Work

Gelsemium low doses protect against serum deprivation-induced stress on mitochondria in neuronal cells

Year: 2024

Type: article

Abstract: Gelsemium dynamized dilutions (GDD) are known as a remedy for a wide range of behavioral and psychological symptoms of depression and anxiety at ultra-low doses, yet the underlying mechanisms of the mode of action of G. sempervirens itself are not well understood. The present study was designed to examine the neuroprotective effects of Gelsemium preparations in counteracting stress-related mitochondrial dysfunctions in neuronal cells. We started by studying how serum deprivation affects the mitochondrial functions of human neuroblastoma (SH-SY5Y) cells. Next, we looked into the potential of various Gelsemium dilutions to improve cell survival and ATP levels. After identifying the most effective dilutions, 3C and 5C, we tested their ability to protect SH-SY5Y cells from stress-induced mitochondrial deficits. We measured total and mitochondrial superoxide anion radicals using fluorescent dyes dihydroethidium (DHE) and the red mitochondrial superoxide indicator (MitoSOX). Additionally, we assessed total nitric oxide levels with 4,5-diaminofluorescein diacetate (DAF-2DA), examined the redox state using pRA305 cells stably transfected with a plasmid encoding a redox-sensitive green fluorescent protein, and analyzed mitochondrial network morphology using an automated high-content analysis device, Cytation3. Furthermore, we investigated bioenergetics by measuring ATP production with a bioluminescence assay (ViaLighTM HT) and evaluated mitochondrial respiration (OCR) and glycolysis (ECAR) using the Seahorse Bioscience XF24 Analyzer. Finally, we determined cell survival using an MTT reduction assay. Our research indicates that Gelsemium dilutions (3C and 5C) exhibited neuroprotective effects by: - Normalizing total and mitochondrial superoxide anion radicals and total nitric oxide levels. - Regulating the mitochondrial redox environment and mitochondrial networks morphology. - Increasing ATP generation as well as OCR and ECAR levels, thereby reducing the viability loss induced by serum withdrawal stress. These findings highlight that dynamized 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. • Stress induced by serum deprivation (Sd) exacerbated mitochondrial dysfunctions in human neuroblastoma SH-SY5Y cells. • Gelsemium dynamized dilutions protected against a stress-induced rise of ROS, a drop in NO and an oxidized redox state. • Gelsemium dynamized dilutions prevented stress-induced mitochondrial network impairments, cell death, and a decrease in ATP. • Gelsemium preparations mitigated the stress-induced drop of mitochondrial respiration and glycolysis. • Our results emphasize a novel potential mode of action of Gelsemium on stress-induced mechanisms underlying depression.

Source: Journal of Ethnopharmacology

DOI: 10.1016/j.jep.2024.118714

Authors: Imane Lejri, Amandine Grimm, Pascal Trempat, Naoual Boujedaini, Anne Eckert

Institutions: University of Basel, Universitäre Psychiatrische Kliniken Basel, Boiron (France)

Language: English

Topic: Mitochondrial Function and Pathology

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,610