Effects of Curcumin Analogs for the Treatment of Endometriosis

姜黄素类似物治疗子宫内膜异位症的作用

• 批准号: 8111213
• 负责人: Friedrich Alfred Wieser
• 金额: $ 18.6万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8111213
• 关键词: Address; Adverse effects; Agonist; Angiogenesis Inhibitors; Animal Model; Anti-Inflammatory Agents; Anti-inflammatory; Antioxidants; Biological Availability; Cell Proliferation; Chronic; Clinical Trials; Curcumin; Danazol; Development; Disease; Drug effect disorder; Endometrium; Estrous Cycle; Exhibits; Fertility; Future; Goals; Grant; Greater sac of peritoneum; Growth; Health Benefit; Hirsutism; Hormonal; Immunocompetent; In Vitro; Inflammatory; Knowledge; Lesion; Lipids; Mediating; Medical; Medroxyprogesterone 17-Acetate; Modality; Modeling; Molecular; Mus; Osteoporosis; Ovary; Peritoneal Fluid; Peritoneal Macrophages; Pharmaceutical Preparations; Postmenopause; Public Health; Rattus; Safety; Symptoms; Testing; Therapeutic Agents; Thioglycolates; Thrombosis; Vascular Endothelial Growth Factors; Woman; Work; alternative treatment; analog; angiogenesis; cell growth; cytokine; endometriosis; hormone therapy; in vivo; in vivo Model; insight; macrophage; mouse model; new therapeutic target; novel therapeutics; pre-clinical; preclinical study; public health relevance; reproductive; response; steroid hormone; transcription factor

DESCRIPTION (provided by applicant): Curcuminoids have been shown to have significant potential in the medical management of chronic inflammatory diseases such as endometriosis. Currently only hormonal therapies including medroxyprogesterone acetate, GnRH-agonists, and danazol are available for the medical treatment of endometriosis. These hormonal treatments are often of limited efficacy and can elicit untoward side-effects due to suppression of endogenous steroid hormone levels. Our application addresses the pressing need for effective alternative endometriosis drugs that do not exhibit hormonal side-effects. We have shown that EF24, our most promising curcumin analog to date, suppresses endometriotic cell growth in an in vitro and in vivo model of endometriosis. Our long-term approach is to develop new endometriosis treatments with higher efficacy and fewer side effects. The overall goal of this grant is to test the mode of action of curcumin analogs on macrophage function, and test their efficacy in an in vivo animal model of endometriosis. This goal will be accomplished by two specific aims. In Aim 1, we will investigate the mechanism of action of curcumin analogs on macrophages. Mechanistic studies will be performed on peritoneal macrophages from thioglycollate treated mice to evaluate anti-inflammatory and antiangiogenic effects of curcumin analogs. In Aim 2, we will evaluate the effects of curcumin analogs on endometriosis in an in vivo model of endometriosis. Using an immunocompetent mouse model, we aim to investigate the effects of curcumin analogs on inflammatory and angiogenic responses of macrophages and on growth of endometriotic lesions. These studies should provide significant insight into the efficacy of curcumin analogs in an endometriosis model and identify novel therapeutic targets for future studies. It is our hope that knowledge gained from these preclinical studies will support the development of new drugs for clinical trials for women with endometriosis. PUBLIC HEALTH RELEVANCE: Endometriosis is a major public health issue. Standard endometriosis treatments are often of limited efficacy and can elicit untoward side-effects due to suppression of endogenous steroid hormone levels and therefore alternative treatments are needed. Knowledge gained from this work will support the development of new drugs for clinical trials for women with endometriosis.

描述（由申请人提供）：姜黄素类化合物已被证明在慢性炎症性疾病（如子宫内膜异位症）的医学管理中具有显著的潜力。目前，只有激素疗法，包括醋酸甲羟孕酮，促性腺激素释放激素激动剂，达那唑可用于子宫内膜异位症的药物治疗。这些激素治疗通常疗效有限，并且由于内源性类固醇激素水平的抑制而可能引起不良副作用。我们的申请解决了对有效的替代子宫内膜异位症药物的迫切需求，这些药物不会产生激素副作用。我们已经证明，EF24，我们最有前途的姜黄素类似物，迄今为止，抑制子宫内膜异位症的体外和体内模型中的增生细胞的生长。我们的长期方法是开发新的子宫内膜异位症治疗方法，具有更高的疗效和更少的副作用。这项资助的总体目标是测试姜黄素类似物对巨噬细胞功能的作用模式，并测试其在子宫内膜异位症体内动物模型中的功效。这一目标将通过两个具体目标来实现。在目的1中，我们将研究姜黄素类似物对巨噬细胞的作用机制。将对巯基乙酸盐处理的小鼠的腹膜巨噬细胞进行机制研究，以评价姜黄素类似物的抗炎和抗血管生成作用。在目标2中，我们将评估姜黄素类似物在子宫内膜异位症体内模型中对子宫内膜异位症的影响。使用免疫活性小鼠模型，我们的目的是研究姜黄素类似物对巨噬细胞的炎症和血管生成反应以及对增生性病变生长的影响。这些研究将为姜黄素类似物在子宫内膜异位症模型中的疗效提供重要的见解，并为未来的研究确定新的治疗靶点。我们希望从这些临床前研究中获得的知识将支持子宫内膜异位症妇女临床试验新药的开发。 公共卫生相关性：子宫内膜异位症是一个主要的公共卫生问题。标准的子宫内膜异位症治疗通常疗效有限，并且由于内源性类固醇激素水平的抑制而可能引起不良副作用，因此需要替代治疗。从这项工作中获得的知识将支持开发用于子宫内膜异位症妇女临床试验的新药。