The goal of this clinical trial is to test the effects of MitoQ supplementation in older adults and frail older adults with physical dysfunction and/or cognitive dysfunction. The main question[s] it aims to answer are:
* To compare vascular function, oxidative stress levels, and physical and cognitive function among older adults and frail older adults with physical and cognitive dysfunction
* To determine whether MitoQ supplementation has the potential to improve vascular function in central and cerebral vessels
* To determine whether MitoQ supplementation can enhance physical and cognitive capabilities.

开始日期2024-09-26

申办/合作机构

University of Connecticut Health Center

[+2]

NCT06191965 / Not yet recruiting临床2/3期IIT

Double Blind, Randomized, Placebo-Controlled Study of MitoQ as Adjunctive Treatment for Patients With Early-phase Schizophrenia-spectrum Disorder and Mitochondrial Dysfunction

The goal of this double-blind, placebo-controlled randomized clinical trial is to test the effect of 12 weeks of orally administered MitoQ (mitoquinol mesylate) supplementation on cognition in 50 people with early phase schizophrenia-spectrum disorders (E-SSD) who have mitochondrial dysfunction (called high risk, or HR). Cognitive impairments in SSD can cause significant disability. Yet, there are no effective treatments for cognitive impairments in SSD. It has been shown that alterations in a certain type of brain cell (parvalbumin interneurons, or PVI) underlie cognitive deficits in SSD. These PVI, which fire at a fast rate, utilize high amounts of energy from the mitochondria and are highly vulnerable to oxidative stress. MitoQ is an antioxidant. Research has shown that, in mice, MitoQ can reduce oxidative stress in the mitochondria. The main question that this clinical trial aims to answer is:
• Does MitoQ supplementation, compared to placebo, improve cognition in HR patients?
Secondary questions that this clinical trial aims to answer are the following: Does MitoQ supplementation, compared to placebo:
Improve positive and negative symptoms of SSD in HR patients?
Improve functioning in HR patients?
Improve/normalize blood markers of mitochondrial dysfunction in HR patients?
The investigators will enroll 100 individuals with E-SSD. These enrolled participants will participate in an initial screening visit to determine if they qualify for the actual clinical trial. At the screening visit, the investigators will ask about psychiatric history to determine diagnosis; ask about medical history; do a physical exam; collect blood and urine samples; do a pregnancy test; and ask participants to bring in their current medications in their original packaging so it is known what they are taking.
After the screening visit, the investigators will invite 50 HR patients (identified with a blood test) to continue with the clinical trial. Participants who qualify for the clinical trial will be asked to:
Take a supplement (MitoQ or placebo) once per day for 12 weeks in addition to their usual medications.
Come in for a study visit every 4 weeks over the 16-week study period. At these study visits, the investigators will do a physical exam; ask about symptoms and side effects; take blood and urine samples; and ask questions about general health and well-being, quality of life, mental health, emotional health, and mood. At visits 1 (baseline) and 4 (12 weeks), participants will also take a cognitive assessment.

开始日期2024-06-01

申办/合作机构

McLean Hospital, Inc.

[+2]

NCT06351683 / Recruiting临床2期IIT

Mito-LUTS: A Pilot Study of the Effect of MitoQ on Lower Urinary Tract Symptoms in Older Women With Metabolic Syndrome

The goal of this clinical trial is to test the effect of a supplement called MitoQ (mitoquinol mesylate) on bladder symptoms such as urgency and frequency in women aged 50-75 years old who have the metabolic syndrome. The main questions it aims to answer are:
Is the study design feasible and acceptable to participants?
Do participants taking the study drug get any improvement to their bladder symptoms compared to participants taking a placebo (a look-alike substance that contains no drug)?
Participants will take 2 capsules of the study drug every morning for 4 months, answer many questions about their health including questions about their bladder health, perform physical and cognitive testing, give blood and urine samples, collect urine over 24 hour periods 3 times over the 4 months of the study, complete 3 day bladder diaries about how much they drink and void, undergo electrocardiograms, have their vitals and measurements (weight, height, waist circumference) taken, participate in 4 visits to the clinical research area and participate in many phone calls of varying length. Researchers will compare participants who were taking capsules containing MitoQ and participants taking capsules not containing MitoQ to see if MitoQ improves their bladder symptoms (urgency, frequency, nocturia, incontinence, etc.)

开始日期2024-04-03

申办/合作机构

University of Connecticut Health Center

[+1]

100 项与 Mitoquinone mesylate 相关的临床结果

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100 项与 Mitoquinone mesylate 相关的转化医学

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100 项与 Mitoquinone mesylate 相关的专利（医药）

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项与 Mitoquinone mesylate 相关的文献（医药）

2025-01-01·THERIOGENOLOGY

Mitoquinone improves porcine embryo development through modulating oxidative stress and mitochondrial function

