Neuroprotective effects of Gelsemium in tauopathy: Restoration of mitochondrial function and cellular bioenergetics in P301L human neuroblastoma cells

Mitochondrial dysfunction is a pivotal factor in the pathogenesis of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s. These disorders are often marked by energy deficits, oxidative stress, and compromised cellular maintenance mechanisms in the brain. Low-dose of Gelsemium sempervirens L. (Gelsemium) preparations at centesimal dilutions enhanced neurite outgrowth in vitro , likely by modulating mitochondrial activity and improving cellular energy balance [ 1 ]. Recently, we showed that Gelsemium preparations may have neuroprotective effects against stress-induced cellular changes in the brain by regulating mitochondrial functions, essential for the survival, plasticity, and function of neurons in depression [ 2 ]. The present study seeks to evaluate the ability of Gelsemium preparations to mitigate mitochondrial dysfunction on cell survival, ATP production, mitochondrial respiration and membrane potential in a human cellular model of Alzheimer’s disease (AD). To achieve this, we studied the effects of selected Gelsemium preparations (3CH, 5CH and 30CH) using a sophisticated AD cell model, P301L cells, neuroblastoma cells stably transfected with human mutant tau (P301L mutation). Our results showed that 3CH, 5CH, 30CH exerted neuroprotective effects by i) improving viability, ii) regulating specific levels of mitochondrial or total superoxide anion radicals and total nitric oxide levels, iii) increasing ATP production, enhancing mitochondrial membrane potential, iv) shifting the bioenergetic profile towards a more metabolic state, in control and P301L cells, with the optimal treatment period being 24 hours. These findings provide promising insights into the neuroprotective properties of Gelsemium and its role in modulating mitochondrial function, oxidative stress and cellular metabolism in the context of tau-related neurodegenerative diseases. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany