Ubiquinone Research Articles

Menaquinone production in genetically engineered E. coli.

Menaquinone (MK) is an important electron transporter in Escherichia coli. This isoprenoid quinone can transfer electrons to many terminal acceptors, such as fumarate and nitrate, which helps this organism survive under diverse and challenging conditions. As the isoprenoid quinones with various length of isoprenyl tail are widely distributed in nature, the heterologous expression of polyprenyl diphosphate synthases (PDSs) has been investigated using its counterpart, ubiquinone (UQ). In this study, we investigated the MK production by the expression of various heterologous PDS genes from prokaryotic and eukaryotic species, including Saccharomyces cerevisiae COQ1 (hexa-PDS), Haemophilus influenzae hi0881 (hepta-PDS), Synechocystis sp. strain PCC6803 slr0611 (nona-PDS) and Glunocobacter suboxydans ddsA (deca-PDS) in E. coli. We detected specific isoforms of MK, including MK7, MK9, and MK10, via the expression of HI0881, Slr0611 and DdsA respectively, but rarely detect MK6 via the expression of Coq1. As UQ6 was detected in E. coli harboring COQ1, the acceptance of the side chain lengths by MenA (prenyl transferase for MK) was narrower than UbiA (prenyl transferase for UQ). We also identified a mutation in menA in the E. coli AN386 strain and a transposon insertion of IS186 in menC in E. coli KO229 (∆ispB) and its parental strain FS1576. Taken together, these results elucidate the different nature of MenA from UbiA.

Drug therapy versus placebo or usual care for comatose survivors of cardiac arrest; a systematic review with meta-analysis.

In Europe, approximately 291,000 cardiac arrests occur annually. Despite critical care therapy, hospital mortality remains high. This systematic review assessed whether, in comatose survivors of cardiac arrest, any drug therapy, compared to placebo or usual care, improves outcomes. We searched Medline, EMBASE, the Cochrane Central Register of Controlled Trials, and The International Clinical Trials Registry Platform for randomized controlled trials of drug therapy in comatose survivors of cardiac arrest (last searched 20th October 2024). The primary outcome was mortality at 30 days / hospital discharge. Other outcomes reflected those of the Core Outcome Set for Cardiac Arrest. Risk of bias was assessed using Cochrane Risk-Of-Bias Version 1. Studies of steroids, coenzyme Q10 and thiamine were meta-analysed. From 2,562 records, 207 full texts were screened and 45 studies (5,800 patients) investigating 30 therapies were included. Studies were grouped thematically as supportive drug therapies (n = 10), neuroprotective agents (n = 19), and anti-inflammatory / antioxidants (n = 16). Four studies reported reduced mortality at 30 days / hospital discharge: one of the anticholinergic penehyclidine hydrochloride, two of intra-arrest vasopressin and methylprednisolone plus hydrocortisone for post resuscitation shock, and one of the traditional Chinese medicine, shenfu. Studies of steroids, coenzyme Q10 and thiamine were meta-analysed. We could not detect an effect on mortality with steroids (n = 739, risk ratio (RR), 0.93; 95 % CI 0.83-1.04, p = 0.21; I2 = 60 %, low certainty), coenzyme Q10 (n = 107, RR, 0.91; 95 % CI 0.61-1.37, p = 0.65; I2 = 0 %, low certainty), or thiamine (n = 149, RR, 1.11; 95 % CI 0.88-1.40, p = 0.39; I2 = 0 %, very low certainty). In comatose survivors of cardiac arrest, the majority of trials of drug therapy reported no effect on mortality. Meta-analyses of steroids, coenzyme Q10 and thiamine demonstrated no evidence of an effect on mortality. However, the low certainty of evidence warrants further research.

Abstract Sa1105: The Effect of a Combination of Neuroprotective Medications on Post-Cardiac Arrest Survival

Introduction: Reperfusion injury after cardiac arrest (CA) leads to poor survival and neurological outcomes. We hypothesized that a combination of pharmacologic neuroprotection therapies administered 24-72 hours post-CA [“combination therapy”] that target key steps in reperfusion injury; 1) excitotoxicity (Magnesium, Memantine, Perampanel, Minocycline), 2) mitochondrial dysfunction (Thiamine, Coenzyme Q10), 3) oxidative stress (Vitamin C, Vitamin E), and 4) inflammation (Hydrocortisone), would improve survival. AIMS: We compared survival between subjects with combination therapy and those without. Methods: A retrospective analysis of post-CA patients (01/01/2019 - 06/01/2023) was conducted as part of a quality improvement project. Inclusion: in-hospital CA, age ≥ 18 years, non-COVID, ≥ 5 min CPR, sustained ROSC (≥ 20 min). Exclusion: out-of-hospital CA. Combination therapy was at the discretion of the provider and given in addition to current post-CA standard critical care: targeted temperature management (TTM) (32-36°C), glucose (target 140 mg/dL), PaO2 (target 100 mmHg), PaCO2 (target 40 mmHg), and MAP (target 80 - 100 mmHg). Survival was assessed at hospital discharge. Results: Among 196 subjects, 146 received combination therapy (study group) and 50 did not (control group). Demographic variables (age, race, ethnicity) and intra-cardiac arrest variables (initial rhythm, CPR duration, and hospital site) were not statistically different between groups. Post-CA variables (mean PaCO2, PaO2, and glucose) were not statistically different between groups. MAP was 76 (69, 83) for study group and 65 (46, 72) for control group ( P = <0.001). Lowest temperature in study group was 34.8°C vs. 35.9°C in control group ( P = 0.034). Survival at hospital discharge was 33% for study group and 14% for control group ( P = 0.01). There were no known safety concerns or adverse events. Conclusions: The administration of a combination of neuroprotective medications that target key pathways in reperfusion injury appears to be feasible and safe, and may improve survival beyond current post-CA standard critical care. A future randomized controlled trial that includes the assessment of neurological outcomes is warranted.

Associations between dietary coenzyme Q10 intake and lipid profiles in adults: a national cross-sectional study

ObjectiveThis study aimed to determine the average intake of CoQ10 from dietary sources and explore the dose–response relationships between the dietary-derived CoQ10 intake and lipid profiles.MethodsWe performed a cross-sectional study based on the China Health and Nutrition Survey, which included 7,938 adults. The dietary intake assessment used three consecutive 24-h recalls combined with a household inventory. Serum was used for lipid profiling.ResultsThe average dietary-derived CoQ10 intake was 5.4 mg/day in Chinese adults. The dietary CoQ10 intake of the highest quartile (Q4 ≥ 6.96 mg/day) was negatively associated with total cholesterol (TC) [−0.12 (−0.19, −0.06) mmol/L], low-density lipoprotein cholesterol (LDL-C) [−0.17 (−0.23, −0.10) mmol/L], and non-high-density lipoprotein cholesterol (non-HDL-C) [−0.12 (−0.18, −0.05) mmol/L], while positively associated with apolipoprotein A-1 (ApoA1) [0.10 (0.08, 0.13) g/L] and triglycerides (TG) [0.14 (0.05, 0.23) mmol/L], compared to the lowest quartile (Q1 < 1.88 mg/day). Besides, dietary CoQ10 intake showed nonlinear dose–response associations with the above lipid variables (all Pnonlinear < 0.05).ConclusionDietary-derived CoQ10 intake may be associated with some lipid profiles, such as TG, ApoA1, TC, LDL-C, and non-HDL-C. However, CoQ10 from dietary sources may not be a good choice for individuals who need to CoQ10 supplement.

DDDR-13. OPTIMIZING BRAIN CANCER THERAPY: BALANCING TUMOR ERADICATION AND NORMAL TISSUE PRESERVATION WITH BPM31510

Abstract The challenges translating glioblastoma therapies lie in safeguarding normal neuronal and glial tissue. Considering that the central nervous system has the lowest regenerative capacity, the exclusive focus on tumor eradication while neglecting normal tissue response, impedes proper healing. This oversight leads to toxicities ultimately culminating in patient demise with marginal gain in survival. BPM31510 is a nanodispersion encapsulating highly hydrophobic oxidized Coenzyme Q10 (CoQ10), allowing for delivery of supraphysiological CoQ10 concentrations into cancer cells. Initial investigations demonstrated differential responsiveness between cancer and non-cancer cells in vitro, an effect associated with high superoxide levels exclusively in cancer cells. To evaluate this divergence between cancer and non-cancer cells, a competitive co-culture cell-based assay was developed with labeled pairs of glioblastoma and non-cancer cells incubated up to three weeks with various concentrations of BPM31510 to ascertain optimal concentration leading to preferential growth of non-cancer cells. Human astrocyte (HA), mouse fibroblast (NIH 3T3), and rat astrocyte (TNC1) cells were paired with U251 human glioma, mouse GL261 and rat C6 glioma, respectively. Cell growth and spatial extent of the plate containing non-cancer or tumor cells were monitored every other day. Using doxorubicin as control, no dosage was discerned in which non-cancer cells exhibited advantage over tumor cells (i.e., either cultures became all tumor cells or both cell lines were eradicated). Using various concentrations of BPM31510, we identified an optimal dose in which cancer cells diminished while non-cancer cells predominated, reflected by markedly elevated mitochondrial superoxide levels in cancer cells prior to cell death. A co-culture cell-based assay was developed to identify an optimal dose of BPM31510 with selective preservation of non-cancer cells alongside tumor cell death. This approach elucidates developing a “fine tuning” strategy, wherein BPM31510 is titrated over time, thereby promoting normal tissue and healing, and ultimately leading to superior and prolonged functional outcomes.

