Neuron-targeted liposomal coenzyme Q10 attenuates neuronal ferroptosis after subarachnoid hemorrhage by activating the ferroptosis suppressor protein 1/coenzyme Q10 system.

Subarachnoid hemorrhage (SAH) is primarily attributed to the rupture of intracranial aneurysms and is associated with a high incidence of disability and mortality. SAH disrupts the blood‒brain barrier, leading to the release of iron ions from blood within the subarachnoid space, subsequently inducing neuronal ferroptosis. A recently discovered protein, known as ferroptosis suppressor protein 1 (FSP1), exerts anti-ferroptotic effects by facilitating the conversion of oxidative coenzyme Q 10 (CoQ10) to its reduced form, which effectively scavenges reactive oxygen radicals and mitigates iron-induced ferroptosis. In our investigation, we observed an increase in FSP1 levels following SAH. However, the depletion of CoQ10 caused by SAH hindered the biological function of FSP1. Therefore, we created neuron-targeted liposomal CoQ10 by introducing the neuron-targeting peptide Tet1 onto the surface of liposomal CoQ10. Our objective was to determine whether this formulation could activate the FSP1 system and subsequently inhibit neuronal ferroptosis. Our findings revealed that neuron-targeted liposomal CoQ10 effectively localized to neurons at the lesion site after SAH. Furthermore, it facilitated the upregulation of FSP1, reduced the accumulation of malondialdehyde and reactive oxygen species, inhibited neuronal ferroptosis, and exerted neuroprotective effects both in vitro and in vivo. Our study provides evidence that supplementation with CoQ10 can effectively activate the FSP1 system. Additionally, we developed a neuron-targeted liposomal CoQ10 formulation that can be selectively delivered to neurons at the site of SAH. This innovative approach represents a promising therapeutic strategy for neuronal ferroptosis following SAH. STATEMENT OF SIGNIFICANCE: Subarachnoid hemorrhage (SAH) is primarily attributed to the rupture of intracranial aneurysms and is associated with a high incidence of disability and mortality. Ferroptosis suppressor protein 1 (FSP1), exerts anti-ferroptotic effects by facilitating the conversion of oxidative coenzyme Q 10 (CoQ10) to its reduced form, which effectively scavenges reactive oxygen radicals and mitigates iron-induced ferroptosis. In our investigation, we observed an increase in FSP1 levels following SAH. However, the depletion of CoQ10 caused by SAH hindered the biological function of FSP1. Therefore, we created neuron-targeted liposomal CoQ10. We find that it effectively localized to neurons at the lesion site after SAH and activated the FSP1/CoQ10 system. This innovative approach represents a promising therapeutic strategy for neuronal ferroptosis following SAH and other central nervous system diseases characterized by disruption of the blood-brain barrier.

Effect of Coenzyme Q10 Supplementation on Vascular Endothelial Function: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Coenzyme Q10 (CoQ10) has gained attention as a potential therapeutic agent for improving endothelial function. Several randomized clinical trials have investigated CoQ10 supplementation's effect on endothelial function. However, these studies have yielded conflicting results, therefore this systematic review and meta-analysis were conducted. AIM: This systematic review and meta-analysis were conducted to assess the effects of CoQ10 supplementation on endothelial factors. METHODS: A comprehensive search was done in numerous databases until July 19th, 2023. Quantitative data synthesis was performed using a random-effects model, with weight mean difference (WMD) and 95% confidence intervals (CI). Standard methods were used for the assessment of heterogeneity, meta-regression, sensitivity analysis, and publication bias. RESULTS: 12 studies comprising 489 subjects were included in the meta-analysis. The results demonstrated significant increases in Flow Mediated Dilation (FMD) after CoQ10 supplementation (WMD: 1.45; 95% CI: 0.55 to 2.36; p < 0.02), but there is no increase in Vascular cell adhesion protein (VCAM), and Intercellular adhesion molecule (ICAM) following Q10 supplementation (VCAM: SMD: - 0.34; 95% CI: - 0.74 to - 0.06; p < 0.10) (ICAM: SMD: - 0.18; 95% CI: - 0.82 to 0.46; p < 0.57). The sensitivity analysis showed that the effect size was robust in FMD and VCAM. In meta-regression, changes in FMD percent were associated with the dose of supplementation (slope: 0.01; 95% CI: 0.004 to 0.03; p = 0.006). CONCLUSIONS: CoQ10 supplementation has a positive effect on FMD in a dose-dependent manner. Our findings show that CoQ10 has an effect on FMD after 8 weeks of consumption. Additional research is warranted to establish the relationship between CoQ10 supplementation and endothelial function.