Article

作者: Lee, Yumin ; Lee, Sanghoon ; Cho, Jongki ; Choi, Seunghyun ; Cha, Dabin

Oxidative stress caused by excess reactive oxygen species (ROS) is one of the main causes of low efficiency in in vitro production of embryos. These ROS can cause mitochondrial dysfunction and apoptosis, resulting in poor embryo development. Therefore, to prevent mitochondrial damage and apoptosis caused by ROS, we investigated the effects of mitoquinone (MitoQ), a mitochondrial-targeted antioxidant, on the in vitro culture (IVC) of porcine embryos. Various concentrations of MitoQ (0, 0.01, 0.1, or 1 nM) were supplemented during the entire period of IVC. The results showed that supplementation with 0.1 nM MitoQ significantly increased the blastocyst formation rate, with a higher total cell number including trophectoderm cell number and higher transcript expression of lineage-specific transcription factors in blastocysts. In addition, the 0.1 nM MitoQ-treated group showed a significantly lower percentage and number of apoptotic cells in blastocysts with positively regulated transcript expression of apoptosis-related genes. Therefore, 0.1 nM MitoQ was suggested as optimal concentration for porcine IVC and used for further investigations. MitoQ treatment significantly reduced intracellular ROS levels and increased glutathione levels in Day 2 embryos, with upregulated the transcript expression of antioxidant enzymes-related genes. Furthermore, the MitoQ group exhibited a significantly higher mitochondrial quantity, mitochondrial membrane potential, and ATP content in Day 2 embryos, with increased transcript expression of mitochondrial biogenesis-related genes. Taken together, these findings reveal that MitoQ supplementation can enhance the developmental competence of porcine embryos by decreasing oxidative stress and improving mitochondrial function.

2024-12-01·Molecular biology reports

Evaluation of the effect of mitoquinone on functional parameters, DNA structure, and genes expression related to the apoptotic and antioxidants of human sperm after freezing–thawing

Article

作者: Mazaheri, Fahime ; Tavakolpoor Saleh, Nafiseh ; Karami, Somayeh ; Shahandeh, Erfan ; Mirzaei Azandaryani, Zahra ; Mohammadi, Hiwa ; Moradi Gardeshi, Tohid

OBJECTIVE:

Sperm freezing is considered as an effective way in assisted reproductive technology (ART) programs, it has detrimental effects on sperm function, due to the production of reactive oxygen species (ROS). This study aimed to investigate the potential of Mitoquinone (MitoQ) in inhibiting the production of mitochondrial ROS during sperm freezing.

METHODS:

A total of 20 human normozoosperm samples were collected for this study. The samples were divided into four groups, each containing different concentrations of MitoQ (0, 0.2, 2, and 20 nM), and then subjected to the freezing process. After thawing, the sperm suspensions were evaluated for parameters including motility, morphology, acrosome integrity, adenosine triphosphate (ATP) level, intracellular ROS, viability, chromatin packaging, DNA denaturation, DNA fragmentation, as well as the expression of antioxidants (GPX, SOD) and apoptotic (Bax, Bcl₂) genes.

RESULTS:

The results showed that total and progressive mobility of sperms significantly increased in the 2 nM group, while significantly decreased in the 20 nM group (p ≤ 0.05). Sperm morphology did not significantly improve across all the tested concentrations (p ≥ 0.05). Intracellular ROS levels showed a significant decrease and increase in the concentrations of 2 and 20 nM, respectively (p ≤ 0.05). Furthermore, a significant increase was observed in viability, ATP, acrosome integrity, chromatin packaging, and non-denatured and non-fragmented DNA after treatment with 2 nM of MitoQ, compared with the control group (p ≤ 0.05). Regarding gene expressions, the relative expressions of oxidative stress genes were increased in the 2 nM group and decreased in the 20 nM group (p ≤ 0.05), while no significant difference was observed in the expressions of apoptotic genes compared with the control group (p ≥ 0.05). All the comparisons were made with respect to the control group.

CONCLUSION:

Adding the optimal concentration of MitoQ (2 nM) to the sperm freezing medium not only improves sperm functional parameters and reduces DNA damages, but also stimulates the expression of antioxidant genes, leading to even greater benefits for sperm cryopreservation.

2024-12-01·Current drug delivery

Volatile Oil of Magnolia biondii Pamp. for Transnasal Administration: Its Preparation, Characterization, and Mechanism of Action in the Treatment of Allergic Rhinitis

Article

作者: Wang, Xuan ; Zhou, Peijie ; Zhang, Xiaofei ; Wang, Yao ; Guo, Qiuting

Background::

Allergic Rhinitis (AR) is a common chronic nasal condition usually caused by allergens. The immune system overreacts when the body is exposed to allergens, releasing a lot of tissue chemicals that cause congestion, more secretions, and an inflammatory reaction in the nasal mucosa.

Method::

In clinical practice, it remains a significant public health issue. Modern pharmacological studies have demonstrated that Magnolia Volatile Oil (MVO) has good anti-inflammatory, antibacterial, immunomodulatory, and other pharmacological effects. Previous research and literature reports have reported that MVO has good therapeutic effects on allergic rhinitis. However, due to the poor water solubility of Magnolia, its bioavailability is low. The purpose of this present work is to develop a new microemulsion formulation to improve the stability and bioavailability of MVO.

Results::

The droplet size, PDI, and zeta potential of Magnolia volatile oil microemulsion (MVOME) were characterized along with its physical characteristics, and these values were found to be 14.270.03 nm, 0.09410.31, and -0.35850.12 mV, respectively, demonstrating the successful formation of microemulsion. In OVA-induced AR rats, MVO-ME dramatically reduced the serum levels of TNF-α, IL-1β, and IL-6 inflammatory factors. In addition, MVO-ME significantly inhibited the expression of protein levels of PPAR-γ and P65 in the nasal mucosa of AR rats. In this regard, we hypothesized that MVO-ME may play a therapeutic role in AR by activating the PPAR signaling pathway as well as inhibiting the activation of the NF/κB signaling pathway.

