Effects of STW3-VI (St. John's wort) on molecular mechanisms of depression in vitro
Bibliographic record
Abstract
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. Publication History Article published online: 16 November 2023 © 2023. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".