Dantrolene and coenzyme Q10 as a suggested combination therapy to statin-induced myopathy in high fat diet rats: A possible interference with ROS/ TGF-ß / Smad4 signaling pathway.

One of the major hitches for statins' utilization is the development of myotoxicity. Versatile studies reported that the underlining molecular mechanisms including coenzyme Q10 (CoQ10)/ubiquinone depletion, as well as the disturbance in the cytoplasmic Ca2+ homeostasis. Therefore, we investigated the consequences of supplementing CoQ10 and dantrolene, a cytoplasmic Ca2+ reducing agent, in combination with simvastatin. This adjuvant therapy normalized the simvastatin-mediated elevation in serum ALT, AST, CK-MM, as well as tissue Ca2+ content, in addition to suppressing the simvastatin-mediated oxidative stress in simvastatin-treated rats, while having no effect upon statin-induced antihyperlipidemic effect. Additionally, the combination inhibited the simvastatin-induced TGF-ß/ Smad4 pathway activation. Collectively, the current study emphasizes on the potential utilization of dantrolene and CoQ10 as an adjuvant therapy to statins treatment for improving their side effect profile.

Selenium reduction of ubiquinone via SQOR suppresses ferroptosis.

The canonical biological function of selenium is in the production of selenocysteine residues of selenoproteins, and this forms the basis for its role as an essential antioxidant and cytoprotective micronutrient. Here we demonstrate that, via its metabolic intermediate hydrogen selenide, selenium reduces ubiquinone in the mitochondria through catalysis by sulfide quinone oxidoreductase. Through this mechanism, selenium rapidly protects against lipid peroxidation and ferroptosis in a timescale that precedes selenoprotein production, doing so even when selenoprotein production has been eliminated. Our findings identify a regulatory mechanism against ferroptosis that implicates sulfide quinone oxidoreductase and expands our understanding of selenium in biology.

Ameliorating impact of coenzyme Q10 on the profile of adipokines, cardiomyopathy, and hematological markers correlated with the glucotoxicity sequelae in diabetic rats.

