8-Prenylnaringenin: A Natural Therapy for Estrogen Deficiency

项目总结 所有女性都会经历更年期，这会使女性面临许多慢性病的风险，包括 肥胖风险增加。尽管绝经后雌激素的替代疗法(激素替代疗法-- HRT)已被证明有效地预防与代谢和炎症有关的扰动 由于雌激素缺乏，荷尔蒙替代疗法已被证明会带来不必要的健康风险，包括增加 中风、心脏病发作和多种癌症。正因为如此，它已经成为国家研究中心的优先事项。 补充和综合健康投资于开发既安全又安全的疗法 有效对抗更年期引起的副作用，包括过量脂肪堆积及其相关 消极的新陈代谢和炎症干扰。一种这样的潜在替代疗法是有效的 从狼疮属植物中提取的植物雌激素，8-戊烯基柚皮苷(8-PN)。整体研究 本应用的目的是：1)确定安全有效的8-PN的剂量 在雌激素缺乏的情况下与肥胖有关的代谢和炎症干扰，2)组织 3)阐明了8-PN作用的体内信号机制。 长期目标是开发一种安全有效的自然疗法来治疗更年期的临床-- 相关的代谢损伤和炎症驱动的健康扰动。中心假设是 8-PN可作为一种有效而安全的天然疗法来治疗雌激素缺乏所致的炎性和 代谢紊乱。这个项目的基本原理是，这项临床前工作将为 8-PN对代谢受损和炎症加重的有效治疗作用 由雌激素缺乏引起的。核心假设将通过追求两个具体目标来检验：1) 确定8-PN作为代谢和炎症治疗的有效和安全剂量 雌激素缺乏模型中的扰动，2)将检验骨骼肌是组织的假设 大多数代谢反应通过雌激素受体的阿尔法作用对8-PN治疗。这项研究 申请人认为，在本申请中提出的建议是创新的，因为到目前为止，还没有系统的研究 检查8-PN对代谢和炎症干扰的保护能力或彻底 在雌激素缺乏模型中评估长期使用8-PN的潜在毒性。拟议的研究 这项调查的结果将对所有女性产生重要的积极影响 因为他们将为未来的临床试验奠定基础，使用8-PN作为治疗负面健康的方法 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.