Xanthohumol and Metabolic Syndrome

黄腐酚和代谢综合征

基本信息

  • 批准号:
    7898150
  • 负责人:
  • 金额:
    $ 30.64万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-05-01 至 2012-04-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Recent estimates show that over 50 million Americans have metabolic syndrome (MetS) and are at risk for developing cardiovascular disease and type-2 diabetes. Risk factors that contribute to MetS include atherogenic dyslipidemia and glucose intolerance. Many genes involved in dyslipidemia and glucose metabolism are regulated by modulation of the farnesoid X receptor (FXR). Xanthohumol (XN), the principal prenylflavonoid of hops (Humulus lupulus), modulates FXR and was shown to lower plasma triglycerides and glucose in a mouse model of MetS. Dietary XN supplements have recently become available on the market to 'improve general health', but little is known regarding their efficacy and safety in humans. Our long-term goal is to determine the health benefits of XN and related prenylflavonoids in humans. The objective of this application is to determine the effects of XN on triglyceride, cholesterol and glucose homeostasis in cultured hepatoma cells and in humans diagnosed with MetS. Our central hypothesis is that XN exerts its effects on lipid and glucose metabolism by modulation of FXR. The rationale for the proposed research is that successful completion of the studies will provide an assessment of the therapeutic potential of XN as a novel CAM modality in the treatment of MetS-related disorders. In Specific Aim 1, the overall effect of XN on triglyceride, cholesterol and glucose levels will be determined in HepG2 hepatoma cells. Our working hypothesis is that XN dose-dependently affects triglyceride, cholesterol, and glucose metabolism by modulation of FXR. In Specific Aim 2, the overall effect of XN on markers of MetS will be determined in humans. A double-blinded, randomized, placebo-controlled study of 36 subjects with diagnosed MetS will be conducted to determine safety and efficacy of XN at two doses (20 mg and 60 mg XN once/day) and the magnitude of the effect on the biomarkers will be related to steady-state plasma levels of XN and its metabolites. The clinical trial will be preceded by a single-dose pharmacokinetic (PK) study with the aim to determine PK parameters and to calculate steady-state plasma XN levels for each of the human subjects. The proposed research in innovative, because XN has not previously been evaluated as a biologically active agent in the amelioration of MetS in humans. Human data are urgently needed in view of the fact that thousands of Americans are consuming XN supplements over prolonged periods of time without knowledge of XN's efficacy and safety. PUBLIC HEALTH RELEVANCE: Thousands of Americans are taking dietary supplements containing xanthohumol (XN), a prenylflavonoid from hops (Humulus lupulus), for improving general health, but XN's safety and efficacy have not been investigated in humans. As a modulator of the farnesoid X receptor, XN could be an attractive natural product for the complementary treatment of metabolic syndrome-related disorders and could provide an alternative for currently used antihyperlipidemics and antiglycemics, especially for patients that do not tolerate drugs in these therapeutic classes.
描述(由申请人提供):最近的估计显示,超过5000万美国人患有代谢综合征(METS),并面临发展为心血管疾病和2型糖尿病的风险。导致代谢综合征的危险因素包括致动脉粥样硬化性血脂异常和糖耐量减低。许多参与血脂异常和糖代谢的基因都受法尼醇X受体(FXR)的调节。黄腐酚(xanthohumol,XN)是啤酒花(Humulus Lupulus)中主要的戊烯基黄酮类化合物,它调节FXR,并被证明能降低Mets小鼠模型的甘油三酯和血糖。XN膳食补充剂最近已在市场上上市,以“改善一般健康”,但人们对其在人体内的有效性和安全性知之甚少。我们的长期目标是确定XN和相关的戊烯基黄酮类化合物对人类的健康益处。本应用的目的是确定XN对培养的肝癌细胞和诊断为甲硫氨酸的人的甘油三酯、胆固醇和葡萄糖稳态的影响。我们的中心假设是XN通过调节FXR而对脂和糖代谢产生影响。这项拟议研究的基本原理是,这些研究的成功完成将为XN作为一种治疗甲硫氨酸相关疾病的新的CAM方式的治疗潜力提供评估。在具体目标1中,XN对HepG2肝癌细胞甘油三酯、胆固醇和葡萄糖水平的整体影响将被确定。我们的工作假设是XN通过调节FXR来剂量依赖地影响甘油三酯、胆固醇和葡萄糖代谢。在具体目标2中,将确定XN对人类甲硫氨酸标志物的总体影响。一项针对36名确诊为甲型肝炎的受试者的双盲、随机、安慰剂对照研究将被用来确定两种剂量(每天一次,每次20毫克和60毫克)XN的安全性和有效性,对生物标志物的影响程度将与XN及其代谢物的稳态血浆水平有关。在临床试验之前,将进行单剂量药代动力学(PK)研究,目的是确定PK参数并计算每个受试者的稳态血浆XN水平。这项拟议中的研究具有创新性,因为XN之前尚未被评估为改善人类甲硫氨酸水平的生物活性制剂。鉴于数以千计的美国人在长期服用XN补充剂,而不知道XN的有效性和安全性,迫切需要人类数据。 与公共健康相关:数以千计的美国人正在服用含有黄腐酚(XN)的膳食补充剂,XN是一种来自啤酒花(Humulus Lupulus)的戊烯基黄酮类化合物,以改善一般健康,但XN的安全性和有效性尚未在人类身上进行调查。作为法尼类X受体的调节剂,XN可能是一种有吸引力的天然产品,用于代谢综合征相关疾病的补充治疗,并可能为目前使用的降血脂和降血糖药物提供替代药物,特别是对于那些不耐受这些治疗类别的药物的患者。