BACKGROUND: In diabetes, high blood glucose induces glucotoxicity, resulting in the further damage of pancreatic beta-cells and then precipitating diabetic complications. This study was aimed to investigate the relationship between glucotoxicity with the level of adipokines, diabetic cardiomyopathy, and hematological markers. Moreover, the study examined the potential modulatory effect of coenzyme Q10 (CoQ10) on the aforementioned markers associated with the sequelae of diabetes mellitus. MATERIAL AND METHODS: Twenty-four male rats were randomly assigned to receive an injection of STZ to induce diabetes (n = 16) or to remain uninduced (n = 8). The hyperglycemic status was induced in fasting rats by single intraperitoneal injection of STZ (45 mg /kg b.w.) dissolved in citrate buffer (pH 4.5). Three days after STZ injection, rats were divided into three groups; Normal control group (A), Diabetic control group (B), and CoQ10- treated diabetic group (C). The group (C) was fed with the basal diet supplemented with 5 g of CoQ10 per kilogram of diet for three weeks after the diabetes induction. After 21 days, the blood and serum samples were taken to conduct biochemical analyses. Blood glucose was determined by Blood Glucose Monitoring System. Adipokines or cytokines were evaluated by ELISA from a serum sample. Cardiac myopathy biomarkers were estimated by UP-Converting Phosphor Immunoassay Analyzer, and hematological parameters were measured by automatic hematology analyzer. RESULTS: In hyperglycemic rats, the level of fasting blood glucose, and serum level of resistin, omentin, TNF-α, and cardiomyopathy biomarkers significantly increased (P < 0.05). The treatment with CoQ10 significantly decreased the profile of adipokines and cardiomyopathy markers (cardiac enzymes and LPPLA2) in diabetic rats and also reduced glucose levels (P < 0.05). Lymphocyte percentages significantly decreased while significant increases were observed in granulocytes and MID percentages in hyperglycemic rats. CONCLUSION: Diabetic rats had higher serum levels of adipokines and cardiomyopathy markers. Among the hematological markers, GRA% and MID% increased while LYM% decreased. The profile of adipokines and cardiomyopathy markers improved when CoQ10 was supplemented. The study suggests that CoQ10 may have a beneficial effect on improving diabetic complications.

Comparison of Coenzyme Q10 (Ubiquinone) and Reduced Coenzyme Q10 (Ubiquinol) as Supplement to Prevent Cardiovascular Disease and Reduce Cardiovascular Mortality.

PURPOSE OF REVIEW: According to the World Health Organization (WHO), cardiovascular disease is the leading cause of death worldwide. Heart failure has been defined as a global pandemic leading to millions of deaths. Recent research clearly approved the beneficial effect of Coenzyme Q10 supplementation in treatment and prevention of cardiovascular disease in patients with heart failure in clinical trials but did not distinguish between the oxidised form CoQ10 and reduced form CoQH2 of Coenzyme Q10. The aim of this study is to determine differences in medical application of CoQ10 and CoQH2 supplementation and evaluate the efficacy of CoQ10 and CoQH2 supplementation to prevent cardiovascular disease in patients with heart failure. RECENT FINDINGS: A PubMed search for the terms "ubiquinone" and "ubiquinol" was conducted, and 28 clinical trials were included. Our findings go along with the biochemical description of CoQ10 and CoQH2, recording cardiovascular benefits for CoQ10 and antioxidative and anti-inflammatory properties for CoQH2. Our main outcomes are the following: (I) CoQ10 supplementation reduced cardiovascular death in patients with heart failure. This is not reported for CoQH2. (II) Test concentrations leading to cardiovascular benefits are much lower in CoQ10 studies than in CoQH2 studies. (III) Positive long-term effects reducing cardiovascular mortality are only observed in CoQ10 studies. Based on the existing literature, the authors recommend CoQ10 instead of CoQH2 to treat and prevent cardiovascular disease in patients with heart failure.

Coenzyme Q-related compounds to maintain healthy mitochondria during aging.

Mitochondrial dysfunction is one of the main factors that affects aging progression and many age-related diseases. Accumulation of dysfunctional mitochondria can be driven by unbalanced mito/autophagy or by decrease in mitochondrial biosynthesis and turnover. Coenzyme Q is an essential component of the mitochondrial electron transport chain and a key factor in the protection of membrane and mitochondrial DNA against oxidation. Coenzyme Q levels decay during aging and this can be considered an accelerating factor in mitochondrial dysfunction and aging progression. Supplementation with coenzyme Q is successful for some tissues and organs but not for others. For this reason, the role of coenzyme Q in systemic aging is a complex picture that needs different strategies depending on the organ considered the main objective to be addressed. In this chapter we focus on the different effects of coenzyme Q and related compounds and the probable strategies to induce endogenous synthesis to maintain healthy aging.

Effect of Coenzyme Q10 Supplementation on Sarcopenia, Frailty, and Falls: A Scoping Review.

Coenzyme Q10 (CoQ10) is well-known for its antioxidant effects and has been highlighted in research related to aging and many age-related conditions. However, there is limited research on the benefit of CoQ10 supplementation in conditions impacting the physical robustness of older adults, such as sarcopenia, frailty, falls and osteoporosis. This scoping review identified and summarized 4 studies that assessed the effects of exogenous CoQ10 on outcomes relating to sarcopenia, frailty, and falls. Results of the studies showed statistically significant improvements in a variety of physical robustness related outcomes, however several limitations of these studies prevent conclusive recommendations from being drawn regarding the benefit of CoQ10 supplementation in these conditions. A well-designed randomized control trial assessing the benefit of CoQ10 supplementation on clinically relevant outcomes related to sarcopenia, frailty, and falls may be warranted.

Mutant SPART causes defects in mitochondrial protein import and bioenergetics reversed by Coenzyme Q.

Pathogenic variants in SPART cause Troyer syndrome, characterized by lower extremity spasticity and weakness, short stature and cognitive impairment, and a severe mitochondrial impairment. Herein, we report the identification of a role of Spartin in nuclear-encoded mitochondrial proteins. SPART biallelic missense variants were detected in a 5-year-old boy with short stature, developmental delay and muscle weakness with impaired walking distance. Patient-derived fibroblasts showed an altered mitochondrial network, decreased mitochondrial respiration, increased mitochondrial reactive oxygen species and altered Ca2+ versus control cells. We investigated the mitochondrial import of nuclear-encoded proteins in these fibroblasts and in another cell model carrying a SPART loss-of-function mutation. In both cell models the mitochondrial import was impaired, leading to a significant decrease in different proteins, including two key enzymes involved in CoQ10 (CoQ) synthesis, COQ7 and COQ9, with a severe reduction in CoQ content, versus control cells. CoQ supplementation restored cellular ATP levels to the same extent shown by the re-expression of wild-type SPART, suggesting CoQ treatment as a promising therapeutic approach for patients carrying mutations in SPART.

Redox-crippled MitoQ potently inhibits breast cancer and glioma cell proliferation: A negative control for verifying the antioxidant mechanism of MitoQ in cancer and other oxidative pathologies.

Mitochondria-targeted coenzyme Q10 (Mito-ubiquinone, Mito-quinone mesylate, or MitoQ) was shown to be an effective antimetastatic drug in patients with triple-negative breast cancer. MitoQ, sold as a nutritional supplement, prevents breast cancer recurrence. It potently inhibited tumor growth and tumor cell proliferation in preclinical xenograft models and in vitro breast cancer cells. The proposed mechanism of action involves the inhibition of reactive oxygen species by MitoQ via a redox-cycling mechanism between the oxidized form, MitoQ, and the fully reduced form, MitoQH2 (also called Mito-ubiquinol). To fully corroborate this antioxidant mechanism, we substituted the hydroquinone group (-OH) with the methoxy group (-OCH3). Unlike MitoQ, the modified form, dimethoxy MitoQ (DM-MitoQ), lacks redox-cycling between the quinone and hydroquinone forms. DM-MitoQ was not converted to MitoQ in MDA-MB-231 cells. We tested the antiproliferative effects of both MitoQ and DM-MitoQ in human breast cancer (MDA-MB-231), brain-homing cancer (MDA-MB-231BR), and glioma (U87MG) cells. Surprisingly, DM-MitoQ was slightly more potent than MitoQ (IC50 = 0.26 µM versus 0.38 µM) at inhibiting proliferation of these cells. Both MitoQ and DM-MitoQ potently inhibited mitochondrial complex I-dependent oxygen consumption (IC50 = 0.52 µM and 0.17 µM, respectively). This study also suggests that DM-MitoQ, which is a more hydrophobic analog of MitoQ (logP: 10.1 and 8.7) devoid of antioxidant function and reactive oxygen species scavenging ability, can inhibit cancer cell proliferation. We conclude that inhibition of mitochondrial oxidative phosphorylation by MitoQ is responsible for inhibition of breast cancer and glioma proliferation and metastasis. Blunting the antioxidant effect using the redox-crippled DM-MitoQ can serve as a useful negative control in corroborating the involvement of free radical-mediated processes (e.g., ferroptosis, protein oxidation/nitration) using MitoQ in other oxidative pathologies.

