,9-trione core and a benzoyl group, belonged to type B bicyclic polyprenylated acylphloroglucinols (BPAPs). Their structures and absolute configurations were established based on spectroscopic analyses and calculated electronic circular dichroism (ECD) data. The anti-inflammatory, neuroprotective and cytotoxicity activities of compounds 1 − 4 and 6 − 9 were evaluated. Compound 6 exhibited obvious anti-inflammatory activity in lipopolysaccharide (LPS)-induced RAW264.7 cells. Compounds 1 and 9 exhibited slight cytotoxicity against Hep3B cells. Meanwhile, compound 1 showed mild neuroprotective activity against corticosterone (CORT)-induced PC12 cell damage at10 μmol·L⁻¹.