Gelsemium Low doses Increases Bioenergetics and Neurite Outgrowth

Background: Gelsemium sempervirens (GS) is a traditional medicinal plant, described at ultra-low doses as a remedy for a variety of psychological and behavioral symptoms of anxiety and depression. Changes in neural plasticity have been shown to play a significant role in the onset and development of those mental illnesses. Mitochondria play an extremely important role in the central nervous system by being the main energy producer through the oxidative phosphorylation and being involved particularly in the regulation of cell survival or death, as well as synaptic plasticity. Neurite outgrowth is the differentiation process by which neurons establish synapses through the protrusion of neurons and their extension. Methods: Because the effects of GS dilutions on mitochondrial function and neuroplasticity remain elusive, we aimed to investigate whether a treatment with GS at low doses (centesimal dilutions, C) improved bioenergetics parameters such as ATP production, mitochondrial respiration as well as cellular glycolysis before to characterize its effects on neurite outgrowth. Nerve growth factor (NGF), which is known as a promotor of cell growth and survival, was used as a positive control. Results: Our results demonstrate that GS dilutions (3C and 5C) efficiently ameliorated the bioenergetics of SH-SY5Y neuroblastoma cells by increasing cellular ATP level and mitochondrial respiration as well as promoting the cell survival. In addition, GS dilutions significantly improved neurite extension in the 2D as well as 3D culture model after 3 days of treatment. 3C and 5C dilutions showed similar functional effects than those obtained with the positive control nerve growth factor (NGF). Conclusions: These findings indicate that GS dilutions modulate the mitochondrial bioenergetic phenotype and improve the neurite formation. The mitochondrial function improving properties of GS dilutions might represent one possible important pathway contributing to its neuroprotective effectiveness. Key words: Gelsemium dilutions, mitochondria, bioenergetics, neurite outgrowth.