Therapeutic Potential and Immunomodulatory Role of Coenzyme Q10 and Its Analogues in Systemic Autoimmune Diseases

Chary López-Pedrera, José Manuel Villalba, Alejandra Mª Patiño-Trives, Maria Luque-Tévar, Nuria Barbarroja, Mª Ángeles Aguirre, Alejandro Escudero-Contreras, Carlos Pérez-Sánchez, Chary López-Pedrera, José Manuel Villalba, Alejandra Mª Patiño-Trives, Maria Luque-Tévar, Nuria Barbarroja, Mª Ángeles Aguirre, Alejandro Escudero-Contreras, Carlos Pérez-Sánchez

Abstract

Coenzyme Q10 (CoQ10) is a mitochondrial electron carrier and a powerful lipophilic antioxidant located in membranes and plasma lipoproteins. CoQ10 is endogenously synthesized and obtained from the diet, which has raised interest in its therapeutic potential against pathologies related to mitochondrial dysfunction and enhanced oxidative stress. Novel formulations of solubilized CoQ10 and the stabilization of reduced CoQ10 (ubiquinol) have improved its bioavailability and efficacy. Synthetic analogues with increased solubility, such as idebenone, or accumulated selectively in mitochondria, such as MitoQ, have also demonstrated promising properties. CoQ10 has shown beneficial effects in autoimmune diseases. Leukocytes from antiphospholipid syndrome (APS) patients exhibit an oxidative perturbation closely related to the prothrombotic status. In vivo ubiquinol supplementation in APS modulated the overexpression of inflammatory and thrombotic risk-markers. Mitochondrial abnormalities also contribute to immune dysregulation and organ damage in systemic lupus erythematosus (SLE). Idebenone and MitoQ improved clinical and immunological features of lupus-like disease in mice. Clinical trials and experimental models have further demonstrated a therapeutic role for CoQ10 in Rheumatoid Arthritis, multiple sclerosis and type 1 diabetes. This review summarizes the effects of CoQ10 and its analogs in modulating processes involved in autoimmune disorders, highlighting the potential of these therapeutic approaches for patients with immune-mediated diseases.

Keywords: autoimmune disorders; cardiovascular disease; coenzyme Q10; inflammation.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Pathogenic role of oxidative stress and mitochondrial dysfunction in Systemic Autoimmune Diseases. Enhanced oxidative status and mitochondrial dysfunction are hallmarks of Systemic Autoimmune Diseases. These processes promote the alteration of key physiological functions such as the ability to repair vascular tissue, the control of apoptosis and the development of NETosis. The impaired functions are directly associated with tissue and organ damage in the long term. The dysregulation of the immune system leads to the loss of tolerance which drives autoantibody production, inflammation and the consequent increase of the disease activity. Furthermore, the chronic establishment of an altered oxidative status can trigger the development of cardiovascular comorbidities such as atherosclerosis and endothelial dysfunction. ROS, Reactive oxygen species.
Figure 2
Figure 2
Clinical trial: Ubiquinol supplementation in antiphospholipid (APS) Patients. A randomized, crossover, placebo-controlled trial was carried out in 36 APS patients to analyze the beneficial effects of supplementation with Ubiquinol (200 mg/day) for one month. Changes in several parameters related to inflammation, oxidative stress, mitochondrial function, atherosclerosis, and NETosis, along with regulatory microRNAs, were assessed. The results demonstrated the high potential of Ubiquinol to modulate markers associated with thrombosis and cardiovascular disease in APS patients, highlighting its role as a safe adjunct to standard therapies in this autoimmune disorder.
Figure 3
Figure 3
Beneficial effects of CoQ10 in Systemic Autoimmune Diseases. The therapeutic potential of CoQ10 in Systemic Autoimmune Diseases has been widely investigated. Thus, numerous studies comprising in vitro analysis, preclinical murine models and randomized controlled clinical trials have demonstrated the capacity of CoQ10 to improve the main clinical features of each disease, through both immunomodulatory and antioxidant effects. DAS28, Disease Activity Score using 28 joint counts; EDSS, Expanded disability status scale; FSS, Fatigue severity scale; BDI, Beck’s depression inventory; VAS, Visual analogue scale for pain.

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