Chemical Constituents and Neuroprotective Activity ofHypericum hookerianum

Objective/Background The Hypericum hookerianum is widely distributed in Asian countries and prevalently used in traditional herbal medicines for its significant antioxidant, antipyretic, and anticancer properties. To date, very limited reports are available regarding the phytochemical profile, and there are no reports that have studied the neuroprotective potentials of this plant. Experimental Methods The aerial parts of H. hookerianum were collected from the Sapa mountainous district, Lao Cai province of Vietnam. The extracts were prepared using methanol, n-butanol, ethyl acetate, and chloroform and fractionated by normal-phase silica gel column chromatography to isolate compounds. The purity of the isolated compounds was analyzed by liquid chromatography combined with mass spectrometry. The structures were studied using nuclear magnetic resonance spectroscopy. All the isolates were evaluated for their neuroprotective activity against the neurotoxicity induced by glutamate in HT-22 hippocampal cells and 6-hydroxydopamine (6-OHDA) in SH-SY5Y neuroblastoma cells. The fluorescent dye calcein-AM image assay was used to measure the cell viability. Results Bioassay-guided fractionation of the aerial parts of H. hookerianum led to the isolation of 20 previously reported compounds (1-20), including 3 flavonoids (1-3), 2 xanthones (4 and 5), 1 chalcone (6), 4 lignans (7-0), 1 chromone-C-glycoside (11), 1 cinnamic acid derivative (12), 7 phloroglucinols (13-9), and 1 stilbene (20). The structures of the compounds were determined by spectroscopic methods and compared with the reported data. The extracts and isolated compounds showed neuroprotection in both cell models. The compounds 4-hydroxy-2,6,4′-trimethoxydihydrochalcone (6, EC 50 = 1.48 µM) and sesamin (10, EC 50 = 2.85 µM) exhibited significant neuroprotective effects in HT-22 and SH-SY5Y cells, respectively. Conclusion This is the first report on the neuroprotection of extracts and isolated compounds from H. hookerianum. The results provide information for further studies to develop products for the prevention and treatment of neurological disorders.