Curcumin Supplementation for Improving Vascular and Cognitive Function

补充姜黄素可改善血管和认知功能

• 批准号: 9754868
• 负责人: Diana I Jalal
• 金额: $ 56.47万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-11-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9754868
• 关键词: Adult; Aging; Anti-inflammatory; Antioxidants; Ascorbic Acid; Attention; Blood Vessels; Cardiovascular Diseases; Center for Translational Science Activities; Characteristics; Chronic Kidney Failure; Clinical; Clinical Pharmacology; Clinical Practice Guideline; Clinical Research; Clinical Trials; Cognition; Cognitive; Collaborations; Colorado; Complication; Curcumin; Data; Diabetes Mellitus; Disease; Double-Blind Method; Elderly; Endothelial Cells; Endothelium; Episodic memory; Funding; Goals; High Prevalence; Human; Hypertension; Impaired cognition; Impairment; Incidence; Inflammation; Inflammatory; Infusion procedures; Intervention; Language; Measurement; Mediating; Medical; Memory; Mus; Nitric Oxide; Nutraceutical; Oral; Oxidants; Oxidative Stress; Patients; Physiologic pulse; Pilot Projects; Placebos; Population; Prevalence; Protocols documentation; Randomized; Reporting; Research; Research Personnel; Risk Factors; Short-Term Memory; Signal Transduction; Spices; Supplementation; System; Therapeutic; Therapeutic Effect; Therapeutic Intervention; Treatment Efficacy; Tumeric; United States National Institutes of Health; Universities; Vascular Diseases; Vascular Endothelial Cell; Vascular Endothelium; age related; arterial stiffness; brachial artery; cardiovascular disorder risk; cognitive function; cost; dietary supplements; effective therapy; endothelial dysfunction; epidemiology study; executive function; experience; high risk; improved; improved functioning; inflammatory marker; middle age; mortality risk; novel; patient population; peer; polyphenol; pre-clinical; processing speed; seal

Project Summary Patients with chronic kidney disease (CKD) are at increased risk of death from cardiovascular disease (CVD). Inflammation, oxidative stress, and vascular dysfunction (impaired endothelial function and increased large elastic artery stiffness) are highly prevalent in CKD and contribute to the high incidence of CVD in this patient population. In addition, patients with CKD suffer from high rates of cognitive decline for which we lack effective therapies. Thus, therapeutic interventions targeting inflammation, oxidative stress, vascular dysfunction, and cognitive impairment in CKD are a biomedical priority. Curcumin is a natural polyphenol with anti-inflammatory and antioxidant characteristics. It is safe and widely-available. Our preliminary data in old mice and healthy middle-aged (MA)/older adult humans indicate that curcumin administration improves endothelial dysfunction and large artery stiffness by reducing oxidative stress and inflammation. We also found that 12 weeks of curcumin supplementation improves episodic memory in MA/older adults. The primary goal of this R01 application is to extend our findings in healthy MA/older adults to patients with CKD, a growing clinical population with extensive baseline vascular dysfunction and cognitive impairment who presently have few treatment options. We propose that curcumin improves vascular endothelial function and large elastic artery stiffness in MA/older adults with stage IIIb and IV CKD (estimated GFR 15- 45 mL/min/1.73m2). We will also assess the possible mechanisms by which curcumin improves vascular function and determine if curcumin improves cognitive function in these patients. Specific aim 1a will determine if 12 months of curcumin supplementation will improve brachial artery-flow mediated dilation (BA-FMD) (endothelial function) and aortic pulse wave velocity (aPWV) (arterial stiffness) compared to placebo (randomized placebo-controlled double-blind study). Specific aim 1b will evaluate whether the curcumin-induced improvements in BA-FMD and aPWV are mediated by reduced oxidative stress, and will evaluate the effects of curcumin on systemic and endothelial cell markers of inflammation and oxidative stress. Importantly, specific aim 2 will evaluate the effects of curcumin supplementation on cognitive function, an important complication of CKD, using the NIH Cognitive Toolbox Battery. The study will be conducted by a highly experienced team of investigators at the Clinical and Translational Research Center at the University of Colorado-Denver Anschutz Medical Campus with support from Dr. Seals at the University of Colorado Boulder Campus and in collaboration with Dr. Tamura from Stanford University. Overall, the study has the potential to influence clinical practice guidelines in patients with CKD by establishing a novel, safe, and low-cost dietary supplement to reduce the burden of CVD in patients with CKD.

项目摘要 慢性肾脏病（CKD）患者死于心血管疾病的风险增加 （心血管疾病）。炎症、氧化应激和血管功能障碍（内皮功能受损， 增加的大弹性动脉硬度）在CKD中非常普遍，并导致 这一患者人群中的CVD。此外，CKD患者的认知能力下降率很高， 我们缺乏有效的治疗方法。因此，针对炎症、氧化应激， CKD中的血管功能障碍和认知障碍是生物医学优先考虑的问题。 姜黄素是一种天然多酚，具有抗炎和抗氧化特性。是安全 广泛可用。我们在老年小鼠和健康中年（MA）/老年人中的初步数据 表明姜黄素给药通过以下方式改善了内皮功能障碍和大动脉僵硬度 减少氧化应激和炎症。我们还发现，12周的姜黄素补充 改善MA/老年人的情景记忆。 本R 01应用的主要目标是将我们在健康MA/老年人中的发现扩展到以下患者： CKD，具有广泛基线血管功能障碍和认知障碍的临床人群不断增加 他们目前几乎没有治疗选择。我们认为姜黄素可以改善血管内皮细胞 功能和大弹性动脉僵硬度在MA/患有IIIb和IV期CKD的老年人中（估计GFR 15- 45 mL/min/1.73m2）。我们还将评估姜黄素改善血管内皮细胞的可能机制。 功能，并确定姜黄素是否改善这些患者的认知功能。 具体目标1a将确定12个月的姜黄素补充是否会改善肱动脉血流 介导的舒张（BA-FMD）（内皮功能）和主动脉脉搏波速度（aPWV）（动脉硬度） 与安慰剂相比（随机安慰剂对照双盲研究）。具体目标1b将评估 姜黄素诱导的BA-FMD和aPWV的改善是否是通过减少氧化应激介导的， 并将评估姜黄素对炎症的全身和内皮细胞标志物的影响 和氧化应激。重要的是，具体目标2将评估姜黄素补充剂对 认知功能，CKD的一个重要并发症，使用NIH认知功能成套测验。 本研究将由临床和转化中心经验丰富的研究者团队进行。 科罗拉多大学丹佛分校安舒茨医学院的研究中心。 在科罗拉多大学博尔德校区与斯坦福大学的田村博士合作 大学总体而言，该研究有可能影响CKD患者的临床实践指南 通过建立一种新的，安全的，低成本的膳食补充剂，以减少心血管疾病患者的负担， CKD。