Multifunctional antistress effects of standardized aqueous extracts from Hippophae rhamnoides L.

This study aims to screen and identify the multi-mechanism antistress effects of an extract of Hippophae rhamnoides L. (HR) leaves on corticosterone (CORT)-induced injury, N-methyl-d-aspartate (NMDA) receptor and serotonin 6 (5-hydroxytryptamine 6, 5-HT₆) receptor activity tests (in vitro), electric foot shock and forced swimming tests (FSTs) (in vivo), and tests for hippocampal CORT and monoamine levels (ex vivo), in search of active principles and underlying mechanisms of action. We confirmed that the water extract of HR (HRW) and various ethanol extracts of HR confer protective effects against CORT-induced impairments in SH-SY5Y cells and antagonistic effects on NMDA receptors and the 5-HT₆ receptor by using primary cultured rat hippocampal neurons and a stable 5-HT₆ receptor-expressing cell line, respectively. In addition, we confirmed the antistress effects of HRW in an electric foot shock stress model in mice and explored the underlying mechanisms of its action. We observed that HRW treatment significantly reversed the reduction in immobility times and increased climbing times in FSTs induced by electric foot shocks in the stress model. The levels of CORT, dopamine, and norepinephrine were increased, and the level of serotonin in the hippocampus was decreased in the electric foot shock stress model. The standardized HRW effectively restored abnormal CORT and monoamine levels in the hippocampus that were induced by stress. The results of the present study demonstrate that the standardized HRW produces novel multifunctional antistress effects.