Conclusion::

MVO-ME has systematic advantages, such as high solubility, bioavailability, etc. It is expected to be an efficient nano-drug delivery system for the clinical treatment of allergic rhinitis.

项与 Mitoquinone mesylate 相关的新闻（医药）

2024-08-08

·梅斯医学

解密肝脏健康的密钥：“新星”成分与“老将”成分谁能更胜一筹？

在中国，每100个人里面，就有将近一半的人可能被检查出患有脂肪肝1。高糖高脂肪的饮食结构、长期饮酒、熬夜加班等，都可能是伤害肝脏的“凶手”。身体出现的乏力、肝部隐痛、食欲减退、恶心呕吐2等问题，都可能是肝脏发出的“求救信号”。对于已经受损的肝脏而言，仅靠生活习惯的调整和日常养护，其帮助肝脏恢复最佳状态的效果收效甚微。因此我们首先要帮助肝脏“净化”已经出现的伤口，才能做到“净肝”“护肝”双结合，在此基础上才能重新拥有一个健康的肝脏。 01 肝脏与脂肪肝肝脏是人体内最活跃的一个器官，它就像一个大工厂，掌管着我们体内的新陈代谢，负责包括碳水化合物、脂质、蛋白质和氨基酸等多种物质在内的代谢活动3。肝细胞就像是这个大工厂中不停运转的“机器”，肝脏大部分的生理任务都由他们完成。为了更高效地执行任务，他们需要线粒体作为“电池”，源源不断的为他们提供能量。每个肝细胞内都含有1000-2000个线粒体，参与包括尿素循环、铁代谢、钙储存稳态、细胞增殖和信号转导等多种重要的细胞活动。所以一旦线粒体功能出现异常，就容易导致肝脏的功能也会相应受损，无法完成代谢、解毒等任务，并引发一系列健康问题，如脂肪肝、肝硬化和肝癌等4。为什么线粒体受损会容易引起脂肪肝等肝脏问题呢？这是因为肝脏作为脂肪代谢的工厂，脂肪酸的摄取、储存、输出和氧化都能在此完成。一旦脂肪酸的摄取、储存与输出、氧化之间失去平衡，就有可能出现脂肪酸过度累积的现象。线粒体作为这条“生产链”上的“电池”，支持着脂肪酸氧化释放能量。所以一旦线粒体受损“停电”，就有可能导致脂肪酸没有动力进行氧化分解，而在体内不断累积，最终就有可能形成脂肪肝5。线粒体氧化产生过量的自由基（ROS）是其“停电”的主要原因之一。所以恢复肝脏功能的首要任务就是帮助线粒体抗氧化、解决ROS。如果将ROS视作线粒体工作过程中的“电阻”，有两种方法能将它解决。一种是给线粒体通行开辟另一条道路，绕过这个“电阻”中断它的反应。体现这种抗氧化方法的抗氧化剂常见的有辅酶Q10、还原型辅酶I（NADH）、微量元素（锌）、维生素A等。另一种方法则是直接将“电阻”去除。如超氧化物歧化酶（SOD）、过氧化氢酶等通常具备这种能力。这些都是线粒体抗氧化领域常见的“老将”，在解决脂肪肝问题上具有举足轻重的地位。然而近些年来，抗氧化界冉冉升起了一颗“新星”——MitoQ分子，目前国内外已有诸多学者对MitoQ分子展开了研究。今年6月份，由我国浙江大学和新西兰奥克兰大学针对于MitoQ分子的科研项目合作也已展开。那么作为后起之秀，它是否能成功“上位”，创造线粒体抗氧化领域的另一个传奇呢？作为一颗“新星”，它又具备了哪些与众不同的能力？ 02 解密线粒体抗氧化领域的“新星”成分 ——MitoQ 上世纪90年代，剑桥大学的Mike Murphy教授研发出一种线粒体靶向抗氧化剂——米托醌（MitoQ分子，后简称MitoQ）。和辅酶Q10一样，MitoQ也是通过中断“电阻”反应恢复线粒体功能。不同的是，辅酶Q10经常会被线粒体的双层膜结构“拒之门外”；而MitoQ在辅酶Q10的基础上还与亲脂性阳离子三苯基磷（TPP）结合，其中TPP就像一串“门禁密码”，帮助MitoQ直接进入线粒体内并不断累积，能更有效地防止线粒体氧化损伤和细胞死亡6。MitoQ的这个独到之处，让它在肝脏健康领域备受关注。它也通过各种证据向大家证明了它的实力。左图：MitoQ分子式；右图：MitoQ作用机制图。 1 MitoQ与酒精相关性脂肪肝炎：减少酒精诱导的脂肪变性和氧化损伤酒精会造成线粒体蛋白不可逆地被氧化，还会导致肝细胞膨胀和脂肪变性，造成脂肪酸代谢失调，引起脂质积累而发展成脂肪肝7。研究发现MitoQ可以抑制线粒体氧化和肝脂肪变性。实验中，研究人员通过给大鼠喂食乙醇制造出类似于人体内长期饮酒后的肝脏状态，并给它们使用不同剂量的MitoQ（5 和 25 mg/kg/天）。一段时间后，研究人员发现使用MitoQ能改善这些大鼠体内的脂肪变性，减少了含有不饱和脂质的脂肪性囊泡的数量和大小7。这个实验向大家证明了MitoQ能很好地改善酒精引起的脂肪变性，保护肝脏免受酒精诱导的氧化损伤。上图：MitoQ降低酒精引起的脂肪变性脂肪变性；下图：MitoQ减少脂肪性囊泡的数量和大小。 