The roots of Valeriana officinalis L. (Valerianaceae) are used for treating sleep disorders and/or mild nerve tension. The effect of valerenic acid on brain-derived neurotrophic factor (BDNF) has not yet been studied, although it is known that gamma-amino butyric acid A (GABAA) receptor is regulated by BDNF, which modulates the depressive-like behavior and neurogenesis. The purpose of this study is to determine the effect of V. officinalis root extract (VO), its main constituents valerenic acid (VA) and acetoxy valerenic acid (AVA) as well as valerenic acid-free (VAF), acetoxy valerenic acid-free (AVAF) extracts and increasing amounts of valerenic acid containing extracts on the BDNF expression in SH-SY5Y cell lines. The effect of methanolic extracts of VO, VA, AVA, VAF, AVAF, and the extracts whose amount of VA were increased gradually, were tested using a Human BDNF ELISA kit with 17β-estradiol as a positive control. The VO and VA extracts caused a significant (p < 0.001) increase in the BDNF expression in SH-SY5Y cells compared to control. This effect completely disappeared when cells were treated with VAF extract. AVA alone did not show any significant change in the BDNF levels. The extracts with increasing amount of VA led to a concentration- dependent effect on the cells. In conclusion, our findings suggest that the antidepressant-like effect of the VO extract is also related to BDNF expression, and that this is mainly due to the presence of VA in the extract. Removing VA from VO extract leads to a loss of activity. Moreover, the concentration of VA plays a role for BDNF expressions in SH-SY5Y cells, which demonstrates the importance of quality control on the commercially available products.

Phytomics or metabolomics is analysis of large-scale primary and secondary metabolites of plant extracts and provides very meaningful data to monitor or evaluate cellular function or systems biology. The activity of plant extracts depends on the synergistic/antagonistic effect of different metabolites rather than single active metabolites. Matrix metalloproteinases (MMPs) have an active role in the formation of many diseases. To our knowledge, there is no study on the correlation between the phytomics and MMP inhibitory activity of Achillea millefolium, Achillea filipendulina (Asteraceae), Mentha piperita, and Salvia officinalis (Lamiaceae), (AAMS). Therefore, this study aimed to correlate the metabolomics profiling of AAMS extracts to identify the metabolites responsible for the MMP inhibitory activity based on phytomics data. The AAMS extracts showed a significant MMP inhibitory effect (57.73-92.73%) at different concentrations (25-500 μg/mL). In order to identify the metabolites responsible for such activities in the extract, the metabolomic profiling of the plants was investigated using gas chromatography-mass spectrometry (GC-MS). After deconvolution and aligning of the chromatograms, 284 metabolites were detected, of which 149 were annotated using retention index libraries. Multivariate analyses results indicated that A. millefolium and A. filipendulina showed similar metabolomic profiles, while M. piperita and S. officinalis differed both from each other and from Achillea species. The correlation analysis was applied to evaluate the correlation between metabolomic levels and MMP inhibitory activities, and 96 metabolites had a negative correlation (r ≤ -0.70) and 55 had a highly positive correlation (r ≥ 0.70) with MMP inhibitory activity. This is the first study which revealed that phytomics, plant metabolomics, can be used for activity evaluation and a single metabolite may not be responsible for a specific activity. In conclusion, phytomics can be a more useful tool for the evaluation of the activities than investigating a single metabolite. This new perspective can also provide a better understanding of plant metabolomics and can be easily employed for future research on plant activity.