Metabolomics and proteomics profiles of some medicinal plants and correlation with BDNF activity

Identification of the low abundance of phytochemicals in plant extracts is very difficult. Pharmacological activity observed in such plants is not due to a single compound. In most cases, plant extracts show activity based on synergistic or antagonistic effects. Therefore, the idea of a holistic approach is more rational.

This study was planned to compare the metabolomics and proteomics profiles of Valeriana officinalis L. (Valerianaceae), Melissa officinalis L. (Lamiaceae), Hypericum perforatum L. (Hypericaceae) and Passiflora incarnata L. (Passifloraceae) used in sedative anxiolytic and sleep disorders. Integrated omics analyses were used to provide a better understanding of the effect of plant extracts on the brain-derived neurotrophic factor (BDNF) expression levels on the SH-SY5Y cell line by a holistic approach.

Metabolomic profiling of the plants was performed using the GC-MS and LC-qTOF-MS systems, and the proteomics analysis using the LC-qTOF-MS system after trypsin digestion. The Human BDNF Quantikine ELISA kit was utilized to test BDNF expression activity on the SH-SY5Y cell line.

The investigated plant extracts showed a significant increase in BDNF expression (p < 0.05). M. officinalis was found as the most active extract. According to the correlation analyses between BDNF activity and metabolomics or proteomics level, 94 metabolites had a positive correlation while 23 metabolites had a highly negative correlation; those for proteins are 24 and 6, respectively.

The multivariate data analysis revealed a similar metabolomics profile of H. perforatum and P. incarnata, which also had a similar activity profile. Remarkably, all the primary metabolites belonging to the Krebs Cycle (citric acid, fumaric acid, succinic acid, pyruvic acid, malic acid and citramalic acid, an analog of malic acid) were positively correlated with BDNF activity. Secondary metabolites with a high BDNF expression belonged to flavonoids, xanthone, coumarines, tannin, naphtalenes, terpenoids and carotenoid skeleton. Two proteins from the cytochrome P450 family (P450 71B11 and P450 94B3) were positively correlated with BDNF activity. Employing omics technologies in the plant research area will offer a better understanding of the role of plant extracts and may lead to the discovery of new compounds with specific activity.