2 MitoQ改善非酒精性脂肪肝炎：减少脂肪变性，增加抗氧化分子 2023年MitoQ再次向大家证明，它不仅能改善酒精引起的脂肪肝，还能改善非酒精性脂肪肝炎。这项实验向大家证明了对于饮食诱导的脂肪肝，MitoQ也一样能有效减少脂肪变性和炎性病灶。而且，MitoQ治疗还能显著增加另一种形式的抗氧化剂分子：SOD和过氧化氢酶等，帮助线粒体抗氧化8。上图所示，添加MitoQ能减少脂肪变性和坏死性炎症反应。图a：肝脏脂肪变性和坏死性炎症的组织学评估。 3 MitoQ与酒精肝：恢复ALDH活性，加速乙醛清除酒精会导致肝脏内不断累积一种“剧毒”物质——乙醛。虽然线粒体中的乙醛脱氢酶2（ALDH2）就具有“解毒”作用。但是线粒体“解毒”同时会产生过量ROS/RON（活性氮），削弱ALDH2的功能9。研究发现，MitoQ能显著降低肝脏和血浆内的乙醛水平，帮助恢复ALDH的活性以加速乙醛清除9。上图所示使用MitoQ能降低乙醛水平，恢复ALDH活力。图： (A) 肝乙醇和乙醛浓度； (B) 血浆乙醇和乙醛浓度； (C) 肝脏 ALDH 活性； (D) 肝乙醇和乙醛代谢酶的表达。除了能对肝脏进行细胞级养护的MitoQ之外，一些其他成分也能有助于受损肝脏的恢复，如常见于咖啡豆中的绿原酸、保肝类产品中常出现的奶蓟草成分以及一些矿物质如锌、铬等，这些常见于市场的“老将”成分对于受损肝脏的恢复也能起到不错的疗效。 03 传统抗氧化剂：“前浪”选手的稳定发挥 1 绿原酸——减少脂肪堆积，提升肝脏代谢能力绿原酸是咖啡中仅次于咖啡因的物质，同样具备中和ROS的抗氧化功能10。同时它也能促进人体代谢，越来越多的研究证明绿原酸可以用来改善包括肥胖、血脂异常、胰岛素抵抗、非酒精性脂肪性肝等在内的疾病。研究人员发现使用绿原酸能帮助体脂含量在12周内下降3.6%，葡萄糖吸收减少6.9%11。这证明绿原酸能帮助人体维持血糖平衡，这对于肝脏调节糖分和改善新陈代谢具有重要作用。上表所示含绿原酸能帮助体脂从27.2%下降到23.6%。表：体脂平均值±标准差，持续12周 2 奶蓟草——降低肝脏脂质含量和MDA含量在很多传统保肝类产品中都能看到水飞蓟的存在。奶蓟草作为它的高纯度提取物同样具备这些功效。研究发现，奶蓟草不仅能加快体内代谢，降低肝脏内脂质含量，同时还能显著降低体内丙二醛（MDA）含量。其中MDA是脂质过氧化反应会产生的一种“有害物质”，它的存在会损伤肝细胞，影响其功能12。而奶蓟草能通过降低其含量，“净化”肝脏内环境。上图所示使用82天水飞蓟后血清超氧化物歧化（SOD）活性和丙二醛（MDA）含量。如图B所示，血清中MDA含量下降。图A：SOD活性；图B：MDA含量。 3 锌+铬——改善肝脏脂质代谢，减少甘油三酯累积锌作为一种常见的矿物质，以“促进生长发育，增强免疫力”的功能而被人们熟知。但其实它还能改善代谢紊乱和血脂异常13。有研究证明体内锌元素缺乏时，可能会引起肝脏的脂肪变性。所以，及时补充锌元素，也能使肝脏减少脂肪变性的可能14。同样是矿物质，铬元素通常会被忽视，但它也是人体所必需的存在。研究证明，铬同样具备保护肝脏的作用，能减少肝脏内甘油三酯的累积，升高代谢酶帮助肝脏脂质分解，对非酒精性脂肪肝具有一定保护作用15。肝脏作为一个默默无闻的“奉献者”，总是容易被人忽略。往往等人们意识到肝脏出现问题时，可能它已经跳跃式的发展成了“肝癌”等重症。因此需要我们主动给予它更多的关注和呵护，选择科学有效的成分能帮助人体修复受损肝细胞，清除自由基，让肝脏保持“通电”。当然，是选择“新星”成分还是相信传统“老将”成分，还需要更多时间去验证。如果这两者能强强联合，又会产生什么样奇妙的化学反应？当然，选择科学的成分很重要，改变生活习惯的重要性也不容忽视哦~ ---参考文献--- 1. Man S, Deng Y, Ma Y, et al. Prevalence of Liver Steatosis and Fibrosis in the General Population and Various High-Risk Populations: A Nationwide Study With 5.7 Million Adults in China. Gastroenterology. 2023 Oct;165(4):1025-1040. 2. 内科学第9版[M]. :人民卫生出版社, 2018. 391-405. 3. 中华医学会肝病学分会. 代谢相关（非酒精性）脂肪性肝病防治指南（2024年版）.2024，32（5）：418-434. 4. Chen P, Yao L, Yuan M, et al.Mitochondrial dysfunction: A promising therapeutic target for liver diseases. Genes Dis. 2023 Sep 17;11(3):101115. 