Xanthohumol and Metabolic Syndrome
黄腐酚和代谢综合征
基本信息
- 批准号:8068856
- 负责人:
- 金额:$ 30.66万
- 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 2013-04-30
- 项目状态:已结题
- 来源:
- 关键词:AffectAmericanAnimal ModelAnimalsAntilipemic AgentsBeveragesBile AcidsBiochemicalBiologicalBiological AssayBiological FactorsBiological MarkersCYP7A1 geneCardiovascular DiseasesCatabolismCell Culture TechniquesCellsCenter for Translational Science ActivitiesChemopreventive AgentCholesterolCholesterol HomeostasisClinicalClinical ResearchClinical TrialsConsumptionDataDiagnosisDiseaseDoseDouble-Blind MethodDrug KineticsDyslipidemiasEndocrinologistEnzymesExcretory functionFlavonoidsFundingGenesGluconeogenesisGlucoseGlucose IntoleranceGoalsHealthHealth BenefitHealth SciencesHigh Density Lipoprotein CholesterolHumanHumulusHypertriglyceridemiaInsulin ResistanceKnowledgeLDL Cholesterol LipoproteinsLaboratoriesLiverLiver MicrosomesMarketingMass Spectrum AnalysisMeasuresMetabolic syndromeMetabolismMethodsModalityModelingNIH Program AnnouncementsNatural Products ChemistryNon-Insulin-Dependent Diabetes MellitusNonesterified Fatty AcidsOregonPatientsPharmaceutical PreparationsPlasmaProductionPublishingResearchResearch PersonnelRiskRisk FactorsSafetySalesSample SizeStructureTestingTherapeuticTimeTriglyceride MetabolismTriglyceridesUnited States National Institutes of HealthUniversitiesWorkbile acid transporterblood glucose regulationdietary supplementsefficacy trialglucose metabolismhepatoma cellhuman datahuman subjectimprovedinnovationinterestlipid metabolismmouse modelnovelpublic health relevancerandomized placebo controlled trialrapid growthreceptorresponse
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):最近的估计表明,超过5000万美国人患有代谢综合征(MetS),并有患心血管疾病和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葡萄糖耐受不良。参与血脂异常和葡萄糖代谢的许多基因通过调节法尼醇X受体(FXR)来调节。黄腐酚(XN),啤酒花(啤酒花)的主要异戊二烯类黄酮,调节FXR,并显示在MetS小鼠模型中降低血浆甘油三酯和葡萄糖。膳食XN补充剂最近已在市场上上市,以“改善整体健康”,但对其在人类中的功效和安全性知之甚少。我们的长期目标是确定XN和相关的异戊二烯类黄酮对人类的健康益处。本申请的目的是确定XN对培养的肝癌细胞和诊断为MetS的人中甘油三酯、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对脂质和葡萄糖代谢产生影响。拟议研究的基本原理是,成功完成研究将评估XN作为治疗MetS相关疾病的新型CAM模式的治疗潜力。 在具体目标1中,将在HepG 2肝癌细胞中确定XN对甘油三酯、胆固醇和葡萄糖水平的总体影响。我们的工作假设是XN剂量依赖性地影响甘油三酯,胆固醇,和葡萄糖代谢的FXR的调制。在特定目标2中,将在人体中确定XN对MetS标志物的总体影响。将对36名诊断为MetS的受试者进行双盲、随机、安慰剂对照研究,以确定两种剂量(20 mg和60 mg XN,一次/天)XN的安全性和疗效,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相关。临床试验之前将进行单次给药药代动力学(PK)研究,目的是确定PK参数并计算每个人类受试者的稳态血浆XN水平。 这项研究具有创新性,因为XN以前没有被评估为改善人类MetS的生物活性剂。鉴于成千上万的美国人在不了解XN的有效性和安全性的情况下长时间服用XN补充剂,迫切需要人体数据。
公共卫生相关性:成千上万的美国人正在服用含有黄腐酚(XN)的膳食补充剂,这是一种来自啤酒花(啤酒花)的异戊二烯类黄酮,用于改善一般健康状况,但XN的安全性和有效性尚未在人类中进行过研究。作为法尼醇X受体的调节剂,XN可能是一种有吸引力的天然产物,用于补充治疗代谢综合征相关疾病,并可为目前使用的抗高血压药和抗血糖药提供替代品,特别是对于不耐受这些治疗类药物的患者。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(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
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10791213 - 财政年份:2023
- 资助金额:
$ 30.66万 - 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
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7796306 - 财政年份:2010
- 资助金额:
$ 30.66万 - 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:
$ 30.66万 - 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:
$ 30.66万 - 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:
$ 30.66万 - 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:
$ 30.66万 - 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:
$ 30.66万 - 项目类别:
HYBRID TRIPLE QUADRUPOLE LINEAR ION TRAP MASS SPECTROMETER: CARDIOVASCULAR
混合三重四极杆线性离子阱质谱仪:心血管
- 批准号:
7335270 - 财政年份:2006
- 资助金额:
$ 30.66万 - 项目类别:
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