Regulatory effects of coenzyme Q10 on the immunological activity of mice

To examine how coenzyme Q10 (CoQ₁₀)regulates immunity, experiments using low, middle and high doses of CoQ₁₀were conducted in mice to confirm its non-toxicity and non-genotoxicity. Delayed type hypersensitivity (DTH) and MTT assays were used to to examine various lymphocyte transformations, the proliferation of antibody-producing cells, the phagocytotsis activity of macrophages, and the activity of nature killer cell (NK). High-dose (0.50 g/kg.bw) CoQ₁₀ increased DTH levels and promoted the proliferation of antibody-producing cells and levels of red blood cell hemolysis. Medium and high doses enhanced the phagocytic ratio of macrophages but didnot influence other indexes. These results showed that the applied CoQ₁₀ did not exhibit any toxicity or genotoxicity, and CoQ₁₀ can actually improve immunologic function in mice.     

复方丹参注射液、辅酶Q10治疗病毒性心肌炎疗效观察

目的观察复方丹参注射液、辅酶Q10治疗病毒性心肌炎(VMC)的临床疗效.方法22例VMC患儿在常规治疗基础上加用复方丹参注射液及辅酶Q10治疗并观察4周,并与20例常规治疗患儿对照.结果治疗组总有效率(86.4%)明显优于对照组(65.0%),P＜0.05.结论复方丹参注射液、辅酶Q10治疗VMC有较好的疗效.     

环磷腺苷联合辅酶Q10在病毒性心肌炎患者临床治疗中的应用价值

目的探究环磷腺苷联合辅酶Q10应用于病毒性心肌炎患者临床治疗中的效果。方法选取2020年4月至2022年4月在聊城市第二人民医院进行治疗的病毒性心肌炎患者95例为本次研究对象, 采用电脑随机数字表法将其分为对照组与联合组。对照组48例, 其中男27例, 女21例, 年龄20～50(35.21±7.04)岁;联合组47例, 其中男22例, 女25例, 年龄为20～45(33.74±6.75)岁。对照组予以常规疗法加环磷腺苷治疗, 联合组予以常规疗法加环磷腺苷和辅酶Q10治疗。比较两组患者的临床疗效、氧化应激指标水平、心肌损伤标志物水平及用药不良反应, 采用t检验、χ2检验进行统计分析。结果联合组有效率为97.87%(46/47), 对照组为83.33%(40/48), 两组比较, 差异有统计学意义(P<0.05)。治疗后, 两组超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)水平均高于治疗前, 丙二醛(MDA)水平均低于治疗前(均P<0.05);治疗后, 联合组SOD为(84.31±12.04)IU/L、GSH-Px为(95.47±11.93...     

Effect of coenzyme Q10 on cutaneous healing in skin-incised mice

Coenzyme Q10 (CoQ10) is a biosynthesized quinone with 10 isoprene side chains in humans. To investigate the anti-inflammatory and wound healing effect of CoQ10, we performed in vivo and in vitro experiments. In vivo studies, there were 3 groups; Naive (without skin incision), Control (with skin incision) and CoQ10 (100 mg/kg treatment with skin incision). Collagen-like polymer (CLP) level of CoQ10 group was increased significantly compared to the control group (p<0.05). Also, CoQ10 group showed significant inhibition on myeloperoxidase (MPO) and PLA₂ level compared to the control group (p<0.05). These data show that CoQ10 may have an anti-inflammatory and a wound healing effect. CoQ10 showed significant antioxidant activity in vivo on malondialdehyde (MDA) and superoxide dismutase (SOD) levels compared to the control group (p<0.05). Although CoQ10 did not show antioxidant activity in cell free system of DPPH radical scavenge, it had a potent antioxidant activity in cell culture system of both silica- and zymosan-induced reactive oxygen species generation using Raw 264.7 cells. This result may be associated with the conversion of CoQ10 to the reduced form (CoQ10H₂) in the presence of some kinds of intracellular reducing agents. In conclusion, it is considered that CoQ10 appears to have a cutaneous healing effect in vivo, which may be related to the secondary action of CoQ10.     

Survival effect of coenzyme Q10 and naloxone on experimental stroke gerbils

Coenzyme Q10 (CoQ10) and the opiate antagonist naloxone were compared as to their effect on the survival of mongolian gerbils with unilateral carotid ligation-induced stroke. Without medication all of the stroke gerbils died within 28 hours, but with a subcutaneous implantation of a 10 mg pellet of naloxone, 20% of the gerbils lived for 4 weeks. When a 250 mg pellet of CoQ10 was implanted subcutaneously, a definite effect on survival was observed, with 45% of the stroke gerbils living for 4 weeks. Considering that the action mechanisms of CoQ10 and naloxone are different, the combined use of these drugs in the treatment of stroke needs to be investigated.     