Efficacy and Optimal Dose of Coenzyme Q10 Supplementation on Inflammation-Related Biomarkers: A GRADE-Assessed Systematic Review and Updated Meta-Analysis of Randomized Controlled Trials.

SCOPE: Coenzyme Q10 (CoQ10) has become a popular nutritional supplement due to its wide range of beneficial biological effects. Previous meta-analyses show that the attenuation of CoQ10 on inflammatory biomarkers remains controversial. This meta-analysis aims to assess the efficacy and optimal dose of CoQ10 supplementation on inflammatory indicators in the general population. METHODS AND RESULTS: Databases are searched up to December 2022 resulting in 6713 articles, of which 31 are retrieved for full-text assessment and included 1517 subjects. Double-blind randomized controlled trials (RCTs) of CoQ10 supplementation are eligible if they contain C reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). CoQ10 supplementation can significantly reduce the levels of circulating CRP (SMD: -0.40, 95% CI: [-0.67 to -0.13], p = 0.003), IL-6 (SMD: -0.67, 95% CI: [-1.01 to -0.33], p < 0.001), and TNF-α (SMD: -1.06, 95% CI: [-1.59 to -0.52], p < 0.001) and increase the concentration of circulating CoQ10. CONCLUSION: This meta-analysis provides evidence for CoQ10 supplementation to reduce the level of inflammatory mediators in the general population and proposes that daily supplementation of 300-400 mg CoQ10 show superior inhibition of inflammatory factors.

Coenzyme Q10 supplementation improves the motor function of middle-aged mice by restoring the neuronal activity of the motor cortex.

Physiological aging causes motor function decline and anatomical and biochemical changes in the motor cortex. We confirmed that middle-aged mice at 15-18 months old show motor function decline, which can be restored to the young adult level by supplementing with mitochondrial electron transporter coenzyme Q10 (CoQ10) as a water-soluble nanoformula by drinking water for 1 week. CoQ10 supplementation concurrently improved brain mitochondrial respiration but not muscle strength. Notably, we identified an age-related decline in field excitatory postsynaptic potential (fEPSP) amplitude in the pathway from layers II/III to V of the primary motor area of middle-aged mice, which was restored to the young adult level by supplementing with CoQ10 for 1 week but not by administering CoQ10 acutely to brain slices. Interestingly, CoQ10 with high-frequency stimulation induced NMDA receptor-dependent long-term potentiation (LTP) in layer V of the primary motor cortex of middle-aged mice. Importantly, the fEPSP amplitude showed a larger input‒output relationship after CoQ10-dependent LTP expression. These data suggest that CoQ10 restores the motor function of middle-aged mice by improving brain mitochondrial function and the basal fEPSP level of the motor cortex, potentially by enhancing synaptic plasticity efficacy. Thus, CoQ10 supplementation may ameliorate the age-related decline in motor function in humans.

MitoQ alleviates triptolide-induced cardiotoxicity via activation of p62/Nrf2 axis in H9c2 cells.

