Gelsemium Low Doses Increases Bioenergetics and Neurite Outgrowth

Abstract

Gelsemium sempervirens (GS) is a traditional medicinal plant, previously identified as a remedy for a variety of psychological and behavioral symptoms of anxiety and depression at ultra-low doses. 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 oxidative phosphorylation and being involved in the regulation of cell survival and 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. 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 bioenergetic parameters such as ATP production, mitochondrial respiration, cellular glycolysis, and neurite outgrowth. Nerve growth factor (NGF), which is known as a promotor of cell growth and survival, was used as a positive control. 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 cell survival. In addition, GS dilutions significantly improved neurite extension in 2D as well as 3D culture models after 3 days of treatment. 3C and 5C dilutions showed similar functional effects to those obtained with the positive control nerve growth factor (NGF). These findings indicate that GS dilutions modulate mitochondrial bioenergetic phenotype and improve neurite formation. The mitochondrial function-improving properties of GS dilutions may represent one possible pathway contributing to its neuroprotective effects.