Cinnamon, CNTF and EAE

肉桂、CNTF 和 EAE

基本信息

批准号：
8675192
负责人：
KALIPADA PAHAN
金额：
$ 36.38万
依托单位：
RUSH UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-06-01 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8675192
关键词：
Animal Model Anti-Inflammatory Agents Anti-inflammatory Applications Grants Astrocytes Attenuated Autoimmune Process Benzoates Bone Marrow Brain Brain-Derived Neurotrophic Factor CREB1 gene Chimera organism Chronic Ciliary Neurotrophic Factor Cinnamon - dietary Clinical Cocoa Powder Demyelinating Diseases Demyelinations Disease Dose Drug Costs Experimental Autoimmune Encephalomyelitis Flavoring Genes Honey Infiltration Inflammatory Injection of therapeutic agent Milk Molecular Multiple Sclerosis Mus Myelin Oligodendroglia Oral Oral Administration Outcome Pathogenesis Patients Plasma Powder dose form Process Production Property Recruitment Activity Relapse Relative (related person)Research Sodium Spices Symptoms Tea Testing Therapeutic Tissues effective therapy feeding glial cell-line derived neurotrophic factor neurotrophic factor neurotrophin 4 neurturin novel oligodendrocyte precursor prevent promoter remyelination repaired research study

项目摘要

DESCRIPTION (provided by applicant): In spite of extensive research on the pathogenesis of MS, no effective therapy is available to halt this demyelinating disease process. In MS, myelin repair is generally insufficient despite the relative survival of oligodendrocytes within the plaques and the recruitment of oligodendrocyte precursors. Promoting remyelination, therefore, appears to be a crucial therapeutic challenge. While neurotrophins (NGF, NT-3, NT-4/5, and BDNF) and glial cell line-derived neurotrophic factor (GDNF)-related factors (GDNF, neurturin) do not increase myelinogenesis, ciliary neurotrophic factor (CNTF) induces a strong promyelinating effect. Therefore, increasing the level of CNTF in the CNS is an important step in repairing axonal damage in MS. Although gene manipulation and stereotaxic injection of CNTF into the brain are available options, it seems from the therapeutic angle, the best option is to stimulate/induce the production of CNTF within the CNS of patients with MS. Is it really possible? Our exciting preliminary results demonstrate that it is possible by a natural compound. Cinnamon is a natural spice and flavoring material used for centuries throughout the world. We have found that oral feeding of ground cinnamon increases the level of CNTF in the CNS of normal mice and mice with experimental allergic encephalomyelitis (EAE); an animal model of MS. Consistently, cinnamon metabolite sodium benzoate (NaB) also increases the expression of CNTF in astrocytes. Therefore, from the academic angle, we have planned experiments in Specific aim I to investigate molecular mechanisms by which cinnamon metabolite NaB increases CNTF in astrocytes. Specific aim II has been devoted for therapeutic purposes. Here we would like to delineate the efficacy of orally administered cinnamon in inhibiting the disease process of EAE. Specific aim III has been enshrined to delineate if cinnamon requires CNTF to inhibit the disease process of EAE. If our study becomes successful, it will describe a novel myelinotrophic activity of cinnamon and ~ 1 teaspoonful of ground cinnamon per day may help MS patients to manage the disease process bringing down the drug cost to <$10 per month for each patient.

描述（由申请人提供）：尽管对多发性硬化症的发病机制进行了广泛的研究，但没有有效的疗法可以阻止这种脱髓鞘疾病的过程。在多发性硬化症中，尽管斑块内少突胶质细胞相对存活并且少突胶质细胞前体细胞募集，但髓磷脂修复通常不足。因此，促进髓鞘再生似乎是一个关键的治疗挑战。虽然神经营养因子（NGF、NT-3、NT-4/5 和 BDNF）和神经胶质细胞源性神经营养因子（GDNF）相关因子（GDNF、neurturin）不会增加髓鞘形成，但睫状神经营养因子（CNTF）会诱导髓鞘形成。强的促髓鞘作用。因此，增加CNS中CNTF的水平是修复MS轴突损伤的重要步骤。虽然基因操作和将CNTF立体定向注射到大脑中是可行的选择，但从治疗角度来看，最好的选择是刺激/诱导MS患者中枢神经系统内CNTF的产生。真的可能吗？我们令人兴奋的初步结果表明，通过天然化合物这是可能的。肉桂是一种天然香料和调味材料，在世界各地使用了几个世纪。我们发现，口服肉桂粉会增加正常小鼠和实验性过敏性脑脊髓炎（EAE）小鼠中枢神经系统中 CNTF 的水平； MS 的动物模型。同样，肉桂代谢物苯甲酸钠 (NaB) 也会增加星形胶质细胞中 CNTF 的表达。因此，从学术角度出发，我们在具体目标一中计划进行实验，研究肉桂代谢物NaB增加星形胶质细胞中CNTF的分子机制。具体目标 II 致力于治疗目的。在这里，我们想描述一下口服肉桂在抑制 EAE 疾病过程中的功效。具体目标 III 已确定肉桂是否需要 CNTF 来抑制 EAE 的疾病过程。如果我们的研究取得成功，它将描述肉桂的一种新型髓磷脂活性，每天约 1 茶匙肉桂粉可以帮助多发性硬化症患者控制疾病过程，从而将每位患者每月的药物成本降低到 <10 美元。