Modulation of Tropomyosin-related Kinase (Trk) signaling by Ballota nigra L., Crataegus oxycantha L., Passiflora incarnata L. and Valeriana officinalis L. in vitro

We reported earlier the modulation of the neurotrophic activity by the standardized plant extracts of Ballota nigra L., Crataegus oxycantha L., Passiflora incarnata L. and Valeriana officinalis L. alone and in combination [ 1 ]. Data were obtained from in vitro studies in human neuroblastoma SH-SY5Y cells treated with the plant extracts and Lorezapam (LZ) as reference drug. Neither single plant extracts nor the combination nor LZ reduced cell viability or stimulated TNF-α or IL-1β releases. They induced GABA- and melatonin-releases and increased the gene expression (GE) of the brain derived neurotrophic factor (BDNF). Recently a positive allosteric modulation of neurotrophin/Trk receptors was proposed to influence mood disorders as a potential new therapeutic concept [ 2 ]. To investigate the neurothrophin/Trk-signaling by the four plant extracts alone and in combination and LZ as reference. Based on deep sequencing data obtained from our previous study1, the GEs involved in the neurotrophin/ Trk-signaling pathway (Log2FC, average expression, p-value) were analyzed for all single plant extracts and their combination in three different dosages (2.5,5,25 μg/ml) and for LZ. RT-PCR was performed for selected genes involved in neurogenesis/neuroprotection. Results : At high concentrations all four plant extracts, LZ and the plant combination significantly modulated members of the neurotrophin/Trk signaling pathway with individual profiles, with NTRK2 (TrkB) regulated most prominently. The GE of superoxide dismutase (SOD) was increased concentration-dependently by the four plant extracts, LZ and the plant combination. Based on GEs all four plant extracts and their combination activate the neurotrophin/Trk-pathway while oxidative stress is reduced. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany