8-Prenylnaringenin: A Natural Therapy for Estrogen Deficiency

8-异戊二烯柚皮素：雌激素缺乏的自然疗法

• 批准号: 9892455
• 负责人: Reilly Enos
• 金额: $ 14.32万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-15 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9892455
• 关键词: Adipose tissue; Alternative Therapies; Anti-Inflammatory Agents; Biological Availability; Blood Chemical Analysis; Body Weight Changes; Cells; Chronic Disease; Clinical Treatment; Clinical Trials; Complementary Health; Data; Dose; Drug Kinetics; Estrogen Receptor alpha; Estrogen Replacements; Estrogen Therapy; Estrogens; Exhibits; Fatty acid glycerol esters; Female; Foundations; Future; Glucose Clamp; Goals; Gold; Health; Health Sciences; Hormone replacement therapy; Humulus; Hyperinsulinism; Immunologic Monitoring; Impairment; Inflammation; Inflammatory; Integrative Medicine; Investigation; Knockout Mice; Link; Lupus; Malignant Neoplasms; Mediating; Mediator of activation protein; Menopause; Menstruation; Metabolic; Modeling; Mus; Muscle; Muscle Fibers; Myocardial Infarction; Obesity; Ovarian; Pathologic; Phenotype; Phytoestrogens; Plants; Postmenopause; Process; Publishing; Radioisotopes; Research; Risk; Rodent Model; Side; Signal Transduction; Skeletal Muscle; Strategic Planning; Supplementation; Techniques; Technology; Testing; Therapeutic; Therapeutic Effect; Tissues; Toxic effect; Toxicology; Tracer; Training; United States National Institutes of Health; Woman; Women' s Health; Work; career; combat; effective therapy; experience; experimental study; falls; glucose metabolism; glucose uptake; in vivo; inflammatory milieu; innovation; insulin sensitivity; insulin sensitizing drugs; macrophage; obesity risk; pre-clinical; public health relevance; response; side effect; stroke risk; therapy development

PROJECT SUMMARY All women experience menopause, putting a female at risk for a number of chronic diseases, including an increased risk of obesity. Although post-menopausal replacement of estrogen (hormone replacement therapy - HRT) has been shown to be effective at protecting against the metabolic and inflammatory perturbations linked to estrogen-deficiency, HRT has been shown to pose unwanted health risks including an increased risk of stroke, heart attack, and a variety of cancers. As such, it has become a priority of the National Center for Complementary and Integrative Health to invest in the development of therapies that are both safe AND effective at combating menopause-induced side effects, including excess fat mass accrual and its related negative metabolic and inflammatory perturbations. One such potential alternative therapy is the potent phytoestrogen from the Humulus Lupus plant (hops), 8-prenylnaringenin (8-PN). The overall research objectives in this application are to determine 1) the dose of 8-PN that is both safe and effective at combating the metabolic and inflammatory perturbations linked to obesity in a setting of estrogen deficiency, 2) the tissue most responsive to 8-PN supplementation, and 3) elucidate the in vivo signaling mechanism of 8-PN action. The long-term goal is to develop a safe and effective natural therapy for the clinical treatment of menopause- associated metabolic impairments and inflammatory-driven health perturbations. The central hypothesis is that 8-PN can serve as a potent and safe natural therapeutic for estrogen-deficient-induced inflammatory and metabolic perturbations. The rationale for this project is that this pre-clinical work will lay the foundation for the utilization of 8-PN as a potent therapeutic for impaired metabolic and exacerbated inflammatory processes resulting from estrogen deficiency. The central hypothesis will be tested by pursuing two specific aims: 1) Determine the effective and safe dose of 8-PN to serve as a therapy for metabolic and inflammatory perturbations in an estrogen-deficient model, 2) will examine the hypothesis that skeletal muscle is the tissue most metabolically responsive to 8-PN therapy through estrogen-receptor alpha action. The research proposed in this application is innovative, in the applicant’s opinion, as, to date, no studies have systematically examined the protective capacity of 8-PN against metabolic and inflammatory perturbations or thoroughly assessed the potential toxicity of 8-PN’s long-term use in an estrogen-deficient model. The proposed research is significant as the results from this investigation will have an important positive impact for ALL women because they will lay the groundwork for future clinical trials using 8-PN as a therapy for the negative health side effects linked to estrogen deficiency.

项目摘要 所有女性都经历了更年期，使女性有多种慢性疾病的风险，包括 肥胖的风险增加。尽管绝经后替代雌激素（激素替代疗法 - HRT）已被证明有效地防止了相关的代谢和炎症扰动 对于雌激素缺乏性，HRT已被证明会带来不必要的健康风险 中风，心脏病发作和各种癌症。因此，它已成为国家国家中心的优先事项 互补和综合健康，以投资于既安全又有疗法的发展 有效地打击更年期引起的副作用，包括超过脂肪的准确性及其相关的副作用 负代谢和炎症扰动。一种潜在的替代疗法是有效的 来自Humulus Lupus植物（HOPS），8-丙烯基宁蛋白（8-PN）的植物雌激素。总体研究 本应用程序中的目标是确定1）既安全又有效作斗争的8-pn剂量 在雌激素缺乏症情况下与肥胖相关的代谢和炎症扰动，2） 最能响应8-PN补充，3）阐明了8-PN作用的体内信号传导机制。 长期目标是开发一种安全有效的自然疗法，用于对更年期的临床治疗 相关的代谢障碍和炎症驱动的健康扰动。中心假设是 8-PN可以作为雌激素缺陷引起的炎症性和的潜在安全自然疗法 代谢扰动。该项目的理由是，这项临床前的工作将为 利用8-PN作为代谢和加剧炎症过程受损的潜在疗法 雌激素缺乏症。中央假设将通过追求两个具体目标来检验：1） 确定8-PN的有效和安全剂量作为代谢和炎症的疗法 雌激素缺陷模型中的扰动，2）将检查骨骼肌是组织的假设 通过雌激素受体α动作对8-PN治疗的代谢最有反应。研究 该应用程序认为，在本应用程序中提出的是创新的，迄今为止，没有研究 检查了8-PN对代谢和炎症扰动的保护能力或彻底 评估了8-PN在雌激素缺陷模型中长期使用的潜在毒性。拟议的研究 意义重大，因为这项投资的结果将对所有妇女产生重要的积极影响 因为他们将使用8-PN作为负面健康的疗法为将来的临床试验奠定基础 与雌激素缺乏有关的副作用。