Extreme sensitivity of gene expression in human neurocytes SH-SY5Y to ultra-low doses of a medicinal plant with anxiolytic-like properties

ABSTRACT: Gelsemium sempervirens L. (Gelsemium) is a traditional medicinal plant which at ultra-low doses is employed as anxiolytic and antidepressant, but consistent evidence is lacking and the possible mechanisms involved at the level of nervous system are largely unknown. In this study we have investigated the gene expression of a human neurocyte cell line treated in vitro with increasing dilutions of Gelsemium extract. Starting from a crude extract containing the active principle gelsemine at the concentration of 6.5×10−4 M, six centesimal (c) dilutions of Gelsemium were prepared according to the French homeopathic pharmacopoeia: 2c, 3c, 4c, 5c, 9c and 30c. Human neuroblastoma cells SHSY5Y were exposed for 24h to Gelsemium and their transcriptome was compared with control cells treated with the corresponding vehicle solutions. RNA from cells treated with Gelsemium/controls dilutions was isolated and analyzed by microarray. Four biological replicates were tested for each condition. The exposure to the Gelsemium 2c dilution (the highest dose employed, corresponding to 6.5x10-9 M gelsemine) significantly changed the expression of 56 genes, 49 of which were down-regulated and 7 were overexpressed. These genes belong to G-protein coupled protein signalling pathways, calcium homeostasis, inflammatory response and neuropeptide receptors. Cytotoxicity was excluded by WST-1 viability test. The mean fold change of the Gelsemium-downregulated geneset was negative compared to controls in each treatment condition. Although the effect in general decreased with increasing drug dilutions, cluster analysis allowed to identify some groups with typical profile of changes with different dilutions. Among the 49 genes down regulated by Gelsemium 2c, most showed decreased expression after treatment with all dilutions of Gelsemium and comparison with respective controls (Wilcoxon test) was highly significant: 47 genes were down regulated with 3c (p<0.0001), 42 with 4c (p<0.0001), 38 with 5c (p<0.0001), 30 with 9c (p<0.0001), 27 in 30c (p<0.0001). No significant differences of gene expression due to Gelsemium were found in a randomly chosen geneset of the whole cell trascriptome. In conclusion this study showed that Gelsemium, a medicinal plant used in traditional medicine, modulates several genes possibly involved in neuronal function. High throughput microarray technology allowed to detect a small but statistically significant response to extremely low doses/high dilutions, thus revealing an extreme sensitivity of human genome to this kind of pharmacological regulation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE42236 | GEO | 2015/11/01

SECONDARY ACCESSION(S): PRJNA179380

REPOSITORIES: GEO