Neuroprotection via High-Dilution Gelsemium: Mitochondrial Optimization and Akt/mTOR Pathway Activation

Background: Mitochondria are essential for cellular energy production, maintenance, survival, and the regulation of synaptic plasticity. As the primary energy producers, they are also major sources of reactive oxygen species (ROS). The brain, with its high energy demands, is particularly susceptible to mitochondrial dysregulation, which can impair bioenergetics and neurite outgrowth, contributing to conditions such as anxiety, depression, and age-related neurodegenerative disorders. Previous studies demonstrated that low doses of Gelsemium sempervirens L. ( Gelsemium ) at centesimal (C) dilutions (3C, 5C) promote neurite outgrowth by stimulating mitochondrial bioenergetics. This study aimed to evaluate the neuroprotective effects of Gelsemium homeopathic dilutions (9C, 15C, 30C) on mitochondrial function after prolonged treatment. Methods: We investigated the effects of chronic treatment (14 days) with Gelsemium preparations 9C, 15C, and 30C on mitochondrial bioenergetics, including ATP production and respiration, cell survival, and ROS generation. Additionally, we assessed their impact on neurite outgrowth and analyzed the underlying signalling pathways in human neuroblastoma cells, focusing on the Akt/mTOR axis. Results: Chronic treatment with high-dilution Gelsemium (9C, 15C, and 30C) demonstrated significant neuroprotective effects by: (1) enhancing ATP production and mitochondrial respiration; (2) promoting cell survival and modulating mitochondrial superoxide anion radical levels; (3) facilitating neurite outgrowth via activation of the Akt/mTOR signaling pathway. Conclusion: These findings suggest that high-dilution Gelsemium preparations (9C, 15C, and 30C) may provide neuroprotective benefits in brain disorders when used as part of a prolonged treatment strategy. Their effects are mediated through the modulation of mitochondrial function and associated signalling pathways, highlighting their potential therapeutic value. Conflict of Interest: This study was funded by Laboratoires Boiron, France, which actively participated in the study’s design, data collection, analysis, and interpretation.