Auxiliary effect of trolox on coenzyme Q10 restricts angiogenesis and proliferation of retinoblastoma cells via the ERK/Akt pathway

Reactive oxygen species (ROS) are essential for cancer signalling pathways and tumour maintenance, making ROS targeting a promising anti-cancer strategy. Coenzyme Q10 (CoQ10) has been shown to be effective against various cancers, but its impact on retinoblastoma, alone or with trolox, remains unreported. Cytotoxicity of CoQ10 alone and with trolox was evaluated in normal human retinal pigment epithelium cells (ARPE-19) and Y79 retinoblastoma cells using CCK-8. Flow cytometry was used to assess apoptosis, cell cycle, ROS, and mitochondrial membrane potential (MMP). Anti-angiogenic potential was tested using human umbilical vein endothelial cells (HUVECs) and chick chorioallantoic membrane (CAM) assays. Mechanistic studies were conducted via RT-PCR and western blotting. CoQ10, alone and with trolox, reduced Y79 cell viability, induced apoptosis through excess ROS generation, and decreased MMP significantly. Both treatments caused G2/M phase cell arrest. The CAM assay showed a significant reduction in endothelial cell proliferation, evidenced by fewer number of co-cultured HUVECs when exposed to CoQ10 or CoQ10 with trolox. The combination of CoQ10 and trolox significantly reduced VEGF-A, ERK, and Akt receptor levels, while CoQ10 alone significantly inhibited ERK and Akt phosphorylation. Together, CoQ10 and trolox reduced protein expression of VEGFA. CoQ10 alone and with trolox, induces apoptosis in Y79 retinoblastoma cells by inhibiting the ERK/Akt pathway and downregulating VEGFA. This study is the first to report the in vitro and in-ovo anti-cancer potential of CoQ10 alone or when combined with trolox, on human retinoblastoma Y79 cells.

Exposure to Sunset Yellow FCF since post-weaning causes hippocampal structural changes and memory impairment in the adult rat: The neuroprotective effects of Coenzyme Q10.

This study aimed to investigate whether exposure to Sunset Yellow FCF (SY) since post-weaning can lead to hippocampal structural changes and memory impairment in adult rat and whether the Coenzyme Q10 (CoQ10) can protect against these adverse effects. The weanling rats were randomly divided into six groups and were treated daily by oral gavage for 6 weeks, as follows: (I) control group, administered distilled water (0.3mL/100 g/day); (II) CoQ10 group, received 10mg/kg/day CoQ10; (III) low SY group, received 2.5mg/kg/day SY; (IV) high SY group, received 70 mg/kg/day SY; (V) low SY + CoQ10 group; and (VI) high SY + CoQ10 group. At the end of the sixth week, the novel object recognition (NOR) test was conducted to evaluate memory. Then, after sacrificing animals, the cerebral hemispheres were removed for stereological study and evaluation of MDA levels. The low and high doses of SY led to significant neuronal loss and a decrease in the volume of the hippocampus (CA1 and DG subregions), as well as increased the MDA level, which was associated with short- and long-term memory impairment. Although, administration of CoQ10 prevented the hippocampal neural loss and volume, and caused a reduction in MDA and improved memory in the low and high SY groups. It seems that CoQ10 could prevent the neuronal loss and hippocampal atrophy caused by post-weaning exposure to SY through preventing oxidative stress, ultimately improving memory impairment in rats.

The Effects of Antioxidant Supplementation on Soccer Performance and Recovery: A Critical Review of the Available Evidence

Background Soccer is linked to an acute inflammatory response and the release of reactive oxygen species (ROS). Antioxidant supplements have shown promising effects in reducing muscle damage and oxidative stress and enhancing the recovery process after eccentric exercise. This critical review highlights the influence of antioxidant supplements on performance and recovery following soccer-related activity, training, or competition. Methods: English-language publications from the main databases that examine how antioxidant-based nutrition and supplements affect the recovery process before, during, and after soccer practice or competition were used. Results: Coenzyme Q10 (CoQ10), astaxanthin (Asx), red orange juice (ROJS), L-carnitine (LC), N-acetyl cysteine (NAC), beetroot (BET), turmeric root, and tangeretin reduce muscle damage (creatine kinase, myoglobin, cortisol, lactate dehudrogenase, muscle soreness). Tangeretin, docosahexaenoic acid (DHA), turmeric root, and aronia melanocarpa restrict inflammation (leukocytes, prostalagdin E2, C-reactive protein, IL-6 and 10). Q10, DHA, Asx, tangeretin, lippia citriodora, quercetin, allopurinol, turmeric root, ROJS, aronia melanocarpa, vitamins C-E, green tea (GTE), and sour tea (STE) reduce oxidative stress (malondialdehude, glutathione, total antioxidant capacity, superoxide dismutases, protein carbonyls, ascorbate, glutathione peroxidase, and paraoxonase 1). BET and NAC reinforce performance (endurance, jump, speed, strength). Conclusions: Further research is needed to determine the main mechanism and the acute and long-term impacts of antioxidant supplements in soccer.