Therapeutic use of coenzyme Q10 and coenzyme Q10-related compounds and formulations

Importance of the field: Coenzyme Q₁₀ (CoQ₁₀) is found in blood and in all organs. CoQ₁₀ deficiencies are due to autosomal recessive mutations, ageing-related oxidative stress and carcinogenesis processes, and also statin treatment. Many neurodegenerative disorders, diabetes, cancer and muscular and cardiovascular diseases have been associated with low CoQ₁₀ levels, as well as different ataxias and encephalomyopathies.

Areas covered in this review: We review the efficacy of a variety of commercial formulations which have been developed to solubilise CoQ₁₀ and promote its better absorption in vivo, and its use in the therapy of pathologies associated with low CoQ₁₀ levels, with emphasis in the results of the clinical trials. Also, we review the use of its analogues idebenone and MitoQ^®.

What the reader will gain: This review covers the most relevant aspects related with the therapeutic use of CoQ₁₀, including existing formulations and their effects on its bioavailability.

Take home message: CoQ₁₀ does not cause serious adverse effects in humans and new formulations have been developed that increase CoQ₁₀ absorption. Oral CoQ₁₀ is a viable antioxidant strategy in many diseases, providing a significant to mild symptomatic benefit. Idebenone and MitoQ are promising substitutive CoQ₁₀-related drugs which are well tolerated and safe.     

辅酶Q10对他汀类药物引起肌病的影响

羟甲基戊二酸单酰辅酶A(HMG-CoA)还原酶抑制剂即他汀类药物,目前临床广泛用于高血脂症的治疗.他汀类药物引起的不良反应肌病越来越受到关注.辅酶Q10(CoQ10)的缺乏则是引起肌病的重要原因,而他汀药物可能通过抑制CoQ10的合成及转运,减少血液循环中的CoQ10,对肌肉组织和线粒体中CoQ10的水平也有一定影响.试验证明,CoQ10和他汀类药物联合使用可以缓解他汀类药物引起的肌痛症状.文中综述了他汀类药物对血液循环和肌肉组织中CoQ10影响、他汀类药物对线粒体损伤及联用CoQ10后缓解他汀类药物引起的肌痛的研究进展.     

Inhibitory effects of several anthracyclines on mitochondrial respiration and coenzyme Q10 protection

A set of three novel anthracyclines, active as antitumour agents, has been examined for their possible effects on rat heart mitochondrial respiration. The in vitro inhibiting effects of the compounds have been compared with that of the older doxorubicin. Aclacinomycin was generally more inhibitory than doxorubicin, 4'-epi-doxorubicin and 4'-epi-tetrahydropyranyl-adriamycin, with both succinate and NAD+-linked substrates. Attempts to prevent anthracycline from inhibiting the succinate oxidase activity by means of adding exogenous coenzyme Q10 gave encouraging results, the inhibiting effect being in fact reduced.     

Testicular toxicity effects of magnetic field exposure and prophylactic role of coenzyme Q10 and L-carnitine in mice.

The protective effect of L-carnitine or coenzyme Q10 (CoQ10) against high magnetic field (20 mT) induced testicular toxicity in mice were evaluated. Animals were injected with L-carnitine (200 mg kg(-1), i.p.) or CoQ10 (200 mg kg(-1), p.o.) 1h before exposure to fractionated doses (30 min per day, three times per week for 2 weeks) or acute dose (3h) of magnetic field. Total sperm count, motility, daily sperm production, and testicular LDH-X activity as well as histopathological examination were investigated. Exposure of mice to fractionated doses of magnetic field caused a significant decrease in sperm count, motility, daily sperm production, and LDH-X activity, which was more pronounced than that of acute dose. Moreover, a marked testicular histopathological changes were observed after exposure to fractionated doses of magnetic field. Pretreatment of mice with L-carnitine or CoQ10 1h before exposure to magnetic field caused a significant recovery of mice testes damage induced by high magnetic field (20 mT).     

