8-Prenylnaringenin: A Natural Therapy for Estrogen Deficiency

项目摘要 所有女性都会经历更年期，这使女性面临许多慢性疾病的风险，包括 增加肥胖的风险。虽然绝经后雌激素替代（激素替代疗法- 激素替代疗法）已被证明是有效的，在保护对代谢和炎症扰动相关的 对于雌激素缺乏症，HRT已被证明会造成不必要的健康风险，包括增加 中风心脏病和各种癌症因此，它已成为国家中心的优先事项， 补充和综合健康投资于开发既安全又 有效对抗绝经引起的副作用，包括过量脂肪量增加及其相关的 负代谢和炎症紊乱。其中一种潜在的替代疗法是 来自啤酒花植物（啤酒花）的植物雌激素，8-异戊二烯基柚皮素（8-PN）。整体研究 本申请的目的是确定1）安全有效地对抗 在雌激素缺乏的情况下，与肥胖相关的代谢和炎症扰动，2）组织 最响应于8-PN补充，和3）阐明8-PN作用的体内信号传导机制。 长期目标是为更年期的临床治疗开发一种安全有效的自然疗法- 相关的代谢障碍和炎症驱动的健康干扰。核心假设是， 8-PN可以作为一种有效和安全的天然治疗雌激素缺乏诱导的炎症和 代谢紊乱该项目的基本原理是，该临床前工作将为 利用8-PN作为代谢受损和炎症过程恶化的有效治疗剂 因为雌激素缺乏。中心假设将通过追求两个具体目标进行测试：1） 确定8-PN作为代谢和炎症治疗的有效和安全剂量 扰动雌激素缺乏模型，2）将检查骨骼肌是组织的假设， 通过雌激素受体α作用对8-PN治疗最有代谢反应。研究 在申请人看来，本申请中提出的方法是创新的，因为迄今为止，没有研究系统地 检查了8-PN对代谢和炎症干扰的保护能力，或彻底检查了8-PN对代谢和炎症干扰的保护能力， 评估了在雌激素缺乏模型中长期使用8-PN的潜在毒性。拟议研究 这项调查的结果将对所有妇女产生重要的积极影响， 因为他们将为未来使用8-PN作为治疗负面健康的临床试验奠定基础 与雌激素缺乏有关的副作用

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.