Precise regulating the specific oxygen consumption rate to strengthen the CoQ10 biosynthesis by Rhodobater sphaeroides

Coenzyme Q10 (CoQ10) is the most consumed dietary supplement and mainly biosynthesized by aerobic fermentation of Rhodobacter sphaeroides (R. sphaeroides). Oxygen supply was identified as a bottleneck for improving CoQ10 yield in R. sphaeroides. In this study, a precise regulation strategy based on dielectric spectroscopy (DS) was applied to further improve CoQ10 biosynthesis by R. sphaeroide. First, a quantitative response model among viable cells, cell morphology, and oxygen uptake rate (OUR) was established. DS could be used to detect viable R. sphaeroides cells, and the relationship among cell morphology, CoQ10 biosynthesis, and OUR was found to be significant. Based on this model, the online specific oxygen consumption rate (QO2) control strategy was successfully applied to the CoQ10 fermentation process. QO2 controlled at 0.07 ± 0.01 × 10− 7mmol/cell/h was most favorable for CoQ10 biosynthesis, resulting in a 28.3% increase in CoQ10 production. Based on the multi-parameters analysis and online QO2 control, a precise online nutrient feeding strategy was established using conductivity detected by DS. CoQ10 production was improved by 35%, reaching 3384 mg/L in 50 L bioreactors. This online control strategy would be effectively applied for improving industrial CoQ10 production, and the precise fermentation control strategy could also be applied to other fermentation process.

Cellular oxygen consumption in patients with diabetic ketoacidosis

BackgroundDiabetic ketoacidosis (DKA) is a potentially life-threatening disorder associated with severe alterations in metabolism and acid–base status. Mitochondrial dysfunction is associated with diabetes and its complications. Thiamine and coenzyme Q10 (CoQ10) are important factors in aerobic metabolism. In this study, we measured cellular oxygen consumption rates (OCRs) and the effects of in vitro administration of thiamine and CoQ10 on OCRs in patients with DKA versus healthy controls.MethodsBlood samples were collected from a prospective cohort of patients with DKA and from controls. Cellular OCRs were measured in peripheral blood mononuclear cells (PBMC) without treatment and after treatment with thiamine, CoQ10, or both. The mitochondrial profile was measured using an XFe96 Extracellular Flux Analyzer and XF Cell Mito Stress Test Kit (Seahorse Bioscience). A linear quantile mixed model was used to compare OCRs and estimate treatment effects.ResultsA total of 62 patients with DKA and 48 controls were included in the study. The median basal and maximal OCRs were lower in the DKA group than in the control group (basal: 4.7 [IQR: 3.3, 7.9] vs. 7.9 [5.0, 9.5], p = 0.036; maximal: 16.4 [9.5, 28.1] vs. 31.5 [20.6, 46.0] pmol/min/µg protein, p < 0.001). In DKA samples, basal and maximal OCRs were significantly increased when treated with thiamine, CoQ10, or both. In controls, basal and maximal OCR were significantly increased only with thiamine treatment.ConclusionMitochondrial metabolic profiles of patients with DKA demonstrated lower cellular oxygen consumption when compared to healthy controls. Oxygen consumption increased significantly in cells of patients with DKA treated with thiamine or CoQ10. These results suggest that thiamine and CoQ10 could potentially have therapeutic benefits in DKA via their metabolic effects on mitochondrial cellular respiration.

Protective effect and mechanism of CoQ10 in mitochondrial dysfunction in diquat-induced renal proximal tubular injury.

Coenzyme Q10 (CoQ10) plays an important role in improving mitochondrial function and has many beneficial effects on the kidney. However, whether CoQ10 protects against diquat (DQ)-induced acute kidney injury (AKI) remains unclear. In this study, we investigated the protective effects and mechanism of action of CoQ10 against DQ-induced AKI. Institute of Cancer Research (ICR) mice were intraperitoneally injected with DQ to induce AKI. The expression levels of serum creatinine (Cr), urea, and kidney injury molecule-1 (KIM-1) increased, those of aquaporin 1 (AQP-1) decreased, and those of mitochondrial reactive oxygen species (ROS) increased with increased depolarization of mitochondrial membranes and mitochondrial rupture. In contrast, treatment with CoQ10 significantly improved DQ-induced AKI. CoQ10 treatment reduced serum Cr, urea, and KIM-1 contents, increased the AQP-1 expression, and reduced ROS contents in mice with DQ poisoning. Our results suggest that AKI caused by DQ poisoning may be related to the disruption of mitochondrial homeostasis and that CoQ10 treatment protects against AKI caused by DQ poisoning by improving mitochondrial kinetic homeostasis. Thus, CoQ10 represents a new therapeutic option for the prevention and treatment of AKI caused by DQ poisoning.