The mechanism of carvedilol in experimental viral myocarditis

Carvedilol is a nonselective β-blocker with α1-adrenergic blocking and antioxidant properties. A number of preclinical experiments and clinical trials have demonstrated that carvedilol provides prominent benefit in heart failure. However, less research has been done in the area of animal models of viral myocarditis. This paper reviews the use of carvedilol in animal models of viral myocarditis. The experimental evidence strongly suggests that carvedilol, but not metoprolol (a selective β1-adrenergic blocking agent), protects against viral myocarditis and the superior cardioprotection effect of carvedilol to metoprolol may be due to its upregulating the production of antiinflammatory cytokines, downregulating the production of proinflammatory cytokines, antioxidative effects, the suppression of matrix metalloproteinases production, and positive hemodynamic effects.     

国产辅酶Q10有关物质的评价研究

目的综合考察国产辅酶Q10有关物质的含量情况。方法参考美国药典和欧洲药典,采用HPLC法测定了31批辅酶Q10原料及其各种类型制剂中辅酶Q9和(2Z)-异构体的含量。结果辅酶Q10原料及其各种类型制剂中均检出辅酶Q9和(2Z)-异构体。结论该研究可为国产辅酶Q10质量评价提供实验数据。     

Research on coenzyme Q10 in clinical medicine and in immunomodulation

Coenzyme Q10 (CoQ10) is a redox component in the respiratory chain. CoQ10 is necessary for human life to exist; and a deficiency can be contributory to ill health and disease. A deficiency of CoQ10 in myocardial disease has been found and controlled therapeutic trials have established CoQ10 as a major advance in the therapy of resistant myocardial failure. The cardiotoxicity of adriamycin, used in treatment modalities of cancer, is significantly reduced by CoQ10, apparently because the side-effects of adriamycin include inhibition of mitochondrial CoQ10 enzymes. Models of the immune system including phagocytic rate, circulating antibody level, neoplasia, viral and parasitic infections were used to demonstrate that CoQ10 is an immunomodulating agent. It was concluded that CoQ10, at the mitochondrial level, is essential for the optimal function of the immune system.     

辅酶Q10中枢神经系统的安全性评价

目的 考察大剂量ig辅酶Q10对小鼠中枢神经系统的影响,为临床安全性评价提供实验依据。方法 将小鼠随机分为溶媒对照组、紫苏油对照组、阳性对照组（氯丙嗪或地西泮）和辅酶Q10低、中、高剂量组（1.5、3.0和6.0 g/kg,相当于临床等效剂量的75、150和300倍）,每组12只,雌雄各半,40 mL/kg单次ig给药。直接观察小鼠一般行为活动;转棒法观察小鼠运动协调能力;Anymaze动物行为学视频分析系统观察小鼠自发活动和与阈下剂量戊巴比妥钠的协同作用。结果 与溶媒对照组、紫苏油对照组比较,辅酶Q10 3个剂量组对小鼠一般行为活动、自发活动、运动协调能力和与阈下剂量戊巴比妥钠的协同作用均无显著差异。结论 大剂量ig辅酶Q10对小鼠中枢神经系统未见明显毒性作用。     

纳米脂质体包载辅酶Q10改善血管性痴呆小鼠学习记忆功能的实验研究

目的：研究新型纳米脂质体包载辅酶Q10对血管性痴呆小鼠学习记忆功能的影响及其作用机制。方法：采用薄膜分散法结合超声水合法制备包载辅酶Q10的纳米脂质体并对其进行质量表征。应用双侧颈总动脉夹闭法建立小鼠血管性痴呆（Vascular Dementia,VaD）模型,将实验小鼠随机分成假手术组、模型组、辅酶Q10溶液组及辅酶Q10纳米脂质体组并给于相应的药物治疗。药物干预结束后,应用Morris水迷宫的定位航行及空间探索实验评价各组小鼠的学习及记忆功能,同时采用Western blot结合ELISA分析小鼠海马组织核因子E-2-相关因子-2（Nuclearfactor erythroid-2-related factor-2,Nrf-2）表达及超氧化物歧化酶（Superoxide dismutase,SOD）、丙二醛（Malonaldehyde,MDA）含量探讨辅酶Q10对于血管性痴呆的作用机制。结果：载药纳米脂质体形态圆整、分散性好,粒径小于100 nm,包封率高达89.43%±3.43%。Morris水迷宫实验显示,模型组小鼠的平均逃避潜伏期显著高于假手术组（P<0.05）,平台穿越次数及停留时间显著低于假手术组（P<0.05）,相比于模型组,辅酶Q10溶液组及纳米脂质体组的平均逃避潜伏期显著降低（P<0.05）,平台穿越次数及停留时间显著升高（P<0.05）,其中纳米脂质体组行为学改善更加明显,水迷宫指标较单纯溶液组相比有显著性差异（P<0.05）。Western blot及ELISA分析证实,相比于模型组,应用不同形式辅酶Q10治疗干预组小鼠海马组织Nrf-2蛋白表达及SOD含量显著升高（P<0.05）,MDA含量显著下降（P<0.05）。结论：应用纳米脂质体包载辅酶Q10能够增加药物的入脑效率,通过调控Nrf-2/ARE途径抑制VaD小鼠脑内的氧化应激损伤,改善VaD动物的学习及认知功能,有望成为治疗VaD的新型药物形式。     