Triptolide (TP) is one of the major components of Tripterygium wilfordii, which is a traditional Chinese medicine widely used in the treatment of various autoimmune and inflammatory diseases. However, the cardiotoxicity induced by TP greatly limits its widespread clinical application. In view of the role of ROS-mediated oxidative stress in TP-induced cardiotoxicity, mitoQ, a mitochondria-targeted ROS scavenger, was used in this study to investigate its protective effect against TP-induced cardiomyocyte toxicity and its possible underlying mechanism. Here we demonstrated that mitoQ could significantly attenuate TP-induced cardiotoxicity in cardiomyocyte H9c2 cells, with a remarkable improvement in cell viability and reduction in ROS levels. P62-Nrf2 signaling pathway has been reported to play a critical role in regulating oxidative stress and protecting cells from harmful stimuli. In this study, we found that mitoQ significantly activated p62-Nrf2 signaling pathway in H9c2 cells with or without TP treatment. Moreover, knockdown of p62 or Nrf2 could block the protective effect of mitoQ against TP in H9c2 cells. Taken together, our study demonstrates that mitoQ can alleviate TP-induced cardiotoxicity via the activation of p62-Nrf2 signaling pathway, which provides new potential strategies to combat TP-induced cardiomyocyte toxicity.

Taurine, Coenzyme Q10, and Hydrogen Water Prevents Germanium Dioxide-Induced Mitochondrial Dysfunction and Associated Sensorineural Hearing Loss in mouse.

Mitochondrial dysfunction has been implicated in numerous common diseases as well as aging and plays an important role in the pathogenesis of sensorineural hearing loss (SNHL). In the current study, we showed that supplementation with germanium dioxide (GeO2) in CBA/J mice resulted in SNHL due to the degeneration of the stria vascularis and spiral ganglion, which were associated with down-regulation of mitochondrial respiratory chain associated genes and up-regulation in apoptosis associated genes in the cochlea. Supplementation with taurine, coenzyme Q10, or hydrogen-rich water, attenuated the cochlear degeneration and associated SNHL induced by GeO2. These results suggest that daily supplements or consumption of antioxidants, such as taurine, coenzyme Q10, and hydrogen-rich water, may be a promising intervention to slow SNHL associated with mitochondrial dysfunction.

Modulatory effect of exogenous Coenzyme Q10 on redox and inflammatory biomarkers during aging in rats.

An impaired redox homeostasis is an important hallmark of biological aging. Coenzyme Q10 is an endogenous lipophilic antioxidant that decreases with age and has been linked to oxidative stress. The purpose of this study was to evaluate the effect of CoQ10 supplementation on redox homeostasis and levels of inflammatory cytokines in young and old rats. Male Wistar rats (young and old) were randomly divided into four groups (n = 6). Group I: young control, Group II: young rats treated with CoQ10, Group III: old control, Group IV: old rats treated with CoQ10. CoQ10 (20 mg/kg) was administered daily to Group II and IV via oral gavage. After 28 days of treatment, rats were sacrificed and biomarkers of oxidative stress and inflammatory cytokines were evaluated. Results demonstrated a significant (p ≤ 0.05) increase in malondialdehyde, protein carbonyl oxidation, advanced oxidation protein products, inflammatory cytokines: CRP, IL-6, TNF-α, and a decline in levels of superoxide dismutase, catalase, reduced glutathione, ferric reducing antioxidant potential in plasma and plasma membrane redox system in old rats when compared to young rats. After treatment with CoQ10 significant decrease in the level of MDA, PCO, AOPP, CRP, IL-6, and TNF-α was observed. Also, significant up-regulation of SOD, CAT, GSH, FRAP, and PMRS was observed. The results show that supplementing rats with CoQ10 aids in the maintenance of redox equilibrium with replenishment of antioxidant reserves and down-regulation of inflammatory biomarkers. Thus CoQ10 supplementation could be a potential anti-aging therapy.

Selenium and Coenzyme Q10 Intervention Prevents Telomere Attrition, with Association to Reduced Cardiovascular Mortality-Sub-Study of a Randomized Clinical Trial.