5. 陈佳豪, 周振华. 肝细胞脂质代谢异常与线粒体功能障碍在NAFLD发病和疾病进程中的研究进展. 肝脏. 2023, 28(11):1372- 75. 6. Gane EJ, Weilert F, Orr DW, et al. The mitochondria-targeted anti-oxidant mitoquinone decreases liver damage in a phase II study of hepatitis C patients. Liver Int. 2010 Aug;30(7):1019-26. 7. Chacko BK, Srivastava A, Johnson MS, et al. Mitochondria-targeted ubiquinone (MitoQ) decreases ethanol-dependent micro and macro hepatosteatosis. Hepatology. 2011 Jul;54(1):153-63. 8. Turkseven S, Turato C, Villano G, et al. Low-Dose Acetylsalicylic Acid and Mitochondria-Targeted Antioxidant Mitoquinone Attenuate Non-Alcoholic Steatohepatitis in Mice. Antioxidants (Basel). 2023 Apr 21;12(4):971. 9. Hao L, Sun Q, Zhong W, et al. Mitochondria-targeted ubiquinone (MitoQ) enhances acetaldehyde clearance by reversing alcohol-induced posttranslational modification of aldehyde dehydrogenase 2: A molecular mechanism of protection against alcoholic liver disease. Redox Biol. 2018 Apr;14:626-636. 10. Olthof MR, Hollman PCH, Katan MB: Chlorogenic acid and caffeic acid are absorbed in humans. J Nutr 2000; 131: 66 – 71. 11. Thom E. The effect of chlorogenic acid enriched coffee on glucose absorption in healthy volunteers and its effect on body mass when used long-term in overweight and obese people. J Int Med Res. 2007 Nov-Dec;35(6):900-8. 12. Xiao, P., Ji, H., Ye, Y. et al. Dietary silymarin supplementation promotes growth performance and improves lipid metabolism and health status in grass carp (Ctenopharyngodon idellus) fed diets with elevated lipid levels. Fish Physiol Biochem 43, 245–263 (2017). 13. 中国营养学会. 中国居民膳食营养素参考摄入量（2013版）. 科学出版社. 14. Himoto, T., Nomura, T., Tani, J. et al. Exacerbation of Insulin Resistance and Hepatic Steatosis Deriving from Zinc Deficiency in Patients with HCV-Related Chronic Liver Disease. Biol Trace Elem Res 163, 81–88 (2015). 15. Chen WY, Chen CJ, Liu CH, Mao FC. Chromium attenuates high-fat diet-induced nonalcoholic fatty liver disease in KK/HlJ mice. Biochem Biophys Res Commun. 2010 Jul 2;397(3):459-64.