辅酶Q_(10)微生物发酵生产的研究进展

利用微生物发酵生产的辅酶Q10(CoQ10)产物活性好,并可通过诱变育种和优化工艺大幅度提高生产能力。文章综述菌种的突变育种、发酵工艺的优化。     

The effect of coenzyme Q10 on the action of phospholipase

Using dimyristoyl L-alpha-phosphatidylcholine as a substrate, the effect of coenzyme Q10 on phospholipid digestion by phospholipase A2 and phospholipase C was investigated. Free myristic acids released by phospholipase A2, and myristic acids of dimyristoyl glyceride released by phospholipase C were methylated and determined quantitatively by gas-chromatography. Phospholipase A2 or phospholipase C released myristic acids dose-dependently from the substrate. Coenzyme Q10 prevented dose-dependently the hydrolysis of the substrate caused by phospholipase. These results suggest that pharmacological action of coenzyme Q10 could be attributed to its protection of membrane phospholipids against the attack of phospholipases.     

辅酶Q10在正己烷溶液中的稳定性研究

目的 考察辅酶Q10 在其异构体检测配制的正己烷溶液中的稳定性情况。方法 参考《美国药典》、《欧洲药典》、《中国药典》2010 年版等法定标准要求的辅酶Q10 原料异构体检测方法,最终采用《中国药典》方法,选取5 批,3 个不同来源的辅酶Q10 产品,分别将异构体检测溶液置于棕色量瓶和透明量瓶中,放置0、3、5 h,对比异构体检测HPLC 图谱各杂质峰面积归一化百分比的变化情况。结果 该研究通过一系列试验证实了异构体检测溶液在存放过程会发生降解,从而导致检测结果的偏差。结论 辅酶Q10 异构体检测样品溶液配制必须临用新配,避光操作。     

Synthesis of deuterium‐labelled coenzyme Q10

Deuterium‐labelled coenzyme Q₁₀ ([2‐CD₃‐1′‐CD₂]coenzyme Q₁₀, coenzyme Q₁₀‐d₅ ) was synthesized by condensation of 2,3‐dimethoxy‐[5‐CD₃]methyl‐1, 4‐hydroquinone with [1‐CD₂]decaprenol. Five positions were selected for deuteration as replacement at these positions allowed examination of every step of the synthesis. This examination was carried out by a combination of ¹H‐ and ¹³C‐nuclear magnetic spectrometry and mass spectrometry. Further, these positions have been proved to be metabolically stable. This reagent makes simultaneous quantification of the source of coenzyme Q₁₀ (exogenously supplied or endogenously supplied) possible in biological samples by measurements on gas chromatography–mass spectrometry. Copyright © 2002 John Wiley & Sons, Ltd.     

Effect of coenzyme Q10 on hemodynamic response to ocular timolol

Coenzyme Q10 (CoQ10) is an essential component of the mitochondrial membrane and plays an important role in the maintenance of normal cardiac function. To evaluate the effects of ocular timolol on the cardiovascular system and determine the protective effect of CoQ10, 16 patients with glaucoma were studied using impedance cardiography. Following instillation of 1 mg timolol maleate in each eye, heart rate (HR) and stroke index (SI) decreased, and total peripheral resistance index (TPRI) increased significantly. Reexamination was performed after 6 weeks of 90 mg oral CoQ10. Despite decreases in HR, percent changes in HR were significantly less after CoQ10 at 120 min. Stroke index showed an initial increase which was not observed without CoQ10. These data suggest that CoQ10 delayed the appearance of inotropic blockade of timolol and hastened the disappearance of chronotropic blockade. Additional study of six normal volunteers with 6 weeks of oral CoQ10 showed a similar decrease of intraocular pressure after timolol instillation as compared to those without CoQ10. Thus, administration of oral CoQ10 in patients receiving ocular timolol may be useful in mitigating cardiovascular side effects without affecting intraocular pressure in the treatment of glaucoma.