Short telomeres have been associated with ageing and cardiovascular disease. The influence on leukocyte telomere length (LTL) of long-term intervention with combined selenium and coenzyme Q10 is unknown. Our aim was to determine whether 42 months of selenium and coenzyme Q10 supplementation prevented telomere attrition and further cardiovascular mortality. The investigation is an explorative sub-study of a double-blind, placebo-controlled, randomized trial. Swedish citizens low in selenium (n = 118), aged 70−80 years, were included. Intervention time was 4 years, with 10 years' follow-up time. LTL was relatively quantified with PCR at baseline and after 42 months. At baseline, LTL (SD) was 0.954 (0.260) in the active treatment group and 1.018 (0.317) in the placebo group (p = 0.23). At 42 months, less shortening of LTL was observed after active treatment compared with placebo (+0.019 vs. −0.129, respectively, p = 0.02), with a significant difference in change basing the analysis on individual changes in LTL (p < 0.001). Subjects suffering future death presented with significantly shorter LTL at 42 months than survivors [0.791 (0.190) vs. 0.941 (0.279), p = 0.01], with a significant difference in change of LTL according to cardiovascular mortality and survival (p = 0.03). To conclude, preservation of LTL after selenium and coenzyme Q10 supplementation associated with reduced cardiovascular mortality.

Coenzyme Q10 alleviates testicular endocrine and spermatogenic dysfunction induced by high-fat diet in male Wistar rats: Role of adipokines, oxidative stress and MAPK/ERK/JNK pathway.

The current study investigated the possible protective effects of Coenzyme Q10 (Co Q10 ) on rat model of high-fat diet (HFD) induced testicular dysfunction. Thirty male Wistar rats were allocated randomly into three groups: control, HFD, HFD + Co Q10 (75 mg/kg/day) groups. Animals were sacrificed after 3 months and epididymal sperm suspension, blood, and testes were collected for further analysis. In comparison to the untreated HFD group, the Co Q10 treated group revealed significantly increased serum testosterone, adiponectin levels, and decreased LH, FSH, and leptin levels. In addition, HFD resulted in significant increase in testicular oxidative stress (increased MDA, iNOS, NO, XO & decreased catalase, SOD, GSH) and inflammation (increased pJNK/JNK, pERK/ERK, and p-p38MAPK/MAPK), while Co Q10 was effective to ameliorate these changes. In addition, Co Q10 significantly increased sperm count, motility and viability that were markedly deteriorated by HFD. Regarding testicular ultrastructure, seminiferous tubular diameter and epithelium height were reduced in HFD group and Co Q10 significantly improved these testicular changes. Finally, a significant reduction in spermatogenic cell proliferation was detected by PCNA fluorescent expression and Co Q10 significantly reversed this change. In summary, our results indicated that Co Q10 could suppress testicular dysfunction produced by HFD. This protective effect could be attributed to its antioxidant, anti-inflammatory properties and to its effect on adipokines and spermatogenic cell proliferation. So, Co Q10 may be a promising food supplement to protect against testicular dysfunction induced by HFD.

Preclinical and Clinical Role of Coenzyme Q10 Supplementation in Various Pathological States.

Coenzyme Q10 (CoQ10) is an efficient antioxidant produced endogenously in a living organism. It acts as an important cofactor in the electron transport system of mitochondria and reported as a safe supplement in humans and animals with minimal adverse effect. CoQ10 is found naturally, as a trans configuration, chemical nomenclature of which is 2,3- dimethoxy-5- methyl-6-decaprenyle -1,4-benzoquinone. It is found in the body in two forms. In quinone form (oxidized form), it serves as an electron transporter that transfers the electrons in the electron transport chain between various complexes, and in ubiquinol form (reduced form), it serves as potent antioxidants by scavenging free radicals or by tocopherol regeneration in the living organism. Its primary roles include synthesis of adenosine triphosphate (ATP), stabilizes lipid membrane, antioxidant activity, cell growth stimulation, and cell death inhibition. CoQ10 has shown a variety of pharmacological and clinical effects including neuroprotective, hepatoprotective, anti-atherosclerotic, anticonvulsant, antidepressant, anti-inflammatory, antinociceptive, cardiovascular, antimicrobial, immunomodulatory, and various effects on the central nervous system. Present review has set about to bring updated information regarding to clinical and preclinical activities of CoQ10, which may be helpful to researchers to explore a new bioactive molecules for various therapeutic application.