核酸药物

2024-07-02

·梅斯医学

深度解读中新两国备忘录：MitoQ分子解锁抗衰密码

2024年6月14日，中方赴新访问期间，签署了两国在推进健康老龄化慢性病防治的战略合作备忘录，该科研项目由浙江大学和新西兰奥克兰大学合作开展，由新西兰企业MitoQ LIMIT独家支持，成为此次新西兰中国商业伙伴关系签约仪式的唯一一个健康科研项目，致力于为全球健康老龄化提供有效方案。新西兰总理拉克森(Christopher Luxon)和贸易部长麦克莱(Todd McClay)及十二家新西兰企业与各自的中国合作伙伴签约代表贸易部长麦克莱(Todd McClay)与MitoQ LIMITED首席执行官Mahara lnglis、浙江大学杨廷忠教授及奥克兰大学代表 01 两国最新科研项目引领抗衰老领域新方向探索我国健康老龄化之路我国是世界上老年人口最多、老龄化速度最快的国家之一，预计2025年每5名中国人中就有1名60岁以上的老年人，近80%的老年人至少患有一种以上慢性病，健康状况不容乐观1。衰老是每个人必经且不可逆转的生命历程2，实现健康老龄化已成为全球主流课题。目前，线粒体靶向抗氧化剂是全球抗衰老研究热门方向。上世纪90年代，剑桥大学的Mike Murphy教授研发出一种线粒体靶向抗氧化剂——米托醌（MitoQ分子，后简称MitoQ）。经历漫长的沉淀，已有数百篇研究积极探索了MitoQ在抗衰老、改善心血管功能等细胞健康相关维度的益处。在此背景下，我国浙江大学和新西兰奥克兰大学展开合作，继续探索“健康老龄化”的前沿科技——MitoQ在临床中的作用与价值。 MitoQ分子，靶向直达细胞线粒体 02 衰老起始于人体内每一个细胞维持人体内“能量工厂”的正常运转是关键衰老是每一条皱纹，每一根白发，还是每一次体力衰退？其实这些都只是外在表现，真正的衰老悄然无声，始于体内每一个细胞，当其基本功能开始衰退，器官逐渐失去功能3，随之发生衰老相关慢性疾病4。是什么让细胞开始衰老？让我们深入内部，解开衰老“密码”。人体由37万亿细胞组成5，每个细胞中有数千个“能量工厂”——线粒体6，负责提供生命活动所需能量的80%-90%7。它们负责将食物中营养物质（葡萄糖、脂肪、蛋白质等）和氧气转化为ATP8——这是人体最主要、最基本的燃料，驱动细胞完成生理活动。然而“工厂”还会产生额外的副产物，这就是自由基9。自由基是一种含有不成对电子的化学物质，在人体内是一把“双刃剑”。正常情况下自由基对细胞信号传递、维持内环境稳态等多方面起重要作用10，但是随着年龄增长，线粒体功能下降，对自由基的“管理能力”下降，过量的自由基就会破坏细胞的形态和功能，引发氧化损伤，进一步加速衰老及相关慢性疾病的发生11,12。 03 MitoQ深入细胞内部的“能量工厂” 结合自由基助力细胞修复与机体年轻化有效对抗自由基对线粒体的破坏是抗衰老及心血管疾病的重要方向之一，近年来科学家们特别关注针对线粒体的抗氧化剂，帮助中和自由基，减轻氧化损伤，帮助延缓衰老13。MitoQ是目前研究最为热门的线粒体靶向抗氧化剂之一，与普通抗氧化剂相比，MitoQ有何神奇之处呢？ 1 MitoQ精准靶向线粒体，深入自由基产生“源头”，较其他非靶向抗氧化剂清除能力增强数百倍10 线粒体内部是产生自由基的“源头”，然而其双层膜结构通常会将普通的抗氧化剂“拒之门外”，导致较低的自由基清除效率，对抗线粒体氧化损伤的效果并不理想。而MitoQ在辅酶Q10的基础上结合了亲脂性阳离子三苯基磷 (TPP)，相当于搭载“智能导航系统”，快速定位并进入细胞线粒体，相比其他非靶向抗氧化剂，MitoQ在线粒体内的浓度大约高出 1000 倍，清除自由基的能力增强数百倍，有效减少线粒体损伤，发挥强大的抗氧化作用14,15。临床研究发现，MitoQ抑制并清除线粒体内部自由基的积累，保护细胞免受氧化应激损伤，焕发细胞活力16,17。 MitoQ显著降低线粒体氧自由基水平17 上图所示细胞内线粒体氧自由基变化平均荧光强度。相比HG组，添加MitoQ后荧光强度减弱，代表线粒体内自由基水平降低。 CON：正常对照组 HG：高糖损伤组（自由基水平增强） HG+MitoQ：高糖损伤组添加MitoQ MitoQ显著增强细胞活性17 上图所示细胞活性水平。相比HG组，添加MitoQ后细胞活性水平显著增强，接近正常细胞。 CON：正常对照组 HG：高糖损伤组，细胞活性下降 HG+MitoQ：高糖损伤组添加MitoQ 2 MitoQ在体内可循环利用，提高生物利用率，延长抗氧化作用时间 MitoQ具有“自我修复”的能力，可以在体内不断循环利用。进入线粒体后，首先完成清除自由基的“使命”，之后它会与线粒体里的其他复合物发生反应，再次变得活跃，实现循环再利用，从而清除更多的自由基。这种独特的循环利用机制，使得MitoQ能够在长时间内持续发挥抗氧化作用，保护线粒体免受氧化应激的损害19。 3 MitoQ改善人体内氧化应激水平，支持抗击衰老的同时改善血管功能、抑制大脑皮层神经元凋亡，多领域协同助力健康老龄化的实现自由基水平升高导致氧化应激，严重损害细胞健康，并加速机体衰老19。为了促进健康老龄化，体外研究发现，MitoQ提高机体抗氧化功能，提升细胞健康20，助力延缓衰老。首个改善人体血管功能的抗氧化剂临床研究发现，健康人群服用MitoQ 6周后氧化应激水平降低，血管功能显著改善21。 MitoQ显著改善体内氧化应激水平21 上图所示氧化应激标志物（氧化低密度脂蛋白）水平。相比安慰剂组，服用MitoQ明显降低13%氧化应激标志物浓度。 Placebo：安慰剂组 MitoQ：服用MitoQ组 MitoQ动脉扩张水平增加了42%21，这意味着血管“年轻”了15-20岁上图所示肱动脉血流介导扩张 (BAFMD)水平。相比安慰剂组，服用MitoQ明显提高42%动脉扩张率。 Placebo：安慰剂组 MitoQ：服用MitoQ组随着大众对健康意识的提升，不仅关注良好的生活方式，更重视饮食和营养成分的摄入。作为近年来抗衰研究的热门“黑科技”，MitoQ快速并持久降低线粒体内自由基水平，帮助改善血管功能，降低与年龄相关心血管疾病风险等。本次浙江大学和奥克兰大学的科研合作，积极践行《“健康中国2030”规划纲要》，进一步探索MitoQ在抗衰等更多细胞健康领域的突破与创新，迎接细胞的健康新生。 ---参考文献--- 1. 国家卫健委等. “十四五”健康老龄化规划. 国卫老龄发〔2022〕4号 2. China Kadoorie Biobank Collaborative Group. Healthy lifestyle and life expectancy free of major chronic diseases at age 40 in China. Nat Hum Behav. 