Changes in sperm quality with an antioxidant formula in mild-moderate male infertility: a prospective study

IntroductionThis study aimed to examine for an association between an antioxidant formula and sperm quality as well as safety in males with mild to moderate sub-fertility. MethodsA prospective, open-label single-arm study examined the association between 24 weeks treatment with a proprietary formula containing 15 vitamins, minerals and antioxidants (including L-carnitine, acetyl-L-carnitine, selenium, folic acid, L-cysteine and Co-enzyme Q10) and sperm quality in healthy males aged 20 – 60 with idiopathic teratospermia, asthenospermia and/or mild-moderate oligospermia. The primary outcome was simultaneous change in sperm concentration, progressive motility and morphology between screening, week 16 and week 24. Secondary outcomes included safety, pregnancy rates, sperm oxidative stress, sperm DNA fragmentation, and serum/plasma nutrient levels. ResultsSixty-one participants, with a mean age of 35.8 years, were included in the intention-to-treat analysis. No improvement in overall sperm quality was observed (i.e. simultaneous improvement in all three measures) as only two of the three sperm quality measures improved. Mean sperm concentration decreased by 0.24 standard deviations (SD) while mean morphology and motility improved by 0.28 and 0.04 SD respectively, however, these changes did not reach clinical significance (set at ≥ 0.4 SD improvement in means). There were no changes in secondary outcomes apart from an increase in homocysteine and vitamin B12 levels and decrease in high DNA stainability. Fifteen pregnancies were reported (pregnancy rate 29%). Twenty-one of 62 (33.8%) of participants reported 36 adverse events (AEs), one of which was serious leading to study withdrawal. Most AEs were of mild intensity and resolved. ConclusionTwenty-four weeks of an antioxidant formula was not associated with clinically significant changes in overall sperm quality. The formula was generally safe and well tolerated. Our findings are limited by the single- arm design, and randomised controlled trials are required to confirm or refute our findings.

Idebenone Attenuates Diabetic Retinopathy by Modulating Autophagy Via Targeting Akt Signaling.

Diabetic Retinopathy (DR) is a common microvascular issue caused by diabetes. Idebenone (IDE) is a coenzyme Q10 analog and antioxidant that has been utilized in the treatment of neurodegenerative diseases. Our goal was to investigate how IDE might treat diabetic retinopathy. An in vivo DR model was established by injecting a single dose of streptozotocin (STZ). Rats were treated with IDE, and their vascular function was measured by ultrasound. The retina structure was checked by haematoxylin and eosin (HE) staining. The expression of biomarkers of autophagy and apoptosis was measured by western blotting assay. The retina endothelial cell line RF/6A was stimulated with high glucose (HG) and treated with IDE. Cell proliferation and apoptosis were assessed using the Edu assay, TUNEL assay, and flow cytometry, respectively. Reduced peak systolic velocity (PSV), mean velocity (MV), end-diastolic velocity (EDV), and increased pulsatility index (PI) and resistance index (RI) were observed in diabetic rats; however, these traits were reversed by IDE therapy. IDE alleviated the STZ-induced disordered retina structure. The IDE administration suppressed DR-induced apoptosis and autophagy both in vivo and in vitro. IDE suppressed the activation of Phosphatidylinositol 3 kinase (PI3K) signaling. Activation of PI3K abolished the IDE-alleviated retina damage and cell death. IDE regulated the autophagy of retina cells to alleviate diabetic retinopathy via regulating the PI3K signaling pathway.

Comparative study of the protective effects of coenzyme Q10 and cinnamon extract on possible kidney damage and dysfunction of amiodarone in rats.

An increase in free oxygen radicals and proinflammatory cytokines and decrease in intracellular adenosine triphosphate account for the nephrotoxic effect of amiodarone. This study investigated the protective effects of Coenzyme Q10 (CoQ10), cinnamon extract (CE) and the combination of the two (CoCE) on possible amiodarone-induced renal injury in rats. Thirty male albino Wistar rats were cetegorized into healthy (HG), amiodarone (ADG), CoQ10 + amiodarone (CoQA), CE + amiodarone (CEA), and CoCE + amiodarone (CoCEA) groups. First, CoQ10 (10mg/kg) and CE (100mg/kg) were orally given. After 1h, 50mg/kg amiodarone was orally given to all groups except for HG. Amiodarone, CoQ10, and CE administration was continued orally at the indicated doses once daily for 10days.Then, blood samples were collected from all groups to determine creatinine, blood urea nitrogen (BUN), and kidney injury molecule (KIM-1) levels, followed by euthanasia and removal of kidney tissues. Oxidative stress and inflammatory parameters were analysed in the tissue samples. Histopathological examination was also performed on the tissues. Amiodarone increased malondialdehyde levels and decreased total glutathione, superoxide dismutase, and catalase levels (p < 0.001). Amiodarone increased the expression and tissue levels of tissue nuclear factor kappa B, tumor necrosis factor-alpha, interleukin-1β and interleukin-6, and led to increases in serum creatinine and BUN and KIM-1 levels (p < 0.001). Amiodarone also caused histopathological damage (p < 0.001).CoQ10, CE and especially CoCE inhibited biochemical changes and tissue damage (p < 0.001). Although CoQ10, CE, and CoCE effectively prevent amiodarone-induced oxidative and inflammatory nephrotoxicity, CoCE appears to be superior.

