Polycyclic polyprenylated acylphloroglucinols with immunosuppressive activity from Hypericum perforatum and absolute...

Hyperformitins A-I (1-9), nine undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs) with double-bond migration, along with four new isomers hyperformitins J-M (10-13), were isolated from Hypericum perforatum. Their structures and absolute configurations were determined by spectroscopic analyses including HRESIMS, IR, UV, NMR, and ECD, as well as optical rotation (OR) calculations. The absolute configurations of previously reported analogues, garsubellins D and C as well as garcinielliptones L and M, were assigned for the first time by NMR spectra and specific rotations analyses assisting with OR calculations. Selected compounds were tested for their immunosuppressive activities against lipopolysaccharide (LPS)-induced B lymphocyte proliferation. Compounds 1, 3, 4, 5, 7, and 11 showed inhibition activities against the proliferation of B lymphocyte with IC₅₀ values ranging from 4.1 to 9.7 μM. Furthermore, the neuroprotective activities of the isolates against corticosterone (CORT)-induced injury in PC12 cells were also tested, and compounds 1, 12, and 13 exhibited neuroprotective effects with cell viabilities of 68.0%, 71.3%, and 68.4%, respectively under the concentration of 10 μM.