Coenzyme Q10 supplementation improves cholesterol efflux capacity and antiinflammatory properties of high-density lipoprotein in Chinese adults with dyslipidemia.

OBJECTIVES: Coenzyme Q10 (CoQ10) had shown promising effects in improving the lipid and glycemic profile in dyslipidemic individuals in our previous work, but little is known about how it affects high-density lipoprotein (HDL) function in patients with dyslipidemia. The aim of this study was to explore the effects of CoQ10 supplementation on HDL function in people with dyslipidemia. METHODS: A 24-wk, randomized, double-blind, placebo-controlled trial was conducted in 101 people with dyslipidemia. All patients were randomized into the CoQ10 group (120 mg/d, n = 51) or the placebo group (n = 50). High-density lipoprotein-mediated cholesterol efflux capacity (CEC), HDL inflammatory index (HII), and HDL intrinsic oxidation were measured at baseline, 12 wk, and 24 wk. RESULTS: CoQ10 supplementation for 24 wk significantly improved HDL-mediated CEC (mean change, 1.21±2.44 versus -0.12±2.94; P = 0.014) and reduced HII (mean change, -0.32±0.58 versus -0.05±0.49, P = 0.014) compared with placebo. However, there was no significant difference in the effect of CoQ10 on HDL intrinsic oxidation between the two groups after 24 wk (P = 0.290). A positive correlation was found between the changes in CEC and HDL cholesterol in the CoQ10 group (r, 0.30; P = 0.032). Furthermore, we also found that the improved HDL functions were more obvious in elderly, female, or non-obese individuals, which indicated a specific population that benefits most from CoQ10 intervention. CONCLUSIONS: This study suggested that supplementation of CoQ10 for 24 wk can significantly improve HDL-mediated CEC and antiinflammatory function of HDL in patients with dyslipidemia.

Co-Adjuvancy of Solasodine & CoQ10 Against High Fat Diet-Induced Insulin Resistance Rats Via Modulating IRS-I and PPAR-γ Proteins Expression.

Insulin resistance (IR) is a condition in which target cells become insensitive to normal insulin concentrations in order to deliver glucose. The goal of this study was to see if solasodine combined with coenzyme Q10 could help rats with insulin resistance caused by a high-fat diet (HFD) by regulating the expression of IRS-I and PPAR-γ proteins.One of the six groups (n=6) got a conventional diet for 16 weeks as a control (normal), the HFD was given to the other five groups for 16 weeks, which further classified as-one group as HFD control while others treated with pioglitazone (10 mg/kg), coenzyme Q10 (50 mg/kg), solasodine (50 mg/kg) and combination of solasodine and coenzyme Q10i.e. SDQ10 (total 50 mg/kg) for the last 4 weeks orally once daily. Blood and tissue samples were collected by the end of study period for the biochemical and histological studies. As a result, HFD fed rats exhibited a significant increase in food and energy intake, body mass index, kidney and pancreas weight, fasting glucose, glycosylated haemoglobin, insulin level, liver enzyme ALT and AST and decrease antioxidant activity of superoxide dismutase and catalase. HFD received animals also produced a lower level of p-IRS1 and PPAR-y protein expression in western blot analysis. SDQ10 in combination successfully restored the above-mentioned complexity of insulin resistance caused by aHFD. Besides, increasesthe antioxidant activity of superoxide dismutase and catalase and normalized the architecture of kidney, pancreas and adipose tissue as well astreatment with SDQ10 raised the level of p-IRS1 and PPAR-y protein in liver tissue. As a result, supplementing with solasodine and coenzyme Q10 reversed the effect of the HFD on p-IRS1 and PPAR-y protein in liver tissue while also alleviating insulin resistance symptoms.