Practical supplements for prevention and management of migraine attacks: a narrative review.

Migraine is one of the most debilitating neurological disorders that causes frequent attacks of headaches and affects approximately 11% of the global population. Deficient or even insufficient levels of vital nutrients would increase the severity and frequency of migraine attacks. Therefore, we aimed to examine the practical supplements for the prevention and management of migraine attacks. This narrative review study was conducted by searching PubMed, ISI web of science, EMBASE, Google Scholar, and Scopus using the keywords of "dietary supplement" and "migraine" plus their MeSH terms. Original articles published in English language from their inception to July 27th, 2024, studies that investigated adult population (aged >18 years), and those assessing the impact of intended nutrient supplementation on clinical symptoms of migraine were included in the study. Oxidative stress and low intake of antioxidants would be risk factors for migraine attacks by inducing inflammation. The secretion of inflammatory cytokines, such as tumor necrosis factor (TNF)-a, would lead to neuroinflammation and migraine episodes by increasing the cellular permeability and interactions. Evidence also indicated a direct association between phases of migraine attacks and calcitonin gene-related peptide (CGRP), mitochondrial disorders, monoaminergic pathway, disruption in brain energy metabolism, and higher serum levels of glutamate and homocysteine. Therefore, supplementation with nutrients involved in mitochondrial function, brain energy metabolism, and even methyl donors would relieve migraine attacks. Evidence indicated that supplementation with riboflavin, omega-3 fatty acids, alpha lipoic acid, magnesium, probiotics, coenzyme Q10, ginger, and caffeine would have favorable effects on migraine patients. However, more prospective studies are required to evaluate the effect of other nutrients on migraine patients.

Cardioprotective effects of novel antioxidants post-myocardial infarction: An integrative review of preclinical and clinical data

Myocardial infarction (MI), is still a major public health problem, and oxidative stress contributes to the degree of myocardial damage after MI. Oxygen-derived free radicals (ODFR) worsen myocardial injury and result in chronic heart failure in many patients. These harms have led to interest in antioxidant treatment to reduce these adverse effects; new antioxidants with the potential for cardioprotection are the subject of significant interest. This review summarizes basic and clinical research comparing the effectiveness of newly synthesized antioxidants in attenuating oxidative stress and enhancing recovery after myocardial infarction. The review synthesizes evidence of a reduction in infarct size, enhancement of cardiac function, and repression of apoptosis in myocardial cells by the use of antioxidants from animal models. Melatonin, N-acetylcysteine, edaravone, and coenzyme Q10 demonstrated a wide range of preclinical positive effects by acting as ROS free radicals scavengers, modulating mitochondria dysfunction, and reducing inflammation. These findings are extrapolated from humans, although advances in antioxidant therapy are beginning to be viewed in initial clinical trials. From human data, although clinical trials are scarce, the evidence of new antioxidants can improve point and long-term outcomes in patients undergoing MI, help to increase the contractility of the injured myocardium, and decrease the mortality level. However, some issues are still there, such as high inter- and intra-individual variability in patient response and dosing schedule, as well as adverse effects such as pro-oxidant activity at high Oral administered doses of melatonin. The limitations of the current research discussed in this review include the general lack of large-scale, well-controlled clinical trials and the need for long-term follow-up studies. This review also proposed future research directions for improving antioxidant applications in post-MI management.

Experimental study on the treatment of diabetic cardiomyopathy in rats by using ultrasound-targeted microbubble destruction combined with coenzyme Q10 loaded long-circulating nanoliposomes