项目成果

期刊论文数量(0)
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会议论文数量(0)
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Jan Frederik Stevens其他文献

Correction to: Xanthohumol microbiome and signature in healthy adults (the XMaS trial): a phase I triple-masked, placebo-controlled clinical trial
  • DOI:
    10.1186/s13063-020-04834-w
  • 发表时间:
    2020-10-26
  • 期刊:
  • 影响因子:
    2.000
  • 作者:
    Ryan Bradley;Blake O. Langley;Jennifer J. Ryan;John Phipps;Douglas A. Hanes;Emily Stack;Janet K. Jansson;Thomas O. Metz;Jan Frederik Stevens
  • 通讯作者:
    Jan Frederik Stevens
Antiobesogenic Potential of Seaweed Dulse (Palmaria palmata) in High-fat Fed C57BL/6 J Mice (P21-014-19)
  • DOI:
    10.1093/cdn/nzz041.p21-014-19
  • 发表时间:
    2019-06-01
  • 期刊:
  • 影响因子:
  • 作者:
    Rufa Mendez;Cristobal Miranda;Courtney Armour;Thomas Sharpton;Jan Frederik Stevens;Jung Kwon
  • 通讯作者:
    Jung Kwon
Hop polyphenols for mitigating metabolic syndrome
蛇麻草多酚对代谢综合征的缓解作用
  • DOI:
    10.1016/j.freeradbiomed.2022.06.020
  • 发表时间:
    2022-08-20
  • 期刊:
  • 影响因子:
    8.200
  • 作者:
    Jan Frederik Stevens
  • 通讯作者:
    Jan Frederik Stevens

Jan Frederik Stevens的其他文献

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{{ truncateString('Jan Frederik Stevens', 18)}}的其他基金

Computation-assisted discovery of bioactive minor cannabinoids from hemp
计算辅助从大麻中发现生物活性次要大麻素
  • 批准号:
    10791213
  • 财政年份:
    2023
  • 资助金额:
    $ 30.64万
  • 项目类别:
Xanthohumol and Metabolic Syndrome
黄腐酚和代谢综合征
  • 批准号:
    8468320
  • 财政年份:
    2012
  • 资助金额:
    $ 30.64万
  • 项目类别:
Xanthohumol and Metabolic Syndrome
黄腐酚和代谢综合征
  • 批准号:
    8068856
  • 财政年份:
    2010
  • 资助金额:
    $ 30.64万
  • 项目类别:
Triple Quadrupole/Linear Ion Trap LC-MS/MS for LPI
用于 LPI 的三重四极杆/线性离子阱 LC-MS/MS
  • 批准号:
    7796306
  • 财政年份:
    2010
  • 资助金额:
    $ 30.64万
  • 项目类别:
Ascorbylation of Oxidized Lipids and Atherosclerosis
氧化脂质的抗坏血酸与动脉粥样硬化
  • 批准号:
    7230442
  • 财政年份:
    2006
  • 资助金额:
    $ 30.64万
  • 项目类别:
HYBRID TRIPLE QUADRUPOLE LINEAR ION TRAP MASS SPECTROMETER
混合三重四极杆线性离子阱质谱仪
  • 批准号:
    7335272
  • 财政年份:
    2006
  • 资助金额:
    $ 30.64万
  • 项目类别:
Hybrid triple quadrupole linear ion trap mass spectrometer
混合三重四极杆线性离子阱质谱仪
  • 批准号:
    7047369
  • 财政年份:
    2006
  • 资助金额:
    $ 30.64万
  • 项目类别:
Ascorbylation of Oxidized Lipids and Atherosclerosis
氧化脂质的抗坏血酸与动脉粥样硬化
  • 批准号:
    7619615
  • 财政年份:
    2006
  • 资助金额:
    $ 30.64万
  • 项目类别:
Ascorbylation of Oxidized Lipids and Atherosclerosis
氧化脂质的抗坏血酸与动脉粥样硬化
  • 批准号:
    7094437
  • 财政年份:
    2006
  • 资助金额:
    $ 30.64万
  • 项目类别:
Ascorbylation of Oxidized Lipids and Atherosclerosis
氧化脂质的抗坏血酸与动脉粥样硬化
  • 批准号:
    7413609
  • 财政年份:
    2006
  • 资助金额:
    $ 30.64万
  • 项目类别:

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