Chronic Exposure to Gelsemium Preparations Alters Mitochondrial Bioenergetics, Neurite Outgrowth, and Akt/mTOR Signaling in Human Neuronal Cells.

Stress-related psychiatric disorders are frequently associated with impaired mitochondrial function, altered neuronal energy metabolism, and reduced neuroplasticity. Intracellular pathways such as PI3K/Akt and mTOR play central roles in regulating mitochondrial bioenergetics and neuronal structural adaptation. Gelsemium is traditionally used in integrative and homeopathic practice; however, the cellular effects of prolonged exposure to high serial dilutions remain insufficiently characterized. This study aimed to examine the effects of chronic exposure to Gelsemium preparations on mitochondrial function and neuronal plasticity in vitro. Human SH-SY5Y neuroblastoma cells were treated for 14 days with different Gelsemium preparations 9C, 15C, 30C. Mitochondrial bioenergetics, reactive oxygen species (ROS) production, cell viability, neurite outgrowth, and phosphorylation of Akt and mTOR were assessed using complementary biochemical, imaging, and signaling analyses. Chronic exposure to Gelsemium preparations was associated with increased ATP production, increased mitochondrial respiration and glycolytic activity, reduced oxidative stress, improved cell viability, and increased neurite outgrowth compared with untreated controls. These changes were accompanied by increased phosphorylation of Akt and mTOR. The convergence of bioenergetic, redox, morphological, and signaling readouts suggests a coordinated cellular response under prolonged exposure conditions. These findings indicate that chronic exposure to Gelsemium preparations (9C, 15C, 30C) is associated with coordinated changes in mitochondrial bioenergetics, redox balance, and Akt/mTOR signaling in neuronal cells under in vitro conditions.