STW 3-VI (Hypericum perforatum L.) increases plasticity of hippocampal neurons, as well as the migration of microglia cells and inhibits oxLDL-induced ROS production

Introduction:

Depressive symptoms may be induced by chronic stressful life events, which affect the neuronal and microglia function. Microglia activation and remodeling of dendrites in the hippocampus are apparently relating to depression development and healing, but the molecular mechanism is not fully understood. Extracts of Hypericum perforatum L., like STW 3-VI have been recommended for the treatment of depression. The aim of our investigation was to determine in vitro the effects of STW 3-VI on neuronal plasticity and microglia functions.

Methods:

Mouse microglia SIM-A9 cells and differentiated hippocampal HT-22 neurons were treated with different concentrations of STW 3-VI (0.5 – 10 µg/ml) or desipramine (1µM). Neurite outgrowth and morphological changes were microscopically analyzed and quantified. After treatment with different concentrations of STW3-VI or desipramine viability/cytotoxicity and migration were measured. Additionally, TNF-α was measured by ELISA, as well as ROS production by using the cell permeant reagent 2',7'-dichlorofluorescin-diacetate.

Results:

Neither STW 3-VI nor desipramine showed cytotoxic effects on neurons or microglia cells. Differentiation of mouse hippocampal HT-22 neurons induced the expression of the NMDA receptor. After treatment with 5 µg/ml STW 3-VI the neurite outgrowth was increased for 25% (p ≤0.05) compared to the control (medium alone). Furthermore, STW 3-VI increased the viability of microglia cells. Activation of microglia cells with lipopolysaccharides (LPS) (0.25 µg/ml), but not STW 3-VI itself, 2.4-fold increased the TNF-α release compared to the control. Incubation of microglia cells with 100 µg/ml oxidized low-density lipoprotein (OxLDL) increased the ROS production 7.5-fold, which thereafter could be significantly inhibited 1.8-fold by treatment with 10 µg/ml STW 3-VI. Moreover, STW 3-VI (10 µg/ml) stimulated 2.2-fold the migration compared to control, whereas LPS inhibited it.

Conclusions:

Our results indicate that the Hypericum perforatum L. extract STW 3-VI improves the plasticity of hippocampal neurons, protects from oxLDL-induced ROS production and stimulates the migratory capacity of microglia cells. These reparative/protective properties may support the therapeutic use in neurodegenerative diseases like depression.