Citicoline/Coenzyme Q10/Vitamin B3 Fixed Combination Exerts Synergistic Protective Effects on Neuronal Cells Exposed to Oxidative Stress

Background: The present study aimed to investigate the rationale and efficacy of using a citicoline, coenzyme Q10 (CAVAQ10) and vitamin B3 fixed combination in combating inflammation and oxidation in neuronal cells exposed to oxidative stress. Methods: HypoE22 cells and isolated hypothalamic specimens were selected as in vitro models to conduct the experiments. The efficacy of citicoline, CAVAQ10, and vitamin B3, with their fixed combination, were assayed after the exposure of hypothalamic cells to hydrogen peroxide (concentration range 1 nM-10 mu M), in order to evaluate the biocompatibility of treatments. The activity of neuroprotective and pro-inflammatory factors, namely, brain-derived neurotrophic factor (BDNF), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF alpha), involved in the neuronal cell damage in neurodegenerative diseases, were assayed in isolated hypothalamus. Results: Neither citicoline, CAVAQ10, nor vitamin B3 significantly altered hypothalamic cell viability, thus suggesting the biocompatibility of single ingredients and fixed combination in the concentration range considered for the study. In the same condition, citicoline and CAVAQ10 were also effective in reducing the gene expression of monoaminoxidase-B, involved in dopamine degradation. However, only citicoline demonstrated an ability to reduce dopamine levels. Conversely, all compounds were effective in reducing the gene expression of IL-6, and TNF alpha, and in inducing the gene expression of BDNF, with the co-administration of citicoline/CAVAQ10/vitamin B3 being generally more effective than single ingredients. Conclusions: The present findings support the beneficial and synergistic effects of citicoline, CAVAQ10, and vitamin B3 in fixed combination in reducing inflammation and oxidation, and in stimulating neurotrophin production in neuronal cells.