Polycyclic polyprenylated acylphloroglucinol and phenolic metabolites from the aerial parts of Hypericum elatoides and their neuroprotective and anti-neuroinflammatory activities

A phytochemical study on the aerial parts of Hypericum elatoides led to the isolation of a previously undescribed polycyclic polyprenylated acylphloroglucinol derivative, hyperelatone A, seven previously undescribed phenolic metabolites, hyperelatones B-H, along with ten known analogues. The structures of hyperelatones A-H were elucidated by 1D and 2D NMR spectroscopy, HRESIMS experiment, single-crystal X-ray diffraction and comparison of experimental and calculated ECD spectra, as well as chemical derivatization. All compounds were evaluated for their neuroprotective activity against hydrogen peroxide (H2O2)-induced cell injury in rat pheochromocytoma PC-12 cells and inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV-2 microglial cells. Hyperelatones B-D and H, cinchonain Ib, and tenuiside A showed noticeable neuroprotection at concentrations of 1.0-100.0 mu M. Hyperelatones D, G, and H, (-)-epicatechin, tenuiside A, and (Z)-3-hexenyl-beta-D-glucopyranoside exhibited significant anti-neuroinflammatory activity with IC50 values ranging from 0.75 +/- 0.02 to 5.83 +/- 0.23 mu M.