Effects of STW3-VI (St. John's wort) on molecular mechanisms of depression in vitro

Depression may be induced by chronic stress, affecting neuronal and microglia function. Microglia are involved in the plasticity of the hippocampus by synaptic remodelling, which is related to depression, development and healing [1]. However, the molecular mechanisms are not entirely understood. Extracts of Hypericum perforatum L., like STW3-VI, have been recommended to treat depression [2]. Our investigation aimed to determine the effects of STW3-VI on the paracrine signalling between neurons and microglia in vitro.

Co-cultures of mouse SIM-A9 microglia and hippocampal HT-22 neurons were treated with different concentrations of STW3-VI, hyperoside, an active component of Hypericum perforatum L., escitalopram and NGF as a positive control. BDNF and TNF-α releases were quantified by ELISA. Quantification of neurogenesis was performed by a neurite outgrowth staining kit. Incubation of HT-22 with STW3-VI, escitalopram, hyperoside, and NGF, with/without co-culture with SIM-A9 stimulated the neurite formation by 2 to 5-fold compared to the untreated control. However, co-incubation with SIM-A9 inhibited the neurite outgrowth in the untreated control by 2.4-fold (p≤0.05). Interestingly, the BDNF release of HT-22 neurons was significantly decreased with SIM-A9 microglia compared to without microglia. Incubation of SIM-A9 with STW3-VI, escitalopram, hyperoside, and NGF alone did not stimulate a pro-inflammatory TNF-α release. STW3-VI and hyperoside stimulate neurite formation in HT-22 neurons with/without microglia under non-inflammatory conditions. These effects on neuronal plasticity might contribute to the clinically proven antidepressant activity of STW3-VI.

Conflict of Interest C.K., H.A-K and O.K are employees of Steigerwald Arzneimittelwerk GmbH, Darmstadt.

Funding The study was supported by Steigerwald Arzneimittelwerk GmbH, Darmstadt.

 

MissingLinkText

• References

• 1 Cornell J. et al. Neural. Regen. Res. 2022; 17 (04) 705-716
• 2 Bonaterra GA. et al. Front.Pharmacol. 2020; 11: 603575

Publication History

Article published online:
16 November 2023