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

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.

Mitochondrial impairment and repair in the pathogenesis of systemic lupus erythematosus

“…With the further understanding of the unique energy metabolism feature of mitochondria in a distinct population of immunocytes, tissue or organ-specific therapeutics of mitochondria-targeting intervention may provide promising strategies for SLE treatment. Due to the critical role of mROS in many pathophysiological processes, the majority of mitochondria-targeted drug focus on antioxidants ( 183 ). The antioxidant lipophilic cations have great potential for the treatment of a wide range of pathologies.…”

The Potential Role of Ferroptosis in Systemic Lupus Erythematosus

“…AMPK activation exerts functions in metformin treatment of lupus by inhibiting B cell differentiation into germinal center and plasma cells ( 32 ). Another powerful antioxidant, coenzyme Q10 (CoQ10), which has shown beneficial effects in autoimmune diseases ( 33 ), can suppress lipid peroxidation and ferroptosis ( 34 ). The CoQ10 analog idebenone has been demonstrated that can attenuate murine lupus by modulating mitochondrial biology and reducing inflammation ( 35 ).…”

Combined Supplementation of Coenzyme Q10 and Other Nutrients in Specific Medical Conditions

“…In chronic inflammatory conditions, the 2019 meta-analysis of nine RCTs supported the significant impacts of CoQ 10 supplementation on the modulation of pro-inflammatory signals, including TNF-α and IL-6 [ 50 ]. Several RCTs on other immune-related conditions, including fibromyalgia, rheumatoid arthritis, and multiple sclerosis, supported the immunomodulatory effects of supplementation [ 138 , 139 , 140 , 141 , 142 ]. For instance, a 2015 RCT of 500 mg CoQ 10 supplementation documented the amelioration of pro-inflammatory biomarkers such as TNF-α, IL-6, and MMP-9 in patients with relapsing-remitting multiple sclerosis [ 143 ].…”