2023 Sep;7(9):1542-1550. 3. O'Loghlen A. The potential of aging rejuvenation. Cell Cycle. 2022 Jan;21(2):111-116. 4. Guo, J., et al. Aging and aging-related diseases: from molecular mechanisms to interventions and treatments. Sig Transduct Target Ther 7, 391 (2022). https://doi.org/10.1038/s41392-022-01251-0 5. Roy AL, Conroy RS. Toward mapping the human body at a cellular resolution. Mol Biol Cell. 2018 Aug 1;29(15):1779-1785. 6. Pizzorno J. Mitochondria-Fundamental to Life and Health. Integr Med (Encinitas). 2014 Apr;13(2):8-15. 7. 付玉, 等. 线粒体生物学性状及细胞衰老和运动的影响. 中国组织工程研究. 2012, (11): 2063 -2066. 8. Khalil M, et al. The Potential of the Mediterranean Diet to Improve Mitochondrial Function in Experimental Models of Obesity and Metabolic Syndrome. Nutrients. 2022 Jul 28;14(15):3112. 9. Kowalczyk P, et al. Mitochondrial Oxidative Stress-A Causative Factor and Therapeutic Target in Many Diseases. Int J Mol Sci. 2021 Dec 13;22(24):13384. 10.汪启兵, 许凡萍, 魏超贤, 彭娟, 董旭东 . 人体内自由基的研究进展. 中华流行病学杂志, 2016, 37(8): 1175-1182 11. Lee YH, et al. Targeting Mitochondrial Oxidative Stress as a Strategy to Treat Aging and Age-Related Diseases. Antioxidants (Basel). 2023 Apr 15;12(4):934. 12. Stefanatos R, Sanz A. The role of mitochondrial ROS in the aging brain. FEBS Lett. 2018 Mar;592(5):743-758. 13. Braakhuis AJ, Nagulan R, Somerville V. The Effect of MitoQ on Aging-Related Biomarkers: A Systematic Review and Meta-Analysis. Oxid Med Cell Longev. 2018 Jul 12;2018:8575263. 14. Mao H, et al. Mitochondria-Targeted Antioxidant Mitoquinone Maintains Mitochondrial Homeostasis through the Sirt3-Dependent Pathway to Mitigate Oxidative Damage Caused by Renal Ischemia/Reperfusion. Oxid Med Cell Longev. 2022 Sep 20;2022:2213503. 15. Sun C, et al. MitoQ regulates autophagy by inducing a pseudo-mitochondrial membrane potential. Autophagy. 2017 Apr 3;13(4):730-738. 16. Pletjushkina OY, et al. Effect of oxidative stress on dynamics of mitochondrial reticulum. Biochim Biophys Acta. 2006 May-Jun;1757(5-6):518-24. 17. 王佳慧, et al. 抑制线粒体活性氧自由基可减轻高糖诱导的心肌细胞焦亡和铁死亡[J]. 南方医科大学学报, 2021, 41(7): 980-987. 18. Capeloa T, et al. Inhibition of Mitochondrial Redox Signaling with MitoQ Prevents Metastasis of Human Pancreatic Cancer in Mice. Cancers (Basel). 2022 Oct 7;14(19):4918. 19. Maldonado, E.; Morales-Pison, S.; Urbina, F.; Solari, A. Aging Hallmarks and the Role of Oxidative Stress. Antioxidants 2023, 12, 651. https://doi.org/10.3390/antiox12030651 20. Zhang S, et al. MitoQ Modulates Lipopolysaccharide-Induced Intestinal Barrier Dysfunction via Regulating Nrf2 Signaling. Mediators Inflamm. 2020 Apr 11;2020:3276148. 21. Rossman MJ, et al. Chronic Supplementation With a Mitochondrial Antioxidant (MitoQ) Improves Vascular Function in Healthy Older Adults. Hypertension. 2018 Jun;71(6):1056-1063. 免责声明：本文仅作最新前沿信息交流之目的，文中所有观点不代表梅斯医学立场，亦不代表梅斯医学支持或反对文中观点。如需获得治疗方案指导，请前往正规医院就诊！

