Cytoprotective and anti-inflammatory effects of STW 3-VI (Hypericum perforatum extract) in vitro

Inflammation and glutamate toxicity play an integral role in a variety of disorders as depression. Additionally, a large body of evidence indicates that adaptation to chronic stress involves response from both, the neuroendocrine and immune systems. Depression also has been linked to an inflammatory response since pro-inflammatory cytokines like interleukin 6 (IL-6) and tumor necrosis factor (TNFα) are increased in depressed patients. In this context, the combined antioxidant and anti-inflammatory properties of Hypericum perforatum (St. John's wort) extract is suggested to contribute to the antidepressant effects by normalization of an overactive hypothalamic-pituitary-adrenal axis. Thus, the aim of our in vitro investigations is to determine the effects of STW3-VI on protection of differentiated mouse hippocampal HT22 cells from the cytotoxic effects of glutamate or NMDA and the possible anti-inflammatory properties on LPS-activated macrophages (MΦ).

Differentiated-hippocampal HT22 cells were pre-treated with STW3-VI to investigate the protective effects against glutamate or NMDA cytotoxicity. The anti-inflammatory properties of STW3-VI were evaluated by quantification of the TNFα release on LPS activated PMA-differentiated THP-1 MΦ using ELISA assay and the mRNA expression of TNFα and IL-6 by real-time-RT-PCR. Glutamate or NMDA (0.1mM) induced cytotoxicity to about 30% in HT22 cells. Pre-incubation (24h) with 10 µg/ml of STW3-VI improved the viability by 30% compared to the control. Pre-treatment (48h) of LPS activated MΦ with STW3-VI (60, 80 or 100 µg/ml) induced a significant lowering (54%, 64% and 53% respectively) of TNFα release. Real-time RT-PCR revealed that pre-treatment (48h) with 60 – 80 µg/ml STW3-VI exhibited inhibitory effects on the IL-6 and 80 µg/ml the TNFα mRNA expression by LPS-activated MΦ.

STW3-VI is suggested to protect hippocampal cells from glutamate or NMDA induced cytotoxicity and activates the anti-inflammatory defense by inhibition of the cytokine production by MΦ. These effects are in accordance with the therapeutic use of STW3-VI in depression.