Objective: To investigate the therapeutic effects and mechanisms of Ultrasound-targeted microbubble destruction (UTMD) technology combined with CoQ10 loaded PEGylated nanoliposomes (CoQ10-PEG-lips) on diabetic cardiomyopathy (DCM) in rats. Methods: CoQ10-PEG-lips were prepared using the thin-film dispersion method combined with ultrasonic hydration, followed by quality assessment. Sixty healthy and clean male SD rats were selected, and 50 were randomly chosen using a random number table to establish a type 1 diabetes mellitus (DM) model via a single intraperitoneal injection of streptozotocin. The remaining 10 rats were assigned as the normal control group. A total of 47 rats successfully developed the DM model, and 40 were selected using the random number table method. Based on different intervention methods, these rats were then randomly divided into DM model group, CoQ10 solution group, CoQ10-PEG-Lips group, and CoQ10-PEG-Lips+UTMD group (n=10 per group). Normal control group and DM model group rats were injected with 1 ml of normal saline through caudal vein. CoQ10 solution group and CoQ10-PEG-Lips group were injected with 1 ml of CoQ10 solution or CoQ10-PEG-Lips solution containing 10 mg/kg of CoQ10 through caudal vein, respectively. Rats in the CoQ10-PEG-Lips+UTMD group were injected with 1 ml of CoQ10-PEG-Lips solution containing 10 mg/kg of CoQ10+100 mg of freeze-dried ultrasound microbubble powder through caudal vein and were given UTMD treatment at the same time, with the intervention given twice a week. After 12 weeks of intervention, cardiac function indexes [left ventricular end-systolic diameter (LVEDs), left ventricular end-diastolic diameter (LVEDd), and left ventricular ejection fraction (LVEF)]of each group were measured by ultrasonic cardiac function detection in vivo. Simultaneously, ex-vivo histopathological examination was conducted to assess myocardial cell morphology, cross-sectional area, collagen volume fraction (CVF), and apoptosis index (AI) in each group. Additionally, molecular biology techniques were employed to measure oxidative stress-related indicators and the expression of apoptosis-related pathway proteins. Results: The prepared CoQ10-PEG-lips had a well-rounded morphology, good dispersibility, and a high encapsulation efficiency of 87.45%±3.23%. After 12 weeks of intervention, the myocardial cell morphology in the CoQ10-PEG-Lips+UTMD group was intact, with orderly arrangement, closely resembling that of the normal control group. There were no statistically significant differences between the two groups in terms of LVEDs [(1.53±0.07) mm vs (1.42±0.04) mm], LVEDd [(2.93±0.15) mm vs (2.81±0.05) mm], or LVEF (80.76%±3.42% vs 84.60%±2.10%) (all P>0.05). Similarly, there were no significant differences between the two groups in myocardial cell cross-sectional area, CVF, or AI (all P>0.05). The CoQ10-PEG-Lips+UTMD group showed statistically significant differences in the above-mentioned indicators compared to the DM group, CoQ10 solution group, and CoQ10-PEG-Lips group (all P<0.05). In the CoQ10-PEG-Lips+UTMD group, the levels of myocardial superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and the expression of the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) were significantly higher compared to the DM model group, CoQ10 solution group, and CoQ10-PEG-Lips group (all P<0.05), while malondialdehyde levels and the expression of Bcl-2-associated X protein (Bax) and caspase-3 were lower (all P<0.05). Conclusions: Using PEG-lips to encapsulate the poorly soluble drug CoQ10 in combination with UTMD technology enables targeted delivery of the drug to the myocardium, which can help reduce myocardial cell damage, fibrosis, and apoptosis caused by diabetes mellitus (DM) by inhibiting oxidative stress damage and the Bcl-2/Bax/caspase-3 apoptosis signaling pathway, ultimately improving cardiac function in DCM rats.

The effect of 6-month treatment with coenzyme Q10 on endothelial, vascular and myocardial function in patients with nonalcoholic fatty liver disease

Abstract Background Patients with Non-alcoholic fatty liver disease (NAFLD) hold an increased cardiovascular risk and present impaired markers of vascular, endothelial and myocardial function. Coenzyme Q10 (CQ10) is a powerful antioxidant that enhances mitochondrial function. Patients/methods: 52 patients (52±10 years old) with NAFLD were randomized to 240 mg CQ10 (n=25) or placebo (n=27). We measured at baseline and at six months post-treatment: i) Perfused boundary Region (PBR) of the sublingual arterial microvessels (Microscan, Glycocheck), ii) Carotid femoral pulse wave velocity - PWV (Complior ALAM), iii) Flow-mediated dilation (FMD) of the brachial artery, iv) Global left ventricular longitudinal strain (GLS) by speckle tracking imaging, v) Controlled attenuation parameter (CAP) measurement (FibroScan, Echosens). Results Six months post treatment with cQ10, values of PBR (2.12±0.19 vs. 2.28±0.23 μm), PWV (9.5±2.3 vs. 10.5±2.4m/s), CAP score (278.1±50, 2 vs. 305.3±44.5dB/m), FMD (6.61±4 vs. 5.02±2.6 %) and GLS (-19.3±1.9 vs -18.2±2 %) were improved (p&amp;lt;0.05 for all comparisons). On the contrary, the patients who were treated with placebo did not show statistically significant differences in PBR, PWV, CAP score, FMD and GLS after from 6 months (p&amp;gt;0.05). In the patients who received cQ10, the percentage reduction of CAP score at 6 months was directly proportional to the percent reduction in PWV (r=0.31, p=0.045) and inversely proportional to the percentage increase in FMD (r=-0.58, p=0.014). Conclusion Six-month treatment with CoQ10 reduces liver steatosis in patients with NAFLD. CoQ10 is associated with improved endothelial, vascular and LV myocardial function in patients with NAFLD.