2024-06-28

·今日头条

山西医科大学解军教授团队发文：线粒体移植，提高心肌能量供应，缓解心力衰竭

研究背景 01 心脏是新陈代谢旺盛、线粒体丰富的重要器官。线粒体稳态的破坏可降低心肌细胞的收缩功能，增加心力衰竭的风险。靶向线粒体已成为心力衰竭治疗的新方向。近年来间充质干细胞(MSCs)治疗在心力衰竭领域的应用逐渐受到关注，旨在通过直接细胞介导和/或间接旁分泌的机制保护心脏功能。MSCs治疗心力衰竭的潜在机制可能包括通过线粒体转移与微环境进行交流，以及修复线粒体功能障碍引起的心肌损伤。因此本研究提出了一种针对线粒体功能障碍的治疗方法，即人脐带间充质干细胞(hu-MSCs)衍生线粒体(MSC-Mito)移植治疗心力衰竭。这一治疗方法为心力衰竭患者提供了一种新的治疗策略，有望提高心力衰竭患者的生存率。文章要点 02 2024年5月31日，山西医科大学煤炭环境治病与防治教育部重点实验室的解军教授团队在《FASEB Journal》杂志的第38卷、第10期发表了题为《Mitochondria transplantation alleviates cardiomyocytes apoptosis through inhibiting AMPKα-mTOR mediated excessive autophagy》的文章，该研究成功地通过无创静脉注射将MSC-Mito移植到心肌，为心力衰竭提供了有效的治疗方法，并且探讨了线粒体移植治疗心力衰竭的机制。 https://doi.org/10.1096/fj.202400375R 该研究首先分离出hu-MSC来源的线粒体，通过流式和动态光散射(DLS)对其进行了详细的表征。通过对分离线粒体的膜电位（MMP）分析发现从hu-MSCs分离的线粒体在细胞外能够维持短期活性。随后将hu-MSC来源的线粒体通过无创静脉注射移植到小鼠心肌，并在体外与小鼠心肌细胞共培养，发现能被心肌成功摄取（图1）。图1 MSC - Mito的表征及其在HL-1细胞和小鼠心肌中的示踪接着，在小鼠心衰模型中进行线粒体移植，通过超声心动图和组织学分析等发现MSC-Mito移植能够缓解药物诱导的心脏毒性（图2），减少心肌线粒体损伤和心肌细胞凋亡（图3）。图2 MSC-Mito移植减轻DOX诱导的心力衰竭图3 MSC-Mito抑制心肌线粒体损伤及心肌细胞凋亡进一步通过测序（图4）及验证实验揭示MSC-Mito移植改善心力衰竭的机制。通过评估自噬相关基因表达及富集相关通路，发现MSC-Mito移植能够减轻心肌过度自噬（图5）。图4 mRNA表达谱及DE mRNA的GO和KEGG通路分析图5 MSC-Mito移植减轻心肌过度自噬及心肌凋亡最后从细胞水平验证得出，线粒体移植通过恢复心肌能量供应，抑制AMPK/mTOR通路介导的过度自噬来发挥心脏保护作用（图6）。图6 MSC-Mito移植提高心肌能量水平，抑制AMPK/mTOR诱导的过度自噬及示意图研究小结 03 近年来，心率衰竭的死亡率居高不下，现有的治疗药物仍不能扭转局面，因此，寻找改善患者预后的新疗法十分迫切。本研究首次分析了MSC-Mito移植对心肌能量产生及AMPK-mTOR信号轴的影响，阐明了其对心肌的潜在保护作用，此研究可能为心力衰竭提供一种新的治疗策略。参考资料： https://doi.org/10.1096/fj.202400375R 【关于投稿】转化医学网（360zhyx.com）是转化医学核心门户，旨在推动基础研究、临床诊疗和产业的发展，核心内容涵盖组学、检验、免疫、肿瘤、心血管、糖尿病等。如您有最新的研究内容发表，欢迎联系我们进行免费报道（公众号菜单栏-在线客服联系），我们的理念：内容创造价值，转化铸就未来！转化医学网（360zhyx.com）发布的文章旨在介绍前沿医学研究进展，不能作为治疗方案使用；如需获得健康指导，请至正规医院就诊。热门·直播/活动 🕓 上海｜06月20日 ▶ 【日程公布】合成生物学前沿技术与临床应用研讨会 🕓 北京｜09月20日-21日 ▶ 第五届单细胞技术应用研讨会暨空间组学前沿研讨会欢迎您的参与！点击对应文字查看详情

信使RNA临床1期

100 项与 Mitoquinone mesylate 相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
下尿路症状	临床2期	美国	University of Connecticut Health Center	2024-04-03
膀胱过度活动症综合征	临床2期	美国	University of Connecticut Health Center	2024-04-03
慢性丙型肝炎	临床2期	新西兰	Antipodean Pharmaceuticals, Inc.	2007-03-01
帕金森病	临床2期	澳大利亚	Antipodean Pharmaceuticals, Inc.	2006-05-01
帕金森病	临床2期	新西兰	Antipodean Pharmaceuticals, Inc.	2006-05-01
丙型肝炎	临床2期	-	Antipodean (UK) Ltd.	-
肝硬化	临床2期	新西兰	Antipodean Pharmaceuticals, Inc.	-
Friedreich共济失调	临床1期	新西兰	Antipodean Pharmaceuticals, Inc.	-
乳腺癌	临床前	-	Korea National University of Transportation	2024-04-30
阿尔茨海默症	临床前	新西兰	Antipodean Pharmaceuticals, Inc.	-

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05381454 (Pubmed) 人工标引	临床1/2期	新型冠状病毒感染	80	Mito-MES 20 mg	膚網艱鬱醖鹹鬱簾夢齋(鑰餘衊醖築壓願繭醖蓋) = 膚構壓餘鬱願製網鹹衊淵淵餘鏇廠網顧繭壓製 (齋糧鑰獵壓鑰齋選艱鏇 ) 更多	积极	2024-03-07
				Mitoquinone mesylateate	膚網艱鬱醖鹹鬱簾夢齋(鑰餘衊醖築壓願繭醖蓋) = 窪積簾顧鬱餘膚製鹹餘淵淵餘鏇廠網顧繭壓製 (齋糧鑰獵壓鑰齋選艱鏇 ) 更多
ASN2014	N/A	常染色体显性多囊肾病	-	MitoQ	憲膚範艱鑰顧網範壓壓(襯鹽襯鹹夢鑰選構鬱糧) = 範鹽網遞選鹽糧鑰廠膚選鏇遞鏇鑰簾築積築醖 (鬱艱廠鏇網範築憲齋膚 )	积极	2014-11-11
ASN2013	N/A	普通感冒	-	MitoQ	廠網網蓋製積窪鏇糧製(網製構夢餘襯蓋網鏇遞) = We also showed that adding MitoQ increased ATP after cold storage (24 hr) alone 觸鹽選積鏇膚網憲壓範 (鏇蓋範積積襯簾艱鬱窪 ) 更多	积极	2013-11-05
				Cold storage + MitoQ (100 μM)