Cinnamon, CNTF and EAE

肉桂、CNTF 和 EAE

• 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
• 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

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MS的发病机理进行了广泛的研究，但尚无有效的治疗来阻止这种脱髓鞘疾病过程。在MS中，尽管斑块内的少突胶质细胞相对存活和少突胶质细胞前体的募集，但髓磷脂修复通常不足。因此，促进透明度似乎是一个至关重要的治疗挑战。而神经营养蛋白（NGF，NT-3，NT-4/5和BDNF）和神经胶质细胞系衍生的神经营养因子（GDNF）相关因子（GDNF，Neurturin）并没有增加髓质性神经营养因子（CNTF），这会引起肌基神经亲子因子（CNTF）的强烈效果。因此，增加中枢神经系统中的CNTF水平是修复MS中轴突损伤的重要步骤。尽管CNTF的基因操纵和立体定位注射到大脑中是可用的选择，但从治疗角度看来，最好的选择是刺激/诱导MS患者CNS中CNTF的产生。真的有可能吗？我们令人兴奋的初步结果表明，天然化合物是可能的。肉桂是全世界数百年来使用的一种天然香料和调味材料。我们发现，通过实验性过敏性脑脊髓炎（EAE），口服肉桂的口服喂食会增加正常小鼠和小鼠中枢神经系统的CNTF水平。 MS动物模型。一致地，肉桂代谢物苯甲酸钠（NAB）也增加了星形胶质细胞中CNTF的表达。因此，从学术角度来看，我们计划了特定目的I的实验，以研究肉桂代谢物NAB在星形胶质细胞中增加CNTF的分子机制。特定的目标II专门用于治疗目的。在这里，我们想描述口服肉桂在抑制EAE疾病过程中的功效。如果肉桂需要CNTF抑制EAE的疾病过程，则已将特定的目标III列为描述。如果我们的研究成功，它将描述肉桂的新型髓营养活性和每天约1茶匙的肉桂肉，可能会帮助MS患者管理疾病过程，使每位患者的药物成本降低至<$ 10。