Twenty-Week Dietary Supplementation with Beeswax Alcohol (BWA; Raydel®) Ameliorates High-Cholesterol-Induced Long-Term Dyslipidemia and Organ Damage in Hyperlipidemic Zebrafish in a Dose-Dependent Manner: A Comparative Analysis Between BWA and Coenzyme Q10

Background/Objectives: Beeswax alcohol (BWA; Raydel®) is a blend of six long-chain aliphatic alcohols extracted from honeybee wax and is well known for its diverse functionality and health benefits. Herein, the efficacy of a BWA dietary intervention for 20 weeks was assessed to ameliorate high-cholesterol diet (HCD)-induced dyslipidemia and adverse effects on the vital organs of adult zebrafish. Methods: Adult zebrafish were fed different high-cholesterol diets (HCDs; final concentration of 4%, w/w) supplemented with BWA (final concentrations of 0.1%, 0.5% and 1.0%, w/w) or CoQ10 (final concentration of 1.0%). Following 20 weeks of supplementation, blood and different organs (liver, kidney, testes and ovaries) were collected, and biochemical, histological and immunohistochemical analyses were performed. Results: The results demonstrate a dose-dependent effect of BWA of mitigating HCD-induced mortality in zebrafish over the 20-week supplementation period, which was noticeably better than the effect exerted by coenzyme Q10 (CoQ10). Consistently, a dose-dependent effect of BWA consumption of curtailing HCD-induced total cholesterol (TC) and triglyceride (TG) levels and increasing high-density-lipoprotein cholesterol (HDL-C) levels was noticed. Compared with CoQ10 (final concentration of 1.0%, w/w), BWA (final concentration of 1.0%, w/w) displayed a significantly better effect of mitigating HCD-induced dyslipidemia, as evidenced by 1.2-fold (p &lt; 0.05) and 2.0-fold (p &lt; 0.05) lower TC and TG levels and 2.4-fold (p &lt; 0.01) higher HDL-C levels. The histological analysis revealed substantial prevention of fatty liver changes, reactive oxygen species (ROS) generation, cellular senescence and interleukin (IL)-6 production in the hepatic tissue of BWA zebrafish, which was significantly better than the effect exerted by CoQ10. Consistently, compared with CoQ10, significant 25% (p &lt; 0.05) and 35% (p &lt; 0.01) reductions in the HCD-induced elevated levels of the hepatic function biomarkers aspartate aminotransferase and alanine aminotransferase was observed in the BWA group. Likewise, BWA consumption efficiently ameliorated HCD-induced kidney, ovary and testis damage by inhibiting ROS generation, cellular senescence and lipid accumulation. Conclusion: Supplementation with BWA demonstrated higher therapeutic potential than that with CoQ10 to prevent dyslipidemia and organ damage associated with long-term consumption of HCDs.

ETFDH mutation involves excessive apoptosis and neurite outgrowth defect via Bcl2 pathway

The most common mutation in southern Chinese individuals with late-onset multiple acyl-coenzyme A dehydrogenase deficiency (MADD; a fatty acid metabolism disorder) is c.250G > A (p.Ala84Thr) in the electron transfer flavoprotein dehydrogenase gene (ETFDH). Various phenotypes, including episodic weakness or rhabdomyolysis, exercise intolerance, and peripheral neuropathy, have been reported in both muscular and neuronal contexts. Our cellular models of MADD exhibit neurite growth defects and excessive apoptosis. Given that axonal degeneration and neuronal apoptosis may be regulated by B-cell lymphoma (BCL)-2 family proteins and mitochondrial outer membrane permeabilization through the activation of proapoptotic molecules, we measured the expression levels of proapoptotic BCL-2 family proteins (e.g., BCL-2-associated X protein and p53-upregulated modulator of apoptosis), cytochrome c, caspase-3, and caspase-9 in NSC-34 cells carrying the most common ETFDH mutation. The levels of these proteins were higher in the mutant cells than in the wide-type cells. Subsequent treatment of the mutant cells with coenzyme Q10 downregulated activated protein expression and mitigated neurite growth defects. These results suggest that the activation of the BCL-2/mitochondrial outer membrane permeabilization/apoptosis pathway promotes apoptosis in cellular models of MADD and that coenzyme Q10 can reverse this effect. Our findings aid the development of novel therapeutic strategies for reducing axonal degeneration and neuronal apoptosis in MADD.